Toluene → 3-Chloro-8,8-dimethyl-1-morpholin-4-yl-5,8-dihydro-6H-7-oxa-9-thia-2,4-diaza-fluorene

HRID 334155Notes

Reaction equation

[Cl:1][C:2]1[N:3]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:5]2[S:10][C:9]([C:11](O)([CH3:13])[CH3:12])=[C:8]([CH2:15][CH2:16][OH:17])[C:6]=2[N:7]=1.C1(C)C=CC=CC=1.FC(F)(F)C(O)=O>O>[Cl:1][C:2]1[N:3]=[C:4]([N:18]2[CH2:19][CH2:20][O:21][CH2:22][CH2:23]2)[C:5]2[S:10][C:9]3[C:11]([CH3:12])([CH3:13])[O:17][CH2:16][CH2:15][C:8]=3[C:6]=2[N:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Impure 2-(2-chloro-7-(2-hydroxyethyl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-ol (30 mg) was dissolved in toluene (5 mL, 50 mmol). Trifluoroacetic acid (0.5 mL, 6 mmol) was added and the reaction mixture was heated at 120° C. for two h. Complete reaction was confirmed by LCMS. Diluted with water and extracted with ethyl acetate, dried over magnesium sulfate, concentrated in vacuo and was purified by silica gel chromatography (0 to 100% ethyl acetate/heptanes) on the CombiFlash® Rf system using an amine column and concentrated in vacuo to give 3-Chloro-8,8-dimethyl-1-morpholin-4-yl-5,8-dihydro-6H-7-oxa-9-thia-2,4-diaza-fluorene (10 mg, 10% yield)

Workup

customComplete reaction
extractionextracted with ethyl acetate
dry with materialdried over magnesium sulfate
concentrationconcentrated in vacuo
customwas purified by silica gel chromatography (0 to 100% ethyl acetate/heptanes) on the CombiFlash® Rf system
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-f4c4b18172de40a689c57303d1527bd7
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883799B2

Reaction notes

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