Water → HCID 131717965, compound

HRID 1586977Notes

Reaction equation

HRID 1586977 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:21]=[CH:20][C:12]([C:13]([N:15]([CH2:18][CH3:19])[CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.Cl.[Cl:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]([NH:34][C:35]3[CH:42]=[CH:41][C:38]([CH:39]=O)=[CH:37][CH:36]=3)=[CH:29][CH:30]=[N:31]2)=[CH:26][CH:25]=1.O.[BH4-].[Na+]>C1(C)C=CC=CC=1>[ClH:23].[Cl:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]([NH:34][C:35]3[CH:42]=[CH:41][C:38]([CH2:39][NH:1][CH:2]4[CH2:3][CH2:4][N:5]([CH2:8][C:9]5[CH:21]=[CH:20][C:12]([C:13]([N:15]([CH2:16][CH3:17])[CH2:18][CH3:19])=[O:14])=[CH:11][CH:10]=5)[CH2:6][CH2:7]4)=[CH:37][CH:36]=3)=[CH:29][CH:30]=[N:31]2)=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 962WaterHCID 4311764Sodium borohydride2×HCID 19760337HCID 19760337, compoundHCID 19760350HCID 19760350, compound

Product 1

HCID 131717965HCID 131717965, compoundYield 42.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

4-[(4-Amino-1-piperidinyl)methyl]-N,N-diethylbenzamide (3.81 g, 13.16 mmol) and 4-[(7-chloro-4-quinolinyl)amino]benzaldehyde hydrochloride (13.16 mmol, 4.20 g) are refluxed for 28 hours in 52 mL of toluene under nitrogen with azeotropic removal of water. The toluene is poured off the thick oil, which is then rinsed once with fresh toluene. The remaining traces of solvent are removed in vacuo and the resulting gum is dissolved in 55 mL of ethanol and treated with NaBH4 (14.6 mmol, 552 mg). The reaction mixture is refluxed for 50 minutes, treated with another 200 mg of NaBH4 and refluxed an additional 10 minutes. The reaction mixture is poured over 100 mL of ice, which results in the formation of an orange oil. After stirring rapidly for seven days, the water is decanted and the oil is purified by flash chromatography on silica gel (65 mm column, 5% ammonia saturated methanol in methylene chloride eluent) which affords 1.55 g (2.79 mmol, 21% yield) of the title compound as the free base. Of this, 0.95 g (1.7 mmol) are dissolved in 5 mL of methanol and treated with 1.7 mL of 1N ethereal HCl. The resulting solution is concentrated in vacuo and the residue is triturated with ether for 23 hours. The resulting yellow powder is filtered, washed with ether and dried in vacuo at 60° C. for 16.5 hours, affording 896 mg of the title compound: mp 166°-190° C. (softens slowly over this range); 1H NMR (Me2SO-d6, 400 MHz) δ9.37 (br s, 1H), 8.5 (m, 2H), 7.91 (d,J=2.2 Hz, 1H), 7.6 (m, 3H), 7.28-7.42 (m, 6H), 6.96 (d,J=5.4 Hz, 1H), 4.12 (s, 2H), 2.9-3.6 (m, 10H), 2.1 (m, 4H), 1.7-1.8 (m, 2H), 1-1.2 (m, 6H);

Workup

  1. washis then rinsed once with fresh toluene
  2. customThe remaining traces of solvent are removed in vacuo
  3. dissolutionthe resulting gum is dissolved in 55 mL of ethanol
  4. temperatureThe reaction mixture is refluxed for 50 minutes
  5. temperaturerefluxed an additional 10 minutes
  6. customresults in the formation of an orange oil
  7. customthe water is decanted
  8. customthe oil is purified by flash chromatography on silica gel (65 mm column, 5% ammonia saturated methanol in methylene chloride eluent) which

Sources & evidence

ORD record
ord-142d25b720a34bdba7f6b801c7dbf151
Source dataset
uspto-grants-1993_06
Patent number
US05216165

Reaction notes

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