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

HRID 1486733ノート

反応式

HRID 1486733 の反応式
[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

参加物

7

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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%

出典と根拠

ORDレコード
ord-53809e79fa1741c6a4bc2866f86e7c14
出典データセット
uspto-grants-2016_08
特許番号
US09428456B2

反応ノート

読み込み中…