2-Methanesulfonyl-4-[benzimidazol-1-yl]pyrimidine → 2-[1-(1-Benzyloxycarbonylpiperidin-3-yl)-ethylamino]-4-[benzimidazol-1-yl]pyrimidine

HRID 2268958Notes

Reaction equation

HRID 2268958 reaction equation
CS([C:5]1[N:10]=[C:9]([N:11]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[N:13]=[CH:12]2)[CH:8]=[CH:7][N:6]=1)(=O)=O.[NH2:20][CH:21]([CH:23]1[CH2:28][CH2:27][CH2:26][N:25]([C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])[CH2:24]1)[CH3:22]>CN(C=O)C.C1(C)C=CC=CC=1.CCOC(C)=O>[CH2:32]([O:31][C:29]([N:25]1[CH2:26][CH2:27][CH2:28][CH:23]([CH:21]([NH:20][C:5]2[N:10]=[C:9]([N:11]3[C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=4[N:13]=[CH:12]3)[CH:8]=[CH:7][N:6]=2)[CH3:22])[CH2:24]1)=[O:30])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 2

HCID 155496402-Methanesulfonyl-4-[benzimidazol-1-yl]pyrimidineHCID 155505833-(1-Aminoethyl)-1-(benzyloxycarbonyl)piperidine

Product 1

HCID 155505842-[1-(1-Benzyloxycarbonylpiperidin-3-yl)-ethylamino]-4-[benzimidazol-1-yl]pyrimidineYield 54.8%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Methanesulfonyl-4-[benzimidazol-1-yl]pyrimidine (EXAMPLE 1) (1.1 g, 4.0 mmol) was dissolved in DMF (10 mL), and to this was added 3-(1-aminoethyl)-1-(Benzyloxycarbonyl)piperidine (950 mg, 3.6 mmol) in toluene (10 mL). The mixture was placed in an oil bath at 100° C. and heated for 5 h. After cooling, the reaction mixture was diluted with EtOAc (80 mL) and was washed with H2O (4×40 mL) followed by brine. The organic extract was dried over Na2SO4 and purified by flash chromatography using 3:7 acetone:hexane as an eluent to obtain the title compound (900 mg). Partial 1H NMR (500 MHz, CDCl3): δ 8.6 (s, 1H); 8.36 (br s, 1H); 8.15 (d, J=8 Hz, 1H); 7.85 (d, J=8.5 Hz, 1H); 7.36 (m, 7H); 6.76 (d, J=5.4 Hz, 1H); 5.12 (s, 2H); 4.17 (m, 1H); 1.29 (br d, J=5 Hz, 3H). Mass spectrum 457.6 (ESI, M+1). The enantiomers of the title compound were separated on HPLC (Chiralcel OJ column; 85:15 hexane:EtOH system).

Workup

  1. customThe mixture was placed in an oil bath at 100° C.
  2. temperatureheated for 5 h
  3. temperatureAfter cooling
  4. washwas washed with H2O (4×40 mL)
  5. extractionThe organic extract
  6. dry with materialwas dried over Na2SO4
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-10b709d032f84eb5b3362d39221e32fc
Source dataset
uspto-grants-2001_12
Patent number
US06329380B1

Reaction notes

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