Hydrogen Bromide → 2-[1-(Piperidin-3-yl)-ethylamino]-4-[benzimidazol-1-yl]pyrimidine

HRID 2268959Notes

Reaction equation

HRID 2268959 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([CH:17]([NH:19][C:20]2[N:25]=[C:24]([N:26]3[C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=4[N:28]=[CH:27]3)[CH:23]=[CH:22][N:21]=2)[CH3:18])[CH2:12]1)=O)C1C=CC=CC=1.Br>C(Cl)Cl.C(O)(=O)C>[NH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([CH:17]([NH:19][C:20]2[N:25]=[C:24]([N:26]3[C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=4[N:28]=[CH:27]3)[CH:23]=[CH:22][N:21]=2)[CH3:18])[CH2:12]1

Participants

5

Reactant 2

HCID 260Hydrogen BromideHCID 155505842-[1-(1-Benzyloxycarbonylpiperidin-3-yl)-ethylamino]-4-[benzimidazol-1-yl]pyrimidine

Product 1

HCID 183326302-[1-(Piperidin-3-yl)-ethylamino]-4-[benzimidazol-1-yl]pyrimidineYield 85.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

The 2-[1-(1-benzyloxycarbonylpiperidin-3-yl)-ethylamino]-4-[benzimidazol-1-yl]pyrimidine (900 mg, 1.97 mmol) was dissolved in CH2Cl2 (25 mL), and the mixture was cooled down to 0° C. To this was added 30% HBr in acetic acid (5 mL) slowly and continued stirring at 0° C. for 15 min The bath was removed, and the reaction mixture was stirred at room temperature for 45 min and then was diluted with H2O (25 mL). The reaction mixture was extracted with CH2Cl2 (2×20 mL; discarded), then the aqueous layer was made neutral with 5N NaOH and extracted with EtOAc (3×25 mL; discarded). The aqueous layer was made strongly basic (>pH 12) with SN NaOH, and was extracted with EtOAc (4×30 mL). The combined extracts were washed with brine and dried over Na2SO4. After removal of solvent under reduced pressure, 543 mg of the title compound was obtained which was used without purification. Partial 1H NMR (500 MHz, CDCl3): δ 8.61 (s, 1H); 8.36 (br s, 1H); 8.16 (d, J=8 Hz, 1H); 7.85 (d, J=8.5 Hz, 1H); 7.38 (m, 2H); 6.75 (d, J=5.4 Hz, 1H); 5.14 (s, 2H); 4.1 (m, 1H); 3.18 (d, J=12 Hz, 1H); 3.02 (d, J=12 Hz, 1H); 1.23 (d, J=6.6 Hz, 3H).

Workup

  1. customwas removed
  2. stirringthe reaction mixture was stirred at room temperature for 45 min
  3. additionwas diluted with H2O (25 mL)
  4. extractionThe reaction mixture was extracted with CH2Cl2 (2×20 mL; discarded)
  5. extractionextracted with EtOAc (3×25 mL; discarded)
  6. extractionwas extracted with EtOAc (4×30 mL)
  7. washThe combined extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. customAfter removal of solvent under reduced pressure

Sources & evidence

ORD record
ord-1770ccd01eba42ec8d665ba36c703778
Source dataset
uspto-grants-2001_12
Patent number
US06329380B1

Reaction notes

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