Ammonium Chloride → N-(5-{[2-({[2-(hydroxymethyl)cyclopropyl]carbonyl}amino)imidazo[1,2-b]pyridazin-6-yl]oxy}-2-methylphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide

HRID 2391425

Reaction equation

HRID 2391425 reaction equation
[Cl-].[Ca+2].[Cl-].[BH4-].[Na+].[CH3:6][N:7]1[C:11]([C:12]([NH:14][C:15]2[CH:16]=[C:17]([CH:38]=[CH:39][C:40]=2[CH3:41])[O:18][C:19]2[CH:20]=[CH:21][C:22]3[N:23]([CH:25]=[C:26]([NH:28][C:29]([CH:31]4[CH2:33][CH:32]4[C:34](OC)=[O:35])=[O:30])[N:27]=3)[N:24]=2)=[O:13])=[CH:10][C:9]([CH3:42])=[N:8]1.[Cl-].[NH4+]>O1CCCC1.C(O)C.C(OCC)(=O)C>[OH:35][CH2:34][CH:32]1[CH2:33][CH:31]1[C:29]([NH:28][C:26]1[N:27]=[C:22]2[CH:21]=[CH:20][C:19]([O:18][C:17]3[CH:38]=[CH:39][C:40]([CH3:41])=[C:15]([NH:14][C:12]([C:11]4[N:7]([CH3:6])[N:8]=[C:9]([CH3:42])[CH:10]=4)=[O:13])[CH:16]=3)=[N:24][N:23]2[CH:25]=1)=[O:30]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 57505658HCID 57505658, compound

Product 1

HCID 57505665N-(5-{[2-({[2-(hydroxymethyl)cyclopropyl]carbonyl}amino)imidazo[1,2-b]pyridazin-6-yl]oxy}-2-methylphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamideYield 20%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21873804Tetrahydrofuran ethanolSolvent2×

Procedure

To a suspension of calcium chloride (135 mg, 1.1 mmol) in tetrahydrofuran/ethanol (2/1, 1 mL) was added a solution of sodium borohydride (92 mg, 2.2 mmol) and methyl 2-({[6-(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]amino}-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]amino}carbonyl)cyclopropanecarboxylate (180 mg, 0.37 mmol) in tetrahydrofuran/ethanol (2/1, 1 mL), and the mixture was stirred at room temperature for 18 hr. Saturated aqueous ammonium chloride solution and ethyl acetate were added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate (×3). Combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0, and then methanol/ethyl acetate=0/100→5/95) to give the title compound (35 mg, 20%) as a white solid.

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate (×3)
  2. washCombined organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltrated
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0

Sources & evidence

ORD record
ord-0adeb9f7203d4ddca79052d67f2e354c
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Linked notes

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