Triethylamine → N-[3-(7-chloro-2-oxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl)-4-methylphenyl]-3-trifluoromethylbenzamide

HRID 2222249Notes

Reaction equation

HRID 2222249 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH3:9])[C:5]([CH2:10][NH:11][C:12]2[CH:13]=[C:14]([NH:19][C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[CH:15]=[CH:16][C:17]=2[CH3:18])=[CH:4][N:3]=1.C(N(CC)CC)C.ClC(Cl)([O:42]C(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]2[NH:8][C:9](=[O:42])[N:11]([C:12]3[CH:13]=[C:14]([NH:19][C:20](=[O:31])[C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:29])[F:30])[CH:22]=4)[CH:15]=[CH:16][C:17]=3[CH3:18])[CH2:10][C:5]2=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 86600918N-{3-[(2-chloro-4-methylaminopyrimidin-5-ylmethyl)amino]-4-methylphenyl}-3-trifluoromethylbenzamide

Product 1

HCID 86600919N-[3-(7-chloro-2-oxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl)-4-methylphenyl]-3-trifluoromethylbenzamideYield 185.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of N-{3-[(2-chloro-4-methylaminopyrimidin-5-ylmethyl)amino]-4-methylphenyl}-3-trifluoromethylbenzamide (559 mg, 1.24 mmol) and triethylamine (693 μL, 4.97 mmol) in THF (15 mL) is added triphosgene (147 mg, 0.49 mmol) in THF (5 mL) at 0° C., and the mixture is stirred for 30 minutes at room temperature. The precipitate is filtered off and the filtrate is stirred for 3 hours at 110° C. The reaction mixture is then diluted with EtOAc and washed with saturated NaHCO3. The organic layer is dried over MgSO4 and concentrated under reduced pressure to give crude oil which is purified by flash column chromatography (SiO2, EtOAc/hexane=1/2) to give N-[3-(7-chloro-2-oxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl)-4-methylphenyl]-3-trifluoromethylbenzamide (420 mg, 71%) as a white solid.

Workup

  1. filtrationThe precipitate is filtered off
  2. stirringthe filtrate is stirred for 3 hours at 110° C
  3. additionThe reaction mixture is then diluted with EtOAc
  4. washwashed with saturated NaHCO3
  5. dry with materialThe organic layer is dried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customto give crude oil which
  8. customis purified by flash column chromatography (SiO2, EtOAc/hexane=1/2)

Sources & evidence

ORD record
ord-83842349887549bb99a377c27052fbe0
Source dataset
uspto-grants-2008_05
Patent number
US07371750B2

Reaction notes

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