1-Methylpyrrolidine → HCID 86275386, compound

HRID 626597Notes

Reaction equation

HRID 626597 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].[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([CH:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH2:34][CH2:33]1.CN1CCCC1>O1CCOCC1.CC#N.O>[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([CH:38]2[CH2:43][CH2:42][N:41]([C:24]([NH:23][C:19]3[CH:18]=[C:17]([O:16][C:13]4[CH:14]=[N:15][C:10]([NH:9][C:8]([NH:7][C:1](=[O:6])[C:2]([CH3:4])([CH3:3])[CH3:5])=[O:30])=[CH:11][CH:12]=4)[CH:22]=[CH:21][N:20]=3)=[O:29])[CH2:40][CH2:39]2)[CH2:34][CH2:33]1

Participants

6

Reactant 3

HCID 84541-MethylpyrrolidineHCID 7957071-Methyl-4-(piperidin-4-yl)piperazineHCID 90445670Prop-1-en-2-yl (4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)carbamate

Product 1

HCID 86275386HCID 86275386, compoundYield 40.3%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A mixture of Example C2 (0.120 g, 0.29 mmol), 1-methyl-4-(piperidin-4-yl)piperazine (0.053 g, 0.290 mmol) and N-methylpyrrolidine (0.012 g, 0.15 mmol) in dioxane (5 mL) was heated at 80° C. for 2 days. The reaction mixture was concentrated to dryness. The residue was dissolved in DCM and stirred with sat'd NaHCO3. The aqueous layer was back-extracted with DCM (3×) and the organic phases combined, dried (Na2SO4) and concentrated to afford a light brown oil. The crude residue was purified via silica gel chromatography (MeOH/DCM/Et3N) to afford a light yellow oil, which was dissolved in MeCN/H2O, frozen and lypholized overnight to afford 4-(4-methylpiperazin-1-yl)-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperidine-1-carboxamide as a white solid (63 mg, 40%). 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.44 (s, 1H), 9.22 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.12-8.05 (m, 2H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.36 (d, J=2.4 Hz, 1H), 6.59 (dd, J=5.7, 2.4 Hz, 1H), 4.13-4.02 (m, 2H), 3.38-3.31 (m, 1H), 2.77-2.64 (m, 2H), 2.52-2.26 (m, 8H), 2.16 (s, 3H), 1.75-1.62 (m, 2H), 1.31-1.23 (m, 2H), 1.21 (s, 9H); MS (ESI) m/z: 539.4 (M+H+).

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. dissolutionThe residue was dissolved in DCM
  3. extractionThe aqueous layer was back-extracted with DCM (3×)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customto afford a light brown oil
  7. customThe crude residue was purified via silica gel chromatography (MeOH/DCM/Et3N)
  8. customto afford a light yellow oil, which
  9. temperaturefrozen

Sources & evidence

ORD record
ord-ac09276ed7dc4aa1a681b88c04832a4c
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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