Hydrochloric Acid → HCID 178440302, compound

HRID 1930000Notes

Reaction equation

HRID 1930000 reaction equation
C([O:4][CH2:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:15][C:16]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=3[F:38])=[C:17]([C:19]3[CH:20]=[CH:21][C:22]4[N:23]([C:25]([CH:28]([CH3:30])[CH3:29])=[N:26][N:27]=4)[N:24]=3)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])(=O)C.[OH-].[Na+].Cl>C1COCC1>[F:38][C:32]1[CH:33]=[C:34]([F:37])[CH:35]=[CH:36][C:31]=1[C:16]1[NH:15][C:14]([CH:11]2[CH2:12][CH2:13][N:8]([C:6](=[O:7])[CH2:5][OH:4])[CH2:9][CH2:10]2)=[N:18][C:17]=1[C:19]1[CH:20]=[CH:21][C:22]2[N:23]([C:25]([CH:28]([CH3:30])[CH3:29])=[N:26][N:27]=2)[N:24]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 178476480HCID 178476480, compound

Product 1

HCID 178440302HCID 178440302, compoundYield 80.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 100 mL round-bottomed flask equipped with rubber septum and nitrogen inlet needle was charged with 2-(4-(5-(2,4-difluorophenyl)-4-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-oxoethyl acetate (0.145 g, 0.277 mmol, prepared using General Procedure T from 6-(3-(2,4-difluorophenyl)-2-(piperidin-4-yl)-1H-imidazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (Example #Q.1.2) and acetoxyacetyl chloride) in THF (5.0 mL). A 2.5M aqueous NaOH solution (0.274 mL, 0.685 mmol) was added dropwise via syringe to give a yellow solution. The reaction mixture was stirred at about ambient temperature for about 20 min. Additional 2.5M aqueous NaOH (0.274 mL, 0.685 mmol) was added dropwise via syringe. The reaction mixture was stirred at about ambient temperature for about 1 h. The solution was acidified with 1N HCl to about pH 5. The reaction mixture was partitioned between DCM and water. The layers were separated and the organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography using DCM/MeOH (gradient, 1:0 to 9:1) to provide the title compound (0.107 g, 80%): LC/MS (Table 1, Method b) Rt=1.7 min; MS m/z: 482.2 (M+H)+.

Workup

  1. customA 100 mL round-bottomed flask equipped with rubber septum and nitrogen inlet needle
  2. customto give a yellow solution
  3. stirringThe reaction mixture was stirred at about ambient temperature for about 1 h
  4. customThe reaction mixture was partitioned between DCM and water
  5. customThe layers were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-13d4cdfc71364d3f8736dc6b5edecb84
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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