Cesium carbonate → Ammonia methanol

HRID 422707노트

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HRID 422707 반응식
I[C:2]1[N:3]=[C:4]([CH:12]2[CH2:15][CH:14]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=12.[CH3:23][C:24]1[C:33]2[C:28](=[CH:29][C:30](B3OC(C)(C)[C:36](C)(C)[O:35]3)=[CH:31][CH:32]=2)[N:27]=[C:26]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH3:3].[CH3:36][OH:35].[CH3:23][C:24]1[C:33]2[C:28](=[CH:29][C:30]([C:2]3[N:3]=[C:4]([CH:12]4[CH2:15][CH:14]([N:16]5[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]5)[CH2:13]4)[N:5]4[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=34)=[CH:31][CH:32]=2)[N:27]=[C:26]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:25]=1

참가 물질

8

반응물 3

HCID 10796Cesium carbonateHCID 536290544-Methyl-2-phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolineHCID 576810251-Iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazin-8-ylamine

생성물 2

HCID 21705897Ammonia methanolHCID 576809301-(4-Methyl-2-phenyl-quinolin-7-yl)-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazin-8-ylamine

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
75 °C

실험 절차

A mixture of 1-iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazin-8-ylamine (206 mg, 0.500 mmol) and 4-methyl-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline (190 mg, 0.550 mmol) and cesium carbonate (326 mg, 1.00 mmol) in 1,2-dimethoxyethane (10.0 mL) and water (2.0 mL) was evacuated and refilled with nitrogen (3×), then charged with tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.05 mmol), and the flask was again evacuated and refilled with nitrogen (3×). The mixture was heated at 75° C. overnight. The mixture was cooled to rt and diluted with ethyl acetate (30 mL), then washed with brine (15 mL); the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to afforded a yellow solid, which was purified by silica gel chromatography [CH2Cl2→5% MeOH/CH2Cl2→5% (2N NH3—MeOH)/CH2Cl2, then 10% (2N NH3—MeOH)/CH2Cl2 to give the title compound as a yellow solid; LC-MS (ES, Pos.): 504 [MH+]; 1H NMR (CDCl3, 400 MHz) δ 2.30 (s, 3H), 2.32-2.71 (m, 12H), 2.81 (d, J=0.9 Hz, 3H), 2.95 (m, 1H), 3.49 (m, 1H), 5.19 (brs, 2H), 7.11 (d, J=5.0 Hz, 1H), 7.19 (d, J=5.0 Hz, 1H), 7.45-7.55 (m, 3H), 7.75 (d, J=0.8 Hz, 1H), 7.94 (dd, J=8.6 Hz, 1.8 Hz, 1H), 8.12 (d, J=8.6 Hz, 1H), 8.16-8.19 (m, 2H), 8.39 (d, J=1.4 Hz, 1H).

후처리

  1. customwas evacuated
  2. additionrefilled with nitrogen (3×)
  3. customthe flask was again evacuated
  4. additionrefilled with nitrogen (3×)
  5. temperatureThe mixture was cooled to rt
  6. additiondiluted with ethyl acetate (30 mL)
  7. washwashed with brine (15 mL)
  8. dry with materialthe organic phase was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afforded a yellow solid, which
  12. customwas purified by silica gel chromatography [CH2Cl2→5% MeOH/CH2Cl2→5% (2N NH3—MeOH)/CH2Cl2

출처 및 근거

ORD 기록
ord-f3b2594b047e4c27b0a5e7639c0f5820
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101613B2

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