Pyridine → N-(2-amino-5-pyrimidinyl)-2-methyl-3-(((3-(trifluoromethyl)phenyl)carbonyl)amino)benzamide

HRID 453375노트

반응식

HRID 453375 반응식
[NH2:1][C:2]1[C:3]([CH3:18])=[C:4]([CH:15]=[CH:16][CH:17]=1)[C:5]([NH:7][C:8]1[CH:9]=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1)=[O:6].N1C=CC=CC=1.[F:25][C:26]([F:37])([F:36])[C:27]1[CH:28]=[C:29]([CH:33]=[CH:34][CH:35]=1)[C:30](Cl)=[O:31].CCN(CC)CC>C(Cl)Cl>[NH2:14][C:11]1[N:10]=[CH:9][C:8]([NH:7][C:5](=[O:6])[C:4]2[CH:15]=[CH:16][CH:17]=[C:2]([NH:1][C:30]([C:29]3[CH:33]=[CH:34][CH:35]=[C:27]([C:26]([F:25])([F:36])[F:37])[CH:28]=3)=[O:31])[C:3]=2[CH3:18])=[CH:13][N:12]=1

참가 물질

6

반응물 4

HCID 1049PyridineHCID 8471TriethylamineHCID 752573-(Trifluoromethyl)benzoyl chlorideHCID 593819003-amino-N-(2-aminopyrimidin-5-yl)-2-methylbenzamide

생성물 1

HCID 16118606N-(2-amino-5-pyrimidinyl)-2-methyl-3-(((3-(trifluoromethyl)phenyl)carbonyl)amino)benzamide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

3-amino-N-(2-aminopyrimidin-5-yl)-2-methylbenzamide 42 (113 mg, 0.464 mmol) [prepared according to the procedure described for methylbenzamide5-amino-N-(2-aminopyrimidin-5-yl)-2-methylbenzamide in Example 1] was taken up in CH2Cl2 (4 mL) and pyridine (3 mL) and 3-(trifluoromethyl)benzoyl chloride (0.31 mL, 2.09 mmol) was added followed by NEt3 (0.13 mL, 0.928 mmol). Complete consumption of the amine starting material was indicated by LCMS. The crude reaction mixture was concentrated and the product purified using automated medium pressure chromatography (Isco—40 g column; eluting with a linear gradient from 97% CH2Cl2 (A line) to 100% 90/10/1 CH2Cl2/MeOH/NH3 (B line) on silica gel) to afford N-(2-amino-5-pyrimidinyl)-2-methyl-3-(((3-(trifluoromethyl)phenyl)carbonyl)amino)benzamide 43 as an off-white solid. MS m/z found 416 [MH+]; calc. for C20H16F3N5O2=415.13; and 2-methyl-3-(((3-(trifluoromethyl)phenyl)carbonyl)amino)-N-(2-(((3-(trifluoromethyl)phenyl)carbonyl)amino)-5-pyrimidinyl)benzamide 44 as an off-white solid. MS m/z found 588 [MH+]; calc. for C28H19F6N5O3=587.14.

후처리

  1. customComplete consumption of the amine starting material
  2. customThe crude reaction mixture
  3. concentrationwas concentrated
  4. customthe product purified
  5. washeluting with a linear gradient from 97% CH2Cl2 (A line) to 100% 90/10/1 CH2Cl2/MeOH/NH3 (B line) on silica gel)

출처 및 근거

ORD 기록
ord-ea52f6f79dac4cf4a7220b7ac267124d
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08492404B2

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