Trifluoroacetic acid → (S)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-3-phenyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide

HRID 1971077Notes

Reaction equation

HRID 1971077 reaction equation
[CH3:1][C:2]([CH3:34])([CH3:33])[C@H:3]([NH:8][C:9]([C:11]1[N:12]=[C:13]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:14]2[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][C:15]=12)=[O:10])[C:4]([NH:6][CH3:7])=[O:5].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][C:2]([CH3:34])([CH3:33])[C@H:3]([NH:8][C:9]([C:11]1[N:12]=[C:13]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[N:14]2[CH2:19][CH2:18][NH:17][CH2:16][C:15]=12)=[O:10])[C:4]([NH:6][CH3:7])=[O:5]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 25132454(S)-tert-butyl 1-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)-3-phenyl-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylate

Product 1

HCID 25132789(S)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-3-phenyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamideYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Compound 1 (150 mg, 0.32 mmol) was dissolved in DCM and TFA (0.25 mL, 3.20 mmol) was added. The resulting mixture was stirred overnight. The mixture was concentrated, diluted with DCM and washed with saturated NaHCO3 solution. The filtrate was dried anhydrous Na2SO4, filtered and concentrated. The residue was purified by normal phase chromatography, eluting with 0-30% 1M methanolic ammonia/dichloro-methane to give desired product, Compound 2 as a white solid (0.10 g, 85%). MS: m/z 370.2 [M+H]+. 1H-NMR (400 MHz, CD3OD) δ: 1.05 (s, 9H), 2.76 (s, 3H), 3.16 (m, 2H), 4.11 (m, 2H), 4.37 (m, 3H), 7.53 (m, 3H), 7.71 (m, 2H).

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with DCM
  3. washwashed with saturated NaHCO3 solution
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by normal phase chromatography
  7. washeluting with 0-30% 1M methanolic ammonia/dichloro-methane

Sources & evidence

ORD record
ord-928ce2103be24434887e79143181124c
Source dataset
uspto-grants-2013_04
Patent number
US08431565B2

Reaction notes

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