Triphosgene → HCID 57410335, compound

HRID 527698Notes

Reaction equation

HRID 527698 reaction equation
[C:1]12([C:7]3[C:8]([O:12][C:13]4[N:18]=[CH:17][C:16]([NH:19][C:20](=[O:26])[C@:21]([CH3:25])([CH2:23][CH3:24])[NH2:22])=[CH:15][CH:14]=4)=[CH:9][CH:10]=[CH:11][C:6]=3[O:5][CH2:4]1)[CH2:3][CH2:2]2.Cl[C:28](Cl)([O:30]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH2:23]([C@@:21]1([CH3:25])[NH:22][C:28](=[O:30])[N:19]([C:16]2[CH:17]=[N:18][C:13]([O:12][C:8]3[C:7]4[C:1]5([CH2:4][O:5][C:6]=4[CH:11]=[CH:10][CH:9]=3)[CH2:2][CH2:3]5)=[CH:14][CH:15]=2)[C:20]1=[O:26])[CH3:24]

Participants

4

Reactant 2

HCID 94429Triphosgene2×HCID 86698430HCID 86698430, compound2×

Product 1

HCID 57410335HCID 57410335, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of N1-[6-(spiro[1-benzofuran-3,1′-cyclopropan]-4-yloxy)-3-pyridinyl]-D-isovalinamide (Intermediate 93, 68 mg) and TEA (0.134 mL, 0.962 mmol) in dry dichloromethane (11 ml) at 0° C. was added dropwise a solution of triphosgene (25.7 mg, 0.087 mmol) in dry dichloromethane (3.14 m) and the mixture thus obtained was stirred at the same temperature. After 1 hour a solution of triphosgene (25.7 mg, 0.087 mmol) in dry dichloromethane (3.14 ml) was added. After 3 hours UPLC/MS showed the absence of the starting material and the presence of the desired compound. Water was then added, the organic phase was separated and the aqueous one was extracted again with dichloromethane. The organic phase was washed with brine, dried over sodium sulphate and concentrated under vacuum to give 87 mg of crude. This was purified by flash chromatography (Biotage KP-Sil 10 g SNAP column, eluant cyclohexane/ethyl acetate from 88/12 to 0/100 in 10CV) to give 47 mg of the title compound as a white foam.

Workup

  1. customthe mixture thus obtained

Sources & evidence

ORD record
ord-3cf23a780b264d1b9b25fd7121acfe5f
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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