Triethylamine → (7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[4-(trifluoromethyl)-benzoyl]hexahydropyrrolo[1,2-a]pyrazin-4(1H)-one

HRID 1184610Notes

Reaction equation

HRID 1184610 reaction equation
[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:20][N:14]4[C:15](=[O:19])[CH2:16][NH:17][CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[F:28][C:29]([F:40])([F:39])[C:30]1[CH:38]=[CH:37][C:33]([C:34](Cl)=[O:35])=[CH:32][CH:31]=1>ClCCl>[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:20][N:14]4[C:15](=[O:19])[CH2:16][N:17]([C:34](=[O:35])[C:33]5[CH:37]=[CH:38][C:30]([C:29]([F:28])([F:39])[F:40])=[CH:31][CH:32]=5)[CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 86680524(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]hexahydropyrrolo[1,2-a]-pyrazin-4(1H)-one

Product 1

HCID 86680525(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[4-(trifluoromethyl)-benzoyl]hexahydropyrrolo[1,2-a]pyrazin-4(1H)-oneYield 20.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product from Example 174G (100 mg, 0.365 mmol) in dichloromethane (2 mL) were added triethylamine (50.8 μL, 0.365 mmol) followed by 4-(trifluoromethyl)benzoyl chloride (59.7 μL, 0.401 mmol). The mixture was stirred at ambient temperature for 18 hours, and then partitioned between water and dichloromethane. The organic extract was dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by chromatography on a 12 g silica gel column eluting with 5% ethyl acetate/hexanes for 3 minutes and then a gradient to 100% ethyl acetate over 20 minutes to give the title compound (34 mg, 20.9%). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.16 (t, J=8.3 Hz, 2H), 7.83 (d, J=8.2 Hz, 2H), 7.73-7.60 (m, 2H), 5.62-5.41 (m, 1H), 4.85-4.46 (m, 1H), 4.10-3.61 (m, 4H), 3.50-3.34 (m, 1H), 3.24-2.71 (m, 1H), 2.44-1.65 (m, 3H), 1.05-0.90 (m, 2H), 0.87-0.73 (m, 2H); MS (ESI) m/z 447 (M+H)+.

Workup

  1. custompartitioned between water and dichloromethane
  2. extractionThe organic extract
  3. dry with materialwas dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by chromatography on a 12 g silica gel column
  7. washeluting with 5% ethyl acetate/hexanes for 3 minutes

Sources & evidence

ORD record
ord-8c6f582c7eb24f7da721cc4fceaf2abd
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

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