Triphosgene → HCID 86698473, compound

HRID 527707Notes

Reaction equation

HRID 527707 reaction equation
[C:1]12([C:12]3[C:7](=[CH:8][CH:9]=[CH:10][C:11]=3[O:13][C:14]3[N:19]=[CH:18][C:17]([NH:20][C:21](=[O:27])[C@:22]([CH3:26])([CH2:24][CH3:25])[NH2:23])=[CH:16][N:15]=3)[O:6][CH2:5][CH2:4]1)[CH2:3][CH2:2]2.Cl[C:29](Cl)([O:31]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[C:1]12([C:12]3[C:7](=[CH:8][CH:9]=[CH:10][C:11]=3[O:13][C:14]3[N:19]=[CH:18][C:17]([N:20]4[C:21](=[O:27])[C@:22]([CH2:24][CH3:25])([CH3:26])[NH:23][C:29]4=[O:31])=[CH:16][N:15]=3)[O:6][CH2:5][CH2:4]1)[CH2:2][CH2:3]2

Participants

4

Reactant 2

HCID 94429TriphosgeneHCID 86698466HCID 86698466, compound2×

Product 1

HCID 86698473HCID 86698473, compoundYield 155.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of N1-[2-(2,3-dihydrospiro[chromene-4,1′-cyclopropan]-5-yloxy)-5-pyrimidinyl]-D-isovalinamide (Intermediate 225, 4 mg, 10.86 μmol) in dry Dichloromethane (1 mL) TEA (3.78 μL, 0.027 mmol) was added. The reaction was cooled in an ice-bath, then a solution of triphosgene (1.450 mg, 4.89 μmol) in dry Dichloromethane (0.250 mL) was added once then two other times with 10 minutes in between. The reaction was stirred at 0° C. for 40 minutes, then it was quenched with water (5 mL) maintaining the reaction in the ice-bath. The organic layer was separated, dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography on silica gel using a column isolute 2 g and cyclohexane to cyclohexane/ethyl acetate 1:1 as eluent affording the title compound (3 mg,) as a white solid.

Workup

  1. temperatureThe reaction was cooled in an ice-bath
  2. customit was quenched with water (5 mL)
  3. temperaturemaintaining
  4. customthe reaction in the ice-bath
  5. customThe organic layer was separated
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by chromatography on silica gel using a column isolute 2 g and cyclohexane to cyclohexane/ethyl acetate 1:1 as eluent

Sources & evidence

ORD record
ord-4dc9ea5d0334429595a2dbe1ba398aef
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

Loading…