Triphosgene → 5,5-Dimethyl-3-[6-(spiro[1-benzofuran-3,1'-cyclopropan]-4-yloxy)-3-pyridinyl]-2,4-imidazolidinedione

HRID 1505445Notes

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:20]3[C:21]4([CH2:24][O:25][C:19]=3[CH:18]=[CH:17][CH:16]=2)[CH2:23][CH2:22]4)=[CH:12][CH:13]=1)=[O:6])([CH3:4])[NH2:3].Cl[C:27](Cl)([O:29]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:4][C:2]1([CH3:1])[NH:3][C:27](=[O:29])[N:7]([C:8]2[CH:9]=[N:10][C:11]([O:14][C:15]3[C:20]4[C:21]5([CH2:24][O:25][C:19]=4[CH:18]=[CH:17][CH:16]=3)[CH2:23][CH2:22]5)=[CH:12][CH:13]=2)[C:5]1=[O:6]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 2-methyl-N1-[6-(spiro[1-benzofuran-3,1′-cyclopropan]-4-yloxy)-3-pyridinyl]alaninamide (Reference Intermediate 219, 34 mg) in dry dichloromethane (6 mL) TEA (0.070 mL, 0.501 mmol) was added and the mixture was cooled to 0° C. A solution of triphosgene (13.38 mg, 0.045 mmol) in dry dichloromethane (2 mL) was slowly added and the reaction mixture was stirred for 1 hour at the same temperature. The reaction was quenched with water (3 ml) and two phases were separated. The organic layer was dried over sodium sulphate, filtered and evaporated. The residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column SNAP and cyclohexane/ethyl acetate 7:3 to cyclohexane/ethyl acetate 3:7 as eluents affording the title as a white solid (23 mg).

Workup

customThe reaction was quenched with water (3 ml) and two phases
customwere separated
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 a 10 g SNAP column SNAP and cyclohexane/ethyl acetate 7:3 to cyclohexane/ethyl acetate 3:7 as eluents

Sources & evidence

ORD record: ord-608c73d432784a91a86b957f60bce97f
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216967B2

Reaction notes

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