1-methyl-1H-imidazole-4-carboxylic acid → (S)-N-{1-[3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1-methyl-1H-imidazole-4-carboxamide

HRID 872802Notes

Reaction equation

HRID 872802 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[N:4]=[CH:3]1.[NH2:10][C@@H:11]([CH3:28])[CH2:12][N:13]1[CH:17]=[CH:16][C:15]([C:18]2[CH:25]=[C:24]([F:26])[C:21]([C:22]#[N:23])=[C:20]([Cl:27])[CH:19]=2)=[N:14]1>>[Cl:27][C:20]1[CH:19]=[C:18]([C:15]2[CH:16]=[CH:17][N:13]([CH2:12][C@@H:11]([NH:10][C:7]([C:5]3[N:4]=[CH:3][N:2]([CH3:1])[CH:6]=3)=[O:9])[CH3:28])[N:14]=2)[CH:25]=[C:24]([F:26])[C:21]=1[C:22]#[N:23]

Participants

3

Reactant 2

HCID 5415091-methyl-1H-imidazole-4-carboxylic acidHCID 67170587(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile

Product 1

HCID 66576525(S)-N-{1-[3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1-methyl-1H-imidazole-4-carboxamide

Procedure

The title compound was prepared using the method of Example 247 starting from 1-methyl-1H-imidazole-4-carboxylic acid and (S)-4-[1-(2-aminopropyl)-1H-pyrazol-3-yl]-2-chloro-6-fluorobenzonitrile (which can be prepared according to Example 34(c)). The crude product was purified by flash chromatography on silica gel by using CH2Cl2-MeOH as a gradient eluent (100:0-99:1). The resulting product was triturated in diethyl ether at RT to afford the title product. 1H NMR (400 MHz, DMSO-d6): 1.21 (31-1, d), 3.74 (3H, s), 4.26 (1H, distorted dd), 4.42 (1H, distorted dd), 4.56 (1H, m), 6.60 (1H, d), 7.43 (1H, d), 7.49 (1H, d), 7.50 (1H, d), 7.75 (1H, dd), 7.87 (1H, m), 7.97 (1H, d).

Workup

  1. customThe title compound was prepared
  2. customThe crude product was purified by flash chromatography on silica gel
  3. customThe resulting product was triturated in diethyl ether at RT

Sources & evidence

ORD record
ord-a0ea532384d74feb94d32a2790d30273
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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