Sodium Formate → HCID 86716514, compound

HRID 1501342Notes

Reaction equation

HRID 1501342 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:35]2[CH2:37][CH2:36]2)[C:5]2[N:6]([C:8]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1.C([O-])=O.[Na+]>[Pd].CN(C=O)C.O.CO>[C:29]1([C:8]2[N:6]3[N:7]=[CH:2][CH:3]=[C:4]([CH2:35][CH2:36][CH3:37])[C:5]3=[N:10][C:9]=2[C:11]2[CH:12]=[CH:13][C:14]([C:17]3([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][CH2:18]3)=[CH:15][CH:16]=2)[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

7

Reactant 2

HCID 2723810Sodium FormateHCID 86716515HCID 86716515, compound

Product 1

HCID 86716514HCID 86716514, compoundYield 93%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of tert-butyl {1-[4-(6-chloro-8-cyclopropyl-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-14.6 (0.136 g, 0.26 mmol) and 5% palladium on carbon (0.026 g) in DMF (1 mL) was added a solution of sodium formate (0.18 g, 2.6 mmol, 10.0 eq) in water (0.4 mL). The resulting mixture was stirred at 80° C. for 3 h, diluted with MeOH (10 mL) and stirred at room temperature for 1 h. The resulting solution was filtered through a membrane filter and concentrated under reduced pressure. The resulting material was purified using MPLC (Biotage Isolera; Snap 10 g cartridge, 100% hexane 2.0 min, gradient to 80% hexane/20% EtOAc 4.0 min, 80% hexane/20% EtOAc 2.5 min, gradient to 70% hexane/30% EtOAc 2.5 min, 70% hexane/30% EtOAc 9.6 min) to give tert-butyl {1-[4-(3-phenyl-8-propylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate (0.12 g, 93%):

Workup

  1. customwas prepared in a manner analgous to
  2. stirringstirred at room temperature for 1 h
  3. filtrationThe resulting solution was filtered through a membrane
  4. filtrationfilter
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting material was purified
  7. customMPLC (Biotage Isolera; Snap 10 g cartridge, 100% hexane 2.0 min, gradient to 80% hexane/20% EtOAc 4.0 min, 80% hexane/20% EtOAc 2.5 min, gradient to 70% hexane/30% EtOAc 2.5 min, 70% hexane/30% EtOAc 9.6 min)

Sources & evidence

ORD record
ord-2504c4ed1fd24c02957fd96e62414005
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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