Bromotrichloromethane → Ethyl 2-(6-chloro-4-(isopropylamino)pyridin-3-yl)oxazole-4-carboxylate

HRID 595495Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[O:9][CH2:10][CH:11]([C:13]([O:15][CH3:16])=[O:14])[N:12]=2)=[C:4]([NH:17][CH:18]([CH3:20])[CH3:19])[CH:3]=1.[CH2:21]1CCN2C(=NCCC2)CC1.BrC(Cl)(Cl)Cl>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[O:9][CH:10]=[C:11]([C:13]([O:15][CH2:16][CH3:21])=[O:14])[N:12]=2)=[C:4]([NH:17][CH:18]([CH3:20])[CH3:19])[CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of methyl 2-(6-chloro-4-(isopropylamino)pyridin-3-yl)-4,5-dihydrooxazole-4-carboxylate (37) (100 mg, 0.336 mmol) in DCM (20 mL), DBU (1.008 mmol) and bromotrichloromethane (0.403 mmol) were added at 0° C. and stirred the reaction mixture for 2 h at 0° C. Reaction temperature was raised to room temperature and stirred the reaction for 10 min. The reaction mixture was diluted with DCM and washed with water, 10% NaHCO3 solution and brine solution. The organic layer was collected, dried over Na2SO4, filtered and concentrated. The crude material obtained was purified by flash chromatography using silica gel and EtOAC:pet ether as eluent to afford the title compound, ethyl 2-(6-chloro-4-(isopropylamino)pyridin-3-yl)oxazole-4-carboxylate (38). 1H NMR: 400 MHz, DMSO-d6: δ 1.24-1.27 (m, 6H), 3.87 (s, 3H), 3.92-3.97 (m, 1H), 6.92 (s, 1H), 8.36 (d, J=7.60 Hz, 1H), 8.60 (s, 1H), 9.00 (s, 1H).

Workup

customReaction temperature
temperaturewas raised to room temperature
stirringstirred
customthe reaction for 10 min
washwashed with water, 10% NaHCO3 solution and brine solution
customThe organic layer was collected
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude material obtained
customwas purified by flash chromatography

Sources & evidence

ORD record: ord-48a2ae475bbf421d9c56943b4586b604
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242976B2

Reaction notes

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