Triphosgene → HCID 53241944, compound

HRID 1505425Notes

Reaction equation

HRID 1505425 reaction equation
[NH2:1][C:2]1([C:5]([NH:7][C:8]2[CH:9]=[N:10][C:11]([O:14][C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([O:22][CH3:23])[CH:16]=3)=[CH:12][CH:13]=2)=[O:6])[CH2:4][CH2:3]1.Cl[C:25](Cl)([O:27]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:21][C:18]1[CH:19]=[CH:20][C:15]([O:14][C:11]2[N:10]=[CH:9][C:8]([N:7]3[C:5](=[O:6])[C:2]4([CH2:4][CH2:3]4)[NH:1][C:25]3=[O:27])=[CH:13][CH:12]=2)=[CH:16][C:17]=1[O:22][CH3:23]

Participants

4

Reactant 2

HCID 94429Triphosgene2×HCID 67235871HCID 67235871, compound2×

Product 1

HCID 53241944HCID 53241944, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-amino-N-(6-{[4-methyl-3-(methyloxy)phenyl]oxy}-3-pyridinyl)cyclopropanecarboxamide (Intermediate 105, 58 mg) in dry dichloromethane (2 mL) TEA (0.129 mL, 0.925 mmol) was added. The reaction mixture was cooled in an ice-bath, then a solution of triphosgene (24.72 mg, 0.083 mmol) in dry dichloromethane (0.500 mL) was added dropwise. The reaction mixture was stirred at 0° C. for 30 minutes, then the solution of triphosgene (24.72 mg, 0.083 mmol) in dry dichloromethane (0.500 mL) was added again. The reaction mixture was stirred at 0° C. for 30 minutes. The reaction was maintained in the ice-bath and quenched with water (10 mL). The organic layer was separated, dried over sodium sulphate, filtered and evaporated. The residue was purified by flash chromatography on silica gel using a column 25 g SNAP column and cyclohexane/ethylacetate as eluents from 100:0 to 50:50. This afforded the title compound as a white solid (20 mg).

Workup

  1. temperatureThe reaction mixture was cooled in an ice-bath
  2. stirringThe reaction mixture was stirred at 0° C. for 30 minutes
  3. customquenched with water (10 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash chromatography on silica gel using a column 25 g SNAP column and cyclohexane/ethylacetate as eluents from 100:0 to 50:50

Sources & evidence

ORD record
ord-3d53396b1ad04bee87d9a74f3ce95649
Source dataset
uspto-grants-2015_12
Patent number
US09216967B2

Reaction notes

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