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 2063499노트

반응식

HRID 2063499 반응식
[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

참가 물질

8

반응물 5

HCID 10040ThiophosgeneHCID 81531Diisopropylethylamine2회HCID 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

생성물 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-carbothioamide수율 26.9%

시약·촉매·용매 2

HCID 6344Dichloromethane용매3회HCID 57417360Sodium chloride; water용매

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온도
0 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-463794765f4c4cf28c6f671ddfc22ad9
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08288371B2

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