Acetic Acid → 3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-N-((4-isopropyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-5-(6-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)pyridin-3-yl)benzamide

HRID 1959317Notes

Reaction equation

HRID 1959317 reaction equation
[CH2:1]([N:3]([CH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1)[C:4]1[C:5]([CH3:37])=[C:6]([CH:22]=[C:23]([C:25]2[CH:26]=[N:27][C:28]([N:31]3[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]3)=[CH:29][CH:30]=2)[CH:24]=1)[C:7]([NH:9][CH2:10][C:11]1[C:12](=[O:21])[NH:13][C:14]([CH3:20])=[CH:15][C:16]=1[CH:17]([CH3:19])[CH3:18])=[O:8])[CH3:2].[CH3:44][N:45]1[CH2:50][CH2:49][C:48](=O)[CH2:47][CH2:46]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[CH2:1]([N:3]([CH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1)[C:4]1[C:5]([CH3:37])=[C:6]([CH:22]=[C:23]([C:25]2[CH:26]=[N:27][C:28]([N:31]3[CH2:36][CH2:35][N:34]([CH:48]4[CH2:49][CH2:50][N:45]([CH3:44])[CH2:46][CH2:47]4)[CH2:33][CH2:32]3)=[CH:29][CH:30]=2)[CH:24]=1)[C:7]([NH:9][CH2:10][C:11]1[C:12](=[O:21])[NH:13][C:14]([CH3:20])=[CH:15][C:16]=1[CH:17]([CH3:19])[CH3:18])=[O:8])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 740491-Methyl-4-piperidoneHCID 5049666Sodium triacetoxyborohydrideHCID 708723603-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-N-((4-isopropyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-5-(6-(piperazin-1-yl)pyridin-3-yl)benzamide

Product 1

HCID 708724663-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-N-((4-isopropyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-5-(6-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)pyridin-3-yl)benzamideYield 34.4%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a stirred solution of 3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-N-((4-isopropyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-5-(6-(piperazin-1-yl)pyridin-3-yl)benzamide (0.3 g, 0.51 mmol) and 1-methylpiperidin-4-one (0.086 g, 0.76 mmol) in dichloroethane (5 mL), acetic acid (0.18 g, 3.06 mmol) was added and reaction stirred at room temperature for 20 minutes. Then sodium triacetoxyborohydride (0.33 g, 1.55 mmol) was added at 0° C. and reaction stirred at room temperature for 2 h. On completion, reaction was quenched with aqueous sodium bicarbonate, organic phase was separated and aqueous phase was extracted with dichloromethane. Combined organic layers were dried over sodium sulphate and concentrated under reduced pressure to give crude material was purified by prep. HPLC to afford the title compound (0.12 g, 34.38%).

Workup

  1. customreaction
  2. customreaction
  3. stirringstirred at room temperature for 2 h
  4. customOn completion, reaction
  5. customwas quenched with aqueous sodium bicarbonate, organic phase
  6. customwas separated
  7. extractionaqueous phase was extracted with dichloromethane
  8. dry with materialCombined organic layers were dried over sodium sulphate
  9. concentrationconcentrated under reduced pressure
  10. customto give crude material
  11. customwas purified by prep

Sources & evidence

ORD record
ord-37b463e5646843faa10a5eca4d0eb0f3
Source dataset
uspto-grants-2013_04
Patent number
US08410088B2

Reaction notes

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