Triethylamine → 8-(2-Cyclopropyl-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-one

HRID 928595Notes

Reaction equation

HRID 928595 reaction equation
Cl[C:2]1[C:3]2[C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:12][S:11][C:4]=2[N:5]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[N:7]=1.[CH2:20]1[CH:27]2[NH:28][CH:22]([CH2:23][C:24]([CH2:26]2)=[O:25])[CH2:21]1.Cl.C(N(CC)CC)C>C(O)C.C(OCC)(=O)C.O>[CH:8]1([C:6]2[N:7]=[C:2]([N:28]3[CH:22]4[CH2:21][CH2:20][CH:27]3[CH2:26][C:24](=[O:25])[CH2:23]4)[C:3]3[C:13]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)=[CH:12][S:11][C:4]=3[N:5]=2)[CH2:10][CH2:9]1

Participants

7

Reactant 3

HCID 8471Triethylamine2×HCID 130912188-Azabicyclo[3.2.1]octan-3-one hydrochloride2×HCID 28366880HCID 28366880, compound

Product 1

HCID 895794398-(2-Cyclopropyl-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-oneYield 129.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 4-chloro-2-cyclopropyl-5-phenyl-thieno[2,3-d]pyrimidine (0.30 g, 1.05 mmol, ex Enamine), nortropinone hydrochloride (0.25 g, 1.57 mmol) and triethylamine (0.44 mL, 3.14 mmol) in ethanol (4 mL) was heated to 140° C. for 30 min in a microwave. Heating was repeated. Further portions of triethylamine (0.44 mL, 3.14 mmol) and nortropinone hydrochloride (0.25 g, 1.57 mmol) were added and the mixture was stirred at room temperature for 3 nights. It was diluted with ethyl acetate (20 mL) and water (20 mL). The layers were separated and the aqueous was extracted with ethyl acetate (2×20 mL). The combined organic layers were washed with brine (1×20 mL), dried (magnesium sulfate, filtered and evaporated to give a brown oil (512 mg). This was purified by silica chromatography (10 g cartridge; eluent petroleum ether 40-60/ethyl acetate 0 to 100%; all output collected) to give 8-(2-cyclopropyl-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-oneas a yellow solid (0.15 g). m/z [M+H]+ 376.0. Retention time 4.98 min (LCMS method+ve 6 min).

Workup

  1. temperatureHeating
  2. customThe layers were separated
  3. extractionthe aqueous was extracted with ethyl acetate (2×20 mL)
  4. washThe combined organic layers were washed with brine (1×20 mL)
  5. dry with materialdried (magnesium sulfate
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-10ec7a846da64def8d2f058543620bd2
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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