Triphosgene → HCID 53476472, compound

HRID 1505197Notes

Reaction equation

HRID 1505197 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH2:10])=[C:5]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:4]=1.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[N-:31]=[C:32]=[O:33].N[C:35]1[C:40]2[O:41][CH2:42][C:43](=[O:45])[NH:44][C:39]=2[CH:38]=[CH:37][CH:36]=1>CCOC(C)=O.CN(C=O)C>[F:18][C:2]([F:1])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:32]([NH:31][C:35]2[C:40]3[O:41][CH2:42][C:43](=[O:45])[NH:44][C:39]=3[CH:38]=[CH:37][CH:36]=2)=[O:33])=[C:5]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:4]=1

Participants

7

Reactant 4

HCID 94429TriphosgeneHCID 105034IsocyanateHCID 115934888-Amino-2H-1,4-benzoxazin-3(4H)-oneHCID 58873623(4-(Trifluoromethyl)-2-(piperidin-1-yl)phenyl)-methanamine

Product 1

HCID 53476472HCID 53476472, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
80 °C

Procedure

Amine 2c (420 mg, 1.6 mmol) (Scheme 7) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (475 mg, 1.6 mmol) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and dissolved in 5 ml of DMF. The solution of the isocyanate was added drop wise to a solution in DMF (10 ml) of compound 1f (180 mg, 1.1 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 (30 ml) and washed with water (1×20 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 160 mg of a white solid. Yield=32% 1HNMR (DMSO, 200 MHz) δ 1.57 (2H, bs), 1.68 (4H, bs), 2.85 (4H, m), 4.39 (2H, d, J=5.6 Hz), 4.62 (2H, s), 6.47 (1H, dd, J=7.8 Hz, J′=1.2 Hz), 6.81 (1H, t, J=8 Hz), 7.31 (2H, m), 7.43 (2H, m), 7.74 (1H, dd, J=8.4 Hz, J′=1.2 Hz), 8.18 (1H, bs), 10.65 (1H, bs); [M+1] 449.2 (C22H23F3N4O3 requires 448.4).

Workup

  1. additionwas added to the solution
  2. customthen evaporated
  3. dissolutiondissolved 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 (30 ml)
  7. washwashed with water (1×20 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-d143801a59ac4e1990c132c4f8a0b2f7
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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