Hydrochloric Acid → 7-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[3-(trifluoromethyl)benzoyl]-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one

HRID 1184625Notes

Reaction equation

HRID 1184625 reaction equation
[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][CH:11]3[C:26](=[O:27])[N:14]4[CH2:15][CH2:16][N:17]([C:19](OC(C)(C)C)=[O:20])[CH2:18][CH:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.Cl.[F:29][C:30]([F:41])([F:40])[C:31]1[CH:32]=[C:33]([CH:37]=[CH:38][CH:39]=1)C(Cl)=O.C(N(CC)CC)C>O1CCOCC1.C(Cl)Cl>[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][CH:11]3[C:26](=[O:27])[N:14]4[CH2:15][CH2:16][N:17]([C:19](=[O:20])[C:38]5[CH:37]=[CH:33][CH:32]=[C:31]([C:30]([F:41])([F:40])[F:29])[CH:39]=5)[CH2:18][CH:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 752573-(Trifluoromethyl)benzoyl chlorideHCID 86680465tert-butyl 7-[(5-cyclopropylpyrazin-2-yl)oxy]-6-oxohexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

Product 1

HCID 866805427-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[3-(trifluoromethyl)benzoyl]-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-oneYield 75.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of the product from Example 205C (40 mg, 0.107 mmol) in 1,4-dioxane (0.5 mL) was added a 4 M solution of hydrogen chloride in 1,4-dioxane (0.5 mL, 2.0 mmol). The resulting mixture was stirred at room temperature for 90 minutes, and then it was concentrated in vacuo. To the residue was added CH2Cl2 (1 mL), 3-(trifluoromethyl)benzoyl chloride (0.020 mL, 0.130 mmol), and triethylamine (0.045 mL, 0.324 mmol), and the resulting mixture was stirred at ambient temperature for 90 minutes. The mixture was partitioned between water and CH2Cl2, and the organic layer was dried over Na2SO4. The drying agent was removed by filtration, and the filtrate was concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-5% methanol in dichloromethane to give the title compound (36 mg, 75%). 1H NMR (300 MHz, CDCl3) δ ppm 0.88-1.02 (m, 4 H) 1.37-3.27 (m, 6 H) 3.55-3.93 (m, 2 H) 4.07-4.31 (m, 1 H) 4.64-5.14 (m, 1 H) 5.49-5.68 (m, 1 H) 7.56-7.67 (m, 2 H) 7.68-7.80 (m, 2 H) 7.94 (s, 1 H) 8.08-8.20 (m, 1 H); MS (ESI) m/z 447 (M+H)+.

Workup

  1. concentrationit was concentrated in vacuo
  2. stirringthe resulting mixture was stirred at ambient temperature for 90 minutes
  3. customThe mixture was partitioned between water and CH2Cl2
  4. dry with materialthe organic layer was dried over Na2SO4
  5. customThe drying agent was removed by filtration
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-7e9c74d1f0c149f7b3477a6a04b7c385
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

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