Cesium carbonate → HCID 46215100, compound

HRID 1472553Notes

Reaction equation

HRID 1472553 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]([CH2:28][CH:29]([CH3:31])[CH3:30])[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]([CH2:28][CH:29]([CH3:30])[CH3:31])[N:24]=[CH:23][C:22]=2[CH3:21])=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 214556121-Isobutyl-4-methyl-1H-pyrazol-5-amineHCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

Product 1

HCID 46215100HCID 46215100, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (300 mg, 0.96 mmol), 4-methyl-1-(2-methylpropyl)-1H-pyrazol-5-amine (309 mg, 2.01 mmol), cesium carbonate (939 mg, 2.88 mmol) and DMF (5 ml). The reaction mixture was degassed under nitrogen for 10 min, and palladium (II) acetate (10.8 mg, 0.05 mmol) and BINAP (59.8 mg, 0.096 mmol) were added. The reaction mixture was heated in an oil bath at 90° C. for 5 hrs and then in a microwave at 150° C. for 40 min. Solvent was evaporated and the residue was dissolved in MeOH, filtered thru celite and thru an Acrodisc an purified further using 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 off and dried under vacuum at 40° C. for 5 hrs. LC-MS [M+H]+=429.1. 1H NMR (400 MHz, DMSO-d6) ppm 11.93 (s, 1 H) 9.48 (br. s., 1 H) 8.26 (s, 1 H) 7.94 (s, 1 H) 7.58 (d, J=7.33 Hz, 1 H) 7.44-7.51 (m, 2 H) 7.23 (s, 1 H) 7.08-7.16 (m, 1 H) 6.38 (s, 1 H) 3.70 (s, 3 H) 3.65 (d, J=7.33 Hz, 2 H) 2.03 (dt, J=13.71, 6.92 Hz, 1 H) 1.77 (s, 3 H) 0.75 (d, J=6.57 Hz, 6 H).

Workup

  1. customThe reaction mixture was degassed under nitrogen for 10 min
  2. customSolvent was evaporated
  3. dissolutionthe residue was dissolved in MeOH
  4. filtrationfiltered
  5. customevaporated
  6. additionThe brown oil residue was diluted in DMF
  7. additionwater was added
  8. filtrationIt was filtered off
  9. customdried under vacuum at 40° C. for 5 hrs

Sources & evidence

ORD record
ord-4ff02d428acb4c6995d960c0db9cdb8d
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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