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

HRID 1472549

Reaction equation

HRID 1472549 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[C:26]([CH3:27])=[C:25]([NH2:28])[CH:24]=[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:28][C:25]2[CH:24]=[N:23][N:22]([CH3:21])[C:26]=2[CH3:27])=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5738131,5-dimethyl-1H-pyrazol-4-amineHCID 634876Binap, (A+-)-HCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

Product 1

HCID 462150972-({5-Chloro-2-[(1,5-dimethyl-1H-pyrazol-4-yl)amino]-4-pyridinyl}amino)-N-(methyloxy)benzamideYield 7.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22018518Dioxane tetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

A microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (200 mg, 0.64 mmol), 1,5-dimethyl-1H-pyrazol-4-amine (142 mg, 1.28 mmol), cesium carbonate (626 mg, 1.92 mmol) and dioxane/THF (3:1 ml). The reaction mixture was degassed under nitrogen for 10 min and palladium (II) acetate (5.8 mg, 0.03 mmol) and BINAP (40 mg, 0.06 mmol) were added. The tube was sealed and the mixture was stirred in an oil bath at 150° C. overnight. The dark brown solution was filtered thru celite and evaporated. It was dissolved in MeOH and filtered thru an Acrodisc (Pall Corporation; www.pall.com) and further purified on preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid). The dark brown oil residue was dissolved in DMF and water was slowly added. A tan precipitate crashed out and was filtered off and dried under vacuum at 40° C. for 2 hrs to afford the desired product (18 mg, 7.3%) as a tan solid. LC-MS [M+H]+=387.1, 389.1. 1H NMR (400 MHz, DMSO-d6) d ppm 11.91 (br. s., 1 H) 9.41 (br. s., 1 H) 7.85-7.98 (m, 2 H) 7.49-7.59 (m, 3 H) 7.42 (br. s., 1 H) 7.07-7.13 (m, 1 H) 6.50 (br. s., 1 H) 3.69 (d, J=10.36 Hz, 6 H) 2.11 (s, 3 H).

Workup

  1. customThe reaction mixture was degassed under nitrogen for 10 min
  2. customThe tube was sealed
  3. filtrationThe dark brown solution was filtered thru celite
  4. customevaporated
  5. dissolutionIt was dissolved in MeOH
  6. filtrationfiltered
  7. customfurther purified on preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid)
  8. dissolutionThe dark brown oil residue was dissolved in DMF
  9. additionwater was slowly added
  10. filtrationwas filtered off
  11. customdried under vacuum at 40° C. for 2 hrs

Sources & evidence

ORD record
ord-dde0a3e7dd9441daa8855824aded77eb
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Linked notes

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