Hydrochloric Acid → N-[3-(7-{1-[3-(cyanomethyl)azetidin-3-yl]-1H-pyrazol-4-yl]imidazo[1,2-b]pyridazin-3-yl)phenyl]-N'-(2,2,2-trifluoroethyl)urea

HRID 407049Notes

Reaction equation

HRID 407049 reaction equation
Cl.[C:2]([CH2:4][C:5]1([N:16]2[CH:20]=[C:19]([C:21]3[CH:26]=[N:25][N:24]4[C:27]([C:30]5[CH:35]=[CH:34][CH:33]=[C:32]([NH:36][C:37]([NH:39][CH2:40][C:41]([F:44])([F:43])[F:42])=[O:38])[CH:31]=5)=[CH:28][N:29]=[C:23]4[CH:22]=3)[CH:18]=[N:17]2)[CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6]1)#[N:3].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C(Cl)Cl>[C:2]([CH2:4][C:5]1([N:16]2[CH:20]=[C:19]([C:21]3[CH:26]=[N:25][N:24]4[C:27]([C:30]5[CH:31]=[C:32]([NH:36][C:37]([NH:39][CH2:40][C:41]([F:43])([F:44])[F:42])=[O:38])[CH:33]=[CH:34][CH:35]=5)=[CH:28][N:29]=[C:23]4[CH:22]=3)[CH:18]=[N:17]2)[CH2:6][NH:7][CH2:8]1)#[N:3]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 67980094tert-butyl 3-(cyanomethyl)-3-(4-{3-[3-({[(2,2,2-trifluoro ethyl)amino]carbonyl}amino)phenyl]imidazo[1,2-b]pyridazin-7-yl}-1H-pyrazol-1-yl)azetidine-1-carboxylate

Product 1

HCID 67980375N-[3-(7-{1-[3-(cyanomethyl)azetidin-3-yl]-1H-pyrazol-4-yl]imidazo[1,2-b]pyridazin-3-yl)phenyl]-N'-(2,2,2-trifluoroethyl)urea

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

HCl in 1,4-dioxane (4.0 N, 2 mL) was added to a mixture of tert-butyl 3-(cyanomethyl)-3-(4-{3-[3-({[(2,2,2-trifluoro ethyl)amino]carbonyl}amino)phenyl]imidazo[1,2-b]pyridazin-7-yl}-1H-pyrazol-1-yl)azetidine-1-carboxylate (0.55 g, 0.92 mmol) in methylene chloride (10.0 mL). The reaction mixture was stirred at r.t. for 1 h. The mixture was adjusted to pH=8 with aqueous Na2CO3, and extracted with ethyl acetate (3×40 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with MeOH (with 5% NH3.H2O) in DCM (0-15%) to afford the desired product. LCMS (M+H)+: m/z=496.1.

Workup

  1. extractionextracted with ethyl acetate (3×40 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on a silica gel column with MeOH (with 5% NH3.H2O) in DCM (0-15%)

Sources & evidence

ORD record
ord-a14a1067e0744531866912b3029c1c8b
Source dataset
uspto-grants-2014_06
Patent number
US08754114B2

Reaction notes

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