1,2-Dimethoxyethane → benzyl 4-[8-amino-1-(1H-indol-2-yl)imidazo[1,5-a]pyrazin-3-yl]piperidine-1-carboxylate

HRID 550189노트

반응식

HRID 550189 반응식
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:19])[CH2:14][CH2:13]3)=[N:9][C:10]=2I)[CH:5]=[CH:6][N:7]=1.C(OC([N:35]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:37]=[C:36]1B(O)O)=O)(C)(C)C.COCCOC.C(=O)([O-])[O-].[Cs+].[Cs+]>CCOC(C)=O.O>[NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:19])[CH2:14][CH2:13]3)=[N:9][C:10]=2[C:36]2[NH:35][C:43]3[C:38]([CH:37]=2)=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH:5]=[CH:6][N:7]=1

참가 물질

7

반응물 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 27733021-(tert-Butoxycarbonyl)indole-2-boronic Acid (contains varying amounts of Anhydride)HCID 42609369Benzyl 4-(8-amino-1-iodoimidazo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate

생성물 1

HCID 16679362benzyl 4-[8-amino-1-(1H-indol-2-yl)imidazo[1,5-a]pyrazin-3-yl]piperidine-1-carboxylate

시약·촉매·용매 2

HCID 962Water용매HCID 8857Ethyl Acetate용매

반응 조건

온도
100 °C

실험 절차

A mixture of benzyl 4-(8-amino-1-iodoimidazo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate (1.149 g, 0.002191 mol), 1-(tert-butoxycarbonyl)-1H-indole-2-boronic acid (0.629 g, 0.00241 mol), 1,2-dimethoxyethane (9.3 mL), water (1.8 mL) and cesium carbonate (1.43 g, 0.00438 mol) was degassed three times and then treated with tetrakis(triphenyl phosphine)palladium(0) (200 mg, 0.0002 mol). The mixture was once more degassed and then heated at 100° C. overnight. The resulting reaction mixture was diluted with EtOAc (30 mL) then washed with water (2×30 mL) and brine, dried over Na2SO4 and concentrated in vacuo. The crude product was chromatographed over silica gel eluting with hexane→EtOAc:hexane 1:1:0.05 2M NH3/MeOH to afford the desired product. 1H NMR (400 MHz, CDCl3): δ 2.02-2.06 (m, 4H), 3.03-3.17 (m, 3H), 4.29-4.33 (m, 2H), 5.16 (s, 2H), 5.66 (br, 2H), 6.79-6.80 (m, 1H), 7.11-7.16 (m, 2H), 7.20-7.25 (m, 2H), 7.31-7.45 (m, 5H), 7.44 (m, 1H), 7.64 (d, J=7.6 Hz, 1H), 8.96 (br, 1H). MS (ES+): m/z 467.12 [MH+].

후처리

  1. customwas degassed three times
  2. customThe mixture was once more degassed
  3. customThe resulting reaction mixture
  4. washthen washed with water (2×30 mL) and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was chromatographed over silica gel eluting with hexane→EtOAc:hexane 1:1:0.05 2M NH3/MeOH

출처 및 근거

ORD 기록
ord-e3adbc82991642018803f5102ca63274
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07943767B2

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