Triphosgene → HCID 53241942, compound

HRID 527733Notes

Reaction equation

HRID 527733 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([NH:15][C:16](=[O:22])[C@:17]([CH3:21])([CH2:19][CH3:20])[NH2:18])=[CH:11][CH:10]=2)=[CH:4][C:3]=1[O:23][CH3:24].Cl[C:26](Cl)([O:28]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH2:19]([C@@:17]1([CH3:21])[NH:18][C:26](=[O:28])[N:15]([C:12]2[CH:13]=[N:14][C:9]([O:8][C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([O:23][CH3:24])[CH:4]=3)=[CH:10][CH:11]=2)[C:16]1=[O:22])[CH3:20]

Participants

4

Reactant 2

HCID 94429Triphosgene2×HCID 67235584HCID 67235584, compound

Product 1

HCID 53241942HCID 53241942, compoundYield 118.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of N1-(6-{[4-methyl-3-(methyloxy)phenyl]oxy}-3-pyridinyl)-D-isovalinamide (Reference Intermediate R8 42 mg) in dry dichloromethane (6 mL), TEA (0.089 mL, 0.638 mmol) was added. The mixture was cooled down to 0° C. and a solution of triphosgene (17.03 mg, 0.057 mmol) in dry dichloromethane (1.500 mL) was added dropwise. The mixture was stirred at that temperature for 1 hour, then a solution of triphosgene (17.03 mg, 0.057 mmol) in dry dichloromethane (DCM) (1.500 mL) was added dropwise again. The reaction was stirred for 30 minutes, it was maintained in the ice-bath and quenched with water (10 mL). The mixture was allowed to reach the room temperature then it was extracted with dichloromethane (3×7 mL). The combined organic layers were dried over sodium sulphate, filtered and evaporated. The residue obtained was purified by flash chromatography on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate as eluents from 80/20 to 50/50 (Biotage system). This afforded the title compound as a white solid (24 mg).

Workup

  1. stirringThe reaction was stirred for 30 minutes
  2. customquenched with water (10 mL)
  3. customthe room temperature
  4. extractionit was extracted with dichloromethane (3×7 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue obtained
  9. customwas purified by flash chromatography on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate as eluents from 80/20 to 50/50 (Biotage system)

Sources & evidence

ORD record
ord-9843e00c26794fe2b302b129c5415af9
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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