IMATINIB

Imatinib

CAS No:- [152459-95-5]

IUPAC Name:- 4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]benzamide

M. P.:- 211-213 °C

MW: 493.604

4-[(4-methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide

-[(4-methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide

N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)-4-((4-methylpiperazin-1-
yl)methyl)benzamide

IMATINIB BASE

http://www.rsc.org/suppdata/cc/c0/c001550d/c001550d.pdf

Mp 206 – 207 °C (lit.:1   207 – 210 °C);

1=  1 Y.‐F. Liu, C.‐L. Wang, Y.‐J. Bai, N. Han, J.‐P. Jiao and X.‐L. Qi, Org. Process Res. Dev., 2008, 12, 490.

 

IR νmax/cm-1 3275.0(w), 2928.5(w),
2796.5(w), 1645.9(m), 1586.0(m), 1575.1(s), 1554.0(m), 1531.5(s), 1510.3(m), 1478.1(m),
1448.9(s), 1416.7(m), 1377.7(m), 1352.2(m), 1334.8(m), 1325.6(m), 1308.8(m), 1290.3(s),
1261.1(m), 1204.3(m), 1164.1(m), 1141.7(m), 1124.6(w), 1102.6(m), 1089.2(w), 1052.0(w),
1024.4(w), 1010.0(m), 992.5(w), 968.3(w), 924.5(w), 886.2(w), 857.9(w), 850.3(w),
807.8(m), 795.7(s), 748.1(m), 703.2(m), 690.1(m), 670.7(m);

δH (d6-DMSO, 600 MHz) =
10.14 (1 H, s, NH), 9.26 (1 H, d, J = 1.5 Hz, 2H-pyridin-3-yl), 8.95 (1 H, s, NH), 8.66 (1 H, dd,
J = 4.8 and 1.2 Hz, 6H-pyridin-3-yl), 8.49 (1 H, d, J = 5.1 Hz, 6H-pyridin-2-amine), 8.46 (1 H,
ddd, J = 7.9, 1.5 and 1.2 Hz, 4H-pyridin-3-yl), 8.06 (1 H, d, J = 1.5 Hz, 3H-2-aminotoluene),
7.89 (2 H, d, J = 8.1 Hz, 2H-benzamide), 7.50 (1 H, dd, J = 7.9 and 4.8 Hz, 5H-pyridin-3-yl),
7.46 (1 H, dd, J = 8.3 and 1.5 Hz, 5H-2-aminotoluene), 7.42 – 7.40 (3 H, m, 3H-benzamide
and 5H-pyridin-2-amine), 7.18 (1 H, d, J = 8.3 Hz, 6H-2-aminotoluene), 3.51 (2 H, s, CH2),
2.50 - 2.20 (8 H, m, piperazine CH2), 2.20 (3 H, s, CCH3), 2.13 (3 H, s, NCH3);

δC (CDCl3,
150 MHz) = 165.42(C), 162.72(C), 160.57(C), 158.99(CH), 151.44(CH), 148.48(CH),
142.52(C), 137.77(C), 136.60(C), 134.92(CH), 133.88(C), 132.66(C), 130.75(CH),
129.28(CH), 127.00(CH), 124.23(C), 123.71(CH), 115.35(CH), 113.19(CH), 108.32(CH),
62.49(CH2), 55.07(CH2), 53.10(CH2), 45.98(CH3), 17.65(CH3);

Rf (MeOH) = 0.09; Rt 3.48,

M+H m/z = 494.2; HRMS calculated for C29H31N7ONa [M + Na]+, 516.2488; found 516.2491.

1H NMR

13 C NMR

REPEAT

1H NMR

13 C NMR

Encenicline (EVP-6124, MT-4666)

EVP-6124 , MT-4666, α7-nAChR agonist
Chemical Name: (R)-7-chloro-N-quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide
Therapy Type: Small Molecule
Target Type: Cholinergic System
CAS : 550999-75-2

C₁₆ H₁₇ Cl N₂ O S

Benzo[b]​thiophene-​2-​carboxamide, N-​(3R)​-​1-​azabicyclo[2.2.2]​oct-​3-​yl-​7-​chloro-

(R)​-​7-​Chloro-​N-​(quinuclidin-​3-​yl)​benzo[b]​thiophene-​2-​carboxamide; EVP 6124

Condition(s): Alzheimer’s Disease, Schizophrenia
U.S. FDA Status: Alzheimer’s Disease (Phase 3), Schizophrenia (Phase 3)
Status in Select Countries: Investigational in Japan
Company: FORUM Pharmaceuticals Inc. (was EnVivo Pharmaceuticals), Mitsubishi Tanabe Pharma
Approved for: None  AS ON SEPT 2014



CAS  550999-74-1
Benzo[b]​thiophene-​2-​carboxamide, N-​(3R)​-​1-​azabicyclo[2.2.2]​oct-​3-​yl-​7-​chloro-​, monohydrochloride
(R)​-​7-​Chloro-​N-​(quinuclidin-​3-​yl)​benzo[b]​thiophene-​2-​carboxamide hydrochloride
Mitsubishi Tanabe Pharma  ..Encenicline-hydrochloride (EVP-6124) for Alzheimer’s disease by partner EnVivo Pharmaceuticals. Mitsubishi Tanabe has licensed EVP-6124 from EnVivo and is currently developing the drug under the code MT-4666.
The drug is a new alpha-7 potentiator intended to improve cognition in patients affected with Alzheimer’s disease. T


http://www.google.com.ar/patents/WO2014051055A1?cl=pt-PT
Synthesis (hereinafter, the compound of Reference Example 25) carboxamide hydrochloride (Reference Example 25) (R) -7 – chloro-N-(quinuclidin-3 – – yl) benzo [b] thiophene-2:
[First Step]
Synthesis of carboxamide (R) -7 – chloro-N-(quinuclidin-3 – – yl) benzo [b] thiophene-2:

-N, N, N ‘, N’-tetra-7 – chloro-1 – benzothiophene -2 – – o-(yl benzotriazol-1) chloroform solution (210mg, 1.0mmol) of carboxylic acid in (10mL) was added (0.70mL, 4.0mmol) and (570mg, 1.5mmol), diisopropylethylamine methyl hexafluorophosphate, (R) – (200mg, 1.0mmol) amine hydrochloride – quinuclidine-3 was added, and the mixture was stirred at room temperature. 16 hours later, was added distilled water, 1.0N sodium hydroxide solution, and extracted with chloroform. Was washed with saturated brine and the organic layer was concentrated and then dried over anhydrous sodium sulfate. (Fuji Silysia Chemical amine silica gel DM1020, chloroform alone – chloroform / methanol = 90/10) on silica gel column chromatography of the crude product obtained was purified by the title compound; was obtained as a white solid (170mg 53%).
¹ _H-NMR (400MHz, _DMSO-d 6)
δ :1.22-1 .38 (1H, m) ,1.53-1 .62 (2H, m) ,1.75-1 .82 (2H, m) ,2.63-2 .73 (4H , m) ,2.84-2 .94 (1H, m) ,3.07-3 .18 (1H, m) ,3.90-4 .00 (1H, m), 7.49 (1H, dd , J = 7.6,8.0 Hz), 7.59 (1H, d, J = 7.6Hz), 7.96 (1H, d, J = 8.0Hz), 8.31 (1H, s) ,8.62-8 .66 (1H, m).
MS (ESI): 321 [M ^{+ H]} +
[Second Step]
Synthesis of the compound of Reference Example 25:

Ethyl acetate solution – solution of hydrogen chloride in ethyl acetate (170mg, 0.53mmol) of the (2.0mL) carboxamide – (R) -7 – chloro-N-(quinuclidin-3 – yl) benzo [b] thiophene-2 was added (4.0M, 0.20mL, 0.80mmol), and the mixture was stirred at room temperature. 10 minutes later, by which is filtered off and the resulting solid was washed with ethyl acetate and hexane, and dried, the compound of Reference Example 25; was obtained as a white solid (170mg 90%).
¹ _H-NMR (400MHz, _DMSO-d 6)
δ :1.70-1 .78 (1H, m) ,1.86-1 .94 (2H, m) ,2.10-2 .19 (2H, m) ,3.18-3 .35 (5H , m) ,3.63-3 .72 (1H, m) ,4.27-4 .36 (1H, m), 7.50 (1H, d, J = 7.6,8.0 Hz), 7 .61 (1H, d, J = 7.6Hz), 7.98 (1H, d, J = 8.0Hz), 8.38 (1H, s) ,9.07-9 .10 (1H, m) ,9.80-9 .85 (1H, m).
MS (ESI): 321 [M ^{+ H]} +

SEE
 http://newdrugapprovals.org/2014/09/16/mitsubishi-tanabe-and-envivo-in-phase-iii-trial-of-alzheimers-disease-treatment-mt-4666/

LAPATINIB DITOSYLATE

LAPATINIB

Title: Lapatinib

• N-(3-Chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)furan-2-yl)quinazolin-4-amine bis(4-methylbenzenesulfonate) monohydrate

http://newdrugapprovals.org/2014/09/14/lapatinib/

Preparation of Lapatinib Ditosylate

To a stirred mixture of Sodiumtriacetoxyborohydride (0.21 g) in Tetrahydrofuran (THF)(2.4 ml) was added N-(3-Chloro-4-(3-fluorobenzyloxy)phenyl)-6-(5-((2- (methylsulfonyl)ethylimino)- methyl)furan-2-yl)quinazolin-4-amine (0.2 g) in THF. The reaction mixture was stirred for 1 hour at 20-25 °C. Reaction was monitored by TLC and on completion of reaction, aqueous NaQH (0.16 g NaOH to 0.8 g demineralized water) was added. The organic layer was separated and added p- Toluenesulfonic acid (0.42) in THF (0.6 ml) and stirred for 3 hours. The solid was filtered and dried under vacuum at 60-65°C till constant weight.

Weight: 0.15 g

Yield: 46.9 %

Purity by HPLC: 96.16%

MS (ES+) m/z: 581 [M+H]+ & 583 [M+H+2]+

1H NMR (400 MHz; DMSO-d6): 2.28 (s, 6H), 3.14 (s, 3H), 3.44 (t, J=8.0 Hz, 2H), 3.55 (t, J=8.0 Hz, 2H), 4.46 (s, 2H), 5.31 (s, 2H), 6.89 (br s, 1H), 7.10 (d, J=7.2 Hz, 4H), 7.20 (m, 1H), 7.23 (br s, 1H), 7.31- 7.36 (m, 3H), 7.47 (d, J=7.2 Hz, 4H), 7.63 (d, J=8.8 Hz, IH), 7.89 (br s, IH), 7.92 (d, J=8.8 Hz, IH), 8.39 (d, J=8.8 Hz, IH), 8.89 (s, IH), 8.98 (s, IH), 9.28 (s, IH, NH), 11.18 (s, IH, NH).

Fresenius Kabi Oncology Ltd.WO 2013080218

Lahiri, Saswata; Gupta, Nitin; Singh, Hemant Kumar; Handa, Vishal; Sanghani, Sunil

6 JUNE 2013, http://www.google.com/patents/WO2013080218A1?cl=en

3-(2-methyloxetan-2-yl)pyridine

3-(2-methyloxetan-2-yl)pyridine

Rf 0.28 (Petr. Ether/EtOAc = 20/80). Yellow liquid. 

1H NMR (CDCl3, 399.57 MHz) 

δ 8.63 (d, J = 2.0 Hz, 1H), 

8.50 (dd, J = 4.8, 1.5 Hz, 1H), 

7.80 – 7.67 (m, 1H), 

7.28 (dd, J = 7.9, 4.9 Hz, 1H), 

4.64 (dt, J = 8.6, 6.3 Hz, 1H), 

4.53 (dt, J = 8.7, 6.6 Hz, 1H), 

2.84 (ddd, J = 10.8, 8.7, 7.0 Hz, 1H), 

2.73 (ddd, J = 10.8, 8.8, 6.6 Hz, 1H), 

1.74 (s, 3H). 

13C NMR (CDCl3, 150.92 MHz)

 δ 148.20, 145.89, 

143.17, 131.48, 123.09, 85.06, 64.74, 

35.47, 30.32. 

FTIR (υmax cm-1) 2970, 2883, 1575, 1415, 1289, 1081, 956, 867, 808, 714. 

HRMS Calcd for C9H12NO: 150.0913; Found (M+H) +: 150.0912. 

1H NMR

13 C NMR

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Eritrea (/ˌɛrɨˈtreɪ.ə/ or /ˌɛrɨˈtriːə/; Tigrinya: ኤርትራ ʾErtrā ; Arabic: إرتريا‎ ... Its name Eritrea is based on the Greek name for the Red Sea (Ἐρυθρὰ ...

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asmara















asmara

Massawa Old City

Eritrea – Island of the Red Seo of Eritrea –
keren



 




 


"Asara" traditional sesami oil press - Eritrea (Saied Ibrahim Yehdego)




 
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