Morpholine → 3-Chloro-8,8-dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluorene
Reaction equation
Cl[C:2]1[C:14]2[CH:13]=[C:12]3[N:7]([CH2:8][CH2:9][O:10][C:11]3([CH3:16])[CH3:15])[C:6]=2[N:5]=[C:4]([Cl:17])[N:3]=1.[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C(N(CC)CC)C>>[Cl:17][C:4]1[N:3]=[C:2]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:14]2[CH:13]=[C:12]3[N:7]([C:6]=2[N:5]=1)[CH2:8][CH2:9][O:10][C:11]3([CH3:16])[CH3:15]Participants
Procedure
Cesium carbonate (1.2 g, 3.7 mmol) and 1,2-dibromoethane (316 μL, 3.7 mmol) were added to a solution of 2-(2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-propan-2-ol (304 mg, 1.23 mmol) in DMF (4 mL) and the reaction mixture was heated at 100° C. for 45 min, then partitioned between water and ethyl acetate. The organic extract was separated and washed with brine, then dried (Na2SO4) and concentrated in vacuo affording 1,3-dichloro-8,8-dimethyl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluorene. A mixture of 1,3-dichloro-8,8-dimethyl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluorene (1.23 mmol), morpholine (236 μL, 2.69 mmol) and triethylamine (342 μL, 2.46 mmol) in IMS (3 mL) was heated at reflux for 3 h, then concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, gradient 0 to 40% ethyl acetate in cyclohexane) affording 3-Chloro-8,8-dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluorene (159 mg, 40%). LCMS (method A): RT=3.13 min, [M+H]+=323.
Workup
- temperaturewas heated
- temperatureat reflux for 3 h
- concentrationconcentrated in vacuo
- customThe resulting residue was purified by column chromatography (SiO2, gradient 0 to 40% ethyl acetate in cyclohexane)
Sources & evidence
- ORD record
- ord-b301f27fdbcd490180158916444139b3
- Source dataset
- uspto-grants-2014_11
- Patent number
- US08883799B2
Reaction notes
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