1,2-Dichloroethane → 1,3-dihydro-1-(1-{1-[2-(5-pyrimidinyl)-prop-2-yl]piperidin-4-yl}piperidin-4-yl)-2H-benzimidazol-2-one

HRID 2294945Notes

Reaction equation

HRID 2294945 reaction equation
[N:1]1[CH:6]=[C:5]([C:7]([N:10]2[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]2)([CH3:9])[CH3:8])[CH:4]=[N:3][CH:2]=1.[O:17]=[C:18]1[N:22]([CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[C:21]2[CH:29]=[CH:30][CH:31]=[CH:32][C:20]=2[NH:19]1.ClCCCl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C>[N:1]1[CH:6]=[C:5]([C:7]([N:10]2[CH2:15][CH2:14][CH:13]([N:26]3[CH2:25][CH2:24][CH:23]([N:22]4[C:21]5[CH:29]=[CH:30][CH:31]=[CH:32][C:20]=5[NH:19][C:18]4=[O:17])[CH2:28][CH2:27]3)[CH2:12][CH2:11]2)([CH3:9])[CH3:8])[CH:4]=[N:3][CH:2]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 886381,3-Dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneHCID 5049666Sodium triacetoxyborohydrideHCID 214715951-(2-(5-Pyrimidinyl)-prop-2-yl)-4-oxopiperidine

Product 1

HCID 214716961,3-dihydro-1-(1-{1-[2-(5-pyrimidinyl)-prop-2-yl]piperidin-4-yl}piperidin-4-yl)-2H-benzimidazol-2-oneYield 46.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-(2-(5-pyrimidinyl)-prop-2-yl)-4-oxopiperidine (117 mg), 4-(2-oxo-1-benzimidazolinyl)piperidine (128 mg), 1,2-dichloroethane (2.5 mL), glacial acetic acid (0.031 mL) and sodium triacetoxyborohydride (170 mg) was stirred at room temperature for 48 h. The reaction mixture was poured into dichloromethane (15 mL) and saturated aqueous Na2 CO3 (8 mL) and the layers separated. The aqueous layer was extracted with dichloromethane (2×15 mL) and the combined organic layers dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography, eluting with a gradient of methylene chloride; 0-6% methanol; 1% NH4OH, followed by trituration with diethyl ether gave 104 mg of 1,3-dihydro-1-(1-{1-[2-(5-pyrimidinyl)-prop-2-yl]piperidin-4-yl}piperidin-4-yl)-2H-benzimidazol-2-one as a colorless solid: 1H NMR (400 MHz, CDCl3) 10.37 (br s, 1H), 9.10 (s, 1H), 8.88 (s, 2H), 7.30 (m, 1H), 7.12-7.01 (m, 3H), 4.37 (m, 1H), 3.11 (d, 2H), 2.86 (d, 2H), 2.53-2.30 (m, 5H), 2.18 (t, 2H), 1.85 (m, 4H), 1.57 (m, 2H), 1.40 (s, 6H). Treatment with citric acid in ethanol yielded the citrate salt, analysis calculated for C24H32N6O.0.1 H2O.1.5 C6H8O7 : C: 55.78, H: 6.27, N: 11.83 found C: 55.82, H: 6.56, N: 11.68.

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted with dichloromethane (2×15 mL)
  3. dry with materialthe combined organic layers dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customPurification by column chromatography
  6. washeluting with a gradient of methylene chloride

Sources & evidence

ORD record
ord-519981c501b14b928669f28a8094c5b8
Source dataset
uspto-grants-1997_11
Patent number
US05691323

Reaction notes

Loading…