1,4-Dioxane → 1-(1-Methylethyl)-N-[6-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-yl]-1H-pyrazole-5-carboxamide

HRID 244741Notes

Reaction equation

HRID 244741 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:17][C:18]([C:20]2[N:24]([CH:25]([CH3:27])[CH3:26])[N:23]=[CH:22][CH:21]=2)=[O:19])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7](C1CCCCO1)[CH:6]=2.[CH3:28][C:29]1[NH:40][C:32]2=[N:33][CH:34]=[CH:35][C:36](B(O)O)=[C:31]2[CH:30]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>CO.O>[CH3:27][CH:25]([N:24]1[C:20]([C:18]([NH:17][C:4]2[CH:3]=[C:2]([C:36]3[CH:35]=[CH:34][N:33]=[C:32]4[NH:40][C:29]([CH3:28])=[CH:30][C:31]=34)[CH:10]=[C:9]3[C:5]=2[CH:6]=[N:7][NH:8]3)=[O:19])=[CH:21][CH:22]=[N:23]1)[CH3:26]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, Tribasic2×HCID 58255796N-[6-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-1-(1-methylethyl)-1H-pyrazole-5-carboxamideHCID 59744427(2-Methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)boronic acid3×

Product 1

HCID 583563711-(1-Methylethyl)-N-[6-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-yl]-1H-pyrazole-5-carboxamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with N-[6-bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-1-(1-methylethyl)-1H-pyrazole-5-carboxamide (70 mg), (2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)boronic acid (29 mg), tripotassium phosphate (103 mg) and Solvias catalyst (9 mg), 1,4-dioxane (1.2 ml) and water (0.24 ml). The reaction was heated under microwave irradiation at 100° C. for 30 min, twice. Further (2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)boronic acid (10 mg) and Solvias catalyst (9 mg) were added and the reaction heated under microwave irradiation at 100° C. for 30 min. Again further (2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)boronic acid (11 mg), tripotassium phosphate (30 mg) and Solvias catalyst (9 mg) were added and the reaction heated under microwave irradiation at 100° C. for 30 min. The reaction was passed through a silica cartridge, preconditioned with methanol, washing with methanol. The solvent was evaporated and the residue was dissolved in DMSO:methanol (1:1, v/v) and purified by MDAP (Method A). Appropriate fractions were evaporated to dryness, dissolved in methanol (2 ml) and 2 M HCl (aq) (0.5 ml) and left at room temperature for 30 min. The solvent was evaporated, the residue was dissolved in DMSO:methanol (1:10, v/v) and passed through an aminopropyl cartridge preconditioned with methanol, washing with methanol. The solvent was evaporated and the residue was purified by MDAP (method A). Purified fractions were evaporated to dryness, dissolved in methanol, passed through an aminopropyl cartridge preconditioned with methanol, washing with methanol, then evaporated to dryness to give title compound, 19 mg.

Workup

  1. temperaturethe reaction heated under microwave irradiation at 100° C. for 30 min
  2. temperaturethe reaction heated under microwave irradiation at 100° C. for 30 min
  3. washwashing with methanol
  4. customThe solvent was evaporated
  5. dissolutionthe residue was dissolved in DMSO:methanol (1:1
  6. customv/v) and purified by MDAP (Method A)
  7. customAppropriate fractions were evaporated to dryness
  8. dissolutiondissolved in methanol (2 ml)
  9. customThe solvent was evaporated
  10. dissolutionthe residue was dissolved in DMSO:methanol (1:10
  11. washwashing with methanol
  12. customThe solvent was evaporated
  13. customthe residue was purified by MDAP (method A)
  14. customPurified fractions were evaporated to dryness
  15. dissolutiondissolved in methanol
  16. washwashing with methanol
  17. customevaporated to dryness

Sources & evidence

ORD record
ord-af660087b4ce4a07b8844f3471b80964
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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