HCID 70874270, compound → HCID 66576713, compound

HRID 2208966Notes

Reaction equation

HRID 2208966 reaction equation
C([N:8]1[C@H:13]([CH3:14])[CH2:12][CH:11]([N:15]([CH2:37][CH3:38])[C:16]2[C:17]([CH3:36])=[C:18]([CH:32]=[C:33]([F:35])[CH:34]=2)[C:19]([NH:21][CH2:22][C:23]2[C:24](=[O:31])[NH:25][C:26]([CH3:30])=[CH:27][C:28]=2[CH3:29])=[O:20])[CH2:10][C@H:9]1[CH3:39])C1C=CC=CC=1>CO.[Pd]>[CH3:29][C:28]1[CH:27]=[C:26]([CH3:30])[NH:25][C:24](=[O:31])[C:23]=1[CH2:22][NH:21][C:19](=[O:20])[C:18]1[CH:32]=[C:33]([F:35])[CH:34]=[C:16]([N:15]([CH:11]2[CH2:10][C@@H:9]([CH3:39])[NH:8][C@H:13]([CH3:14])[CH2:12]2)[CH2:37][CH3:38])[C:17]=1[CH3:36]

Participants

4

Reactant 1

HCID 70874270HCID 70874270, compound

Product 1

HCID 66576713HCID 66576713, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
23 °C

Procedure

To a stirred solution of 3-{[(2R,6R)-1-benzyl-2,6-dimethylpiperidin-4-yl](ethyl)amino}-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-5-fluoro-2-methylbenzamide (378 mg, 0.709 mmol) in MeOH (7 mL) was added Pd/C (150 mg). The reaction mixture was stirred at 23° C. for 1 hour under hydrogen atmosphere. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (1. NAM-300H silica gel produced by Nagara Science Co., Ltd., ethylacetate/MeOH=4/1 to ethylacetate/MeOH/triethylamine=1/1/0.01, 2. NH—SiO2, heptane/ethylacetate=30/1 to 8/1) to give title compound as a white solid (235 mg, 75% yield). 1HNMR (400 MHz, CDCl3) δppm; 7.08 (t, J=6.2 Hz, 1H), 6.82 (dd, J=10.7, 2.5 Hz, 1H), 6.75 (dd, J=8.2, 2.7 Hz, 1H), 5.93 (s, 1H), 4.51 (d, J=6.2 Hz, 2H), 3.40-3.48 (m, 1H), 2.95-3.09 (m, 3H), 2.83-2.92 (m, 1H), 2.39 (s, 3H), 2.22 (s×2, 6H), 1.63-1.78 (m, 4H), 1.13 (d, J=7.0 Hz, 3H), 1.02 (d, J=6.2 Hz, 3H), 0.84 (t, J=7.0 Hz, 3H); MS (ES) [M+H] 443.1, [M+Na] 465.2; HPLC; 99.3% purity.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe residue was purified by silica gel column chromatography (1. NAM-300H silica gel produced by Nagara Science Co., Ltd., ethylacetate/MeOH=4/1 to ethylacetate/MeOH/triethylamine=1/1/0.01, 2. NH—SiO2, heptane/ethylacetate=30/1 to 8/1)

Sources & evidence

ORD record
ord-2cfff796512946cdbb6dda9892019a92
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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