Triphosgene → 1-(2-(dimethylamino)-4-(trifluoromethyl)benzyl)-3-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-8-yl)urea

HRID 1505195Notes

Reaction equation

HRID 1505195 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[C:5]([N:11]2[CH:15]=NC=N2)[CH:4]=1.Cl[C:19](Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[N-:30]=[C:31]=[O:32].N[C:34]1[C:39]2[O:40][CH2:41][C:42](=[O:44])[NH:43][C:38]=2[CH:37]=[CH:36][CH:35]=1>CCOC(C)=O.CN(C=O)C>[CH3:19][N:11]([CH3:15])[C:5]1[CH:4]=[C:3]([C:2]([F:1])([F:16])[F:17])[CH:10]=[CH:9][C:6]=1[CH2:7][NH:8][C:31]([NH:30][C:34]1[C:39]2[O:40][CH2:41][C:42](=[O:44])[NH:43][C:38]=2[CH:37]=[CH:36][CH:35]=1)=[O:32]

Participants

7

Reactant 4

HCID 94429TriphosgeneHCID 105034IsocyanateHCID 115934888-Amino-2H-1,4-benzoxazin-3(4H)-oneHCID 674252734-(trifluoromethyl)-2-(1H-1,2,4-triazol-1-yl)benzonitrile

Product 1

HCID 534764701-(2-(dimethylamino)-4-(trifluoromethyl)benzyl)-3-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-8-yl)ureaYield 19%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
80 °C

Procedure

Amine 2a (480 mg, 2.2 mmol) (Scheme 7) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (653 mg, 2.2 mmol) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and the residue was dissolved in 5 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1f (320 mg, 1.6 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt 1/petroleum ether 1). The solvent was evaporated and the crude was dissolved in AcOEt (50 ml) and washed with water (1×30 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 130 mg of a white solid. Yield=19% 1HNMR (DMSO, 200 MHz) δ 2.70 (6H, s), 4.39 (2H, d, J=5.2 Hz), 4.62 (2H, s), 6.48 (1H, dd, J=7.8 Hz, J′=1.2 Hz), 6.81 (1H, t), 7.32 (1H, s), 7.42 (3H, m), 7.72 (1H, dd, J′=1.4 Hz), 8.19 (1H, s), 10.65 (1H, bs); [M+1] 409.1 (C19H19F3N4O3 requires 408.37).

Workup

  1. additionwas added to the solution
  2. customthen evaporated
  3. dissolutionthe residue was dissolved in 5 ml of DMF
  4. temperaturethe mixture was warmed at 80° C. for 8 hours
  5. customThe solvent was evaporated
  6. dissolutionthe crude was dissolved in AcOEt (50 ml)
  7. washwashed with water (1×30 ml) and brine
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. concentrationconcentrated under vacuum
  10. customThe purification of the crude residue by chromatographic column

Sources & evidence

ORD record
ord-a38a8f04a78e46daa8f20c11f08bb1ca
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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