Diisopropylethylamine → 4-Amino-2-methylsulfanyl-pyrimidine-5-carboxylic acid [2-methyl-5-(3-trifluoromethyl-benzoylamino)-phenyl]-amide

HRID 1988596Notes

Reaction equation

HRID 1988596 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([O-:10])=O)=[CH:6][N:5]=[C:4]([S:11][CH3:12])[N:3]=1.[Na].[NH2:14][C:15]1[CH:16]=[C:17]([NH:22][C:23](=[O:34])[C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)[CH:18]=[CH:19][C:20]=1[CH3:21].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH3:21][C:20]1[CH:19]=[CH:18][C:17]([NH:22][C:23](=[O:34])[C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:31])([F:32])[F:33])[CH:25]=2)=[CH:16][C:15]=1[NH:14][C:8]([C:7]1[C:2]([NH2:1])=[N:3][C:4]([S:11][CH3:12])=[N:5][CH:6]=1)=[O:10]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 5360545SodiumHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11529455N-(3-amino-4-methylphenyl)-3-(trifluoromethyl)benzamideHCID 225621764-Amino-2-methylsulfanyl-5-pyrimidinecarboxylate

Product 1

HCID 694477274-Amino-2-methylsulfanyl-pyrimidine-5-carboxylic acid [2-methyl-5-(3-trifluoromethyl-benzoylamino)-phenyl]-amideYield 61%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-amino-2-methylsulfanyl-5-pyrimidinecarboxylate in a sodium salt form (1.28 g, 6.2 mmol), N-(3-Amino-4-methyl-phenyl)-3-trifluoromethyl-benzamide (1.82 g, 6.2 mmol), and DIEA (3.22 mL, 18.5 mmol) in DMF is added HATU (2.82 g, 7.42 mmol), and the mixture is stirred for 1 h at room temperature. The reaction mixture is diluted with EtOAc and washed with 5% aqueous Na2S2O3 solution, saturated aqueous NaHCO3 solution, and brine. The organic layer is dried over MgSO4 and concentrated in reduced pressure. The crude product is crystallized from MeOH to give 4-amino-2-methylsulfanyl-pyrimidine-5-carboxylic acid [2-methyl-5-(3-trifluoromethyl-benzoylamino)-phenyl]-amide (1.79 g, 61%) as a white solid.

Workup

  1. washwashed with 5% aqueous Na2S2O3 solution, saturated aqueous NaHCO3 solution, and brine
  2. dry with materialThe organic layer is dried over MgSO4
  3. concentrationconcentrated in reduced pressure
  4. customThe crude product is crystallized from MeOH

Sources & evidence

ORD record
ord-22bd14917bc4486b97e9c0596a7bf1d5
Source dataset
uspto-grants-2010_01
Patent number
US07642255B2

Reaction notes

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