Acetonitrile → HCID 44124477, compound

HRID 2040974Notes

Reaction equation

HRID 2040974 reaction equation
CS(O[C@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]2[S:13][C:14]3[CH:20]=[C:19]([Br:21])[CH:18]=[CH:17][C:15]=3[N:16]=2)[CH2:7]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].C(#N)C.[NH:31]1[CH2:34][CH2:33][CH2:32]1>C(OCC)C>[N:31]1([C@@H:6]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]3[S:13][C:14]4[CH:20]=[C:19]([Br:21])[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH2:7]2)[CH2:34][CH2:33][CH2:32]1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 10422AzetidineHCID 11430Potassium CarbonateHCID 86631907HCID 86631907, compound

Product 1

HCID 44124477HCID 44124477, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

One equivalent of (S)-1-(6-bromobenzo[d]thiazol-2-yl)piperidin-3-yl methanesulfonate (Reference Example 10, 0.078 g, 0.2 mmol) and two equivalents of potassium carbonate (55.3 mg, 0.40 mmol) were weighed into a 2.5 mL Biotage microwave vial equipped with a magnetic stirbar. Acetonitrile (1 mL) was added, then 6 equivalents of azetidine (68.5 mg, 1.2 mmol) was weighed into the reaction mixture. The vial was sealed with a septum cap and the reaction mixture was stirred at 80° C. for 72 hours. The reaction mixture was transferred to a 100 mL round bottom flask (methanol rinse). Volatiles were removed under reduced pressure and the residue was partitioned between ethyl acetate and saturated aqueous sodium carbonate. The organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to give an oil. The oil was purified by column chromatography on an Analogix IntelliFlash-280 (Analogix SF10-4 g, 100% dichloromethane to 98:2 dichloromethane/2 M NH3 in methanol). Fractions containing product were combined and concentrated under reduced pressure to give an oil that was dissolved in diethyl ether and dried (MgSO4). The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure to give a semi-solid that was triturated with diethyl ether/hexane to give (R)-2-(3-(azetidin-1-yl)piperidin-1-yl)-6-bromobenzo[d]thiazole as a solid. 1H NMR (300 MHz, CD3OD) δ ppm 1.23-1.38 (m, 1H), 1.53-1.69 (m, 1H), 1.80-1.96 (m, 2H), 2.11 (pentet, J=7 Hz, 2H), 2.32-2.43 (m, 1H), 2.93-3.02 (m, 1H), 3.22-3.38 (m, 5H), 3.79 (dt, J=4, 13 Hz, 1H), 3.96 (dd, J=4, 13 Hz, 1H), 7.33 (d, J=9 Hz, 1H), 7.39 (dd, J=2, 9 Hz, 1H), 7.79 (d, J=2 Hz, 1H); MS (DCI/NH3) m/z 352 (M+H)+.

Workup

  1. customvial equipped with a magnetic stirbar
  2. customThe vial was sealed with a septum
  3. customcap
  4. customThe reaction mixture was transferred to a 100 mL round bottom flask
  5. wash(methanol rinse)
  6. customVolatiles were removed under reduced pressure
  7. customthe residue was partitioned between ethyl acetate and saturated aqueous sodium carbonate
  8. dry with materialThe organic layer was dried (MgSO4)
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customto give an oil
  12. customThe oil was purified by column chromatography on an Analogix IntelliFlash-280 (Analogix SF10-4 g, 100% dichloromethane to 98:2 dichloromethane/2 M NH3 in methanol)
  13. additionFractions containing product
  14. concentrationconcentrated under reduced pressure
  15. customto give an oil that
  16. dry with materialdried (MgSO4)
  17. customThe drying agent was removed by filtration
  18. concentrationthe filtrate was concentrated under reduced pressure
  19. customto give a semi-solid
  20. customthat was triturated with diethyl ether/hexane

Sources & evidence

ORD record
ord-e094f48047984377a621bd06a824a820
Source dataset
uspto-grants-2013_11
Patent number
US08580968B2

Reaction notes

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