Triethylamine → HCID 53629161、化合物

HRID 1926744ノート

反応式

HRID 1926744 の反応式
[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

参加物

8

反応物 5

HCID 8471Triethylamine2 回HCID 5049666Sodium triacetoxyborohydride2 回HCID 57742996HCID 57742996、化合物HCID 86631463HCID 86631463、化合物HCID 86631465HCID 86631465、化合物

生成物 1

HCID 53629161HCID 53629161、化合物収率 55%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 6375Nitromethane溶媒

実験手順

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.

後処理

  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))

出典と根拠

ORDレコード
ord-bfe0df0daf3044889c426073aacc0af2
出典データセット
uspto-grants-2012_05
特許番号
US08183241B2

反応ノート

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