1-Phenyl-1H-pyrazole-4-carbaldehyde → HCID 25165321, compound

HRID 1178161Notes

Reaction equation

HRID 1178161 reaction equation
C([BH3-])#N.[Na+].[C:5]1([N:11]2[CH:15]=[C:14]([CH:16]=O)[CH:13]=[N:12]2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Cl.[NH2:19][CH2:20][C:21]([N:23]1[CH2:28][CH2:27][N:26]([C:29](=[O:41])[C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=2[C:37]([F:40])([F:39])[F:38])[CH2:25][CH2:24]1)=[O:22]>CO.[Cl-].[Zn+2].[Cl-]>[F:36][C:34]1[CH:33]=[CH:32][C:31]([C:37]([F:39])([F:38])[F:40])=[C:30]([CH:35]=1)[C:29]([N:26]1[CH2:27][CH2:28][N:23]([C:21](=[O:22])[CH2:20][NH:19][CH2:16][C:14]2[CH:13]=[N:12][N:11]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:15]=2)[CH2:24][CH2:25]1)=[O:41]

Participants

6

Reactant 3

HCID 9520891-Phenyl-1H-pyrazole-4-carbaldehydeHCID 5003444Sodium cyanoborohydrideHCID 669531292-Amino-1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]ethanone hydrochloride

Product 1

HCID 25165321HCID 25165321, compoundYield 18.8%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Procedure

A mixture of sodium cyano borohydride (100 mg, 1.6 mmol) and zinc chloride (100 mg, 0.73 mmol) was added in portions to a cold solution of 1-phenyl-1H-pyrazole-4-carbaldehyde (60 mg, 0.35 mmol) and 2-amino-1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride salt (142 mg, 0.38 mmol) in methanol (10 ml) and stirring was continued at room temperature overnight. The reaction mixture was concentrated under reduced pressure to get the residue. The residue was quenched with saturated aqueous sodium bicarbonate solution and extracted with EtOAc. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to get the residue. The obtained residue was purified by preparative HPLC [(Column-AU/SP/C18-28/006, mobile phase-0.1% TFA in water (A)/acetonitrile (B), flow: 6 mL/minute, gradient: (% B)-0:20; 2:30; 8:70)]) to afford 32 mg (18.8% yield) of 1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-[(1-phenyl-1H-pyrazol-4-ylmethyl)-amino]-ethanone. LCMS Purity: 98.11%. 1H NMR (DMSO-d6): δ 9.2 (s, 2H), 8.6 (d, 1H), 8.0-7.76 (m, 4H), 7.62 (m, 2H), 7.4 (t, 1H), 4.2-4.0 (d, 4H), 3.8 (s, 1H), 3.66-3.44 (m, 4H), 3.3 (d, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto get the residue
  3. customThe residue was quenched with saturated aqueous sodium bicarbonate solution
  4. extractionextracted with EtOAc
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto get the residue
  8. customThe obtained residue was purified by preparative HPLC [(Column-AU/SP/C18-28/006, mobile phase-0.1% TFA in water (A)/acetonitrile (B), flow

Sources & evidence

ORD record
ord-20b6370cf62546c8851a692d51ad1af2
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

Loading…