3-(Trifluoromethyl)benzoyl chloride → HCID 178521885, compound

HRID 2203285Notes

Reaction equation

HRID 2203285 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:22][N:12]3[C:13](=[O:21])[NH:14][C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=4[C:11]3=[N:10][CH2:9]2)=[CH:4][CH:3]=1.[F:23][C:24]([F:35])([F:34])[C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=1)[C:28](Cl)=[O:29]>N1C=CC=CC=1>[O:21]=[C:13]1[N:12]2[CH2:22][CH:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:28](=[O:29])[C:27]4[CH:31]=[CH:32][CH:33]=[C:25]([C:24]([F:23])([F:34])[F:35])[CH:26]=4)=[CH:3][CH:4]=3)[CH2:9][N:10]=[C:11]2[C:20]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[NH:14]1

Participants

4

Reactant 2

HCID 752573-(Trifluoromethyl)benzoyl chloride2×HCID 178507413HCID 178507413, compound

Product 1

HCID 178521885HCID 178521885, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 3-(4-aminophenyl)-2,3,4,7-tetrahydro-6H-pyrimido[1,2-c]quinazolin-6-one (10.8 mg, 0.037 mmol) in 0.7 mL pyridine at rt was added 3-(trifluoromethyl)benzoyl chloride (0.0066 mL, 0.044 mmol) and the reaction stirred at rt. After 5 min, the reaction was briefly warmed to dissolve solids and then allowed to cool to rt. At 45 min an additional amount (pipet tip) of 3-(trifluoromethyl)benzoyl chloride was added, the reaction briefly warmed, and then allowed to stir at rt overnight. At 24 hours the reaction was quenched with MeOH and evaporated. The crude mixture was partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with brine, dried with Na2SO4, and evaporated. The resulting solid was triturated with hot EtOAc, hexane added, the solid filtered and rinsed with 30% EtOAc/hexane to give the title compound as an off-white solid (10.3 mg, 60%). 1H NMR (CD3OD/CDCl3 mixture) δ: 8.25 (s, 1H), 8.18 (d, J=7.6 Hz, 1H), 8.02 (dd, J=8.1, 1.3 Hz, 1H), 7.84 (d, J=7.9 Hz, 1H), 7.65-7.75 (m, 3H), 7.43-7.50 (m, 1H), 7.29-7.35 (m, 2H), 7.10-7.17 (m, 1H), 7.00-7.05 (m, 1H), 4.39-4.47 (m, 1H), 3.81-3.90 (m, 1H), 3.61-3.72 (m, 2H), 3.07-3.18 (m, 1H).

Workup

  1. temperaturethe reaction was briefly warmed
  2. dissolutionto dissolve solids
  3. temperatureto cool to rt
  4. customthe reaction
  5. temperaturebriefly warmed
  6. stirringto stir at rt overnight
  7. customAt 24 hours the reaction was quenched with MeOH
  8. customevaporated
  9. customThe crude mixture was partitioned between EtOAc and aqueous Na2CO3 solution
  10. washthe EtOAc layer washed with brine
  11. dry with materialdried with Na2SO4
  12. customevaporated
  13. customThe resulting solid was triturated with hot EtOAc, hexane
  14. additionadded
  15. filtrationthe solid filtered
  16. washrinsed with 30% EtOAc/hexane

Sources & evidence

ORD record
ord-810e0cd8bc224d10b1f7b1b82ee6d7b6
Source dataset
uspto-grants-2016_06
Patent number
US09365575B2

Reaction notes

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