2-(Cyanomethyl)-1,3-thiazole-4-carboxylic acid → (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(cyanomethyl)thiazole-4-carboxamide

HRID 872579Notes

Reaction equation

HRID 872579 reaction equation
[C:1]([CH2:3][C:4]1[S:5][CH:6]=[C:7]([C:9]([OH:11])=O)[N:8]=1)#[N:2].[NH2:12][C@@H:13]([CH3:29])[CH2:14][N:15]1[CH:19]=[CH:18][C:17]([C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([Cl:28])[CH:21]=2)=[N:16]1>>[Cl:28][C:22]1[CH:21]=[C:20]([C:17]2[CH:18]=[CH:19][N:15]([CH2:14][C@@H:13]([NH:12][C:9]([C:7]3[N:8]=[C:4]([CH2:3][C:1]#[N:2])[S:5][CH:6]=3)=[O:11])[CH3:29])[N:16]=2)[CH:27]=[CH:26][C:23]=1[C:24]#[N:25]

Participants

3

Reactant 2

HCID 431403362-(Cyanomethyl)-1,3-thiazole-4-carboxylic acidHCID 67170882(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile

Product 1

HCID 70656613(S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(cyanomethyl)thiazole-4-carboxamideYield 1%

Procedure

2-(Cyanomethyl)thiazole-4-carboxylic acid (280 mg, 0.10 mmol) was coupled with (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile using the method of Example 34(d). Crude product was purified twice by CombiFlash (1st column: silica, eluent: 0-100% EtOAc in heptane; 2nd column: C-18 silica, eluent: 0-100% MeCN in water) to obtain 4.9 mg (1%) of the title compound. 1H-NMR (400 MHz; CDCl3): δ 1.26 (d, 3H), 4.13 (s, 2H), 4.31 (dd, 1H), 4.43 (dd, 1H), 4.55-4.67 (m, 1H), 6.63 (d, 1H), 7.49 (d, 1H), 7.70 (d, 1H), 7.79 (dd, 1H), 7.84 (d, 1H), 7.97 (d, 1H), 8.12 (d, 1H).

Workup

  1. customCrude product was purified twice by CombiFlash (1st column

Sources & evidence

ORD record
ord-49a5d1556f2a445eb48322519d00add4
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

Loading…