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 2092585

Reaction equation

HRID 2092585 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-b383487efb6b4a3f819a31aa0e9ca37f
Source dataset
uspto-grants-2013_05
Patent number
US08440679B2

Linked notes

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