Methanol → HCID 59159912, compound

HRID 1662037Notes

Reaction equation

HRID 1662037 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:31][C:32]([C:34]2[C:35](=[O:47])[N:36]([C:40]3[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=3)[CH:37]=[CH:38][CH:39]=2)=[O:33])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:17]([N:18]2[CH2:23][CH2:22][O:21][CH:20]([CH3:24])[CH2:19]2)=[CH:16][C:15]2[C:11](=[CH:12][N:13](C3CCCCO3)[N:14]=2)[CH:10]=1.CO.CS(O)(=O)=O.C(Cl)Cl>CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([NH:31][C:32]([C:34]2[C:35](=[O:47])[N:36]([C:40]3[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=3)[CH:37]=[CH:38][CH:39]=2)=[O:33])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][C:17]=1[N:18]1[CH2:23][CH2:22][O:21][CH:20]([CH3:24])[CH2:19]1)[NH:14][N:13]=[CH:12]2

Participants

6

Reactant 4

HCID 887Methanol2×HCID 6344Dichloromethane2×HCID 6395Methanesulfonic AcidHCID 66767280HCID 66767280, compound

Product 1

HCID 59159912HCID 59159912, compoundYield 69.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
40 °C

Procedure

To a round bottom flask is added N-(3-fluoro-4-(6-(2-methylmorpholino)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-5-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (66 mg, 102.86 μmol) and MeOH (5 mL, 123.54 mmol). To the resulting mixture is added MeSO3H (20.229 μL, 308.57 μmol) and the reaction mixture is heated to 40° C. for 6 hours. The reaction mixture is concentrated and dissolved in DCM (100 mL). The solution is washed with a mixture of saturated aqueous sodium chloride (20 mL) and saturated aqueous sodium bicarbonate solution (1×20 mL). The organic solution is extracted with DCM (1×25 mL) and dried over Na2SO4, filtered and concentrated. The residue is purified on a silica gel column eluting with DCM (A) and a 10% MeOH in DCM solution (B), gradient from 100% (A) to 70%(A):30%(B) over 60 min to give a light yellow solid as the desired product (40 mg, 62% yield). MS (m/z): 557.8 (M+H).

Workup

  1. concentrationThe reaction mixture is concentrated
  2. dissolutiondissolved in DCM (100 mL)
  3. washThe solution is washed with a mixture of saturated aqueous sodium chloride (20 mL) and saturated aqueous sodium bicarbonate solution (1×20 mL)
  4. extractionThe organic solution is extracted with DCM (1×25 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is purified on a silica gel column
  9. washeluting with DCM (A)

Sources & evidence

ORD record
ord-1dc501cefb7f46b795f0eed80a80043c
Source dataset
uspto-grants-2011_10
Patent number
US08030302B2

Reaction notes

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