Potassium Carbonate → 1-(1-(3-(Pyrrolidin-1-yl)propyl)-1H-indazol-5-yl)-4-(4(trifluoromethyl)phenyl)pyridin-2(1H)-one

HRID 2390443노트

반응식

HRID 2390443 반응식
Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([N:14]3[CH:19]=[CH:18][C:17]([C:20]4[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=4)=[CH:16][C:15]3=[O:30])=[CH:11][CH:12]=2)[CH:7]=[N:6]1.C([O-])([O-])=O.[K+].[K+].[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1>CN(C=O)C.O>[N:37]1([CH2:2][CH2:3][CH2:4][N:5]2[C:13]3[C:8](=[CH:9][C:10]([N:14]4[CH:19]=[CH:18][C:17]([C:20]5[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=5)=[CH:16][C:15]4=[O:30])=[CH:11][CH:12]=3)[CH:7]=[N:6]2)[CH2:41][CH2:40][CH2:39][CH2:38]1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 31268PyrrolidineHCID 667191041-(1-(3-chloropropyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

생성물 1

HCID 252062941-(1-(3-(Pyrrolidin-1-yl)propyl)-1H-indazol-5-yl)-4-(4(trifluoromethyl)phenyl)pyridin-2(1H)-one수율 91.7%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

To a solution of 1-(1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one (278 mg, 0.783 mmol) in DMSO (4.0 mL) was added 3-bromo-1-chloropropane (1.23 g, 7.83 mmol) and Cs2CO3 (765 mg, 2.35 mmol), and the reaction was stirred at ambient temperature for 18 h. The reaction mixture was diluted with H2O (25 mL) and extracted with EtOAc (3×25 mL). The extracts were washed with brine (25 mL), dried over Na2SO4, and concentrated. Flash chromatography (silica gel, CH2Cl2/MeOH, 100:1) yielded the intermediate 1-(1-(3-chloropropyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one. To a solution of 1-(1-(3-chloropropyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one (78 mg, 0.18 mmol) in DMF (1.0 mL) was added K2CO3 (0.12 g, 0.90 mmol), pyrrolidine (130 mg, 1.8 mmol) and KI (30 mg, 0.18 mmol), and the reaction was heated to 50° C. for 18 h. The reaction mixture was cooled and diluted with H2O (25 mL). The resulting solids were collected by filtration and washed with H2O (10 mL). The collected solid was dissolved in EtOAc (20 mL) and washed with brine (10 mL). The washed organic solution was dried over Na2SO4, filtered and concentrated to provide the title compound (77 mg, 91%): 1H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.77-7.74 (m, 5H), 7.60-7.42 (m, 3H), 6.92 (d, J=2.0 Hz, 1H), 6.53-6.51 (m, 1H), 4.51 (t, J=7.0 Hz, 2H), 2.48-2.44 (m, 6H), 2.16-2.12 (m, 2H), 1.79-1.77 (m, 4H).

후처리

  1. temperatureThe reaction mixture was cooled
  2. filtrationThe resulting solids were collected by filtration
  3. washwashed with H2O (10 mL)
  4. dissolutionThe collected solid was dissolved in EtOAc (20 mL)
  5. washwashed with brine (10 mL)
  6. dry with materialThe washed organic solution was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-fd709c2c33484d41a829e856ca239a29
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08273770B2

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