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 1184589Notes

Reaction equation

HRID 1184589 reaction equation
[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

Participants

7

Reactant 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, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-14601b1ee3d943499e27b9386b747b47
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

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