3-acetyl-1H-pyrazole-5-carboxylic acid → (S)-3-acetyl-N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-5-carboxamide

HRID 872614Notes

Reaction equation

HRID 872614 reaction equation
[NH2:1][C@@H:2]([CH3:19])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([C:9]2[CH:16]=[C:15]([F:17])[C:12]([C:13]#[N:14])=[C:11]([Cl:18])[CH:10]=2)=[N:5]1.[C:20]([C:23]1[CH:27]=[C:26]([C:28](O)=[O:29])[NH:25][N:24]=1)(=[O:22])[CH3:21]>>[C:20]([C:23]1[CH:27]=[C:26]([C:28]([NH:1][C@@H:2]([CH3:19])[CH2:3][N:4]2[CH:8]=[CH:7][C:6]([C:9]3[CH:16]=[C:15]([F:17])[C:12]([C:13]#[N:14])=[C:11]([Cl:18])[CH:10]=3)=[N:5]2)=[O:29])[NH:25][N:24]=1)(=[O:22])[CH3:21]

Participants

3

Reactant 2

HCID 167673463-acetyl-1H-pyrazole-5-carboxylic acidHCID 67170587(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile

Product 1

HCID 66576367(S)-3-acetyl-N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-5-carboxamideYield 21%

Procedure

(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile (0.22 g, 0.55 mmol) was coupled with 3-acetyl-1H-pyrazole-5-carboxylic acid (0.17 g, 1.11 mmol) using the method of Example 34(d). Crude product was purified by CombiFlash (column: C-18, eluent: 0-100% MeCN in water) to yield 47 mg (21%) of the title compound. 1H-NMR (400 MHz; MeOD): δ 1.28 (d, 3H), 2.51 (s, 3H), 4.31 (dd, 1H), 4.41 (dd, 1H), 4.52-4.61 (m, 1H), 6.79 (d, 1H), 7.23 (s, 1H), 7.67 (d, 1H), 7.70 (d, 1H), 7.83 (m, 1H).

Workup

  1. customCrude product was purified by CombiFlash (column: C-18, eluent: 0-100% MeCN in water)

Sources & evidence

ORD record
ord-76ea3f3ced6546d886a1804789cbc1d7
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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