Morpholine → N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)morpholine-4-carboxamide

HRID 626559Notes

Reaction equation

HRID 626559 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].[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.CN1CCCC1>O1CCOCC1>[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]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[O:29])[CH:18]=2)=[CH:12][CH:11]=1)(=[O:6])[C:2]([CH3:4])([CH3:3])[CH3:5]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 84541-MethylpyrrolidineHCID 90445670Prop-1-en-2-yl (4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)carbamate

Product 1

HCID 86273944N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)morpholine-4-carboxamideYield 52%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of Example C2 (0.145 g, 0.351 mmol), morpholine (0.092 g, 1.052 mmol) and N-methylpyrrolidine (2.99 mg, 0.035 mmol) in dioxane (3 mL) was heated at 80° C. overnight, cooled to RT, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)morpholine-4-carboxamide (80 mg, 52%). 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.43 (s, 1H), 9.29 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.13 (d, J=5.7 Hz, 1H), 8.08 (d, J=9.0 Hz, 1H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.37 (d, J=2.4 Hz, 1H), 6.62 (dd, J=5.7, 2.4 Hz, 1H), 3.53 (m, 4H), 3.39 (m, 4H), 1.21 (s, 9H); MS (ESI) m/z: 443.2 (M+H+).

Workup

  1. concentrationconcentrated to dryness
  2. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-4967810f2da249ef9736195eb392a662
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

Loading…