Acetonitrile → HCID 58487345, compound

HRID 874621Notes

Reaction equation

HRID 874621 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])=[O:10])[CH:5]=[CH:4][C:3]=1Br.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C:27](#[N:29])[CH3:28]>O1CCOCC1.O>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])=[O:10])[CH:5]=[CH:4][C:3]=1[C:6]1[N:7]([CH3:2])[N:29]=[C:27]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:28]=1

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 62657Potassium Phosphate, TribasicHCID 58487036HCID 58487036, compound

Product 1

HCID 58487345HCID 58487345, compoundYield 4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of N-(6-amino-5-bromo(2-pyridyl))(2-fluorophenyl)carboxamide (61) (16 mg, 0.05 mmol), bis(ditertbutyl(4-dimethylaminophenyl)phosphine)dichloropalladium (II) (4 mg, 10% mol) and K3PO4 (11 mg, 0.05 mmol) in 0.5 ml ACN, 0.5 ml dioxane, 0.2 ml H2O was bubbled with argon before heated at 85° C. for 4 h. After cooling down to r.t., the reaction mixture was taken up in EA, washed with aq. NaHCO3 and brine. Org. phase was dried over Na2SO4, concentrated to dryness. Flash silica gel column purification (0-90% B, A: hexane; B: 50% EA in hexane) furnished 2.2 mg crude desired product as yellow solid which was re-purified on prep HPLC to give 0.8 mg N-[6-amino-5-(1-methyl-3-phenylpyrazol-5-yl)(2-pyridyl)](2-fluorophenyl)carboxamide (69) as off-white solid. (yield: 4%, purity>90%).

Workup

  1. customwas bubbled with argon
  2. temperatureAfter cooling down to r.t.
  3. washwashed with aq. NaHCO3 and brine
  4. dry with materialphase was dried over Na2SO4
  5. concentrationconcentrated to dryness
  6. customFlash silica gel column purification (0-90% B
  7. customB: 50% EA in hexane) furnished 2.2 mg crude desired product as yellow solid which
  8. customwas re-purified on prep HPLC

Sources & evidence

ORD record
ord-1148613647814d8ab29af9871237aab6
Source dataset
uspto-grants-2015_03
Patent number
US08980629B2

Reaction notes

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