2-(4-Fluorophenyl)acetic acid → 1-[(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-2-(4-fluorophenyl)ethanone

HRID 1184589노트

반응식

HRID 1184589 반응식
[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][NH:17][CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][C:28](O)=[O:29])=[CH:23][CH:22]=1.C(N=C=NCCCN(C)C)C.O.OC1C2N=NNC=2C=CC=1.C(N(C(C)C)CC)(C)C>ClCCl>[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][N:17]([C:28](=[O:29])[CH2:27][C:24]5[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=5)[CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1

참가 물질

7

반응물 5

HCID 98372-(4-Fluorophenyl)acetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 86680449(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]octahydropyrrolo[1,2-a]pyrazineHCID 178526939HCID 178526939, 화합물

생성물 1

HCID 866805101-[(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-2-(4-fluorophenyl)ethanone

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a mixture of the product from Example 54F (30 mg, 0.115 mmol) and 2-(4-fluorophenyl)acetic acid (21.3 mg, 0.138 mmol) was added a solution of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (33.1 mg, 0.173 mmol) in dichloromethane (1.0 mL). To the resulting solution was added hydroxybenzotriazole hydrate (26.5 mg, 0.173 mmol) and diisopropylethylamine (0.040 mL, 0.230 mmol), and the mixture was stirred at room temperature for 16 hours. The mixture was partitioned between water and ethyl acetate, and the organic extract was dried over Na2SO4. The mixture was filtered and concentrated in vacuo, and the crude product was purified by column chromatography on silica gel using a solvent gradient of 0-100% ethyl acetate in hexanes. The title compound was obtained as a colorless solid (16 mg, 35%). 1H NMR (300 MHz, CDCl3) δ ppm 0.85-1.03 (m, 4 H), 1.78-2.06 (m, 3 H), 2.11-2.48 (m, 3 H), 2.63-3.27 (m, 3 H), 3.61-4.00 (m, 4 H), 4.55-4.85 (m, 1 H), 5.25-5.40 (m, 1 H), 6.96-7.06 (m, 2 H), 7.15-7.25 (m, 2 H), 7.93 (d, J=1.36 Hz, 1 H), 8.01 (d, J=1.36 Hz, 1 H); MS (ESI) m/z 397 (M+H)+.

후처리

  1. customThe mixture was partitioned between water and ethyl acetate
  2. extractionthe organic extract
  3. dry with materialwas dried over Na2SO4
  4. filtrationThe mixture was filtered
  5. concentrationconcentrated in vacuo
  6. customthe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-100% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-14601b1ee3d943499e27b9386b747b47
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08669255B2

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