Dimethylformamide → HCID 66905593, compound

HRID 1691997Notes

Reaction equation

HRID 1691997 reaction equation
CS(O[C@@H:6]1[CH2:10][CH2:9][N:8]([C:11]2[S:12][C:13]3[CH:19]=[C:18]([Br:20])[CH:17]=[CH:16][C:14]=3[N:15]=2)[CH2:7]1)(=O)=O.[NH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>C(OCC)C>[N:21]1([C@H:6]2[CH2:10][CH2:9][N:8]([C:11]3[S:12][C:13]4[CH:19]=[C:18]([Br:20])[CH:17]=[CH:16][C:14]=4[N:15]=3)[CH2:7]2)[CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 31268PyrrolidineHCID 57747910HCID 57747910, compound

Product 1

HCID 66905593HCID 66905593, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (R)-1-(6-bromobenzo[d]thiazol-2-yl)pyrrolidin-3-yl methanesulfonate (Reference Example 12, 0.50 g, 1.32 mmol), pyrrolidine (0.221 mL, 2.65 mmol), and potassium carbonate (0.549 g, 3.98 mmol) was placed in a 10 mL CEM microwave vial with a stirbar. N,N-Dimethylformamide (1.5 mL) was added, the vial was capped, and the reaction was heated to 100° C. under microwave irradiation for 15 minutes, then the cooling air was turned on and heating was continued at 70° C. for an additional 15 minutes. The reaction mixture was cooled to room temperature then partitioned between ethyl acetate and saturated aqueous sodium carbonate. The aqueous layer was extracted once more with ethyl acetate. The combined organic extracts were washed twice with brine, then dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to give an oil that solidified on trituration with diethyl ether. The solid was collected by filtration and rinsed with diethyl ether, then purified by column chromatography on an Analogix IntelliFlash-280 (Analogix SF15-12g, 100% dichloromethane to 98:2 dichloromethane/methanol). Fractions containing product were combined and concentrated under reduced pressure to give a solid that was dried overnight in a vacuum oven at 70° C. to give (S)-2-(1,3′-bipyrrolidin-1′-yl)-6-bromobenzo[d]thiazole. 1H NMR (300 MHz, CD3OD) δ ppm 1.78-1.93 (m, 4H), 2.01-2.15 (m, 1H), 2.26-2.37 (m, 1H), 2.58-2.74 (m, 4H), 3.00-3.11 (m, 1H), 3.40-3.48 (m, 1H), 3.49-3.60 (m, 1H), 3.66-3.83 (m, 2H), 7.35 (d, J=9 Hz, 2H), 7.40 (dd, J=2, 9 Hz, 1H), 7.81 (d, J=2 Hz, 1H); MS (DCI/NH3) m/z 352 (M+H)+.

Workup

  1. customthe vial was capped
  2. temperatureheating
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customthen partitioned between ethyl acetate and saturated aqueous sodium carbonate
  5. extractionThe aqueous layer was extracted once more with ethyl acetate
  6. washThe combined organic extracts were washed twice with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customto give an oil that
  11. filtrationThe solid was collected by filtration
  12. washrinsed with diethyl ether
  13. custompurified by column chromatography on an Analogix IntelliFlash-280 (Analogix SF15-12g, 100% dichloromethane to 98:2 dichloromethane/methanol)
  14. additionFractions containing product
  15. concentrationconcentrated under reduced pressure
  16. customto give a solid
  17. customthat was dried overnight in a vacuum oven at 70° C.

Sources & evidence

ORD record
ord-741f91ef76b047f885fe78c1145226b8
Source dataset
uspto-grants-2012_04
Patent number
US08153813B2

Reaction notes

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