tert-butyl 1-[[(2S)-1-[(Z)-1-aminoethylideneamino]oxy-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-3-phenyl-6,8-dihydro-5H-imidazo[1,5-a]pyrazine-7-carboxylate → (S)-tert-butyl 1-(2,2-dimethyl-1-(3-methyl-1,2,4-oxadiazol-5-yl)propylcarbamoyl)-3-phenyl-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylate

HRID 535940Notes

Reaction equation

HRID 535940 reaction equation
[NH2:1]/[C:2](=[N:4]\[O:5][C:6](=O)[C@@H:7]([NH:12][C:13]([C:15]1[N:16]=[C:17]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][C:19]=12)=[O:14])[C:8]([CH3:11])([CH3:10])[CH3:9])/[CH3:3]>CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>[CH3:10][C:8]([CH3:9])([CH3:11])[C@H:7]([NH:12][C:13]([C:15]1[N:16]=[C:17]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[N:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH2:20][C:19]=12)=[O:14])[C:6]1[O:5][N:4]=[C:2]([CH3:3])[N:1]=1

Participants

4

Reactant 1

HCID 57635411tert-butyl 1-[[(2S)-1-[(Z)-1-aminoethylideneamino]oxy-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-3-phenyl-6,8-dihydro-5H-imidazo[1,5-a]pyrazine-7-carboxylate

Product 1

HCID 57635507(S)-tert-butyl 1-(2,2-dimethyl-1-(3-methyl-1,2,4-oxadiazol-5-yl)propylcarbamoyl)-3-phenyl-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylateYield 88.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 2724141Tetrabutylammonium FluorideSolvent

Procedure

Intermediate 22C (0.20 g, 0.39 mmol) was dissolved in a 1N solution of TBAF in THF (0.55 mL). The resulting mixture was stirred overnight, concentrated, diluted with EtOAc and washed successively with water and brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by preparative flash chromatography on silica, eluting with a 20-70% ethyl acetate/hexanes gradient to provide Intermediate 22D (0.17 g, 88%). 1H-NMR (400 MHz, CDCl3-d) δ: 1.09 (s, 9H), 1.51 (s, 9H), 2.40 (s, 3H), 3.78 (m, 2H), 4.11 (m, 2H), 5.01 (m, 2H), 5.37 (d, 1H), 7.35 (m, 3H), 7.64 (m, 2H), 7.78 (d, 1H); LCMS (+ESI) m/z 495.1 [M+H]+.

Workup

  1. concentrationconcentrated
  2. additiondiluted with EtOAc
  3. washwashed successively with water and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative flash chromatography on silica
  8. washeluting with a 20-70% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-e18927ec7ab54234bc1121562f6a6712
Source dataset
uspto-grants-2014_10
Patent number
US08859538B2

Reaction notes

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