Diisopropylethylamine → N-(4-cyano-1-methyl-piperidin-4-yl)-2-(4-cyano-pyrimidin-2-ylamino)-3-cyclohexyl-propionamide

HRID 25255Notes

Reaction equation

HRID 25255 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=1.[NH2:10][CH:11]([CH2:24][CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1)[C:12]([NH:14][C:15]1([C:22]#[N:23])[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]1)=[O:13].C(N(CC)C(C)C)(C)C>C(#N)C>[C:22]([C:15]1([NH:14][C:12](=[O:13])[CH:11]([NH:10][C:2]2[N:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=2)[CH2:24][CH:25]2[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]2)[CH2:16][CH2:17][N:18]([CH3:21])[CH2:19][CH2:20]1)#[N:23]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2466472-Chloropyrimidine-4-carbonitrileHCID 220631432-amino-N-(4-cyano-1-methyl-piperidin-4-yl)-3-cyclohexyl-propionamide

Product 1

HCID 22063248N-(4-cyano-1-methyl-piperidin-4-yl)-2-(4-cyano-pyrimidin-2-ylamino)-3-cyclohexyl-propionamideYield 52%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-Chloro-4-pyrimidinecarbonitrile (0.3 mmol, Daves, G. D. Jr., O'Brien, D. E., Cheng, C. C. J. Het. Chem, 1964, 1, 130) and 2-amino-N-(4-cyano-1-methyl-piperidin-4-yl)-3-cyclohexyl-propionamide (0.7 mmol) were dissolved in acetonitrile (10 mL) containing N,N-diisopropylethylamine (0.6 mmol). The solution was heated to a gentle reflux for 17 h. The volatiles were evaporated and the residue was subjected to chromatography (silica gel, eluant=EtOAc then MeOH). The methanolic fraction was concentrated to a colorless solid which was rechromatographed (10% MeOH/EtOAc) to afford the title compound as a colorless solid (52%). The material was recrystallized from dichloromethane/petroleum ether.

Workup

  1. temperatureThe solution was heated to
  2. temperaturea gentle reflux for 17 h
  3. customThe volatiles were evaporated
  4. concentrationThe methanolic fraction was concentrated to a colorless solid which
  5. customwas rechromatographed (10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-eca241e31d3544f4b003cb27d9c780f0
Source dataset
uspto-grants-2005_02
Patent number
US06858623B2

Reaction notes

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