Dimethylformamide → (S)-N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H,2'H-3,3'-bipyrazole-5-carboxamide

HRID 1409349Notes

Reaction equation

HRID 1409349 reaction equation
[NH:1]1[C:5]([C:6]([OH:8])=O)=[CH:4][C:3]([C:9]2[NH:10][N:11]=[CH:12][CH:13]=2)=[N:2]1.[NH2:14][C@@H:15]([CH3:32])[CH2:16][N:17]1[CH:21]=[CH:20][C:19]([C:22]2[CH:29]=[C:28]([F:30])[C:25]([C:26]#[N:27])=[C:24]([Cl:31])[CH:23]=2)=[N:18]1.CN(C=O)C>O>[Cl:31][C:24]1[CH:23]=[C:22]([C:19]2[CH:20]=[CH:21][N:17]([CH2:16][C@@H:15]([NH:14][C:6]([C:5]3[NH:1][N:2]=[C:3]([C:9]4[NH:10][N:11]=[CH:12][CH:13]=4)[CH:4]=3)=[O:8])[CH3:32])[N:18]=2)[CH:29]=[C:28]([F:30])[C:25]=1[C:26]#[N:27]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 179307531'H,2H-[3,3'-bipyrazole]-5-carboxylic acidHCID 67170587(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile

Product 1

HCID 70980935(S)-N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H,2'H-3,3'-bipyrazole-5-carboxamideYield 15.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The title compound was prepared using the procedure described in Example 3(h) starting from 1H,2′H-3,3′-bipyrazole-5-carboxylic acid (2.245 mmol, 0.4 g) and (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile (1.871 mmol, 0.521 g) and using DMF (10 ml) as the solvent. Water was added to the reaction mixture and the mixture was extracted with EtOAc. The organic phase was washed with 2M Na2CO3, water and brine. The organic phase was dried, filtered and evaporated. The crude product was purified by flash chromatography and preparative HPLC, respectively. 0.1277 g of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6): δ 1.19 (d, 3H), 4.27-4.56 (m, 3H), 6.64 (bs, 1H), 6.84 (bs, 1H), 6.98 (d, 1H), 7.77 (bs, 1H), 7.81-7.87 (m, 2H), 7.93-7.6 (m, 1H), 8.07 (br. s, 1H), 12.57-13.78 (m, 2H).

Workup

  1. customThe title compound was prepared
  2. extractionthe mixture was extracted with EtOAc
  3. washThe organic phase was washed with 2M Na2CO3, water and brine
  4. customThe organic phase was dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by flash chromatography and preparative HPLC

Sources & evidence

ORD record
ord-0776eecd296d48688caefaf43b044b59
Source dataset
uspto-grants-2014_12
Patent number
US08921378B2

Reaction notes

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