2-Fluoro-5-(trifluoromethyl)phenyl isocyanate → HCID 178522002, compound

HRID 2203270Notes

Reaction equation

HRID 2203270 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([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:5]=[CH:6][CH:7]=1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:25]=1[N:34]=[C:35]=[O:36]>C1COCC1>[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:25]=1[NH:34][C:35]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([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:3]=1)=[O:36]

Participants

4

Reactant 2

HCID 27333802-Fluoro-5-(trifluoromethyl)phenyl isocyanateHCID 178507527HCID 178507527, compound

Product 1

HCID 178522002HCID 178522002, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(3-aminophenyl)-2,3,4,7-tetrahydro-6H-pyrimido[1,2-c]quinazolin-6-one (12.2 mg, 0.042 mmol) in 0.9 mL THF was added 2-fluoro-5-(trifluoromethyl)phenyl isocyanate (0.0066 mL, 0.046 mmol) and the reaction stirred at rt. After 15 min, the reaction was briefly warmed to approximately 50° C. and then allowed to cool to rt. At 40 min the reaction was quenched with 1 mL MeOH, evaporated, and chromatographed eluting with 2% to 5% MeOH/CHCl3 gradient. The resulting solid was triturated with 40% EtOAc/hexane to give the title compound as a light tan solid (9.9 mg, 48%). 1H NMR (Acetone-d6) δ: 9.54 (br. s, 1H), 8.77-8.81 (m, 1H), 8.66 (s, 1H), 8.34 (d, J=2.9 Hz, 1H), 8.09-8.13 (m, 1H), 7.29-7.54 (m, 6H), 7.03-7.12 (m, 3H), 4.41 (ddd, J=12.9, 4.4, 2.9 Hz, 1H), 3.81-3.90 (m, 1H), 3.56-3.70 (m, 2H), 3.02-3.14 (m, 1H).

Workup

  1. temperaturethe reaction was briefly warmed to approximately 50° C.
  2. temperatureto cool to rt
  3. customAt 40 min the reaction was quenched with 1 mL MeOH
  4. customevaporated
  5. customchromatographed
  6. washeluting with 2% to 5% MeOH/CHCl3 gradient
  7. customThe resulting solid was triturated with 40% EtOAc/hexane

Sources & evidence

ORD record
ord-06c4c2cd7a24415b8f297a2d070fc6b5
Source dataset
uspto-grants-2016_06
Patent number
US09365575B2

Reaction notes

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