N-methyl-2-pyrrolidone → HCID 57721329, compound

HRID 1986092Notes

Reaction equation

HRID 1986092 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5](Cl)=[C:6]([CH:18]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17])=[O:8].Cl.N1[C:25]2=[N:26][CH:27]=[CH:28][C:29]([O:30][C:31]3[CH:36]=[CH:35][C:34]([NH:37]C4C(C(NC5C=CC(F)=CC=5F)=O)=CN=CC=4)=[CH:33][C:32]=3[F:55])=[C:24]2C=C1.O.C1(C)C(S(O)(=O)=O)=CC=CC=1.C[N:69]1[C:73](=[O:74])CCC1>>[Br:1][C:2]1[CH:18]=[C:6]([C:7](=[O:8])[NH:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[C:5]([NH:37][C:34]2[CH:35]=[CH:36][C:31]([O:30][C:29]3[CH:28]=[CH:27][N:26]=[C:25]([C:73]([NH2:69])=[O:74])[CH:24]=3)=[C:32]([F:55])[CH:33]=2)=[N:4][CH:3]=1

Participants

5

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 124969952-Methylbenzenesulfonic acid hydrateHCID 162230054-(4-(1h-Pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenylamino)-n-(2,4-difluorophenyl)nicotinamide, hydrochloride salt2×HCID 57721353HCID 57721353, compound

Product 1

HCID 57721329HCID 57721329, compoundYield 11%

Conditions

Temperature
160 °C

Procedure

To a solution of 5-bromo-2-chloro-N-(2,4-difluorophenyl)nicotinamide (126 mg, 0.51 mmol) and 4-(4-amino-2-fluorophenoxy)picolinamide (172 mg, 0.49 mmol, Compound C of Example 3) in 3 mL of NMP was added toluenesulfonic acid monohydrate (71 mg, 0.37 mmol). The mixture was stirred at 120° C. for 2 h and at 160° C. for 15 h. The solution was cooled to rt and purified on preparative (RP) HPLC. The fractions containing the desired product pooled and concentrated in vacuo. The residue was then partitioned between 1N NaOH and EtOAc and the two layers were separated. The organic layer washed with brine and dried over MgSO4. After filtration and concentration, the desired product was obtained (30 mg, 11% yield). MS (ESI+) m/z 558.22, 560.22 (M+H)+.

Workup

  1. temperatureThe solution was cooled to rt
  2. custompurified on preparative (RP) HPLC
  3. additionThe fractions containing the desired product
  4. concentrationconcentrated in vacuo
  5. customThe residue was then partitioned between 1N NaOH and EtOAc
  6. customthe two layers were separated
  7. washThe organic layer washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationAfter filtration and concentration

Sources & evidence

ORD record
ord-7805d4a12b25439ea15dada849af039d
Source dataset
uspto-grants-2009_06
Patent number
US07547782B2

Reaction notes

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