Cesium carbonate → HCID 46215099, compound

HRID 62506Notes

Reaction equation

HRID 62506 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.[CH2:21]([N:23]1[C:27]([NH2:28])=[C:26]([CH3:29])[CH:25]=[N:24]1)[CH3:22].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:28][C:27]2[N:23]([CH2:21][CH3:22])[N:24]=[CH:25][C:26]=2[CH3:29])=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 224566581-Ethyl-4-methyl-1H-pyrazol-5-amineHCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

Product 1

HCID 46215099HCID 46215099, 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), 1-ethyl-4-methyl-1H-pyrazol-5-amine (253 mg, 2.01 mmol), cesium carbonate (939 mg, 2.88 mmol) and DMF (7 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 50 min. It was evaporated and the residue was dissolved in MeOH, filtered thru celite and thru an Acrodisc and purified further 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 off and dried under vacuum at 40° C. for 5 hrs. LC-MS [M+H]+=401.1. 1H NMR (400 MHz, DMSO-d6) ppm 11.92 (s, 1 H) 9.48 (br. s., 1 H) 8.27 (s, 1 H) 7.94 (s, 1 H) 7.59 (d, J=7.58 Hz, 1 H) 7.51 (d, J=3.54 Hz, 2 H) 7.22 (s, 1 H) 7.09-7.16 (m, 1 H) 6.40 (s, 1 H) 3.85 (q, J=7.33 Hz, 2 H) 3.71 (s, 3 H) 1.79 (s, 3 H) 1.21 (t, J=7.20 Hz, 3 H).

Workup

  1. customThe reaction mixture was degassed under nitrogen for 10 min
  2. customIt was evaporated
  3. dissolutionthe residue was dissolved in MeOH
  4. filtrationfiltered
  5. custompurified further on preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid)
  6. customevaporated
  7. additionThe brown oil residue was diluted in DMF
  8. additionwater was added
  9. filtrationIt was filtered off
  10. customdried under vacuum at 40° C. for 5 hrs

Sources & evidence

ORD record
ord-ac17fbad583e46e7911a19e95480ed03
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Reaction notes

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