Cesium carbonate → 2-({5-Chloro-2-[(1,3-dimethyl-1H-pyrazol-4-yl)-amino]-4-pyridinyl}amino)-N-(methyloxy)benzamide

HRID 62504

Reaction equation

HRID 62504 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][N:22]1[CH:26]=[C:25]([NH2:27])[C:24]([CH3:28])=[N:23]1.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.O1CCOCC1.C1COCC1>[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:25]2[C:24]([CH3:28])=[N:23][N:22]([CH3:21])[CH:26]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 44310561,3-dimethyl-1H-pyrazol-4-amineHCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

Product 1

HCID 446095112-({5-Chloro-2-[(1,3-dimethyl-1H-pyrazol-4-yl)-amino]-4-pyridinyl}amino)-N-(methyloxy)benzamideYield 18%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22018518Dioxane tetrahydrofuranSolvent

Conditions

Temperature
140 °C

Procedure

A microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (250 mg, 0.8 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (187 mg, 1.68 mmol), cesium carbonate (783 mg, 2.4 mmol) and dioxane/THF (3:1 ml). The reaction mixture was degassed under nitrogen for 10 min and palladium (II) acetate (9 mg, 0.04 mmol) and BINAP (50 mg, 0.08 mmol) were added. The mixture was stirred in a microwave at 140° C. for 40 min. It was evaporated and the residue dissolved in MeOH was filtered thru celite and thru an Acrodisc and purified further using preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid). Fractions were combined and evaporated. Ether was added to the residue and a tan precipitate crashed out. It was filtered off and dried under vacuum at 40° C. for 2 days to afford the desired product (55 mg, 18%) as a tan solid. LC-MS (ES) m/z=387.1, [M+H]+=389.1. 1H NMR (400 MHz, DMSO-d6) ppm 11.93 (br. s., 1 H) 9.51 (br. s., 1 H) 8.03 (s, 1 H) 7.96 (s, 1 H) 7.82 (s, 1 H) 7.51-7.61 (m, 3 H) 7.07-7.15 (m, 1 H) 6.68 (s, 1 H) 3.70 (d, J=4.29 Hz, 6 H) 2.07 (s, 3 H).

Workup

  1. customThe reaction mixture was degassed under nitrogen for 10 min
  2. customIt was evaporated
  3. dissolutionthe residue dissolved in MeOH
  4. filtrationwas filtered thru celite
  5. custompurified further
  6. customevaporated
  7. additionEther was added to the residue
  8. filtrationIt was filtered off
  9. customdried under vacuum at 40° C. for 2 days

Sources & evidence

ORD record
ord-582df86190044f2abe427c196f524eaf
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Linked notes

Loading…