Hydrochloric Acid → HCID 70817816, compound

HRID 1501357Notes

Reaction equation

HRID 1501357 reaction equation
[C:1]1([C:7]2[N:11]3[N:12]=[C:13]([O:18][CH3:19])[CH:14]=[C:15]([O:16][CH3:17])[C:10]3=[N:9][C:8]=2[C:20]2[CH:25]=[CH:24][C:23]([C:26]3([NH:30]C(=O)OC(C)(C)C)[CH2:29][CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)Cl.Cl.[OH-].[Na+]>CO>[CH3:19][O:18][C:13]1[CH:14]=[C:15]([O:16][CH3:17])[C:10]2[N:11]([C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[C:8]([C:20]3[CH:21]=[CH:22][C:23]([C:26]4([NH2:30])[CH2:27][CH2:28][CH2:29]4)=[CH:24][CH:25]=3)[N:9]=2)[N:12]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 86716520HCID 86716520, compound

Product 1

HCID 70817816HCID 70817816, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of tert-butyl (1-{4-[3-phenyl-6,8-dimethoxyimidazo[1,2-b]pyridazin-2-yl]phenyl}cyclobutyl)carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-7 (0.18 g, 0.37 mmol) in methanol (2.2 mL) and DCM (3.5 mL) was added hydrogen chloride (4 M in dioxane, 1.8 mL, 7.3 mmol, 20.0 eq), and the resulting mixture was stirred at room temperature for 20 h. The resulting mixture was added to ice water, made alkaline with aqueous sodium hydroxide (2 N), and extracted with EtOAc (3×25 mL). The combined organic phases were dried (Na2SO4) and concentrated under reduced pressure. The resulting material was purified using MPLC (Biotage Isolera; 10 g SNAP cartridge: 100% DCM 6.0 min., gradient to 95% DCM/5% MeOH 4 min., 95% DCM/5% MeOH 5 min., gradient to 90% DCM/10% MeOH 3.5 min.) to give 1-[4-(6,8-dimethyloxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutanamine (0.11 g, 79%):

Workup

  1. extractionextracted with EtOAc (3×25 mL)
  2. dry with materialThe combined organic phases were dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting material was purified
  5. customMPLC (Biotage Isolera; 10 g SNAP cartridge: 100% DCM 6.0 min., gradient to 95% DCM/5% MeOH 4 min., 95% DCM/5% MeOH 5 min., gradient to 90% DCM/10% MeOH 3.5 min.)

Sources & evidence

ORD record
ord-cb64d09bbfa64a3785e757daa2db8385
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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