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

HRID 625355노트

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HRID 625355 반응식
[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]

참가 물질

7

반응물 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 7016129(3R)-(+)-3-AcetamidopyrrolidineHCID 66586775HCID 66586775, 화합물

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
70 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-d66bc4c1871d428fb7562bed6603d757
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09301951B2

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