2-Fluoro-5-(trifluoromethyl)phenyl isocyanate → HCID 178497207, compound

HRID 2203290Notes

Reaction equation

HRID 2203290 reaction equation
[CH3:1][NH:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:27][N:13]3[C:14](=[O:26])[NH:15][C:16]4[CH:17]=[C:18]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:20][C:21]=4[C:12]3=[N:11][CH2:10]2)=[CH:5][CH:4]=1.[F:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][C:30]=1[N:39]=[C:40]=[O:41]>C1COCC1>[F:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][C:30]=1[NH:39][C:40]([N:2]([CH3:1])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:27][N:13]3[C:14](=[O:26])[NH:15][C:16]4[CH:17]=[C:18]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:20][C:21]=4[C:12]3=[N:11][CH2:10]2)=[CH:5][CH:4]=1)=[O:41]

Participants

4

Reactant 2

HCID 27333802-Fluoro-5-(trifluoromethyl)phenyl isocyanateHCID 178482093HCID 178482093, compound

Product 1

HCID 178497207HCID 178497207, compoundYield 80.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 3-[4-(methylamino)phenyl]-6-oxo-3,4,6,7-tetrahydro-2H-pyrimido[1,2-c]quinazoline-9-carboxylate (5.1 mg, 0.014 mmol) in 0.7 mL THF was added 2-fluoro-5-(trifluoromethyl)phenyl isocyanate (0.0024 mL, 0.017 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 1 hour the reaction was quenched with 1 mL MeOH and evaporated. The resulting solid was crystallized from EtOAc/hexane to give the title compound as an off-white solid (6.4 mg, 80%). 1H NMR (Acetone-d6) δ: 9.70 (br. s, 1H), 8.57 (dd, J=7.3, 2.3 Hz, 1H), 8.21 (d, J=8.2 Hz, 1H), 7.76 (d, J=1.2 Hz, 1H), 7.69 (dd, J=8.4, 1.6 Hz, 1H), 7.50-7.59 (m, 4H), 7.25-7.39 (m, 2H), 7.06 (d, J=2.9 Hz, 1H), 4.39-4.47 (m, 1H), 3.88-3.97 (m, 4H), 3.62-3.79 (m, 2H), 3.34 (s, 3H), 3.15-3.27 (m, 1H).

Workup

  1. temperaturethe reaction was briefly warmed to approximately 50° C.
  2. temperatureto cool to rt
  3. customAt 1 hour the reaction was quenched with 1 mL MeOH
  4. customevaporated
  5. customThe resulting solid was crystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-3402d4c7deb645758286c456b3b35888
Source dataset
uspto-grants-2016_06
Patent number
US09365575B2

Reaction notes

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