Hydrochloric Acid → HCID 70818125, compound

HRID 1501358Notes

Reaction equation

HRID 1501358 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[N:5]([C:9]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4([NH:22]C(=O)OC(C)(C)C)[CH2:21][CH2:20][CH2:19]4)=[CH:14][CH:13]=3)[N:11]=2)[N:6]=[CH:7][CH:8]=1.Cl.[OH-].[Na+].O>CO.C(Cl)Cl.CC#N>[NH3:5].[CH3:1][O:2][C:3]1[C:4]2[N:5]([C:9]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[C:10]([C:12]3[CH:13]=[CH:14][C:15]([C:18]4([NH2:22])[CH2:19][CH2:20][CH2:21]4)=[CH:16][CH:17]=3)[N:11]=2)[N:6]=[CH:7][CH:8]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 86716499HCID 86716499, compound

Product 2

HCID 222AmmoniaHCID 70818125HCID 70818125, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl {1-[4-(8-methoxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-11 (0.055 g, 0.12 mmol) in a mixture of MeOH (0.7 mL) and DCM (1.1 mL) was added a concentrated aqueous HCl solution (approximately 12 N, 0.6 mL). The resulting mixture was stirred at room temperature for 60 h, then poured onto ice water (15 mL). The resulting mixture was made basic with a 2 N NaOH solution, then was extracted with EtOAc (3×20 mL). The combined organic phases were dried (Na2SO4 anh.) and concentrated under reduced pressure. The resulting oil (34 mg) was purified using preparative HPLC (Agilent Prep 1200 equipped with 2× Prep Pump, DLA, MWD, ELSD and Prep FC using an XBrigde C18 5 μm 100×30 mm column; gradient from 70% water with 0.2% NH3/30% CH3CN to 40% water with 0.2% NH3/60% CH3CN over 17.5 min, gradient from 40% water with 0.2% NH3/60% CH3CN to 100% CH3CN over 2.5 min) to give 1-[4-(8-methoxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutanamine (0.021 g, 48% yield): UPLC-MS (Method 3): RT=1.18 min; m/z (rel intensity) 371 (30, (M+H)+).

Workup

  1. additionpoured onto ice water (15 mL)
  2. extractionwas extracted with EtOAc (3×20 mL)
  3. dry with materialThe combined organic phases were dried (Na2SO4 anh.)
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting oil (34 mg) was purified
  6. customequipped with 2× Prep Pump, DLA, MWD, ELSD and Prep FC
  7. waitgradient from 70% water with 0.2% NH3/30% CH3CN to 40% water with 0.2% NH3/60% CH3CN over 17.5 min

Sources & evidence

ORD record
ord-189991149a4d422188f10c89e6be84aa
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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