Diisopropylethylamine → N1-(3-Fluoro-4-(2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-methyl-N3-phenylmalonamide

HRID 418595ノート

反応式

HRID 418595 の反応式
[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]([CH3:23])[CH:20]=[CH:21][N:22]=3)[S:17][C:10]=12.[CH3:25][N:26]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:27](=[O:32])[CH2:28][C:29](O)=[O:30].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O.O>[F:1][C:2]1[CH:3]=[C:4]([NH:24][C:29](=[O:30])[CH2:28][C:27]([N:26]([CH3:25])[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[O:32])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]([CH3:23])[CH:20]=[CH:21][N:22]=3)[S:17][C:10]=12

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 3500563-(Methyl(phenyl)amino)-3-oxopropanoic acidHCID 594244803-Fluoro-4-(2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)benzenamine

生成物 1

HCID 16041059N1-(3-Fluoro-4-(2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-methyl-N3-phenylmalonamide収率 30%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of the amine 9 (80 mg, 0.235 mmol), acid 31 (47 mg, 0.235 mmol), and BOP (114.6 mg, 0.254 mmol) in DMF (2.4 mL), DIPEA (0.164 mL, 0.941 mmol) was added and the mixture was stirred for 2 h at room temperature. The reaction mixture was diluted with EtOAc (100 mL), water (50 mL) was added and the mixture filtered through paper filter. The organic phase was separated, washed with water (50 mL), brine (20 mL), dried (anhydrous Na2SO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (eluent EtOAc/MeOH 10:1) to afford the title compound 32 (36.2 mg, 30% yield) as a creamy solid. 1H NMR (DMSO-d6) δ (ppm): 10.29 (s, 1H), 8.49 (d, J=5.5 Hz, 1H), 7.87 (s, 1H), 7.77 (d, J=12.7 Hz, 1H), 7.46-7.30 (m, 8H), 7.03 (s, 1H), 6.66 (d, J=5.5 Hz, 1H), 3.98 (s, 3H), 3.22 (s, 2H), 2.52 (3H, s). MS (m/z): 516.3 (M+H).

後処理

  1. additionwas added
  2. filtrationthe mixture filtered through paper
  3. filtrationfilter
  4. customThe organic phase was separated
  5. washwashed with water (50 mL), brine (20 mL)
  6. dry with materialdried (anhydrous Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography (eluent EtOAc/MeOH 10:1)

出典と根拠

ORDレコード
ord-7b91d21d77f443719cb6a84324108448
出典データセット
uspto-grants-2012_01
特許番号
US08093264B2

反応ノート

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