4-fluoro-N-((3R,4S)-3-hydroxy-6-(piperazin-1-yl)chroman-4-yl)benzamide

4-fluoro-N-((3R,4S)-3-hydroxy-6-(piperazin-1-yl)chroman-4-yl)benzamide



HPLC purity = 97.3% (tR = 5.7 min) by HPLC method 2. ee = 100% at 4.68 min by Chiral HPLC method 2.

Specific rotation: [α]D20 = 23.02 (c = 10, 95% EtOH-5% H2O).

1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 8.2 Hz, 1H), 8.02–7.92 (m, 2H), 7.33–7.22 (m, 2H), 6.80 (dd, J = 8.9, 2.9 Hz, 1H), 6.71–6.60 (m, 2H), 5.36 (d, J = 3.9 Hz, 1H), 4.95 (dd, J = 8.2, 5.2 Hz, 1H), 4.12 (dd, J = 10.4, 1.8 Hz, 1H), 3.95–3.83 (m, 2H), 2.84–2.71 (m, 8H), 2.17 (s, 1H).


13C NMR (DMSO-d6, 100 MHz): δ 165.6, 163.1, 148.3, 146.7, 131.3, 130.7, 122.2, 118.2, 117.3, 116.8, 115.4, 67.5, 66.2, 51.5, 46.1, 40.8.


HRMS (ESI+): calcd. for C20H22FN3O3 (M+1): 372.1718, found 372.1712.
S6

INCB-039110, Janus kinase-1 (JAK-1) inhibitor

 INCB-39110,

CAS 1334298-90-6

INCB-039110, Jak1 tyrosine kinase inhibitor

3-​Azetidineacetonitril​e, 1-​[1-​[[3-​fluoro-​2-​(trifluoromethyl)​-​4-​pyridinyl]​carbonyl]​-​4-​piperidinyl]​-​3-​[4-​(7H-​pyrrolo[2,​3-​d]​pyrimidin-​4-​yl)​-​1H-​pyrazol-​1-​yl]​-

 C26H23F4N9O (MW, 553.51)

{ l- { l-[3-fluoro-2- (trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)-lH-pyrazol-l-yl]azetidin-3-yl}acetonitrile

2-(3-(4-(7H-pyrrolo[2,3-( Jpyrimidin-4-yl)-lH- pyrazol- 1 -yl)- 1 -( 1 -(3 -fluoro-2-(trifluoromethyl)isonicotinoyl)piperidin-4-yl)azetidin- 3-yl)acetonitrile

2-(3-(4-(7H- Pyrrolo[2,3 -i/]pyrimidin-4-yl)- lH-pyrazol- 1 -yl)- 1 -(1 -(3 -fluoro-2- (trifluoromethyl)isonicotinoyl)piperidin-4-yl)azetidin-3-yl)acetonitrile adipateMAY BE THE DRUG… HAS CAS 1334302-63-4

ADIPATE OF INCB-39110

ALSO/OR

3-​Azetidineacetonitril​e, 1-​[1-​(3-​fluorobenzoyl)​-​4-​methyl-​4-​piperidinyl]​-​3-​[4-​(7H-​pyrrolo[2,​3-​d]​pyrimidin-​4-​yl)​-​1H-​pyrazol-​1-​yl]​-​, 2,​2,​2-​trifluoroacetateMAY BE THE DRUG ????…  HAS CAS  1334300-52-5

US 2011/0224190 is the pdt patent

base

smilesN#CCC6(n3cc(c1ncnc2[n]ccc12)cn3)CN(C5CCN(C(=O)c4ccnc(C(F)(F)F)c4F)CC5)C6

http://www.google.com/patents/US20130060026

free base (22, 7.00 g, 93.5%) as an off-white solid. For 22:

1H NMR (400 MHz, (CD3)2SO) δ 12.17 (d, J=2.8 Hz, 1H), 8.85 (s, 1H), 8.70 (m, 2H), 8.45 (s, 1H), 7.93 (t, J=4.7 Hz, 1H), 7.63 (dd, J=3.6, 2.3 Hz, 1H), 7.09 (dd, J=3.6, 1.7 Hz, 1H), 4.10 (m, 1H), 3.78 (d, J=7.9 Hz, 2H), 3.61 (t, J=7.9 Hz, 1H), 3.58 (s, 2H), 3.46 (m, 1H), 3.28 (t, J=10.5 Hz, 1H), 3.09 (ddd, J=13.2, 9.5, 3.1 Hz, 1H), 2.58 (m, 1H), 1.83-1.75 (m, 1H), 1.70-1.63 (m, 1H), 1.35-1.21 (m, 2H) ppm;

13C NMR (101 MHz, (CD3)2SO) δ 160.28, (153.51, 150.86), 152.20, 150.94, 149.62, (146.30, 146.25), 139.48, (134.78, 134.61), (135.04, 134.92, 134.72, 134.60, 134.38, 134.26, 134.03, 133.92), 129.22, 127.62, 126.84, 121.99, 122.04, (124.77, 122.02, 119.19, 116.52), 117.39, 113.00, 99.99, 61.47, 60.49, 57.05, 44.23, 28.62, 27.88, 27.19 ppm;

C26H23F4N9O (MW, 553.51), LCMS (EI) m/e 554.1 (M′+H).

ADIPATE

Example 8

2-(3-(4-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(1-(3-fluoro-2-(trifluoromethyl)isonicotinoyl)piperidin-4-yl)azetidin-3-yl)acetonitrile adipate (25)

Step 1. 2-(3-(4-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(1-(3-fluoro-2-(trifluoromethyl)isonicotinoyl)piperidin-4-yl)azetidin-3-yl)acetonitrile adipate crude salt (24)

The process of making compound 22 in Example 7 was followed, except that the final organic phase was concentrated by vacuum distillation to the minimum volume to afford crude compound 22, which was not isolated but was directly used in subsequent adipate salt formation process. To the concentrated residue which containing crude compound 22 was added methanol (200 mL) at room temperature. The mixture was the concentrated by vacuum distillation to a minimum volume. The residue was then added methanol (75 mL) and the resulting solution was heated to reflux for 2 hours. Methyl isobutyl ketone (MIBK, 75 mL) was added to the solution and the resulting mixture was distilled under vacuum to about 30 mL while the internal temperature was kept at 40-50° C. Methanol (75 mL) was added and the resulting mixture was heated to reflux for 2 hours. To the solution was added MIBK (75 mL). The mixture was distilled again under vacuum to about 30 mL while the internal temperature was kept at 40-50° C. To the solution was added a solution of adipic acid (23, 2.15 g, 14.77 mmol) in methanol (75 mL). The resultant solution was then heated to reflux for 2 hours. MIBK (75 mL) was added. The mixture was distilled under vacuum to about 60 mL while the internal temperature was kept at 40-50° C. Heating was stopped and heptane (52.5 mL) was added over 1-2 hours. The resultant mixture was stirred at 20±5° C. for 3-4 hours. The white precipitates were collected by filtration, and the filter cake was washed with heptane (2×15 mL). The solid was dried on the filter under nitrogen with a pulling vacuum at 20±5° C. for 12 hours to provide compound 24 (crude adipate salt, 8.98 g, 12.84 mmol., 95.0%). For 24: 1H NMR (400 MHz, (CD3)2SO) δ 12.16 (s, 1H), 12.05 (brs, 2H), 8.85 (s, 1H), 8.72 (s, 1H), 8.69 (d, J=4.7 Hz, 1H), 8.45 (s, 1H), 7.93 (t, J=4.7 Hz, 1H), 7.63 (dd, J=3.6, 2.3 Hz, 1H), 7.09 (dd, J=3.6, 1.7 Hz, 1H), δ 4.11 (dt, J=11.0, 4.4 Hz, 1H), 3.77 (d, J=7.8 Hz, 2H), 3.60 (t, J=7.8 Hz, 2H), 3.58 (s, 2H), 3.44 (dt, J=14.4, 4.6 Hz, 1H), 3.28 (t, J=10.4 Hz, 1H), 3.09 (ddd, J=13.2, 9.6, 3.2 Hz, 1H), 2.58 (tt, J=8.6, 3.5 Hz, 1H), 2.28-2.17 (m, 4H), 1.83-1.74 (m, 1H), 1.67 (d, J=11.0 Hz, 1H), 1.59-1.46 (m, 4H), 1.37-1.21 (m, 2H) ppm; 13C NMR (101 MHz, (CD3)2SO) δ 174.38, 160.29, (153.52, 150.87), 152.20, 150.94, 149.63, (146.30, 146.25), 139.48, (134.79, 134.62), (135.08, 134.97, 134.74, 134.62, 134.38, 134.28, 134.04, 133.93), 129.21, 127.62, 126.84, 122.05, (124.75, 122.02, 119.29, 116.54), 117.39, 113.01, 99.99, 61.47, 60.50, 57.06, 44.24, 33.42, 30.70, 28.63, 27.89, 27.20, 24.07 ppm; C32H33F4N9O5 (Mol. Wt: 699.66; 24: C26H23F4N9O, MW 553.51), LCMS (EI) m/e 554.0 (M++H).

Step 2.

2-(3-(4-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(1-(3-fluoro-2-(trifluoromethyl)isonicotinoyl)piperidin-4-yl)azetidin-3-yl)acetonitrile adipate (25)

In a 100 L dried reactor equipped with a mechanical stirrer, a thermocouple, an addition funnel and a nitrogen inlet was added compound 24 (3.40 kg, 4.86 mol) and acetone (23.8 L). The resulting white turbid was heated to 55-60° C. to provide a clear solution. The resultant solution was filtered through an in-line filter to another 100 L reactor. Heptane (23.8 L) was filtered through an in-line filter to a separated 50 L reactor. The filtered heptane was then charged to the acetone solution in the 100 L reactor at a rate while the internal temperature was kept at 55-60° C. The reaction mixture in the 100 L reactor was then cooled to 20±5° C. and stirred at 20±5° C. for 16 hours. The white precipitates were collected by filtration and the cake was washed with heptane (2×5.1 L) and dried on the filter under nitrogen with a pulling vacuum. The solid was further dried in a vacuum oven at 55-65° C. with nitrogen purge to provide compound 25 (3.11 kg, 92.2%) as white to off-white powder. For 25:

ADIPATE OF INCB 39110

1H NMR (400 MHz, (CD3)2SO) δ 12.16 (s, 1H), 12.05 (brs, 2H), 8.85 (s, 1H), 8.72 (s, 1H), 8.69 (d, J=4.7 Hz, 1H), 8.45 (s, 1H), 7.93 (t, J=4.7 Hz, 1H), 7.63 (dd, J=3.6, 2.3 Hz, 1H), 7.09 (dd, J=3.6, 1.7 Hz, 1H), δ 4.11 (dt, J=11.0, 4.4 Hz, 1H), 3.77 (d, J=7.8 Hz, 2H), 3.60 (t, J=7.8 Hz, 2H), 3.58 (s, 2H), 3.44 (dt, J=14.4, 4.6 Hz, 1H), 3.28 (t, J=10.4 Hz, 1H), 3.09 (ddd, J=13.2, 9.6, 3.2 Hz, 1H), 2.58 (tt, J=8.6, 3.5 Hz, 1H), 2.28-2.17 (m, 4H), 1.83-1.74 (m, 1H), 1.67 (d, J=11.0 Hz, 1H), 1.59-1.46 (m, 4H), 1.37-1.21 (m, 2H) ppm;

13C NMR (101 MHz, (CD3)2SO) δ 174.38, 160.29, (153.52, 150.87), 152.20, 150.94, 149.63, (146.30, 146.25), 139.48, (134.79, 134.62), (135.08, 134.97, 134.74, 134.62, 134.38, 134.28, 134.04, 133.93), 129.21, 127.62, 126.84, 122.05, (124.75, 122.02, 119.29, 116.54), 117.39, 113.01, 99.99, 61.47, 60.50, 57.06, 44.24, 33.42, 30.70, 28.63, 27.89, 27.20, 24.07 ppm;

C32H33F4N9O5 (Mol. Wt: 699.66; free base: C26H23F4N9O (MW, 553.51), LCMS (EI) m/e 554.0 (M++H).

LY 3000328

LY 3000328

Eli Lilly….INNOVATOR

(3R,4S)-4-(4-fluorobenzamido)-6-(4-(oxetan-3-yl)piperazin-1-yl methylcarbamate

Specific rotation: [α]D25 = 55.19 (c = 10,DMSO).

Cathepsin S (Cat S) plays an important role in many pathological conditions, including abdominal aortic aneurysm (AAA). Inhibition of Cat S may provide a new treatment for AAA. To date, several classes of Cat S inhibitors have been reported, many of which form covalent interactions with the active site Cys25. Herein, we report the discovery of a novel series of noncovalent inhibitors of Cat S through a medium-throughput focused cassette screen and the optimization of the resulting hits. Structure-based optimization efforts led to Cat S inhibitors such as 5 and 9 with greatly improved potency and drug disposition properties. This series of compounds binds to the S2 and S3 subsites without interacting with the active site Cys25.

On the basis of in vitro potency, selectivity, and efficacy in a CaCl2-induced AAA in vivo model, 5(LY3000328) was selected for clinical development.

Discovery of Cathepsin S Inhibitor LY3000328 for the Treatment of Abdominal Aortic Aneurysm
http://pubs.acs.org/doi/full/10.1021/ml500283g

Prabhakar K. Jadhav *,et al

Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, United States

ACS Med. Chem. Lett., Article ASAP

DOI: 10.1021/ml500283g

Publication Date (Web): August 27, 2014

Copyright © 2014 American Chemical Society

see

http://pubs.acs.org/doi/suppl/10.1021/ml500283g/suppl_file/ml500283g_si_001.pdf

 http://pubs.acs.org/doi/suppl/10.1021/ml500283g/suppl_file/ml500283g_si_001.pdf

ABDOMINAL AORTIC ANEURYSM
Classification and external resources
CT reconstruction image of an abdominal aortic aneurysm

Abdominal aortic aneurysm (also known as AAA,[1] pronounced “triple-a”) is a localized dilatation (ballooning) of the abdominal aortaexceeding the normal diameter by more than 50 percent, and is the most common form of aortic aneurysm. Approximately 90 percent of abdominal aortic aneurysms occurinfrarenally (below the kidneys), but they can also occur pararenally (at the level of the kidneys) orsuprarenally (above the kidneys). Such aneurysms can extend to include one or both of the iliac arteries in the pelvis.

Abdominal aortic aneurysms occur most commonly in individuals between 65 and 75 years old and are more common among men and smokers. They tend to cause no symptoms, although occasionally they cause pain in the abdomen and back (due to pressure on surrounding tissues) or in the legs (due to disturbed blood flow). The major complication of abdominal aortic aneurysms is rupture, which is life-threatening, as large amounts of blood spill into theabdominal cavity, and can lead to death within minutes.[2] Mortality of rupture repair in the hospital is 60% to 90%.

Treatment is usually recommended when an AAA grows to >5.5 cm in diameter. While in the past the only option for the treatment of AAA was open surgery, today most are treated with Endovascular Aneurysm Repair (EVAR).[3] EVAR has been widely adopted, as EVAR has a lower risk of death associated with surgery (0.5% for EVAR vs 3% for open surgery).[4] Open surgery is sometimes still preferred to EVAR, as EVAR requires long-term surveillance with CT Scans.[5]

There is moderate evidence to support screening in individuals with risk factors for abdominal aortic aneurysms (e.g., males ≥65).

DATA

HPLC purity = 98.6% (tR = 24.2 min) by HPLC method 3. ee = 99.9% (tR = 23.6 min) by Chiral HPLC method 4.

Specific rotation: [α]D25 = +55.19 (c = 10,DMSO).

1H NMR (400 MHz, DMSO-d6) δ 8.92 (d, J = 7.8 Hz, 1H), 8.01 – 7.90 (m, 2H), 7.34 –
7.23 (m, 2H), 7.19 (q, J = 4.5 Hz, 1H), 6.87 (dd, J = 9.0, 2.9 Hz, 1H), 6.78 – 6.69 (m, 2H), 5.03
(dd, J = 8.1, 3.7 Hz, 1H), 4.86 (td, J = 4.1, 1.8 Hz, 1H), 4.52 (t, J = 6.5 Hz, 2H), 4.41 (t, J = 6.0
Hz, 2H), 4.23 (dd, J = 11.8, 1.9 Hz, 1H), 4.13 (ddd, J = 11.8, 4.4, 1.6 Hz, 1H), 3.39 (p, J = 6.3
Hz, 1H), 2.96 (t, J = 4.9 Hz, 4H), 2.52 (d, J = 4.5 Hz, 3H), 2.34 (t, J = 4.9 Hz, 4H).

13C NMR (DMSO-d6, 100 MHz): δ 165.4, 164.5 (d, J = 248.7 Hz), 156.1, 148.2, 146.2, 131.0, 130.8 (d, J =
9.5 Hz), 120.9, 118.6, 117.6, 117.2, 115.6 (d, J = 21.3 Hz), 74.8, 68.7, 64.3, 58.9, 49.8, 49.5,
47.7, 27.4.

HRMS (ESI+): calcd. for C25H30FN4O5 (M+1): 485.2195, found 485.2188.

1H nmr LY3000328

13 C nmr LY3000328

 

1. Logan, Carolynn M.; Rice, M. Katherine (1987). Logan’s Medical and Scientific Abbreviations. Philadelphia: J. B. Lippincott Company. p. 3.ISBN 0-397-54589-4.
2.  Upchurch GR, Schaub TA (2006). “Abdominal aortic aneurysm”. Am Fam Physician 73(7): 1198–204. PMID 16623206.
3.  Chadi SA et al (2012). “Trends in management of abdominal aortic aneurysms”. J Vasc Surg 55 (4): 924–8. doi:10.1016/j.jvs.2011.10.094.PMID 22226189.
4.  Lederle FA, Freishlag JA et al (209). “Outcomes Following Endovascular vs Open Repair of Abdominal Aortic Aneurysm: A Randomized Trial”.JAMA 302 (14): 1535–42.doi:10.1001/jama.2009.1426. PMID 19826022.
5.  Kirkpatrick VE et al (Dec 2013). “Surveillance Computed Tomographic Arteriogram (CTA) Does Not Change Management before Three Years in Patients Who Have a Normal Post-EVAR Study”. Ann Vasc Surg 28 (4): 831–6. doi:10.1016/j.avsg.2013.09.017.PMID 24361383

Keywords:

Cathepsin, abdominal aortic aneurysm, development candidate, noncovalent, Cathepsin S Inhibitor,  LY3000328,

Byakangelicin

C18H20O7, 348.00

IR

(KBr) 1728, 1617, 1479, 1143

MASS

FABMS m/z 349 [M + H]+

1H NMR

(300 MHz, CDCL3) δ : 1.26 (3H, s, H-4"), 1.29 (3H, s, H-5"), 3.81 (1H, m, H-2"), 4.16 (OCH3), 4.23 (1H, dd, J = 7.9, 10.1 Hz, H-1b"), 4.57 (1H, dd, J= 2.7, 10.1 Hz, H-1a"), 6.27 (1H, d, J = 9.7 Hz, H-3), 6.99 (1H, d, J = 2.4 Hz, H-3'), 7.61 (1H, d, J = 2.4 Hz, H-4'), 8.10 (1H, d, J = 9.7 Hz, H-4)

13 C NMR

(75 MHz, CDCL3) 

δ : 24.99 (C-4"), 

26.62 (C-5"), 

60.61 (OCH3), 

71.50 (C-3"), 

75.91 (C-2"), 

76.04 (C-1"),

105.34 (C-3'), 

107.32 (C-10),

112.70 (C-3), 

114.39 (C-6), 

126.67 (C-8), 

139.58 (C-4), 

143.77 (C-9),

144.80 (C-5), 

145.21 (C-2'), 

150.09 (C-7), 

160.33 (C-2)

Tricyclo[3.3.1.13,7]decan-1-amine hydrochloride

Tricyclo[3.3.1.13,7]decan-1-amine hydrochloride


A solution of acetamide (0.97 g, 5.0 mmol) in dry THF (15 mL) was treated with
pyridine (0.485 mL, 6.00 mmol) and cooled to 0 °C. Dropwise addition of oxalyl
chloride (0.480 mL, 5.50 mmol) was accompanied by vigorous bubbling and conversion
of the clear, colorless solution to a bright yellow and then turbid orange solution. After
stirring at 0 °C for 30 min., dry propylene glycol (0.73 mL, 10.0 mmol) was added in one
portion and the reaction warmed to room temperature.
During this warming phase, the solution changed, first turning orange brown before lightening to yellow. The reaction was diluted with ethanol before being concentrated to an orange brown oil. The oil was
partitioned between 1 N HCl (10 mL) and MtBE (10 mL) and the organic layer washed
with 1 N HCl (2 x 5 mL). The combined aqueous layers were basified with 4 N NaOH to
pH 11, extracted with EtOAc (3 x 40 mL), dried over Na2SO4, filtered, and concentrated
in vacuo.
The oily residue was suspended in Et2O (8 mL) and treated with 1 M HCl in
Et2O (8 mL). This addition formed a lightly colored slurry which was filtered and
washed with Et2O. After drying under vacuum at 50oC for 16 h, 0.66 g of an off-white solid was recovered
decomp. >330 °C.

1H NMR (400 MHz, DMSO-d6)
δ 8.06 (br s, 3H),
2.06 (br s, 3H),
1.77 (m, 6H),
1.59 (m, 6H).





13C NMR (100 MHz, DMSO-d6)
δ 50.8,
40.1,
35.1,
28.2.





 Substance data agrees with previously reported information.8

PHENYLMETHANAMIE HYDROCHLORIDE

\
1H NMR

δ 8.61 (br s, 3H), 
7.51 (m, 2H), 
7.35 (m, 3H), 
3.97 (s, 2H). NH-CH2

13 C NMR

13C NMR (100 MHz, DMSO-d6) 

δ 134.1, 
128.9, 
128.4, 
128.3, 
42.0.  NH-CH2

Dasotraline, 1R,4S Transnorsertraline, SEP-225289

Dasotraline,  SEP-225289, DSP-225289  

1R,4S Transnorsertraline

Generic Name:Dasotraline
Synonym: SEP-225289
Chemical Name:(1R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine

4(S)-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1(R)-ylamine hydrochloride
CAS Number:675126-05-3, Cas of THE DRUG SUBSTANCE hydrochloride is 675126-08-6
Indication:Attention deficit hyperactivity disorder (ADHD)
Drug Company:Sunovion Pharmaceuticals. Inc. in phase 2 as on sept 2014, Sunovion Pharmaceuticals Inc.

SEE

http://newdrugapprovals.org/2014/09/19/dasotraline-1r4s-transnorsertraline-sep-225289-for-treatment-of-attention-deficit-hyperactivity-disorder-adhd/

PRONUNCIATION da soe tra’ leen
THERAPEUTIC CLAIM Treatment of attention deficit hyperactivity
disorder (ADHD)
CHEMICAL NAMES
1. 1-Naphthalenamine, 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-, (1R,4S)-
2. (1R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine

MOLECULAR FORMULA C16H15Cl2N
MOLECULAR WEIGHT 292.2

SPONSOR Sunovion Pharmaceuticals. Inc.
CODE DESIGNATION SEP-225289
CAS REGISTRY NUMBER 675126-05-3
UNII 4D28EY0L5T
WHO NUMBER 9885

Koenig, Stefan G.; Vandenbossche, Charles P.; Zhao, Hang; Mousaw, Patrick; Singh, Surendra P.; Bakale, Roger P.
Organic Letters, 2009 ,  vol. 11,  2  pG . 433 - 436

http://pubs.acs.org/doi/abs/10.1021/ol802482d

Imidoyl chlorides, generated from secondary acetamides and oxalyl chloride, can be harnessed for a selective and practical deprotection sequence. Treatment of these intermediates with 2 equiv of propylene glycol and warming enables the rapid release of amine hydrochloride salts in good yields. Notably, the reaction conditions are mild enough to allow for a swift deprotection with no observed epimerization of the amino center.

Supporting Information             A Facile Deprotection of Secondary Acetamides

•      PDF
  • ol802482d_si_001.pdf (913.61 kB)

http://pubs.acs.org/doi/suppl/10.1021/ol802482d/suppl_file/ol802482d_si_001.pdf

(1R,4S)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride – Compound 1, Scheme 1 / Table 3, entry 1A:

decomp. > 290 °C.

1H NMR (400 MHz, DMSO-d6) δ 8.71 (s, 3H), 7.71 (d, 1H, J = 7.7 Hz), 7.53 (d, 1H, J = 8.1 Hz), 7.34 (s, 1H), 
7.29 (m, 1H), 7.22 (m, 1H), 7.01 (d, 1H, J = 8.1 Hz), 6.81 (d, 1H, J = 7.7 Hz), 4.56 (s, 
1H), 4.26 (s, 1H), 2.26 (m, 1H), 2.15 (m, 1H), 1.83 (m, 2H).

13C NMR (100 MHz, DMSO-d6) δ 147.3, 138.8, 133.5, 130.9, 130.5, 130.4, 130.0, 128.9, 128.8, 128.3, 128.1, 
126.7, 47.8, 43.0, 27.7, 25.1.

NMR  GRAPHS GIVEN

 

13 C NMR