Cesium carbonate → 2-[(5-Chloro-2-{[4-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-N-(methyloxy)benzamide

HRID 1472551Notes

Reaction equation

HRID 1472551 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])[C:5]([Cl:20])=[CH:4][N:3]=1.[CH3:21][C:22]1[CH:23]=[N:24][N:25]([CH:28]([CH3:30])[CH3:29])[C:26]=1[NH2:27].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[Cl:20][C:5]1[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])=[CH:7][C:2]([NH:27][C:26]2[N:25]([CH:28]([CH3:30])[CH3:29])[N:24]=[CH:23][C:22]=2[CH3:21])=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 290606024-methyl-1-(propan-2-yl)-1H-pyrazol-5-amineHCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

Product 1

HCID 462150982-[(5-Chloro-2-{[4-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-N-(methyloxy)benzamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

A microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (100 mg, 0.32 mmol), 4-methyl-1-(1-methylethyl)-1H-pyrazol-5-amine (93.6 mg, 0.67 mmol), cesium carbonate (312.8 mg, 0.96 mmol) and DMF (5 mL). The reaction mixture was degassed under nitrogen for 10 min and palladium (II) acetate (3.6 mg, 0.016 mmol) and BINAP (19.9 mg, 0.032 mmol) were added. The reaction mixture was heated in an oil bath for 6 hours and then in a microwave at 150° C. for 40 min. The solvent was evaporated and the residue dissolved in MeOH. It was filtered thru celite and thru an Acrodisc to be purified on preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid). Fractions were combined and evaporated. The brown oil residue was diluted in DMF and water was added. A precipitate crashed out. It was filtered and dried under vacuum at 40° C. for 6 hrs. LC-MS [M+H]+=415.1. 1H NMR (400 MHz, DMSO-d6) ppm 11.93 (s, 1 H) 9.48 (br. s., 1 H) 8.23 (s, 1 H) 7.93 (s, 1 H) 7.58 (d, J=7.83 Hz, 1 H) 7.50 (d, J=3.79 Hz, 2 H) 7.24 (s, 1 H) 7.12 (dt, J=7.83, 4.17 Hz, 1 H) 6.40 (br. s., 1 H) 4.33 (dt, J=13.14, 6.57 Hz, 1 H) 3.71 (s, 3 H) 1.78 (s, 3 H) 1.26 (d, J=6.57 Hz, 6 H).

Workup

  1. customThe reaction mixture was degassed under nitrogen for 10 min
  2. temperatureThe reaction mixture was heated in an oil bath for 6 hours
  3. customThe solvent was evaporated
  4. dissolutionthe residue dissolved in MeOH
  5. filtrationIt was filtered thru celite
  6. customto be purified on preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid)
  7. customevaporated
  8. additionThe brown oil residue was diluted in DMF
  9. additionwater was added
  10. filtrationIt was filtered
  11. customdried under vacuum at 40° C. for 6 hrs

Sources & evidence

ORD record
ord-9644236bb312404c974d6e16f62ff0ca
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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