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

HRID 2373887ノート

反応式

HRID 2373887 の反応式
[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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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].

後処理

  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)]

出典と根拠

ORDレコード
ord-18a9ab348a3e4d1d8cdc4bf9bac50444
出典データセット
uspto-grants-2008_12
特許番号
US07459554B2

反応ノート

読み込み中…