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Water → (5,8-Difluoroquinazolin-4-yl)-{2-[3-methyl-4-(4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-amine

HRID 2386903
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HRID 2386903 반응식
[F:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[C:4]([NH:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([CH3:23])[CH:17]=1)=[N:5][CH:6]=[N:7]2.F[C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][N:26]=1.C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[F:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[C:4]([NH:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:25]3[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][N:26]=3)=[C:18]([CH3:23])[CH:17]=1)=[N:5][CH:6]=[N:7]2
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참가 물질

6

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 111595142-Fluoro-4-(trifluoromethyl)pyridineHCID 592229364-[2-(5,8-Difluoroquinazolin-4-ylamino)-ethyl]-2-methylphenol

생성물 1

HCID 46183670(5,8-Difluoroquinazolin-4-yl)-{2-[3-methyl-4-(4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-amine수율 77.2%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
90 °C

실험 절차

A mixture of 4-[2-(5,8-difluoroquinazolin-4-ylamino)-ethyl]-2-methylphenol (0.47 g, 1.5 mmol), 2-fluoro-4-trifluoromethylpyridine (0.371 g, 2.25 mmol), and potassium carbonate (0.31 g, 2.25 mmol) in DMSO (7 mL) was heated at 90° C. overnight. The reaction was complete, as determined by LC-MS. After cooling to room temperature, water was added and the mixture was stirred for 10 min. The solid precipitate was collected by filtration, washed with water, and dried under vacuum at 50° C. to provide 0.533 g (77%) of (5,8-difluoroquinazolin-4-yl)-{2-[3-methyl-4-(4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-amine as an off-white solid, M.P. 108-110° C. 1H NMR (CDCl3): δ 8.69 (s, 1H), 8.31 (d, J=5.1 Hz, 1H), 7.34 (m, 1H), 7.13-7.21 (m, 4H), 6.96-7.03 (m, 2H), 6.71-6.84 (br, 1H), 3.94 (m, 2H), 3.02 (t, J=6.9 Hz, 2H), 2.17 (s, 3H). LC/MS: 461.13 (M++1).

후처리

  1. temperatureAfter cooling to room temperature
  2. filtrationThe solid precipitate was collected by filtration
  3. washwashed with water
  4. customdried under vacuum at 50° C.

출처 및 근거

ORD 기록
ord-ef164c25af2a4074a84180d330b6f933
출처 데이터셋
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08268843B2

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