1,2-Dibromoethane → 1,3-dichloro-8,8-dimethyl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluorene

HRID 334177Notes

Reaction equation

C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:8][CH2:9]Br.[Cl:11][C:12]1[N:13]=[C:14]([Cl:25])[C:15]2[CH:20]=[C:19]([C:21]([OH:24])([CH3:23])[CH3:22])[NH:18][C:16]=2[N:17]=1>CN(C=O)C>[Cl:25][C:14]1[C:15]2[CH:20]=[C:19]3[N:18]([CH2:8][CH2:9][O:24][C:21]3([CH3:22])[CH3:23])[C:16]=2[N:17]=[C:12]([Cl:11])[N:13]=1

Participants

Conditions

Temperature: 100 °C

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

custompartitioned between water and ethyl acetate
extractionThe organic extract
customwas separated
washwashed with brine
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-a407c22891bd46939b8874ec8cd99424
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883799B2

Reaction notes

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