Diisopropylethylamine → HCID 118307795, compound

HRID 718411Notes

Reaction equation

[CH3:1][C:2](=[C:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)[CH3:3].CCN(C(C)C)C(C)C.[Br:19][C:20]1[C:21](Cl)=[C:22]([C:28](=[O:35])[C:29]([O:31][CH:32]([CH3:34])[CH3:33])=[O:30])[C:23]([CH3:27])=[N:24][C:25]=1[CH3:26]>CC#N.CCOCC>[Br:19][C:20]1[C:21]([N:7]2[CH2:8][CH2:9][C:4](=[C:2]([CH3:3])[CH3:1])[CH2:5][CH2:6]2)=[C:22]([C:28](=[O:35])[C:29]([O:31][CH:32]([CH3:33])[CH3:34])=[O:30])[C:23]([CH3:27])=[N:24][C:25]=1[CH3:26]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 4-(propan-2-ylidene)piperidine (500 mg, 3.99 mmol) and DIEA (2.1 mL, 11.98 mmol) in anhydrous CH3CN (30 mL) was added isopropyl 2-(5-bromo-4-chloro-2,6-dimethylpyridin-3-yl)-2-oxoacetate (1.48 g, 3.99 mmol) at rt. The resulting mixture was placed in a pre-heated oil bath (80° C.) and stirred for 24 h; cooled, diluted with ether, washed with water, brine, and dried (MgSO4). The crude product was charged (DCM) to an 80 g ISCO silica gel cartridge and gradient eluted (0-35% EtOAc/hexanes) using an Isolera chromatography station gave isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-(propan-2-ylidene)piperidin-1-yl)pyridin-3-yl)-2-oxoacetate 1.04 g (61.8%). 1H NMR (500 MHz, DMSO-d6) δ 5.09-5.04 (m, 1H), 3.50-3.48 (br. s, 2H), 3.03 (br. s, 2H), 2.60 (s, 3H), 2.30 (s, 3H), 2.23 (br. s, 4), 1.64 (s, 6H), 1.25 (d, J=6.2 Hz, 6H). UPLC (M+H)=425.3.

Workup

customThe resulting mixture was placed in a pre-heated oil bath
temperaturecooled
washwashed with water, brine
dry with materialdried (MgSO4)
additionThe crude product was charged (DCM) to an 80 g ISCO silica gel cartridge and gradient
washeluted (0-35% EtOAc/hexanes)

Sources & evidence

ORD record: ord-8e61cfefb7934d14b70d03b4337b914e
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193720B2

Reaction notes

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