Morpholine → 4-(2-(1-(2-fluorobenzyl)-5-(thiazol-2-yl)-1H-1,2,4-triazol-3-yl)pyridin-4-yl)morpholine

HRID 2174283Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[N:12]=[C:11]([C:13]3[S:14][CH:15]=[CH:16][N:17]=3)[N:10]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])[N:9]=2)[CH:3]=1.[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1>C(O)CO.O1CCOCC1.[Cl-].[Na+].O.[Cu-]=O>[F:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[CH2:18][N:10]1[C:11]([C:13]2[S:14][CH:15]=[CH:16][N:17]=2)=[N:12][C:8]([C:4]2[CH:3]=[C:2]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[CH:7]=[CH:6][N:5]=2)=[N:9]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a stirring suspension of 2-(3-(4-bromopyridin-2-yl)-1-(2-fluorobenzyl)-1H-1,2,4-triazol-5-yl)thiazole (I-36, 1 eq) and copper(I) oxide (1 eq) in ethylene glycol-dioxane (approx. 4:1) in a sealed tube is added morpholine (30 eq). The resultant reaction mixture was heated at 100° C. for 12 hr. The reaction was cooled to room temperature and treated with brine and then extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, concentrated and purified using SiO2 chromatography (methylene chloride/acetonitrile/methanol) to afford 4-(2-(1-(2-fluorobenzyl)-5-(thiazol-2-yl)-1H-1,2,4-triazol-3-yl)pyridin-4-yl)morpholine as a solid in 79% yield.

Workup

customThe resultant reaction mixture
temperatureThe reaction was cooled to room temperature
extractionextracted with ethyl acetate
dry with materialThe combined organic layers were dried over sodium sulfate
concentrationconcentrated
custompurified

Sources & evidence

ORD record: ord-51ffc228cc0549c28e2c9673b26c6412
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09061030B2

Reaction notes

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