Triphosgene → (5R)-5-ethyl-3-{6-[(3-ethyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-3-pyridinyl}-2,4-imidazolidinedione

HRID 527699Notes

Reaction equation

Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C@H:14]([CH2:36][CH3:37])[C:15]([NH:17][C:18]1[CH:19]=[N:20][C:21]([O:24][C:25]2[C:33]3[CH:32]([CH2:34][CH3:35])[O:31][CH2:30][C:29]=3[CH:28]=[CH:27][CH:26]=2)=[CH:22][CH:23]=1)=[O:16]>ClCCl>[CH2:36]([C@H:14]1[NH:13][C:2](=[O:4])[N:17]([C:18]2[CH:19]=[N:20][C:21]([O:24][C:25]3[C:33]4[CH:32]([CH2:34][CH3:35])[O:31][CH2:30][C:29]=4[CH:28]=[CH:27][CH:26]=3)=[CH:22][CH:23]=2)[C:15]1=[O:16])[CH3:37]

Participants

Conditions

Temperature: 0 °C

Procedure

In a 50 ml round-bottomed flask (2R)-2-amino-N-{6-[(3-ethyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-3-pyridinyl}butanamide (Intermediate 110, 9 mg) was dissolved in dichloromethane (2 ml) to give a pale yellow solution that was cooled at 0° C. TEA (0.017 ml, 0.119 mmol) was added. 0.5 ml of a solution of triphosgene (14 mg in 2 ml of dichloromethane) was added dropwise to the reaction mixture at 0° C. The reaction mixture was stirred at 0° C. After 20 minutes, the reaction was completed. The reaction mixture was evaporated under vacuum to afford the crude product as a pale yellow oil which was purified via Biotage SP1 (with Cyclohexane/EtOAc as eluents from 2:1 to 1:2 in 15 CV; then 1:2 for 10 CV; 10 g SNAP Silica column). The collected fractions afforded the title compound (5R)-5-ethyl-3-{6-[(3-ethyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-3-pyridinyl}-2,4-imidazolidinedione (6.9 mg) as a white solid.

Workup

customto give a pale yellow solution that
customThe reaction mixture was evaporated under vacuum
customto afford the crude product as a pale yellow oil which
customwas purified via Biotage SP1 (with Cyclohexane/EtOAc as eluents from 2:1 to 1:2 in 15 CV

Sources & evidence

ORD record: ord-702c22b8ee494122ae43ded00bdfbcc3
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346790B2

Reaction notes

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