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

HRID 453375Notes

Reaction equation

HRID 453375 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-ea52f6f79dac4cf4a7220b7ac267124d
Source dataset
uspto-grants-2013_07
Patent number
US08492404B2

Reaction notes

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