Triethylamine → 1-(3-Benzyloxyphenyl)-3-tert-butylimidazo[1,5-a]pyrazin-8-ylamine

HRID 2373887Notes

Reaction equation

HRID 2373887 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]([C:23]2[C:28](Cl)=[N:27][CH:26]=[CH:25][N:24]=2)[NH:16][C:17](=O)[C:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC1C=C(C(N)C2C(Cl)=NC=C[N:46]=2)C=CC=1)C1C=CC=CC=1.CCN(CC)CC.C(Cl)(=O)C(C)(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([C:18]([CH3:21])([CH3:20])[CH3:19])[N:24]3[CH:25]=[CH:26][N:27]=[C:28]([NH2:46])[C:23]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 62493Pivaloyl chloride2×HCID 59852773N-[(3-benzyloxyphenyl)-(3-chloropyrazin-2-yl)-methyl]-2,2-dimethylpropionamideHCID 59852826C-(3-benzyloxyphenyl)-C-(3-chloropyrazin-2-yl)-methylamine

Product 1

HCID 112802111-(3-Benzyloxyphenyl)-3-tert-butylimidazo[1,5-a]pyrazin-8-ylamine

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-[(3-Benzyloxyphenyl)-(3-chloropyrazin-2-yl)-methyl]-2,2-dimethylpropionamide: To a solution of the crude C-(3-benzyloxyphenyl)-C-(3-chloropyrazin-2-yl)-methylamine (444 mg, max. 1.36 mmol) in CH2Cl2 (5 mL), cooled by ice/water, are added NEt3 (210 μL, 152 mg, 1.51 mmol), DMAP (8 mg, 0.07 mmol), and pivaloyl chloride (185 μL, 181 mg, 1.50 mmol), then the cooling bath is removed, and the reaction solution is stirred at ambient temperature for 4.5 h. More pivaloyl chloride (90 μL, 88 mg, 0.73 mmol) and NEt3 (100 μL, 73 mg, 0.72 mmol) are added and also after further 2.5 h, and the solution is stirred overnight at ambient temperature. The reaction mixture is taken up in EtOAc (35 mL), washed with diluted HCl, water, NaHCO3 sol., and brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude material is chromatographed on silica gel [Jones Flashmaster, 50 g/150 mL cartridge, eluting with hexanes:EtOAc 10:1 (1-17)→3:1 (18-41)→2:1 (42-56)], yielding the title compound as orange oil; 1H NMR (CDCl3, 400 MHz) δ 1.21 (s, 9H), 5.03 (s, 2H), 6.50 (d, J=8.0 Hz, 1H), 6.86-6.90 (m, 1H), 6.93-6.97 (m, 2H), 7.23 (t, J=7.8 Hz, 1H), 7.29-7.43 (m, 6H), 8.32 (d, J=2.4 Hz, 2H), 8.50 (d, J=2.4 Hz, 1H). MS (ES+): m/z 410.1/412.1 (100/36) [MH+], 309.1/311.1 (32/12) [MH+-tBuCONH2].

Workup

  1. customthe cooling bath is removed
  2. stirringthe solution is stirred overnight at ambient temperature
  3. washwashed with diluted HCl, water, NaHCO3 sol., and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material is chromatographed on silica gel [Jones Flashmaster, 50 g/150 mL cartridge, eluting with hexanes:EtOAc 10:1 (1-17)→3:1 (18-41)→2:1 (42-56)]

Sources & evidence

ORD record
ord-18a9ab348a3e4d1d8cdc4bf9bac50444
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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