Ethanol → HCID 89579938, compound

HRID 928589Notes

Reaction equation

HRID 928589 reaction equation
Cl[C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[CH:9][S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH2:17]1[CH:24]2[NH:25][CH:19]([CH2:20][C:21]([CH2:23]2)=[O:22])[CH2:18]1.Cl.C(N(CC)CC)C.C(O)C>C1COCC1.ClCCl.O>[C:11]1([C:10]2[C:3]3[C:2]([N:25]4[CH:19]5[CH2:18][CH2:17][CH:24]4[CH2:23][C:21](=[O:22])[CH2:20]5)=[N:7][CH:6]=[N:5][C:4]=3[S:8][CH:9]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 8471Triethylamine3×HCID 7087304-Chloro-5-phenylthieno[2,3-d]pyrimidineHCID 130912188-Azabicyclo[3.2.1]octan-3-one hydrochloride3×

Product 1

HCID 89579938HCID 89579938, compoundYield 72.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-chloro-5-phenyl-thieno[2,3-d]pyrimidine (1.00 g, 4.05 mmol), nortropinone hydrochloride (0.983 g, 6.08 mmol) and triethylamine (1.71 mL, 12.2 mmol) in THF (20 mL) was heated to 70° C. overnight. Ethanol (20 mL) was added and the mixture was heated to 70° C. for 3 hr. Further batches of nortropinone hydrochloride (0.983 g, 6.08 mmol) and triethylamine (1.71 mL, 12.2 mmol) were added and the mixture was heated to 70° C. overnight. Further batches of nortropinone hydrochloride (0.983 g, 6.08 mmol) and triethylamine (1.71 mL, 12.2 mmol) were added and the mixture was heated to 70° C. over 3 nights. It was cooled to room temperature and diluted with dichloromethane (40 mL) and water (40 mL). The layers were separated and the aqueous was extracted with dichloromethane (2×40 mL). The combined organic layers were washed with brine (1×40 mL), filtered through a hydrophobic frit and evaporated to give a brown oil. Mass: 3.21 g. This was purified by silica chromatography (100 g cartridge; eluent petrol/ethyl acetate 0 to 40%). Fractions corresponding to the main peak were combined and evaporated to give 8-(5-phenylthieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-one as a white solid (0.99 g).

Workup

  1. temperaturethe mixture was heated to 70° C. for 3 hr
  2. temperaturethe mixture was heated to 70° C. overnight
  3. temperaturethe mixture was heated to 70° C. over 3 nights
  4. temperatureIt was cooled to room temperature
  5. customThe layers were separated
  6. extractionthe aqueous was extracted with dichloromethane (2×40 mL)
  7. washThe combined organic layers were washed with brine (1×40 mL)
  8. filtrationfiltered through a hydrophobic frit
  9. customevaporated
  10. customto give a brown oil
  11. customThis was purified by silica chromatography (100 g cartridge; eluent petrol/ethyl acetate 0 to 40%)
  12. customevaporated

Sources & evidence

ORD record
ord-9a4cdb43f204496d80ae83221a81f4e5
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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