Diisopropylethylamine → 1-(2-Bromo-pyridin-4-ylmethyl)-piperidine-4-carboxylic acid cyclohexylamide

HRID 1486733Notes

Reaction equation

HRID 1486733 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH:8]=O)[CH:5]=[CH:4][N:3]=1.Cl.[CH:11]1([NH:17][C:18]([CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[O:19])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH:11]1([NH:17][C:18]([CH:20]2[CH2:21][CH2:22][N:23]([CH2:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([Br:1])[CH:7]=3)[CH2:24][CH2:25]2)=[O:19])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27629912-Bromo-4-pyridinecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 44630870N-cyclohexylpiperidine-4-carboxamide hydrochloride

Product 1

HCID 867065511-(2-Bromo-pyridin-4-ylmethyl)-piperidine-4-carboxylic acid cyclohexylamideYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-bromo-4-formylpyridine (1 g, 5.38 mmol), piperidine-4-carboxylic acid cyclohexylamide hydrochloride J-1 (1.327 g, 5.38 mmol) and DIPEA (2.78 mL, 16.13 mmol) in DCM (25 mL) is treated with sodium triacetoxy borohydride (2.28 g, 10.75 mmol) in 5 portions over 20 min. and the reaction mixture is stirred for 18 h at RT. Aq. sat. NaHCO3 (25 mL) is added and the mixture is stirred for 30 min. The phases are separated and the aqueous phase is extracted twice with DCM (25 mL). The combined organic phases are dried over MgSO4 and evaporated. The crude residue is purified by flash chromatography on silica gel using a gradient of heptane and EtOAc 1:4 to EtOAc 100%. After concentration of the product-containing fractions, the title compound (1.18 g, 58%) is obtained as a colorless solid LC-MS A: tR=0.59 min; [M+H]+=382.15.

Workup

  1. stirringthe mixture is stirred for 30 min
  2. customThe phases are separated
  3. extractionthe aqueous phase is extracted twice with DCM (25 mL)
  4. dry with materialThe combined organic phases are dried over MgSO4
  5. customevaporated
  6. customThe crude residue is purified by flash chromatography on silica gel using a gradient of heptane and EtOAc 1:4 to EtOAc 100%

Sources & evidence

ORD record
ord-53809e79fa1741c6a4bc2866f86e7c14
Source dataset
uspto-grants-2016_08
Patent number
US09428456B2

Reaction notes

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