Diisopropylethylamine → N-[4-Methyl-3-(7-methylsulfanyl-2,4-dioxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl)-phenyl]-3-trifluoromethyl-benzamide

HRID 2222252Notes

Reaction equation

HRID 2222252 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:20])[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)=[CH:4][C:3]=1[NH:21][C:22]([C:24]1[C:25]([NH2:32])=[N:26][C:27]([S:30][CH3:31])=[N:28][CH:29]=1)=[O:23].C(N(C(C)C)CC)(C)C.Cl[C:43](Cl)([O:45]C(=O)OC(Cl)(Cl)Cl)Cl>O1CCOCC1.CCOC(C)=O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:20])[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:18])([F:19])[F:17])[CH:11]=2)=[CH:4][C:3]=1[N:21]1[C:22](=[O:23])[C:24]2[C:25](=[N:26][C:27]([S:30][CH3:31])=[N:28][CH:29]=2)[NH:32][C:43]1=[O:45]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 694477274-Amino-2-methylsulfanyl-pyrimidine-5-carboxylic acid [2-methyl-5-(3-trifluoromethyl-benzoylamino)-phenyl]-amide

Product 1

HCID 68522440N-[4-Methyl-3-(7-methylsulfanyl-2,4-dioxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl)-phenyl]-3-trifluoromethyl-benzamideYield 55%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 4-amino-2-methylsulfanyl-pyrimidine-5-carboxylic acid [2-methyl-5-(3-trifluoromethyl-benzoylamino)-phenyl]-amide (286 mg, 0.62 mmol) and diisopropylethylamine (864 μL, 4.96 mmol) in dioxane (10 mL) is added a solution of triphosgene (184 mg, 0.62 mmol) in dioxane (2 mL) at 0 C, and the mixture is stirred for 12 h at 100° C. The reaction mixture is diluted with EtOAc (50 mL), and washed with saturated NaHCO3 solution. The organic layer is dried over MgSO4, filtered, concentrated under reduced pressure, and crystallized from MeOH to give N-[4-Methyl-3-(7-methylsulfanyl-2,4-dioxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl)-phenyl]-3-trifluoromethyl-benzamide (166 mg, 55%) as a white crystalline solid.

Workup

  1. washwashed with saturated NaHCO3 solution
  2. dry with materialThe organic layer is dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customcrystallized from MeOH

Sources & evidence

ORD record
ord-cf9c946bc9e945cfb75cffe9bf7f6281
Source dataset
uspto-grants-2008_05
Patent number
US07371750B2

Reaction notes

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