(s)-(+)-3-hydroxytetrahydrofuran

(s)-(+)-3-hydroxytetrahydrofuran
84976-47-6

 CAS NO. 84976-47-6, (S)-(+)-3-HYDROXYTETRAHYDROFURAN 13C-NMR spectral analysis






1h nmr predict

4-Amino-indan-5-carboxylic acid methyl ester

https://www.google.com/patents/WO2006002342A1?cl=en

4-Amino-indan-5-carboxylic acid methyl ester

Add 30% aqueous hydrogen peroxide solution (5 mL) in water (44 mL) to a solution of l,6,7,8-Tetrahydro-l-aza-as-indacene-2,3-dione (3.80 mg, 20.3 mmol) and NaOH (5.03 g, 126 mmol) in water (97 mL) over a period of 30 minutes, stir the mixture at room temperature for 1 h. Acidulate with 1 N hydrochloric acid, filter the solid, wash with water and dry to afford 4-amino-indan-5-carboxylic acid (3.13 g, 87%). Dissolve 4- amino-indan-5-carboxylic acid (3.07 g, 17.3 mmol) in ethyl acetate (87 mL) and ethanol (87 mL) and add (trimethylsilyl) diazomethane (17.3 mL, 34.6 mmol, 2 M in hexanes) at room temperature and stir the solution for 1 h. Remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (2.50 g, 76%). ¹H NMR (MeOD, 300 MHz) δ 2.12 (quintuplet, J = 7.6 Hz, 2H), 2.75 (t, J = 7.5 Hz , 2H), 2.89 (t, / = 7.5 Hz , 2H), 3.83 (s, 3H), 6.53 (d, /= 8.1 Hz, IH), 7.66 (d, J = 8.1 Hz, IH). MS (ES+): 192 (M+H).

Methyl 2-amino-5-iodo-4-trifluoromethylbenzoate.

https://www.google.com/patents/WO2006002342A1?cl=en

 Preparation of methyl 2-amino-5-iodo-4-trifluoromethylbenzoate.

Add a solution of methyl 2-amino-4-trifluoromethylbenzoate (178 g, 812 mmol) in ethanol (3.3 L) to a suspension of iodine (206.1 g, 812 mmol) and silver(II) sulfate (253 g, 812 mmol) in ethanol (5 L) at room temperature under an atmosphere of nitrogen and stir for 2 h. Filter the suspension through a pad of a Celite®, wash the pad with additional ethanol (2 L) and remove the solvents from the combined filtrates under reduced pressure at 40 °C. Dissolve the residue in ethyl acetate (7.5 L) and wash with saturated sodium bicarbonate solution (3 X 1.5 L), water (3 X 1.5 L) and brine (2 L). Dry the organic phase over anhydrous magnesium sulfate, filter and remove the solvent under reduced pressure to give the title compound as a pale brown crystalline solid (276.0 g, 99%). ¹H NMR (300 MHz, CDCl₃) D 
8.39 (1 H, s), 
6.99 (1 H, s), 
5.93 (2 H, s), NH2
3.90 (3 H, s).

Methyl 2-amino-4-(trifluoromethyl)benzoate

Methyl 2-amino-4-(trifluoromethyl)benzoate

61500-87-6 CAS
Synonyms:	4-trifluoromethyl-2-aminobenzoic acid methyl ester; 2-AMINO-4-TRIFLUOROMETHYL-BENZOIC ACID METHYL ESTER;

1H NMR (DMSO-d6) δ 3.79 (s, 3h), 6.75 (dd, j=1.84, 8.46 hz, 1H), 6.96 (br s, 2h), 7.11 (d, j=0.73 hz, 1H), 7.83 (d, j=8.09 hz, 1H)








13 C NMR PREDICT




COSY PREDICT

SYNTHESIS

Hill; Stanley; Karoglan Williams; Loev; Fowler; McCafferty; Macko; Berkoff; Ladd Journal of Medicinal Chemistry, 1983 , vol. 26, # 6 p. 865 - 869

ELI LILLY AND COMPANY Patent: WO2006/2342 A1, 2006 ; Location in patent: Page/Page column 55-56 ;

European Journal of Medicinal Chemistry, , vol. 40, # 9 p. 897 - 907



https://www.google.com/patents/WO2006002342A1?cl=en

Preparation of Methyl 2-amino-4-trifluoromethylbenzoate.

Add a solution of methyl 2-nitro-4-trifluoromethylbenzoate (106 g, 425 mmol) in ethyl acetate (2.2 L) to a slurry of 10% palladium on carbon (11.0 g) in ethyl acetate (200 mL) and stir the suspension at room temperature under an atmosphere of hydrogen at 60 psi for 3 h. Filter the suspension through a pad of Celite® and wash the pad with additional ethyl acetate. Remove the solvents under reduced pressure and purify the residue by column chromatography on silica gel, eluting with isohexane/ethyl acetate (9:1), to provide the title compound as a white crystalline solid (84 g, 95%). 
¹H NMR (300 MHz, CD₃OD)
 δ 7.93 (d, / = 8.48 Hz, IH), 
7.06 (s, IH), 
6.78 (s, IH), 
4.86 (s, 3H), NH2  MAYBE
3.89 (s, 3H).

OFLOXACIN

OFLOXACIN

Molecular Formula: C18H20FN3O4; (Formula Weight: 361.37;

mp: 270-275°C;

Ofloxacin is one kind of white or almost powder or off-white solid.

The Systematic (IUPAC) name of this chemical is (RS)-7-fluoro-2-methyl-6-(4-methylpiperazin-1-yl)-10-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboxylic acid

82419-36-1

Apazix; Bactocin; Exocin; Flobacin; Floxal; Floxil; Floxin; Girasid; Monoflocet; Ocuflox; Oflocet; Oflocin; Oxaldin; Tarivid; Urosin; Visiren; Zanocin

DL-8280; HOE-280; Ofloxacinum

1H NMR PREDICT

13 C NMR PREDICT

 OFLOXACIN COSY NMR

OFLOXACIN 13 C

OFLOXACIN

OFLOXACIN 1H NMR

 OFLOXACIN HSQC NMR

 OFLOXACIN MASS SPECTRUM

 OFLOXACIN 13 C NMR

OFLOXACIN.............http://newdrugapprovals.org/2015/03/12/ofloxacin/

OFLOXACIN.............http://newdrugapprovals.org/2015/03/12/ofloxacin/

OFLOXACIN.............http://newdrugapprovals.org/2015/03/12/ofloxacin/

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COCK SAYS MOM CAN TEACH YOU NMR

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AMG 925

AMG 925

1401033-86-0

2-Hydroxy-1-(2-((9-((1r,4r)-4-methylcyclohexyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)ethanone

2-Hydroxy-1-(2-((9-((1R,4R)-4-methylcyclohexyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)ethanone (AMG 925)

FLT3/CDK4 inhibitor,potent and selective

AMG 925 is a dual kinase inhibitor of FLT3 and CDK4 with IC50 value of 1 nM and 3 nM, respectively

C26H29N7O2., 471.55

AMG-925, Current Lot, COA

AMG-925, Current Lot, NMR

AMG-925, Current Lot, HPLC-MS

BY

http://www.chemietek.com/products.aspx?pid=220

......................................................

J. Med. Chem., 2014, 57 (8), pp 3430–3449

DOI: 10.1021/jm500118j

http://pubs.acs.org/doi/abs/10.1021/jm500118j

2-Hydroxy-1-(2-((9-((1r,4r)-4-methylcyclohexyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)ethanone (28)

 compound 28 as a white solid (468 mg, 99% yield).

1H NMR (500 MHz, acetic acid-d4, 373 K) δ ppm 9.43 (1 H, s), 9.35 (1 H, s), 8.63 (1H, d, J = 6.0 Hz), 8.40 (1 H, d, J = 6.0 Hz), 8.33 (1 H, d, J = 8.5 Hz), 7.76 (1 H, d, J = 8.5 Hz), 4.90 (1 H, m), 4.77 (2 H, br s), 4.46 (2 H, br s), 3.88 (2 H, br s), 3.10 (2 H, t, J = 5.4 Hz), 2.68 (2 H, dq, J = 12.7, 3.3 Hz), 2.06–2.13 (2 H, m), 1.99–2.03 (2 H, m), 1.70–1.80 (1 H, m), 1.31–1.43 (2 H, m), 1.09 (3H, d, J = 6.5 Hz).

HRMS (ESI) m/z: calculated for [M + H]+ 472.2455, found 472.2461.

................................................................................

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/op500367p

http://pubs.acs.org/doi/abs/10.1021/op500367p

The development of a synthetic route to manufacture the drug candidate AMG 925 on kilogram scale is reported herein. The hydrochloride salt of AMG 925 was prepared in 23% overall yield over eight steps from commercially available raw materials, and more than 8 kg of the target molecule were delivered. The synthetic route features a Buchwald–Hartwig amination using BrettPhos as ligand and conducted to afford 12 kg of product in a single batch. In addition, this work highlights the challenges associated with the use of poorly soluble process intermediates in the manufacture of active pharmaceutical ingredients. Creative solutions had to be devised to conduct seemingly routine activities such as salt removal, pH adjustment, and heavy metal scavenging due to the low solubility of the process intermediates. Finally, a slurry-to-slurry amidation protocol was optimized to allow for successful scale-up.

Manufacture of 2-Hydroxy-1-(2-((9-((1R,4R)-4-methylcyclohexyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)ethanone (AMG 925)

AMG 925 was isolated in 91.5% yield (8.31 kg), 95.5% overall mass balance, 99.9 wt %, and 99.7 LCAP.

Mp 213–215 °C;

1H NMR (400 MHz, acetic acid-d4, mixture of two rotamers at 20 °C) 9.47–9.59 (m, 2H), 8.76 (d, 1H, J = 6 Hz), 8.55 (d, 1H, J = 6 Hz), 8.48 (d, 1H,J = 9 Hz), 7.79–7.92 (m, 1H), 4.95 (t, 1H,J = 12 Hz), 4.87 and 4.68 (2 singlets, 2H), 4.47–4.59 (m, 2H), 4.04 and 3.80 (2 triplets, 2H, J= 6 Hz), 3.03–3.17 (m, 2H), 2.65–2.82 (m, 2H), 1.96–2.15 (m, 4H), 1.77 (br s, 1H), 1.39 (q, 2H, J = 12 Hz), 1.09 (d, 3H, J = 7 Hz);

13C NMR (100 MHz, acetic acid-d4, mixture of two rotamers at 20 °C) 171.9, 171.8, 158.4, 157.8, 154.7, 149.0, 148.9, 141.6, 135.2, 132.9, 126.3, 124.1, 123.6, 117.7, 113.7, 113.6, 107.5, 107.4, 60.1, 59.9, 56.3, 43.7, 42.6, 40.5, 38.7, 34.0, 31.5, 29.8, 28.8, 28.1, 21.5.

Manufacture of 2-Hydroxy-1-(2-((9-((1R,4R)-4-methylcyclohexyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)ethanone Hydrochloride (AMG 925 HCl)

AMG 925 HCl was isolated in 92.5% yield (7.96 kg), 99.1% overall mass balance, 83.8 wt % AMG 925, 99.75 LCAP AMG 925, 6.2 wt % Cl, 9.6 wt % water, 3800 ppm AcOH, d10 4.0 μm,d50 15.2 μm, d90 38.8 μ, Vm 18.7 μm, BET surface area 1.5 m2/g.

1H NMR (400 MHz, acetic acid-d4, mixture of two rotamers at 20 °C) 9.63 (s, 1H), 9.56 (s, 1H), 8.71–8.76 (m, 1H), 8.60–8.66 (m, 1H), 8.20–8.29 (m, 1H), 7.90–7.98 (m, 1H), 4.90–5.01 (m, 1H), 4.86 and 4.70 (2 singlets, 2H), 4.53 and 4.51 (2 singlets, 2H), 4.05 and 3.82 (2 triplets, 2H, J = 6 Hz), 3.11–3.26 (m, 2H), 2.68 (q, 2H, J = 12 Hz), 1.95–2.13 (m, 4H), 1.74 (br s, 1H), 1.36 (q, 2H, J = 12 Hz), 1.06 (d, 3H, J = 8 Hz);

13C NMR (100 MHz, acetic acid-d4, mixture of two rotamers at 20 °C) 174.9, 174.8, 161.3, 161.2, 160.5, 157.5, 151.6, 151.5, 149.3, 148.9, 145.5, 138.1, 136.0, 129.3, 129.2, 127.1, 126.6, 120.9, 116.7, 116.6, 110.8, 110.7, 63.0, 62.9, 59.3, 46.4, 45.3, 43.2, 41.3, 36.9, 34.3, 32.6, 31.3, 30.6, 24.4; exact mass [C26H29N7O2 + H]+: calculated = 472.2461, measured = 472.2451.

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