Triethylamine → HCID 53629161, compound

HRID 1926744Notes

Reaction equation

HRID 1926744 reaction equation
[CH3:1][C:2]1[C:6]([CH:7]=O)=[C:5]([CH3:9])[N:4]([S:10]([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[N:3]=1.Cl.[NH2:21][CH2:22][CH:23]([C:30]1[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([F:37])[C:31]=1[F:38])[CH2:24][C:25](OCC)=[O:26].FC1C(F)=CC(F)=CC=1C=CC(OCC)=O.C(N(CC)CC)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.[N+](C)([O-])=O>[CH3:1][C:2]1[C:6]([CH2:7][N:21]2[CH2:22][CH:23]([C:30]3[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([F:37])[C:31]=3[F:38])[CH2:24][C:25]2=[O:26])=[C:5]([CH3:9])[N:4]([S:10]([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[N:3]=1

Participants

8

Reactant 5

HCID 8471Triethylamine2×HCID 5049666Sodium triacetoxyborohydride2×HCID 57742996HCID 57742996, compoundHCID 86631463HCID 86631463, compoundHCID 86631465HCID 86631465, compound

Product 1

HCID 53629161HCID 53629161, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6375NitromethaneSolvent

Procedure

In a 100 ml three-necked flask fitted with a magnetic stirrer, under inert atmosphere, 3,5-dimethyl-1-[(4-methylphenyl)sulfonyl]-1H-pyrazole-4-carbaldehyde x56 (0.87 g, 3.1 mmol) and ethyl 4-amino-3-(2,3,5-trifluorophenyl)butanoate hydrochloride x60 (synthesized from nitromethane and ethyl 3-(2,3,5-trifluorophenyl)acrylate by the same methodology as described in Kenda et al., J. Med. Chem. (2004), 47, 530-49; 0.94 g, 3.1 mmol) are dissolved in CH2Cl2 (30 ml). Triethylamine (0.86 ml, 6.3 mmol) and NaBH(OAc)3 (1.33 g, 6.3 mmol) are added and the heterogeneous mixture became a solution. After 16 h at room temperature, two additional portions of NaBH(OAc)3 are added (1.6 mmol after 16 h and 3.2 mmol after 48 h) and 1.6 mmol of triethylamine are added after 24 h stirring at room temperature. The reaction is quenched with water and the aqueous phase is extracted three times with diethylether. The combined organic phases are washed with brine, dried over MgSO4, filtered and concentrated to dryness. The crude product is purified by column chromatography on silicagel (CH2Cl2/MeOH/NH4OH: 95/4.5/0.5 (v/v/v)) to afford 0.83 g of 1-({3,5-dimethyl-1-[(4-methylphenyl)sulfonyl]-1H-pyrazol-4-yl}methyl)-4-(2,3,5-trifluorophenyl)pyrrolidin-2-one x61.

Workup

  1. additionare added after 24 h
  2. customThe reaction is quenched with water
  3. extractionthe aqueous phase is extracted three times with diethylether
  4. washThe combined organic phases are washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude product is purified by column chromatography on silicagel (CH2Cl2/MeOH/NH4OH: 95/4.5/0.5 (v/v/v))

Sources & evidence

ORD record
ord-bfe0df0daf3044889c426073aacc0af2
Source dataset
uspto-grants-2012_05
Patent number
US08183241B2

Reaction notes

Loading…