Dichloromethane → 8-(2-Chloro-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octane

HRID 928578Notes

Reaction equation

HRID 928578 reaction equation
Cl.[CH:2]12[NH:9][CH:6]([CH2:7][CH2:8]1)[CH2:5][O:4][CH2:3]2.[Cl:10][C:11]1[N:12]=[C:13](Cl)[C:14]2[C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:18][S:17][C:15]=2[N:16]=1.C(N(CC)CC)C.C(Cl)Cl>C(O)C>[Cl:10][C:11]1[N:12]=[C:13]([N:9]2[CH:6]3[CH2:7][CH2:8][CH:2]2[CH2:3][O:4][CH2:5]3)[C:14]2[C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:18][S:17][C:15]=2[N:16]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 127242282,4-Dichloro-5-phenylthieno(2,3-d)pyrimidineHCID 534011293-Oxa-8-azabicyclo(3.2.1)octane hydrochloride

Product 1

HCID 895795878-(2-Chloro-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octaneYield 87.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A slurry of 3-oxa-8-azabicyclo[3.2.1]octane hydrochloride (0.1064 g, 0.7112 mmol) in ethanol (2 mL) was added to 2,4-dichloro-5-phenyl-thieno[2,3-d]pyrimidine (0.1 g, 0.3556 mmol). triethylamine (0.250 mL, 1.778 mmol) was added and the mixture was stirred overnight at room temperature. DCM (2 mL) was added to form a complete solution and the mixture was stirred overnight at room temperature. The solvent was evaporated. The residue was dissolved in DCM (2 mL) and water (2 mL). The layers were separated and the aqueous was extracted with DCM (2×2 mL). The combined organic layers were evaporated to give a brown oil. Mass: 162 mg. This was purified by silica chromatography (10 g cartridge; eluent petrol/ethyl acetate 0 to 15%; all output collected) and the second eluting peak isolated to give 8-(2-chloro-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octane as a white solid (111 mg). LCMS: RT=4.95 min. M+1=358.

Workup

  1. customto form a complete solution
  2. stirringthe mixture was stirred overnight at room temperature
  3. customThe solvent was evaporated
  4. dissolutionThe residue was dissolved in DCM (2 mL)
  5. customThe layers were separated
  6. extractionthe aqueous was extracted with DCM (2×2 mL)
  7. customThe combined organic layers were evaporated
  8. customto give a brown oil
  9. customThis was purified by silica chromatography (10 g cartridge
  10. customall output collected) and the second eluting peak
  11. customisolated

Sources & evidence

ORD record
ord-6ffc79df17124406bdbf57899105cb6d
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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