Cesium fluoride → (s)-3-(2,6-Dimethyl-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridin-2-yl)phenoxy)-propane-1,2-diol

HRID 1177570Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2,6-dimethyl-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenol (36.7 mg, 99 μmol) and cesium fluoride (1.5 mg, 9.9 μmol) in anhydrous DMF (0.5 mL) was stirred at 25° C. for 1 h. (S)-(−)-glycidol (14 μl, 207 μmol) was then added, and the resulting mixture was heated under argon at 80° C. for 7 d. The reaction mixture was subsequently cooled to 25° C., filtered through Celite, diluted with DMSO (1.5 mL), and purified by rpHPLC (10-100% CH3CN/water+0.1% TFA) to provide (S)-3-(2,6-dimethyl-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridin-2-yl)phenoxy)-propane-1,2-diol as a light yellow solid. MS (ESI) m/z: Calculated: 446.2; Observed: 447.2 (M++1).

Workup

additionwas then added
temperatureThe reaction mixture was subsequently cooled to 25° C.
filtrationfiltered through Celite
additiondiluted with DMSO (1.5 mL)
custompurified by rpHPLC (10-100% CH3CN/water+0.1% TFA)

Sources & evidence

ORD record: ord-96437959ac174a9488855ed113faae6e
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842685B2

Reaction notes

Loading…