Diisopropylethylamine → N-[1-[[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]carbamoyl]cyclopropyl]-4-fluoro-benzamide

HRID 2068554ノート

反応式

HRID 2068554 の反応式
[CH:1]1[N:5]2[C:6]3[CH:15]=[CH:14][CH:13]=[CH:12][C:7]=3[CH2:8][CH2:9][C@@H:10]([NH2:11])[C:4]2=[N:3][CH:2]=1.[F:16][C:17]1[CH:31]=[CH:30][C:20]([C:21]([NH:23][C:24]2([C:27](O)=[O:28])[CH2:26][CH2:25]2)=[O:22])=[CH:19][CH:18]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH:1]1[N:5]2[C:6]3[CH:15]=[CH:14][CH:13]=[CH:12][C:7]=3[CH2:8][CH2:9][C@@H:10]([NH:11][C:27]([C:24]3([NH:23][C:21](=[O:22])[C:20]4[CH:30]=[CH:31][C:17]([F:16])=[CH:18][CH:19]=4)[CH2:26][CH2:25]3)=[O:28])[C:4]2=[N:3][CH:2]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58304055(R)-5,6-Dihydro-4H-benzo[F]imidazo[1,2-A]azepin-4-amineHCID 654532291-[(4-Fluorobenzoyl)amino]cyclopropanecarboxylic acid

生成物 1

HCID 67233952N-[1-[[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]carbamoyl]cyclopropyl]-4-fluoro-benzamide収率 68%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Combine (4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-amine (95.0 mg, 0.48 mmol), 1-[(4-fluorobenzoyl)amino]cyclopropanecarboxylic acid (128.0 mg, 0.57 mmol), and O—-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (218.0 mg, 0.57 mmol) in N,N-dimethylformamide (4 mL). Add diisopropylethylamine (0.21 mL, 1.19 mmol) and stir the reaction for approximately 16 hours at ambient temperature under nitrogen. Dilute the reaction with ethyl acetate, wash with saturated sodium bicarbonate and brine, dry over sodium sulfate, and concentrate the organic layer under reduced pressure. Purify the residue by flash chromatography (3% ammonia (2M) solution in methanol/dichloromethane) to give the title compound (131.0 mg, 68%): MS (m/z): 405 (M+1).

後処理

  1. customthe reaction for approximately 16 hours at ambient temperature under nitrogen
  2. additionDilute
  3. washwash with saturated sodium bicarbonate and brine
  4. dry with materialdry over sodium sulfate
  5. concentrationconcentrate the organic layer under reduced pressure
  6. customPurify the residue by flash chromatography (3% ammonia (2M) solution in methanol/dichloromethane)

出典と根拠

ORDレコード
ord-08bbeb7bb91f4ef4a0e0df0bb84a9fbc
出典データセット
uspto-grants-2012_10
特許番号
US08299061B2

反応ノート

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