Thiophosgene → (R)-2-(4-(4-chlorobenzyl)-5-methyl-4H-1,2,4-triazol-3-yl)-N-(2-methyl-6-(trifluoromethyl)pyridin-3-yl)pyrrolidine-1-carbothioamide

HRID 2063499ノート

反応式

HRID 2063499 の反応式
[C:1](Cl)(Cl)=[S:2].[CH3:5][C:6]1[C:11]([NH2:12])=[CH:10][CH:9]=[C:8]([C:13]([F:16])([F:15])[F:14])[N:7]=1.C(N(CC)C(C)C)(C)C.Cl.[Cl:27][C:28]1[CH:46]=[CH:45][C:31]([CH2:32][N:33]2[C:37]([C@H:38]3[CH2:42][CH2:41][CH2:40][NH:39]3)=[N:36][N:35]=[C:34]2[CH2:43]C)=[CH:30][CH:29]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.[Cl-].[Na+].O>[Cl:27][C:28]1[CH:46]=[CH:45][C:31]([CH2:32][N:33]2[C:34]([CH3:43])=[N:35][N:36]=[C:37]2[C@H:38]2[CH2:42][CH2:41][CH2:40][N:39]2[C:1](=[S:2])[NH:12][C:11]2[C:6]([CH3:5])=[N:7][C:8]([C:13]([F:14])([F:16])[F:15])=[CH:9][CH:10]=2)=[CH:30][CH:29]=1

参加物

8

反応物 5

HCID 10040ThiophosgeneHCID 81531Diisopropylethylamine2 回HCID 516892Sodium BicarbonateHCID 35218502-methyl-6-(trifluoromethyl)pyridin-3-amineHCID 68811647(R)-4-(4-chlorobenzyl)-3-ethyl-5-(pyrrolidin-2-yl)-4H-1,2,4-triazole HCl salt

生成物 1

HCID 57650139(R)-2-(4-(4-chlorobenzyl)-5-methyl-4H-1,2,4-triazol-3-yl)-N-(2-methyl-6-(trifluoromethyl)pyridin-3-yl)pyrrolidine-1-carbothioamide収率 26.9%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒3 回HCID 57417360Sodium chloride; water溶媒

反応条件

温度
0 °C

実験手順

To a stirring solution of thiophosgene (0.23 mL, 3 mmol) in 50 mL of CH2Cl2 at 0° C. was added dropwise a mixed solution of 2-methyl-6-(trifluoromethyl)pyridin-3-amine (0.528 g, 3 mmol) and N,N-diisopropylethylamine (0.522 mL, 3 mmol) in dichloromethane (10 mL). The reaction mixture was stirred at 0° C., warming up to room temperature within an hour. Then the mixture was cooled at 0° C. and to it was added a solution of the (R)-4-(4-chlorobenzyl)-3-ethyl-5-(pyrrolidin-2-yl)-4H-1,2,4-triazole HCl salt (1.05 g, 3 mmol) and N,N-diisopropylethylamine (1.044 mL, 6 mmol) in dichloromethane (10 mL) slowly. The resulting mixture was stirred 0° C. for 30 minutes, then at room temperature overnight. The reaction mixture was treated with sat. aqueous NaHCO3 (10 mL) and brine, dried over Na2SO4, and concentrated in vacuo. Flash chromatography purification (Hex/EtOAc with 10% of MeOH) afforded the desired product as yellow solid (0.4 g, 26.9%).

後処理

  1. temperaturewarming up to room temperature within an hour
  2. temperatureThen the mixture was cooled at 0° C. and to it
  3. stirringThe resulting mixture was stirred 0° C. for 30 minutes
  4. customat room temperature
  5. customovernight
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customFlash chromatography purification (Hex/EtOAc with 10% of MeOH)

出典と根拠

ORDレコード
ord-463794765f4c4cf28c6f671ddfc22ad9
出典データセット
uspto-grants-2012_10
特許番号
US08288371B2

反応ノート

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