Triphosgene → HCID 57410581, compound

HRID 527703Notes

Reaction equation

HRID 527703 reaction equation
[CH3:1][C:2]1([CH3:25])[C:6]2[C:7]([O:11][C:12]3[N:17]=[CH:16][C:15]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[NH2:21])=[CH:14][N:13]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3]1.Cl[C:27](Cl)([O:29]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:1][C:2]1([CH3:25])[C:6]2[C:7]([O:11][C:12]3[N:17]=[CH:16][C:15]([N:18]4[C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[NH:21][C:27]4=[O:29])=[CH:14][N:13]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3]1

Participants

4

Reactant 2

HCID 94429TriphosgeneHCID 67966823HCID 67966823, compound2×

Product 1

HCID 57410581HCID 57410581, compoundYield 147%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of N1-{2-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-5-pyrimidinyl}-2-methylalaninamide (Intermediate 143, 18 mg, 0.053 mmol) in dry Dichloromethane (DCM) (3 mL) TEA (0.037 ml, 0.263 mmol) was added and the reaction mixture was cooled to 0° C. A solution of triphosgene (7.02 mg, 0.024 mmol) in dry Dichloromethane (1 mL) was slowly added and the reaction mixture was stirred for 2 hours while the temperature was allowed to reach r.t. The reaction was quenched with water (3 ml) and two phases were separated. The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a column SNAP 10 g and cyclohexane/ethyl acetate from 8:2 to 1:1 as eluents affording the title compound (13 mg) as a white solid.

Workup

  1. customto reach r.t
  2. customThe reaction was quenched with water (3 ml) and two phases
  3. customwere separated
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a column SNAP 10 g and cyclohexane/ethyl acetate from 8:2 to 1:1 as eluents

Sources & evidence

ORD record
ord-793ecd8199ef4d21a58efc716d821d1d
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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