Chloroform → 6-{[3-chloro-5-(2,2-diethoxyethyl)pyridin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine

HRID 1517259

반응식

HRID 1517259 반응식
[Cl:1][C:2]1[C:7](Cl)=[CH:6][C:5]([O:9][CH2:10][CH:11]([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14])=[CH:4][N:3]=1.C[C:19]([CH3:22])([O-])C.[K+].[CH3:24][N:25](C)[C:26](=[O:28])[CH3:27].[CH3:30][N:31]1[CH:35]=[CH:34][C:33]([NH:36][C:37]2[C:46]3[C:41](=[CH:42][CH:43]=[C:44]([OH:47])[CH:45]=3)[N:40]=[CH:39][N:38]=2)=[N:32]1.C(Cl)(Cl)[Cl:49]>O>[Cl:49][C:27]1[C:26]([O:28][C:44]2[CH:45]=[C:46]3[C:41](=[CH:42][CH:43]=2)[N:40]=[CH:39][N:38]=[C:37]3[NH:36][C:33]2[CH:34]=[CH:35][N:31]([CH3:30])[N:32]=2)=[N:25][CH:24]=[C:19]([CH2:10][CH:11]([O:12][CH2:13][CH3:14])[O:15][CH2:16][CH3:17])[CH:22]=1.[Cl:1][C:2]1[C:7]([O:47][C:44]2[CH:45]=[C:46]3[C:41](=[CH:42][CH:43]=2)[N:40]=[CH:39][N:38]=[C:37]3[NH:36][C:33]2[CH:34]=[CH:35][N:31]([CH3:30])[N:32]=2)=[CH:6][C:5]([O:9][CH2:10][CH:11]([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14])=[CH:4][N:3]=1

참가 물질

8

반응물 5

HCID 6212ChloroformHCID 31374DimethylacetamideHCID 231603824-[(1-Methyl-1H-pyrazol-3-yl)amino]quinazolin-6-olHCID 23665647Potassium tert-butoxideHCID 866458962,3-Dichloro-5-(2,2-diethoxyethoxy)pyridine

생성물 2

HCID 684277006-{[3-chloro-5-(2,2-diethoxyethyl)pyridin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine수율 45%HCID 866458956-{[2-chloro-5-(2,2-diethoxyethoxy)pyridin-3-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine수율 28%

시약·촉매·용매 1

HCID 962Water용매

반응 조건

온도
170 °C

실험 절차

2,3-Dichloro-5-(2,2-diethoxyethoxy)pyridine (641 mg, 2.29 mmol) and potassium tert-butoxide (279 mg, 2.49 mmol) were added to an N,N-dimethylacetamide solution (3 ml) of 4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-ol (240 mg, 1.00 mmol), and stirred at 170° C. for 14 hours under a nitrogen atmosphere in a sealed tube. The reaction solution was cooled with ice, then saline water and chloroform were added, the organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by reversed-phase liquid chromatography (YMC CombiPrep Pro C18 AS-360-CC) to obtain 6-{[3-chloro-5-(2,2-diethoxyethyl)pyridin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine (217 mg, yield: 45%) as an orange oil and 6-{[2-chloro-5-(2,2-diethoxyethoxy)pyridin-3-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine (136 mg, yield: 28%) as an orange oil.

후처리

  1. temperatureThe reaction solution was cooled with ice
  2. washthe organic layer was washed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue was purified by reversed-phase liquid chromatography (YMC CombiPrep Pro C18 AS-360-CC)

출처 및 근거

ORD 기록
ord-b1e3fb08da3c46749af94e3278812389
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232284B2

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