Diisopropylethylamine → N-{3-[7-(3-dimethylamino-phenylamino)-1-methyl-2-oxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl]-4-methyl-phenyl}-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide

HRID 2222244Notes

Reaction equation

HRID 2222244 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:30])=[C:6]([N:8]2[CH2:17][C:16]3[C:11](=[N:12][C:13]([NH:18][C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([N:25]([CH3:27])[CH3:26])[CH:20]=4)=[N:14][CH:15]=3)[N:10]([CH3:28])[C:9]2=[O:29])[CH:7]=1.[CH3:31][C:32]1[N:33]=[CH:34][N:35]([C:37]2[CH:38]=[C:39]([CH:43]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:45]=2)[C:40](O)=[O:41])[CH:36]=1.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>[CH3:27][N:25]([CH3:26])[C:21]1[CH:20]=[C:19]([NH:18][C:13]2[N:12]=[C:11]3[N:10]([CH3:28])[C:9](=[O:29])[N:8]([C:6]4[CH:7]=[C:2]([NH:1][C:40](=[O:41])[C:39]5[CH:43]=[C:44]([C:46]([F:47])([F:48])[F:49])[CH:45]=[C:37]([N:35]6[CH:36]=[C:32]([CH3:31])[N:33]=[CH:34]6)[CH:38]=5)[CH:3]=[CH:4][C:5]=4[CH3:30])[CH2:17][C:16]3=[CH:15][N:14]=2)[CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 469002413-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzoic acidHCID 685247583-(5-amino-2-methyl-phenyl)-7-(3-dimethylamino-phenylamino)-1-methyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Product 1

HCID 11388198N-{3-[7-(3-dimethylamino-phenylamino)-1-methyl-2-oxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl]-4-methyl-phenyl}-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamideYield 30%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(5-amino-2-methyl-phenyl)-7-(3-dimethylamino-phenylamino)-1-methyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (52 mg, 0.13 mmol), 3-(4-methyl-imidazol-1-yl)-5-trifluoromethylbenzoic acid (42 mg, 0.15 mmol), and DIEA (78 μL, 0.45 mmol) in DMF is added HATU (59 mg, 0.15 mmol), and the mixture is stirred for 1 hour 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 residue is purified by recrystallization from methanol to give N-{3-[7-(3-dimethylamino-phenylamino)-1-methyl-2-oxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl]-4-methyl-phenyl}-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide (25 mg, 30%) as a yellowish solid; 1H NMR 400 MHz (DMSO-d6) δ 9.34 (s, 1H), 8.43 (s, 1H), 8.38 (s, 1H), 8.23 (s, 1H), 8.16 (s, 1H), 8.13 (s, 1H), 7.74 (s, 1H), 7.69 (s, 1H), 7.65 (d, 1H), 7.34-7.30 (m, 2H), 7.08-7.03 (m, 2H), 6.33 (d, 1H), 4.68 (d, 1H), 4.51 (d, 1H), 3.35 (s, 3H), 2.88 (s, 6H), 2.17 (s, 3H), 2.14 (s, 3H); MS m/z 656.3 (M+1).

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 residue is purified by recrystallization from methanol

Sources & evidence

ORD record
ord-998ec09f580144f1807b900d79390bd3
Source dataset
uspto-grants-2008_05
Patent number
US07371750B2

Reaction notes

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