Dimethylformamide → HCID 44124592, compound

HRID 1692002Notes

Reaction equation

HRID 1692002 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][C:5]2[N:6]=[C:7](Cl)[S:8][C:4]=2[CH:3]=1.[N:12]1([CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[CH2:16][CH2:15][CH2:14][CH2:13]1.CN(C)C=O.C(N(CC)C(C)C)(C)C>C(OCC)(=O)C>[Br:1][C:2]1[CH:11]=[CH:10][C:5]2[N:6]=[C:7]([N:20]3[CH2:21][CH2:22][CH:17]([N:12]4[CH2:16][CH2:15][CH2:14][CH2:13]4)[CH2:18][CH2:19]3)[S:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 787034-(1-Pyrrolidinyl)piperidineHCID 81531DiisopropylethylamineHCID 20498716-Bromo-2-chlorobenzothiazole

Product 1

HCID 44124592HCID 44124592, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

One equivalent of 6-bromo-2-chlorobenzo[d]thiazole (248 mg, 1.0 mmol) and 1.1 equivalents of 4-(pyrrolidin-1-yl)piperidine (0.170 g, 1.1 mmol) were weighed into a 10 mL CEM microwave vial equipped with a magnetic stirbar. N,N-Dimethylformamide (1.0 mL) and three equivalents of N,N-diisopropylethylamine (0.524 ml, 3.00 mmol) were added via syringe. The reaction mixture was heated to 150° C. under microwave irradiation with the cooling power on for 15 minutes. The reaction mixture was transferred to a 250 mL round bottom flask (methanol rinse) and volatiles were removed under reduced pressure. The residue was partitioned between saturated aqueous sodium carbonate and CHCl3. The aqueous layer was extracted once more with CHCl3, then the combined organic extracts were washed with brine, dried (MgSO4), and filtered. The filtrate was concentrated under reduced pressure to give a solid. This crude solid was purified by column chromatography on an Analogix IF-280 (Analogix SF15-12g, 100% dichloromethane to 97:3 dichloromethane/2 M ammonia in methanol). Fractions containing product were combined and concentrated under reduced pressure to give a solid that was dissolved in hot ethyl acetate, dried (MgSO4), and filtered. The filtrate was placed in a 0° C. freezer to promote crystallization. Crystals were collected by filtration and dried in a vacuum oven to give 6-bromo-2-(4-(pyrrolidin-1-yl)piperidin-1-yl)benzo[d]thiazole. 1H NMR (300 MHz, CD3OD) δ ppm 1.51-1.66 (m, 2H), 1.78-1.88 (m, 4H), 2.04-2.14 (m, 2H), 2.34-2.46 (m, 1H), 2.63-2.72 (m, 4H), 3.16-3.27 (m, 2H), 4.06-4.15 (m, 2H), 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 366 (M+H)+.

Workup

  1. customvial equipped with a magnetic stirbar
  2. customThe reaction mixture was transferred to a 250 mL round bottom flask
  3. wash(methanol rinse) and volatiles
  4. customwere removed under reduced pressure
  5. customThe residue was partitioned between saturated aqueous sodium carbonate and CHCl3
  6. extractionThe aqueous layer was extracted once more with CHCl3
  7. washthe combined organic extracts were washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customto give a solid
  12. customThis crude solid was purified by column chromatography on an Analogix IF-280 (Analogix SF15-12g, 100% dichloromethane to 97:3 dichloromethane/2 M ammonia in methanol)
  13. additionFractions containing product
  14. concentrationconcentrated under reduced pressure
  15. customto give a solid
  16. dry with materialdried (MgSO4)
  17. filtrationfiltered
  18. customwas placed in a 0° C.
  19. customcrystallization
  20. filtrationCrystals were collected by filtration
  21. customdried in a vacuum oven

Sources & evidence

ORD record
ord-1d71d4d1968448d0bf2bd0ba843be7f9
Source dataset
uspto-grants-2012_04
Patent number
US08153813B2

Reaction notes

Loading…