Triphosgene → (5R)-3-{2-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-5-pyrimidinyl}-5-ethyl-2,4-imidazolidinedione

HRID 527691Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (2R)-2-amino-N-{2-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-5-pyrimidinyl}butanamide (Intermediate 67, 3 mg) in dry dichloromethane (0.5 ml), TEA (6.11 μL, 0.044 mmol) was added and the reaction mixture was cooled to 0° C. A solution of triphosgene (1.170 mg, 3.94 μmol) in dry dichloromethane (0.125 ml) was then added dropwise and the reaction mixture was stirred at the 0° C. for 30 minutes. The reaction was quenched with water (3 ml), and the organic phase was separated, dried over sodium sulphate, filtered and evaporated. The residue was purified by flash chromatography on silica gel using a column Isolute (1 g) and dichloromethane/methanol from 99.5:0.5 to 9:10 as eluent to afford the title compound (0.7 mg) as a white solid.

Workup

customThe reaction was quenched with water (3 ml)
customthe organic phase was separated
dry with materialdried over sodium sulphate
filtrationfiltered
customevaporated
customThe residue was purified by flash chromatography on silica gel using a column Isolute (1 g) and dichloromethane/methanol from 99.5:0.5 to 9:10 as eluent

Sources & evidence

ORD record: ord-0b272711c9b949ce8fb18f749d4e6659
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346790B2

Reaction notes

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