Triphosgene → HCID 57410463, compound
Reaction equation
[CH3:1][C:2]([C:5]([NH:7][C:8]1[CH:9]=[N:10][C:11]([O:14][C:15]2[C:16]3[CH:17]4[CH2:25][C:18]4([CH3:26])[CH2:19][O:20][C:21]=3[CH:22]=[CH:23][CH:24]=2)=[CH:12][CH:13]=1)=[O:6])([CH3:4])[NH2:3].Cl[C:28](Cl)([O:30]C(=O)OC(Cl)(Cl)Cl)Cl.C1CCCCC1.C(OCC)(=O)C>ClCCl>[CH3:4][C:2]1([CH3:1])[NH:3][C:28](=[O:30])[N:7]([C:8]2[CH:9]=[N:10][C:11]([O:14][C:15]3[C:16]4[CH:17]5[CH2:25][C:18]5([CH3:26])[CH2:19][O:20][C:21]=4[CH:22]=[CH:23][CH:24]=3)=[CH:12][CH:13]=2)[C:5]1=[O:6]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 2-methyl-N1-{6-[(1a-methyl-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-7-yl)oxy]-3-pyridinyl}alaninamide (Intermediate 129, 100 mg) in dry dichloromethane (10 ml) TEA (0.177 ml, 1.273 mmol) was added and the reaction mixture was cooled to 0° C. At this point a solution of triphosgene (37.8 mg, 0.127 mmol) in dry dichloromethane (2.5 ml) was slowly added (over 30 minutes) and the reaction mixture was stirred for 1 hour at the same temperature. The reaction was then quenched with water and the two phases were separated. The organic layer was dried over sodium sulphate, filtered and evaporated and the residue was purified by silica gel chromatography (Companion system, with a gradient from cyclohexane/ethyl acetate 8:2 to cyclohexane/ethyl acetate 1:1) to give the title compound as a white solid (40 mg, 0.103 mmol).
Workup
- customThe reaction was then quenched with water
- customthe two phases were separated
- dry with materialThe organic layer was dried over sodium sulphate
- filtrationfiltered
- customevaporated
- customthe residue was purified by silica gel chromatography (Companion system
Sources & evidence
- ORD record
- ord-e7b2b277ad794ea28284bb753a0c9650
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09346790B2
Reaction notes
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