Potassium Iodide → (S)-2-(2-(3-((3-Acetamidopyrrolidin-1-yl)methyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide

HRID 625355ノート

反応式

HRID 625355 の反応式
[F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([CH:39]=[CH:40][CH:41]=1)[CH2:6][NH:7][C:8](=[O:38])[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]2[CH:20]=[C:19]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:18]=[CH:17][C:16]=2[NH:27][C:28](=[O:37])[C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35]Br)[CH:30]=2)[CH:10]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[NH:52]1[CH2:56][CH2:55][C@@H:54]([NH:57][C:58](=[O:60])[CH3:59])[CH2:53]1>CN(C)C=O.O>[C:58]([NH:57][C@H:54]1[CH2:55][CH2:56][N:52]([CH2:35][C:31]2[CH:30]=[C:29]([CH:34]=[CH:33][CH:32]=2)[C:28]([NH:27][C:16]2[CH:17]=[CH:18][C:19]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:20][C:15]=2[C:11]2[CH:10]=[C:9]([CH:14]=[CH:13][N:12]=2)[C:8]([NH:7][CH2:6][C:5]2[CH:39]=[CH:40][CH:41]=[C:3]([C:2]([F:43])([F:42])[F:1])[CH:4]=2)=[O:38])=[O:37])[CH2:53]1)(=[O:60])[CH3:59]

参加物

7

反応物 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 7016129(3R)-(+)-3-AcetamidopyrrolidineHCID 66586775HCID 66586775、化合物

生成物 1

HCID 66587957(S)-2-(2-(3-((3-Acetamidopyrrolidin-1-yl)methyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide収率 45.8%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

Into a 50-mL round-bottom flask, was placed a solution of N-(3-(trifluoromethyl)benzyl)-2-(2-(3-(bromomethyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide (100 mg, 0.15 mmol, 1.00 equiv) in N,N-dimethylformamide (10 mL), potassium carbonate (62 mg, 0.45 mmol, 2.92 equiv), potassium iodide (5 mg, 0.03 mmol, 0.20 equiv), and (R)—N-(pyrrolidin-3-yl)acetamide (38.5 mg, 0.30 mmol, 1.96 equiv). The resulting solution was stirred for 3 h at 70° C. in an oil bath. The resulting solution was diluted with 150 mL of water. The resulting solution was extracted with 4×100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2×200 mL of brine. The mixture was dried over sodium sulfate and concentrated under vacuum. The crude product (100 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 48 mg (30%) of a light yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.925-8.942 (d, J=5.1 Hz, 1H), 8.642-8.672 (d, J=9.0 Hz, 1H), 8.435 (s, 1H), 8.075-8.141 (m, 3H), 7.863-7.880 (m, 1H), 7.537-7.801 (m, 7H), 4.720 (s, 2H), 4.524-4.594 (m, 2H), 4.374-4.418 (m, 1H), 3.628-3.663 (m, 4H), 2.501 (m, 1H), 2.016-2.031 (m, 5H), 1.947 (m, 3H), 1.810-1.826 (m, 2H). MS (ES, m/z): 699 [M+H]+.

後処理

  1. customInto a 50-mL round-bottom flask, was placed
  2. extractionThe resulting solution was extracted with 4×100 mL of ethyl acetate
  3. washThe resulting mixture was washed with 2×200 mL of brine
  4. dry with materialThe mixture was dried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product (100 mg) was purified by reverse phase HPLC
  7. washeluting with a water/CH3CN gradient
  8. additioncontaining 0.05% TFA

出典と根拠

ORDレコード
ord-d66bc4c1871d428fb7562bed6603d757
出典データセット
uspto-grants-2016_04
特許番号
US09301951B2

反応ノート

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