3-acetyl-1H-pyrazole-5-carboxylic acid → (R)-3-acetyl-N-(2-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propyl)-1H-pyrazole-5-carboxamide

HRID 872601Notes

Reaction equation

HRID 872601 reaction equation
[NH2:1][CH2:2][C@H:3]([N:5]1[CH:9]=[CH:8][C:7]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[C:12]([Cl:18])[CH:11]=2)=[N:6]1)[CH3:4].[C:19]([C:22]1[CH:26]=[C:25]([C:27](O)=[O:28])[NH:24][N:23]=1)(=[O:21])[CH3:20]>>[C:19]([C:22]1[CH:26]=[C:25]([C:27]([NH:1][CH2:2][C@H:3]([N:5]2[CH:9]=[CH:8][C:7]([C:10]3[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[C:12]([Cl:18])[CH:11]=3)=[N:6]2)[CH3:4])=[O:28])[NH:24][N:23]=1)(=[O:21])[CH3:20]

Participants

3

Reactant 2

HCID 167673463-acetyl-1H-pyrazole-5-carboxylic acidHCID 67172099(R)-4-(1-(1-aminopropan-2-yl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile

Product 1

HCID 70655883(R)-3-acetyl-N-(2-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propyl)-1H-pyrazole-5-carboxamideYield 56.3%

Procedure

(R)-4-(1-(1-aminopropan-2-yl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile (1.29 mmol) was coupled with 3-acetyl-1H-pyrazole-5-carboxylic acid (259 mg, 1.68 mmol) using the method of Example 34(d). Crude product was purified twice by CombiFlash (1st column: C-18, eluent: 0-100% MeCN in water; 2nd column: silica, eluent: 0-7% MeOH in DCM) to yield 288 mg (56%) of the title compound. 1H-NMR (400 MHz; d6-DMSO): δ 1.49 (d, 3H), 2.48 (s, 3H), 3.56-3.73 (m, 2H), 4.60-4.75 (m, 1H), 6.94 (d, 1H), 7.27 (bs, 1H), 7.87 (d, 1H), 7.91-8.01 (m, 2H), 8.08 (dd, 1H), 8.58 (bs, 1H), 14.2 (bs, 1H).

Workup

  1. customCrude product was purified twice by CombiFlash (1st column: C-18, eluent: 0-100% MeCN in water; 2nd column: silica, eluent: 0-7% MeOH in DCM)

Sources & evidence

ORD record
ord-5fa31dea565b4239941690b140c2437e
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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