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

HRID 2373887노트

반응식

HRID 2373887 반응식
[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

참가 물질

8

반응물 4

HCID 8471Triethylamine2회HCID 62493Pivaloyl chloride2회HCID 59852773N-[(3-benzyloxyphenyl)-(3-chloropyrazin-2-yl)-methyl]-2,2-dimethylpropionamideHCID 59852826C-(3-benzyloxyphenyl)-C-(3-chloropyrazin-2-yl)-methylamine

생성물 1

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

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

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].

후처리

  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)]

출처 및 근거

ORD 기록
ord-18a9ab348a3e4d1d8cdc4bf9bac50444
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07459554B2

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