1-Methylpyrrolidine → 4-(dimethylamino)-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperidine-1-carboxamide

HRID 626592Notes

Reaction equation

HRID 626592 reaction equation
[C:1]([NH:7][C:8](=[O:30])[NH:9][C:10]1[N:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24](=[O:29])OC(C)=C)[CH:18]=2)=[CH:12][CH:11]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].Cl.Cl.[CH3:33][N:34]([CH3:41])[CH:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.CN1CCCC1>O1CCOCC1>[CH3:33][N:34]([CH3:41])[CH:35]1[CH2:40][CH2:39][N:38]([C:24]([NH:23][C:19]2[CH:18]=[C:17]([O:16][C:13]3[CH:14]=[N:15][C:10]([NH:9][C:8]([NH:7][C:1](=[O:6])[C:2]([CH3:3])([CH3:5])[CH3:4])=[O:30])=[CH:11][CH:12]=3)[CH:22]=[CH:21][N:20]=2)=[O:29])[CH2:37][CH2:36]1

Participants

5

Reactant 3

HCID 84541-MethylpyrrolidineHCID 225914404-(Dimethylamino)piperidine dihydrochlorideHCID 90445670Prop-1-en-2-yl (4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)carbamate

Product 1

HCID 862751484-(dimethylamino)-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperidine-1-carboxamideYield 13%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of Example C2 (0.42 g, 1.02 mmol), 4-(dimethylamino)piperidine dihydrochloride (0.204 g, 1.02 mmol) and N-methylpyrrolidine (0.182 g, 2.13 mmol) in dioxane (5 mL) was heated at 80° C. overnight, cooled to RT, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The resultant material was dissolved in MeCN/H2O, frozen and lyophilized to afford 4-(dimethylamino)-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperidine-1-carboxamide as a yellowish solid (64 mg, 13%). 1H NMR (400 MHz, DMSO-d6): δ 11.17 (s, 1H), 10.40 (s, 1H), 9.23 (s, 1H), 8.18 (d, J=2.9 Hz, 1H), 8.07 (d, J=5.7 Hz, 1H), 8.03 (d, J=9.0 Hz, 1H), 7.66 (dd, J=9.0, 2.9 Hz, 1H), 7.32 (d, J=2.4 Hz, 1H), 6.56 (dd, J=5.7, 2.4 Hz, 1H), 4.13-4.01 (m, 2H), 3.37-3.11 (br s, 1H), 2.74-2.62 (m, 2 H), 2.28 (s, 6H), 1.76-1.70 (m, 2H), 1.29-1.24 (m, 2H), 1.16 (s, 9H); MS (ESI) m/z: 484.3 (M+H+).

Workup

  1. concentrationconcentrated to dryness
  2. custompurified via silica gel chromatography (MeOH/DCM)
  3. dissolutionThe resultant material was dissolved in MeCN/H2O
  4. temperaturefrozen

Sources & evidence

ORD record
ord-090cb23800e44b87bc09daddc8146955
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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