Pyridine → HCID 67252911, compound

HRID 1711713Notes

Reaction equation

HRID 1711713 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:10]=[CH:11][C:12]([F:37])=[C:13]([NH:15][C:16]([NH:18][C:19]3[N:23]([C:24]4[CH:25]=[C:26]5[C:31](=[CH:32][CH:33]=4)[N:30]=[CH:29][CH:28]=[CH:27]5)[N:22]=[C:21]([CH:34]([CH3:36])[CH3:35])[CH:20]=3)=[O:17])[CH:14]=2)=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:44](OC(=O)C)(=[O:46])[CH3:45]>C(Cl)Cl>[C:44]([NH:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:10]=[CH:11][C:12]([F:37])=[C:13]([NH:15][C:16]([NH:18][C:19]3[N:23]([C:24]4[CH:25]=[C:26]5[C:31](=[CH:32][CH:33]=4)[N:30]=[CH:29][CH:28]=[CH:27]5)[N:22]=[C:21]([CH:34]([CH3:35])[CH3:36])[CH:20]=3)=[O:17])[CH:14]=2)=[CH:4][CH:3]=1)(=[O:46])[CH3:45]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 67252895HCID 67252895, compound

Product 1

HCID 67252911HCID 67252911, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-(5-(6-aminopyridin-3-yloxy)-2-fluorophenyl)-3-(3-isopropyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)urea (0.0495 g, 0.099 mmol) was dissolved in DCM (1.0 mL), to which pyridine (0.49 mL, 6.0 mmol) and acetic anhydride (0.066 mL, 0.65 mmol) were added. The reaction mixture was stirred at RT for 12 h. The completed reaction was quenched with 2M NaHCO3 (12 mL) and extracted with EtOAc (25 mL). The organic layer was washed with H2O (15 mL) and brine (10 mL), dried (MgSO4), concentrated in vacuo and purified by chromatography to afford 1-(5-(6-acetamidopyridin-3-yloxy)-2-fluorophenyl)-3-(3-isopropyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)urea (0.0234 g, 44% yield) as a yellow foam. It was converted to corresponding mesylate salt by reacting with MsOH (1.0 eq.). 1H NMR (400 MHz, DMSO-d6) δ 10.54 (s, 1H), 9.09 (s, 1H), 9.07-9.04 (m, 2H), 8.65 (d, J=8.0 Hz, 1H), 8.25 (d, J=2.0 Hz, 1H), 8.21 (d, J=8.8 Hz, 1H), 8.11-8.07 (m, 2H), 8.02 (dd, J=8.8, 2.4 Hz, 1H), 7.85 (m, 1H), 7.75 (m, 1H), 4.48 (dd, J=8.8, 3.2 Hz, 1H), 7.24 (m, 1H), 6.67 (m, 1H), 6.40 (s, 1H), 2.92 (m, 1H), 2.31 (s, 3H), 2.08 (s, 3H), 1.24 (d, J=7.2 Hz, 6H); MS (ESI) m/z: 540.0 (M+H+).

Workup

  1. additionwere added
  2. customThe completed reaction
  3. customwas quenched with 2M NaHCO3 (12 mL)
  4. extractionextracted with EtOAc (25 mL)
  5. washThe organic layer was washed with H2O (15 mL) and brine (10 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. custompurified by chromatography

Sources & evidence

ORD record
ord-99be34b7c79d4508a96ab547e2786ea6
Source dataset
uspto-grants-2010_09
Patent number
US07790756B2

Reaction notes

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