Water → HCID 59526220, compound

HRID 386132Notes

Reaction equation

HRID 386132 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([F:12])[C:3]=1[C:13]1[S:17][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22](=[O:25])[NH:21][N:20]=2)=[C:15]([C:26]([NH2:28])=[O:27])[CH:14]=1.[C:29]([O-])([O-])=O.[K+].[K+].IC.O>CN(C=O)C>[F:12][C:4]1[CH:5]=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:7]=[C:2]([F:1])[C:3]=1[C:13]1[S:17][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22](=[O:25])[N:21]([CH3:29])[N:20]=2)=[C:15]([C:26]([NH2:28])=[O:27])[CH:14]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 59526009HCID 59526009, compound

Product 1

HCID 59526220HCID 59526220, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-[2,6-Difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-[(6-oxo-1,6-dihydropyridazin-3-yl)amino]thiophene-3-carboxamide (Example 578 Step 3) (50 mg, 0.123 mmol), K2CO3 (18.70 mg, 0.135 mmol) and iodomethane (8.08 μL, 0.129 mmol) were stirred in DMF (1 mL) at 80° C. overnight. The reaction mixture was cooled to room temperature, water was added and the products extracted into EtOAc (2×). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue twice by silica gel column chromatography (0-10% MeOH—CHCl3) followed by mass-triggered reverse phase HPLC gave the title compound as a yellow solid.

Workup

  1. extractionthe products extracted into EtOAc (2×)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue twice by silica gel column chromatography (0-10% MeOH—CHCl3)

Sources & evidence

ORD record
ord-ceab857449a443708dda830377d90416
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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