Triphosgene → ((6-chloropyridin-3-yl)methyl)-3-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-8-yl)urea

HRID 1505200Notes

Reaction equation

HRID 1505200 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH2:9])=[CH:4][CH:3]=1.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[N-:22]=[C:23]=[O:24].N[C:26]1[C:31]2[O:32][CH2:33][C:34](=[O:36])[NH:35][C:30]=2[CH:29]=[CH:28][CH:27]=1>CCOC(C)=O.CN(C=O)C.CO>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH:9][C:23]([NH:22][C:26]2[C:31]3[O:32][CH2:33][C:34](=[O:36])[NH:35][C:30]=3[CH:29]=[CH:28][CH:27]=2)=[O:24])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 94429TriphosgeneHCID 105034IsocyanateHCID 70209275-(Aminomethyl)-2-chloropyridineHCID 115934888-Amino-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 53476587((6-chloropyridin-3-yl)methyl)-3-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-8-yl)ureaYield 12%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

Commercially available (6-chloropyridin-3-yl)methanamine (800 mg, 5.61 mmol) was dissolved in 40 ml of AcOEt and at 0° C. triphosgene (1.54 g, 5.6 mmol) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and the residue was dissolved in 10 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1f (900 mg, 4.51 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt 9.5/MeOH 0.5). The solvent was evaporated and the crude was dissolved in AcOEt (80 ml) and washed with water (1×40 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 180 mg of a beige solid. Yield=12% 1HNMR (DMSO, 200 MHz) δ 4.31 (2H, d, J=5.6 Hz), 4.60 (2H, s), 6.47 (1H, dd), 6.81 (1H, t), 7.40 (1H, t), 7.50 (1H, d, J=8.2 Hz), 7.72 (2H, m), 8.13 (1H, bs), 8.34 (1H, bs), 10.66 (1H, bs); [M+1] 332.8 (C15H13ClN4O3 requires 332.74).

Workup

  1. additionwas added to the solution
  2. customthen evaporated
  3. dissolutionthe residue was dissolved in 10 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 (80 ml)
  7. washwashed with water (1×40 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-5545789fbeac4f60811d2a38873a8e55
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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