Water → 2-Amino-6-{[2-(4-chlorophenyl)-1,3-oxazol-4-yl]methoxy}-4-(4-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}phenyl)pyridine-3,5-dicarbonitrile

HRID 2092253Notes

Reaction equation

CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[O:15][CH:16]=[C:17]([CH2:19][OH:20])[N:18]=2)=[CH:10][CH:9]=1.[NH2:21][C:22]1[C:27]([C:28]#[N:29])=[C:26]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH2:37][C@H:38]3[CH2:42][O:41][C:40]([CH3:44])([CH3:43])[O:39]3)=[CH:32][CH:31]=2)[C:25]([C:45]#[N:46])=[C:24](SC2C=CC=CC=2)[N:23]=1.O>COCCOC>[NH2:21][C:22]1[C:27]([C:28]#[N:29])=[C:26]([C:30]2[CH:31]=[CH:32][C:33]([O:36][CH2:37][C@H:38]3[CH2:42][O:41][C:40]([CH3:44])([CH3:43])[O:39]3)=[CH:34][CH:35]=2)[C:25]([C:45]#[N:46])=[C:24]([O:20][CH2:19][C:17]2[N:18]=[C:14]([C:11]3[CH:10]=[CH:9][C:8]([Cl:7])=[CH:13][CH:12]=3)[O:15][CH:16]=2)[N:23]=1

Participants

Conditions

Temperature: 60 °C

Procedure

122 mg (1.09 mmol) of potassium tert-butoxide are suspended in 2 ml of dry 1,2-dimethoxyethane. 229 mg (1.09 mmol) of the compound from Example 100A and 100 mg (0.22 mmol) of the compound from Example 98A are then added successively. The reaction mixture is stirred at 60° C. for 2 h and, after cooling, at RT for a further 10 h. 5 ml of water are then added to the mixture. The precipitate formed is filtered off with suction and washed once with about 2 ml of cold water. This is followed by purification by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5).

Workup

temperatureafter cooling, at RT for a further 10 h
customThe precipitate formed
filtrationis filtered off with suction
washwashed once with about 2 ml of cold water
customThis is followed by purification by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5)

Sources & evidence

ORD record: ord-fd36f0e5fddc46c4b6cf94287a98ceae
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08440700B2

Reaction notes

Loading…