Triphosgene → HCID 67958353, compound

HRID 527700Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

In a 50 ml round-bottomed flask 2-methyl-N1-{6-[(3-methyl-3,4-dihydro-2H-chromen-5-yl)oxy]-3-pyridinyl}alaninamide (Intermediate 121, 72.6 mg) was dissolved in dichloromethane (5 ml) to give a pale yellow solution. TEA (0.142 ml, 1.021 mmol) was added and the reaction mixture was cooled at 0° C. A solution of triphosgene (27.3 mg, 0.092 mmol) in 1 ml of dichloromethane was added to the reaction mixture which was stirred at 0° C. After 15 minutes, additional solution of triphosgene (27.3 mg, 0.092 mmol) in 1 ml of dichloromethane was added to the reaction mixture. After 15 minutes, the reaction mixture was evaporated under vacuum to give the crude product which was purified via Biotage SP1 (using Cyclohexane/EtOAc as eluents from 3:1 to 1:2 in 10 CV; then 1:2 for 5 CV; 10 g SNAP Silica column). The collected fractions afforded the title compound 5,5-dimethyl-3-{6-[(3-methyl-3,4-dihydro-2H-chromen-5-yl)oxy]-3-pyridinyl}-2,4-imidazolidinedione as a colourless oil (41.6 mg).

Workup

customto give a pale yellow solution
waitAfter 15 minutes
customthe reaction mixture was evaporated under vacuum
customto give the crude product which
customwas purified via Biotage SP1 (

Sources & evidence

ORD record: ord-5d66f1fcaeb446ef8a6abc6666c3828c
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346790B2

Reaction notes

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