4-Methylmorpholine → (S)-tert-Butyl 2-(4-(1-(3-(difluoromethoxy)phenyl)-1H-pyrazole-4-carboxamido)-3-fluorophenyl)morpholine-4-carboxylate

HRID 571844ノート

反応式

HRID 571844 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][C:3]=1[F:21].[F:22][CH:23]([F:39])[O:24][C:25]1[CH:26]=[C:27]([N:31]2[CH:35]=[C:34]([C:36](O)=[O:37])[CH:33]=[N:32]2)[CH:28]=[CH:29][CH:30]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>O.CN(C=O)C>[F:39][CH:23]([F:22])[O:24][C:25]1[CH:26]=[C:27]([N:31]2[CH:35]=[C:34]([C:36]([NH:1][C:2]3[CH:7]=[CH:6][C:5]([C@@H:8]4[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:9]4)=[CH:4][C:3]=3[F:21])=[O:37])[CH:33]=[N:32]2)[CH:28]=[CH:29][CH:30]=1

参加物

7

反応物 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68325451(S)-tert-Butyl 2-(4-amino-3-fluorophenyl)morpholine-4-carboxylateHCID 710867371-[3-(Difluoromethoxy)phenyl]-1H-pyrazole-4-carboxylic acid

生成物 1

HCID 71086889(S)-tert-Butyl 2-(4-(1-(3-(difluoromethoxy)phenyl)-1H-pyrazole-4-carboxamido)-3-fluorophenyl)morpholine-4-carboxylate収率 59%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

(S)-tert-Butyl 2-(4-amino-3-fluorophenyl)morpholine-4-carboxylate (104 mg, 0.35 mmol), 1-(3-(difluoromethoxy)phenyl)-1H-pyrazole-4-carboxylic acid (107 mg, 0.42 mmol), HBTU (200 mg, 0.525 mmol) and N-methylmorpholine (106 mg, 115 μl, 1.05 mmol) were combined with DMF (4 ml) to give a light yellow solution. The reaction mixture was stirred at room temperature for 17 hours. The reaction mixture was poured into 50 ml of water and extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (20 g Silica gel, 70 to 50% ethyl acetate in heptane) to yield a white solid (110 mg, 59%). MS (ISP): 477.1 (100%, [M-tBu+H]+), 533.2 (30%, [M+H]+).

後処理

  1. customto give a light yellow solution
  2. extractionextracted with ethyl acetate twice
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (20 g Silica gel, 70 to 50% ethyl acetate in heptane)

出典と根拠

ORDレコード
ord-9e4f941034f148d296dfb0378ac06992
出典データセット
uspto-grants-2015_05
特許番号
US09029370B2

反応ノート

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