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 419315ノート

反応式

HRID 419315 の反応式
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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 64092,2,2-Trifluoroethanol溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-19cf3a6cddcd4bebbb829e01e90b9c53
出典データセット
uspto-grants-2012_01
特許番号
US08093239B2

反応ノート

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