3-(Trifluoromethyl)benzoic acid → N-{3-[2-(4-Chloro-phenylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-4-methyl-phenyl}-3-trifluoromethyl benzamide

HRID 1853951Notes

Reaction equation

HRID 1853951 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:26])=[C:6]([N:8]2[CH2:25][CH2:24][C:11]3[N:12]=[C:13]([NH:16][C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=4)[N:14]=[CH:15][C:10]=3[CH2:9]2)[CH:7]=1.[F:27][C:28]([F:39])([F:38])[C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=1)[C:32](O)=[O:33].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C.C(OCC)(=O)C>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([NH:16][C:13]2[N:14]=[CH:15][C:10]3[CH2:9][N:8]([C:6]4[CH:7]=[C:2]([NH:1][C:32](=[O:33])[C:31]5[CH:35]=[CH:36][CH:37]=[C:29]([C:28]([F:27])([F:38])[F:39])[CH:30]=5)[CH:3]=[CH:4][C:5]=4[CH3:26])[CH2:25][CH2:24][C:11]=3[N:12]=2)=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 99633-(Trifluoromethyl)benzoic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68253436[6-(5-Amino-2-methyl-phenyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-(4-chloro-phenyl)amine

Product 1

HCID 67328929N-{3-[2-(4-Chloro-phenylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-4-methyl-phenyl}-3-trifluoromethyl benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [6-(5-Amino-2-methyl-phenyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-(4-chloro-phenyl)amine (54.87 mg, 0.15 mmol), 3-Trifluoromethylbenzoic acid (28.51 mg, 0.15 mmol), and Diisipropylethylamine (DIPEA) (78 μl, 0.45 mmol) in DMF (7.5 ml) was added 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (59 mg, 0.15 mmol) and the reaction mixture is stirred for 3 hour at room temperature. The reaction mixture was diluted with ethyl acetate and washed with 5% aqueous sodium bisulphate solution, saturated aqueous sodium bicarbonate solution and brine. The organic layer is dried over sodium sulphate and concentrated under reduced pressure. The crude product obtained was purified by column chromatography (SiO2, 2-10% methanol in chloroform to give of N-{3-[2-(4-chlorophenylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-4-methyl-phenyl}-3-trifluoromethylbenzamide [13] as a pale yellow solid. [Yield: 60.6 mg, 75.2%]

Workup

  1. washwashed with 5% aqueous sodium bisulphate solution, saturated aqueous sodium bicarbonate solution and brine
  2. dry with materialThe organic layer is dried over sodium sulphate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product obtained
  5. customwas purified by column chromatography (SiO2, 2-10% methanol in chloroform

Sources & evidence

ORD record
ord-6d8ca7af58ec4bdebdfde2ff36ac2ef0
Source dataset
uspto-grants-2015_02
Patent number
US08962637B2

Reaction notes

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