Potassium Carbonate → HCID 67253050, compound

HRID 2042128Notes

Reaction equation

HRID 2042128 reaction equation
[C:1]([C:3]1[CH:8]=[C:7]([O:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]([NH:19][C:20]3[N:24]([C:25]4[CH:26]=[C:27]5[C:32](=[CH:33][CH:34]=4)[N:31]=[CH:30][CH:29]=[CH:28]5)[N:23]=[C:22]([CH:35]([CH3:37])[CH3:36])[CH:21]=3)=[O:18])=[C:12]([F:38])[CH:11]=2)[CH:6]=[CH:5][N:4]=1)#[N:2].C([NH:42][C@H](C(O)=O)CS)(=O)C.C([O-])(=O)C.[NH4+].C([O-])([O-])=O.[K+].[K+]>CO.O>[C:1]([C:3]1[CH:8]=[C:7]([O:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]([NH:19][C:20]3[N:24]([C:25]4[CH:26]=[C:27]5[C:32](=[CH:33][CH:34]=4)[N:31]=[CH:30][CH:29]=[CH:28]5)[N:23]=[C:22]([CH:35]([CH3:36])[CH3:37])[CH:21]=3)=[O:18])=[C:12]([F:38])[CH:11]=2)[CH:6]=[CH:5][N:4]=1)(=[NH:42])[NH2:2]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 12035N-Acetyl-L-CysteineHCID 517165Ammonium AcetateHCID 67251803HCID 67251803, compound

Product 1

HCID 67253050HCID 67253050, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

1-(4-(2-Cyanopyridin-4-yloxy)-2-fluorophenyl)-3-(3-isopropyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)urea (0.108 g, 0.221 mmol) and N-acetylcysteine (0.072 g, 0.441 mmol) were dissolved in MeOH (0.3 mL). Ammonium acetate (0.041 g, 0.0.529 mmol) was added and the reaction mixture was heated at 60° C. under N2 overnight. The completed reaction was diluted with H2O (10 ml), basified by K2CO3, extracted with EtOAc (2×30 mL) and THF (20 mL). The combined organic layers were washed with brine (20 mL), dried (MgSO4), concentrated in vacuo and purified by chromatography to afford 1-(4-(2-carbamimidoylpyridin-4-yloxy)-2-fluorophenyl)-3-(3-isopropyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)urea (0.019 g, 17% yield) as a white solid. This was converted to corresponding HCl salt by reacting with HCl (4.0 M HCl/dioxane, 1.0 eq.). 1H NMR (DMSO-d6) δ 9.57 (s, 2H), 9.36-9.34 (m, 2H), 9.20 (d, J=1.2 Hz, 1H), 9.09 (dd, J=4.4, 1.2 Hz, 1H), 8.74 (d, J=8.0 Hz, 1H), 8.68 (d, J=5.2 Hz, 1H), 8.35 (d, J=2.0 Hz, 1H), 8.28 (d, J=9.2 Hz, 1H), 8.18-8.10 (m, 2H), 7.92 (d, J=2.4 Hz, 1H), 7.80 (dd, J=8.4, 4.8 Hz, 1H), 7.32-7.26 (m, 2H), 7.05 (dd, J=8.8, 1.2 Hz, 1H), 6.44 (s, 1H), 2.97-2.93 (m, 1H), 1.28 (d, J=6.8 Hz, 6H); MS (ESI) m/z: 525.3 (M+H+).

Workup

  1. customThe completed reaction
  2. extractionextracted with EtOAc (2×30 mL) and THF (20 mL)
  3. washThe combined organic layers were washed with brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. custompurified by chromatography

Sources & evidence

ORD record
ord-64297eb05764475c9ea2272176bba93f
Source dataset
uspto-grants-2013_11
Patent number
US08586565B2

Reaction notes

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