Triphosgene → HCID 57410580, compound
Reaction equation
[C:1]12([C:8]3[C:9]([O:13][C:14]4[N:19]=[CH:18][C:17]([NH:20][C:21](=[O:27])[C@@:22]([CH3:26])([CH2:24][CH3:25])[NH2:23])=[CH:16][CH:15]=4)=[CH:10][CH:11]=[CH:12][C:7]=3[CH2:6][O:5][CH2:4]1)[CH2:3][CH2:2]2.Cl[C:29](Cl)([O:31]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH2:24]([C@@:22]1([CH3:26])[NH:23][C:29](=[O:31])[N:20]([C:17]2[CH:18]=[N:19][C:14]([O:13][C:9]3[C:8]4[C:1]5([CH2:4][O:5][CH2:6][C:7]=4[CH:12]=[CH:11][CH:10]=3)[CH2:2][CH2:3]5)=[CH:15][CH:16]=2)[C:21]1=[O:27])[CH3:25]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of N1-[6-(1H-spiro[2-benzopyran-4,1′-cyclopropan]-5-yloxy)-3-pyridinyl]-isovalinamide (Intermediate 141, 40 mg) in dry dichloromethane (8 mL) TEA (0.076 mL, 0.544 mmol) was added and the reaction mixture was cooled to 0° C. A solution of triphosgene (14.54 mg, 0.049 mmol) in dry dichloromethane (4 ml) was slowly added and the reaction mixture was stirred for 3 hours at the same temperature. The reaction was quenched with water (10 ml) and two phases separated. The organic layer was dried over sodium sulphate, filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using 10 g SNAP column and cyclohexane/ethyl acetate as eluents from 7:3 to 3:7 as eluent. This afforded the title compound (25 mg) as a white solid.
Workup
- customThe reaction was quenched with water (10 ml) and two phases
- customseparated
- dry with materialThe organic layer was dried over sodium sulphate
- filtrationfiltered
- customevaporated
- customthe residue was purified by flash chromatography (Biotage system) on silica gel using 10 g SNAP column and cyclohexane/ethyl acetate as eluents from 7:3 to 3:7 as eluent
Sources & evidence
- ORD record
- ord-e4d47c5f94214c048097da29fca4c8ab
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09346790B2
Reaction notes
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