Hydrochloric Acid → Phenylmethyl 4-([4-({4-[2-(3-cyanophenyl)imidazo[1,2-a]pyridin-3-yl]-2-pyrimidinyl}amino)-3-methylphenyl]oxy}-1-piperidinecarboxylate

HRID 419315노트

반응식

HRID 419315 반응식
Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:17]2[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=2)[C:20]#[N:21])[CH:5]=[CH:4][N:3]=1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH:33]2[CH2:38][CH2:37][N:36]([C:39]([O:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[O:40])[CH2:35][CH2:34]2)=[CH:28][C:27]=1[CH3:49].Cl.C([O-])(O)=O.[Na+]>C(O)C(F)(F)F.C(Cl)Cl>[C:20]([C:19]1[CH:18]=[C:17]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH:33]4[CH2:34][CH2:35][N:36]([C:39]([O:41][CH2:42][C:43]5[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=5)=[O:40])[CH2:37][CH2:38]4)=[CH:28][C:27]=3[CH3:49])[N:7]=2)[CH:24]=[CH:23][CH:22]=1)#[N:21]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 59452998Phenylmethyl 4-[(4-amino-3-methylphenyl)oxy]-1-piperidinecarboxylateHCID 866251873-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzonitrile

생성물 1

HCID 66649613Phenylmethyl 4-([4-({4-[2-(3-cyanophenyl)imidazo[1,2-a]pyridin-3-yl]-2-pyrimidinyl}amino)-3-methylphenyl]oxy}-1-piperidinecarboxylate수율 79.2%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 64092,2,2-Trifluoroethanol용매

실험 절차

3-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzonitrile (Intermediate Example 5) (0.462 g, 1.39 mmol) and phenylmethyl 4-[(4-amino-3-methylphenyl)oxy]-1-piperidinecarboxylate (0.567 g, 1.67 mmol) were dissolved in 16 mL of trifluoroethanol with stirring in a pressure vessel. HCl (4N in dioxane, 0.17 mL, 0.68 mmol) was added via syringe. The vessel was sealed and placed in an 80° C. oil bath. The reaction was stirred at 80° C. for 40 h and cooled to rt. The reaction was poured into half-saturated NaHCO3 solution and DCM. The layers were separated, and the organic layer was washed with brine. The combined aqueous layers were extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford 0.700 g (79%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 9.25 (br. s., 1H), 8.90 (s, 1H), 8.20 (d, J=5.1 Hz, 1H), 8.04 (s, 1H), 7.96-7.86 (m, 2H), 7.72-7.61 (m, 2H), 7.46-7.21 (m, 7H), 6.93-6.79 (m, 3H), 6.41 (d, J=5.3 Hz, 1H), 5.06 (s, 2H), 4.59-4.50 (m, 1H), 3.77-3.65 (m, 2H), 3.36-3.21 (m, 2H), 2.18 (s, 3H), 1.97-1.86 (m, 2H), 1.61-1.49 (m, 2H).

후처리

  1. customThe vessel was sealed
  2. customplaced in an 80° C.
  3. stirringThe reaction was stirred at 80° C. for 40 h
  4. customThe layers were separated
  5. washthe organic layer was washed with brine
  6. extractionThe combined aqueous layers were extracted with EtOAc
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography

출처 및 근거

ORD 기록
ord-19cf3a6cddcd4bebbb829e01e90b9c53
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093239B2

반응 노트

불러오는 중…