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 593370ノート

反応式

HRID 593370 の反応式
[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

参加物

5

反応物 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、化合物

生成物 1

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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-3166208b241646a6b25f36fae3a24cc6
出典データセット
uspto-grants-2016_01
特許番号
US09242943B2

反応ノート

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