1,4-Dioxane hydrochloride → HCID 67084710, compound

HRID 1627576Notes

Reaction equation

HRID 1627576 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:24]=[N:23][C:22]([NH2:25])=[C:21]([O:26][CH:27]([C:29]4[C:34]([Cl:35])=[CH:33][CH:32]=[C:31]([F:36])[C:30]=4[Cl:37])[CH3:28])[N:20]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.[O:39]1CCOCC1>C(Cl)Cl>[C:27]([OH:39])(=[O:26])[CH3:29].[Cl:37][C:30]1[C:31]([F:36])=[CH:32][CH:33]=[C:34]([Cl:35])[C:29]=1[C@H:27]([O:26][C:21]1[C:22]([NH2:25])=[N:23][CH:24]=[C:19]([C:17]2[CH:16]=[N:15][N:14]([CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)[CH:18]=2)[N:20]=1)[CH3:28]

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 67084592HCID 67084592, compound

Product 1

HCID 67084710HCID 67084710, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(4-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (265 mg, 0.48 mmol) in CH2Cl2 was added 4N HCl/dioxane (4 mL). The mixture was stirred at ambient temperature for one hour. After evaporation, the residue was dissolved in methanol (2.5 mL), and was purified on a reverse phase C-18 reparative HPLC eluting with acetonitrile/water containing 0.1% acetic acid with a linear gradient of 10%-40%. After lyophilization, 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyrazin-2-ylamine acetate was obtained as a white solid (125 mg, 51% yield).

Workup

  1. customAfter evaporation
  2. dissolutionthe residue was dissolved in methanol (2.5 mL)
  3. customwas purified on a reverse phase C-18 reparative HPLC
  4. washeluting with acetonitrile/water containing 0.1% acetic acid with a linear gradient of 10%-40%

Sources & evidence

ORD record
ord-790b015d828243e7850aa37ad44b33fc
Source dataset
uspto-grants-2014_07
Patent number
US08785632B2

Reaction notes

Loading…