Potassium Carbonate → Tert-butyl 2-(2-((6-chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)methylamino)pyrimidin-4-yl)pyrrolidine-1-carboxylate

HRID 455115노트

반응식

HRID 455115 반응식
Cl.[Cl:2][C:3]1[CH:4]=[CH:5][C:6]2[N:7]([C:9]([CH2:19]Cl)=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[N:11]=2)[CH:8]=1.[NH2:21][C:22]1[N:27]=[C:26]([CH:28]2[CH2:32][CH2:31][CH2:30][N:29]2[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH:25]=[CH:24][N:23]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.C(OCC)(=O)C>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]2[N:7]([C:9]([CH2:19][NH:21][C:22]3[N:27]=[C:26]([CH:28]4[CH2:32][CH2:31][CH2:30][N:29]4[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH:25]=[CH:24][N:23]=3)=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[N:11]=2)[CH:8]=1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 58336948Tert-butyl 2-(2-aminopyrimidin-4-yl)pyrrolidine-1-carboxylateHCID 670286376-Chloro-3-(chloromethyl)-2-(4-fluorophenyl)imidazo[1,2-a]pyridine hydrochloride

생성물 1

HCID 58336929Tert-butyl 2-(2-((6-chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)methylamino)pyrimidin-4-yl)pyrrolidine-1-carboxylate수율 54%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

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온도
60 °C

실험 절차

To a solution of 6-chloro-3-(chloromethyl)-2-(4-fluorophenyl)imidazo[1,2-a]pyridine hydrochloride (100 mg, 0.35 mmol) in acetonitrile (25 mL) was added tert-butyl 2-(2-aminopyrimidin-4-yl)pyrrolidine-1-carboxylate (prepared according to the procedures described in WO 2007/09117 A1)(190 mg, 0.71 mmol) and freshly ground potassium carbonate (150 mg, 1.1 mmol) and the reaction mixture was heated to 60° C. for 16 h. After this time the reaction mixture was cooled to room temperature, diluted with ethyl acetate (20 mL) and washed with brine (2×20 mL). The organic layer was separated, dried over Na2SO4, concentrated and purified by column chromatography (methanol/methylene chloride) to afford the desired product. (0.10 g, 54% yield). M/e+ 523.1 for C27H28ClFN6O2 (M+H)+, 1H-NMR (500 MHz, CDCl3, δ) 8.45 (d, J=1.0 Hz, 1H), 8.28 (s, 1H), 7.77-7.74 (m, 2H), 7.58 (d, J=9.5 Hz, 1H), 7.20-7.15 (m, 3H), 6.55 (d, J=5.0 Hz, 1H), 5.18 (s, 1H), 5.07-5.01 (m, 2H), 4.62 (s, 1H), 3.61-3.52 (m, 2H), 2.34 (m, 1H), 1.98-1.94 (m, 1H), 1.91-1.86 (m, 2H), 1.26 (s, 9H) and signals due to a minor tautomer (ca. 44%): 4.77 (d, J=5.0 Hz), 1.46 (s).

후처리

  1. customprepared
  2. temperatureAfter this time the reaction mixture was cooled to room temperature
  3. washwashed with brine (2×20 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. custompurified by column chromatography (methanol/methylene chloride)

출처 및 근거

ORD 기록
ord-270a8f89aa5a42da8cf1cdd00218dd28
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08497278B2

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