Acetone → N-(5-Chloropyridin-2-yl)-2-[4-(N,N-dimethylamino)-2-(1-isopropyl-piperidin-4-yloxy)benzoylamino]benzamide Hydrochloride

HRID 644165Notes

Reaction equation

HRID 644165 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:35])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[NH:16][C:17](=[O:34])[C:18]2[CH:23]=[CH:22][C:21]([N:24]([CH3:26])[CH3:25])=[CH:20][C:19]=2[O:27][CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[N:6][CH:7]=1.[CH3:36][C:37]([CH3:39])=O.CC(O)=O.CO.[BH3-]C#N.[Na+].CO>O.C(Cl)Cl>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:35])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[NH:16][C:17](=[O:34])[C:18]2[CH:23]=[CH:22][C:21]([N:24]([CH3:26])[CH3:25])=[CH:20][C:19]=2[O:27][CH:28]2[CH2:33][CH2:32][N:31]([CH:37]([CH3:39])[CH3:36])[CH2:30][CH2:29]2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 180AcetoneHCID 10129899Acetic acid methanolHCID 57860759N-(5-chloropyridin-2-yl)-2-[4-(N,N-dimethylamino)-2-(piperidin-4-yloxy)benzoylamino]benzamideHCID 131728079NaCNBH3 MeOH

Product 1

HCID 68535658N-(5-Chloropyridin-2-yl)-2-[4-(N,N-dimethylamino)-2-(1-isopropyl-piperidin-4-yloxy)benzoylamino]benzamide HydrochlorideYield 45.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of N-(5-chloropyridin-2-yl)-2-[4-(N,N-dimethylamino)-2-(piperidin-4-yloxy)benzoylamino]benzamide (250 mg, 0.51 mmol), acetone (0.07 mL, 1.0 mmol) and 20% AcOH/MeOH (2 mL) was added a solution of 0.25 M NaCNBH3/MeOH (2 mL, 0.5 mmol). The reaction was stirred for 24 hours and then it was diluted with water and CH2Cl2. After partitioning, the organic layer was washed with 50% satd Na2 CO3, dried over Na2 SO4, and concentrated. The residue was HPLC chromatographed (Vydac, 5% CH3 CN in 0.1% TFA/H2O to 70% CH3 CN in 0.1% TFA/H2O, t=28.8 m) and then treated with HCl to give the desired product as a white solid (66 mg, 23%).

Workup

  1. customAfter partitioning
  2. washthe organic layer was washed with 50%
  3. customdried over Na2 SO4
  4. concentrationconcentrated
  5. customchromatographed (Vydac, 5% CH3 CN in 0.1% TFA/H2O to 70% CH3 CN in 0.1% TFA/H2O, t=28.8 m)
  6. additiontreated with HCl

Sources & evidence

ORD record
ord-930ef550e1f64469b0ed11a12adfac64
Source dataset
uspto-grants-2010_04
Patent number
US07700628B2

Reaction notes

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