4-chloro-1-(difluoromethyl)-1H-pyrazole-3-carbaldehyde → (R)-5-{5-[(4-chloro-1-difluoromethyl-1H-pyrazol-3-ylmethyl)-amino]-2-fluoro-phenyl}-5-methyl-morpholine-3-thione

HRID 593370노트

반응식

HRID 593370 반응식
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:16])=[C:6]([C@@:8]2([CH3:15])[NH:13][C:12](=[S:14])[CH2:11][O:10][CH2:9]2)[CH:7]=1.[Cl:17][C:18]1[C:19]([CH:26]=O)=[N:20][N:21]([CH:23]([F:25])[F:24])[CH:22]=1.[B][B][B][B][B][B][B][B][B][B]>CO>[Cl:17][C:18]1[C:19]([CH2:26][NH:1][C:2]2[CH:3]=[CH:4][C:5]([F:16])=[C:6]([C@@:8]3([CH3:15])[NH:13][C:12](=[S:14])[CH2:11][O:10][CH2:9]3)[CH:7]=2)=[N:20][N:21]([CH:23]([F:25])[F:24])[CH:22]=1

참가 물질

5

반응물 3

HCID 574971684-chloro-1-(difluoromethyl)-1H-pyrazole-3-carbaldehydeHCID 58155253(R)-5-(5-Amino-2-fluoro-phenyl)-5-methyl-morpholine-3-thioneHCID 178419135HCID 178419135, 화합물

생성물 1

HCID 86667994(R)-5-{5-[(4-chloro-1-difluoromethyl-1H-pyrazol-3-ylmethyl)-amino]-2-fluoro-phenyl}-5-methyl-morpholine-3-thione

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

In a 5 ml-reaction tube under an inert atmosphere a mixture of (R)-5-(5-amino-2-fluoro-phenyl)-5-methyl-morpholine-3-thione (48 mg, 0.2 mmol) and 4-chloro-1-difluoromethyl-1H-pyrazole-3-carbaldehyde (20 mg, 0.11 mmol) in methanol (0.3 ml) was stirred at room temperature for 1 hour. Then decaborane (24 mg, 0.2 mmol) was added in one portion and the mixture warmed to 45° C. for 15 hours. For the workup, the light yellow solution was quenched with sodium carbonate (10% solution), the methanol removed at reduced pressure and then the residue extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulphate, then evaporated at reduced pressure. The crude product was purified by preparative HPLC using a gradient of water (+0.1% triethylamine) and acetonitrile (90:10 to 10:90). The (R)-5-{5-[(4-chloro-1-difluoromethyl-1H-pyrazol-3-ylmethyl)-amino]-2-fluoro-phenyl}-5-methyl-morpholine-3-thione was obtained as a colourless foam (49 mg, 60%); (calculated) C16H16ClF3N4OS [404.84]; (found) [M+H]+=405.

후처리

  1. customIn a 5 ml-reaction tube under an inert atmosphere
  2. temperaturethe mixture warmed to 45° C. for 15 hours
  3. customFor the workup, the light yellow solution was quenched with sodium carbonate (10% solution)
  4. customthe methanol removed at reduced pressure
  5. extractionthe residue extracted three times with ethyl acetate
  6. dry with materialThe combined organic layers were dried over sodium sulphate
  7. customevaporated at reduced pressure
  8. customThe crude product was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-3166208b241646a6b25f36fae3a24cc6
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242943B2

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