HCID 59568649, compound → HCID 89554259, compound

HRID 2281360Notes

Reaction equation

[CH3:1][C@@H:2]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:12]3[CH2:14][O:13]3)[CH:9]=2)[C:4](=[O:15])[O:3]1.[OH:16][CH:17]([C:25]1[N:30]=[CH:29][C:28]([C:31]#[N:32])=[C:27]([O:33][CH3:34])[CH:26]=1)[CH2:18][N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>C(O)C>[OH:16][CH:17]([C:25]1[CH:26]=[C:27]([O:33][CH3:34])[C:28]([C:31]#[N:32])=[CH:29][N:30]=1)[CH2:18][N:19]1[CH2:20][CH2:21][N:22]([CH2:14][CH:12]([OH:13])[C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[C:4](=[O:15])[O:3][C@@H:2]([CH3:1])[CH2:11]3)[CH2:23][CH2:24]1

Participants

Conditions

Temperature: 140 °C

Procedure

A Pyrex® vessel was charged with magnetic stirring bar and 3-(S)-methyl-6-(oxiran-2-yl)-3,4-dihydro-1H-isochromen-1-one (INTERMEDIATE 23) (78 mg, 0.38 mmol), and isomer A of 6-(1-hydroxy-2-piperazin-1-yl-ethyl)-4-methoxy-pyridine-3-carbonitrile (INTERMEDIATE 38) (100 mg, 0.38 mmol), and 2 mL of ethanol. The resulting mixture was heated in the microwave at 140° C. for 1 hour. The mixture was cooled to room temperature and the solvent was evaporated and the resulting residue was purified by preparative TLC eluting with 10% methanol/dichloromethane. The resulting mixture of two diastereomers was separated to the individual isomers by SFC-HPLC using a Chiralcel® AD-3 column.

Workup

additionA Pyrex® vessel was charged with magnetic stirring bar
temperatureThe mixture was cooled to room temperature
customthe solvent was evaporated
customthe resulting residue was purified by preparative TLC
washeluting with 10% methanol/dichloromethane
additionThe resulting mixture of two diastereomers
customwas separated to the individual isomers by SFC-HPLC

Sources & evidence

ORD record: ord-1796dda4ff374f95b789e8285a7cf94d
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139585B2

Reaction notes

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