Pyridine → HCID 67251941, compound

HRID 2042131Notes

Reaction equation

HRID 2042131 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([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])=[C:11]([F:37])[CH:10]=2)[CH:5]=[CH:4][N: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[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([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])=[C:11]([F:37])[CH:10]=2)[CH:5]=[CH:4][N:3]=1)(=[O:46])[CH3:45]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 67252128HCID 67252128, compound

Product 1

HCID 67251941HCID 67251941, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of the above 1-(4-(2-aminopyridin-4-yloxy)-2-fluorophenyl)-3-(3-isopropyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)urea (44 mg, 0.061 mmol theory) and pyridine (0.30 mL, 3.7 mmol) in CH2Cl2 (1 mL) was treated with acetic anhydride (0.040 mL, 0.39 mmol). The reaction was stirred for 60 h and then partitioned between EtOAc and 2 M aq Na2CO3. The organic layer was washed with water and brine. The aqueous phases were back extracted with EtOAc. The combined organic phases were dried (Na2SO4), concentrated in vacuo and purified by reverse-phase chromatography to provide 1-(4-(2-acetamidopyridin-4-yloxy)-2-fluorophenyl)-3-(3-isopropyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)urea (25 mg, 76% yield). 1H NMR (400 MHz, DMSO-d6) δ 10.53 (s, 1H), 9.01 (s, 1H), 8.96-8.94 (m, 2H), 8.49 (m, 1H), 8.18-8.11 (m, 4H), 7.95 (dd, J=8.8, 2.4 Hz, 1H), 7.64-7.59 (m, 2H), 7.21 (dd, J=11.8, 2.7 Hz, 1H), 6.98 (m, 1H), 6.65 (dd, J=5.8, 2.4 Hz, 1H), 6.43 (s, 1H), 2.93 (m, 1H), 2.03 (s, 3H), 1.26 (d, J=6.8 Hz, 6H); MS (ESI) m/z: 540.3 (M+H+).

Workup

  1. custompartitioned between EtOAc and 2 M aq Na2CO3
  2. washThe organic layer was washed with water and brine
  3. extractionThe aqueous phases were back extracted with EtOAc
  4. dry with materialThe combined organic phases were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. custompurified by reverse-phase chromatography

Sources & evidence

ORD record
ord-c899b2fd34b44174b1e396fb7c1d238b
Source dataset
uspto-grants-2013_11
Patent number
US08586565B2

Reaction notes

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