Piperidine → HCID 44124245, compound

HRID 2040966Notes

Reaction equation

HRID 2040966 reaction equation
CS(O[CH:6]1[CH2:9][N:8]([C:10]2[S:11][C:12]3[CH:18]=[C:17]([Br:19])[CH:16]=[CH:15][C:13]=3[N:14]=2)[CH2:7]1)(=O)=O.[NH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[Br:19][C:17]1[CH:16]=[CH:15][C:13]2[N:14]=[C:10]([N:8]3[CH2:9][CH:6]([N:20]4[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]4)[CH2:7]3)[S:11][C:12]=2[CH:18]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 11430Potassium CarbonateHCID 57747912HCID 57747912, compound

Product 1

HCID 44124245HCID 44124245, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
92.5 °C

Procedure

A mixture of 1-(6-bromobenzo[d]thiazol-2-yl)azetidin-3-yl methanesulfonate (Reference Example 12b, 61.7 mg, 0.17 mmol), piperidine (0.250 mL, 2.5 mmol), and potassium carbonate (0.062 g, 0.44 mmol) in N,N-dimethylformamide (1 mL) was stirred at 90-95° C. for two days. The reaction mixture was cooled to room temperature, diluted with water (10 mL), and extracted with dichloromethane (2×4 mL). The combined organic extracts were washed with water (2×5 mL), then dried (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography (90:10:0 to 88:10:2 dichloromethane/ethyl acetate/methanol). A second column was run with the same eluent gradient. Fractions containing product were combined and concentrated under reduced pressure to give 6-bromo-2-(3-(piperidin-1-yl)azetidin-1-yl)benzo[d]thiazole. 1H NMR (300 MHz, CD3OD) δ ppm 1.47-1.58 (m, 2H), 1.64 (pentet, J=5 Hz, 1H), 2.35-2.45 (m, 4H), 3.36-3.46 (m, 1H), 4.02-4.08 (m, 2H), 4.24 (t, J=8 Hz, 2H), 7.35 (d, J=8 Hz, 1H), 7.42 (dd, J=2, 8 Hz, 1H), 7.83 (d, J=2 Hz, 1H); MS (ESI) m/z 352 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with dichloromethane (2×4 mL)
  3. washThe combined organic extracts were washed with water (2×5 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by silica gel chromatography (90:10:0 to 88:10:2 dichloromethane/ethyl acetate/methanol)
  8. additionFractions containing product
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9ac924557a4e47cc92003c5963b0043f
Source dataset
uspto-grants-2013_11
Patent number
US08580968B2

Reaction notes

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