1,2-Dichloroethane → HCID 86686138, compound

HRID 869187Notes

Reaction equation

HRID 869187 reaction equation
[NH2:1][CH2:2][C:3]1[S:7][C:6]([C:8]2[N:13]=[N:12][C:11]([N:14]([CH2:22][C:23]3([C:27]4[C:32]([F:33])=[CH:31][CH:30]=[CH:29][N:28]=4)[CH2:26][CH2:25][CH2:24]3)[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:10][CH:9]=2)=[N:5][CH:4]=1.[C:34](O)(=[O:37])[CH2:35][OH:36].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(OCC)(=O)C.CN(C=O)C>[F:33][C:32]1[C:27]([C:23]2([CH2:22][N:14]([C:11]3[N:12]=[N:13][C:8]([C:6]4[S:7][C:3]([CH2:2][NH:1][C:35](=[O:36])[CH2:34][OH:37])=[CH:4][N:5]=4)=[CH:9][CH:10]=3)[C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:20])[CH3:18])[CH2:26][CH2:25][CH2:24]2)=[N:28][CH:29]=[CH:30][CH:31]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757Glycolic AcidHCID 757711-HydroxybenzotriazoleHCID 68232205HCID 68232205, compound

Product 1

HCID 86686138HCID 86686138, compoundYield 73.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

t-butyl 6-(5-(aminomethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (4.8 g, 10 mmol), glycolic acid (0.9 g, 12 mmol), HOBt (1.6 g, 12 mmol), EDC (2.3 g, 12 mmol), DMF (50 mL), and TEA (5.9 mL) were added to a 250 mL round bottom flask and the reaction was heated to 60° C. and stirred for 1 h. The reaction was poured into ethyl acetate (400 mL), washed with water (3×100 mL), and the combined organic layers were separated, dried over Na2SO4, filtered, concentrated, and purified by silica gel chromatography (EtOAC/hexanes) to afford 3.9 g of t-butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-(5-((2-hydroxyacetamido)methyl)thiazol-2-yl)pyridazin-3-yl)carbamate as a white solid. This compound was dissolved in 30% TFA/CH2Cl2 (30 mL) and stirred for 1 h. The reaction was concentrated, dissolved in EtOAc (200 mL), washed with potassium carbonate (3×30 mL), concentrated, and then recrystallized with ethanol to give a white solid that was further purified with reverse phase chromatography to give 305 mg of N-((2-(6((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)thiazol-5-yl)methyl)-2-hydroxyacetamide as a white solid (M+H=429.1).

Workup

  1. washwashed with water (3×100 mL)
  2. customthe combined organic layers were separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (EtOAC/hexanes)

Sources & evidence

ORD record
ord-fceea99e104f4c1da3b1104bc62dfea8
Source dataset
uspto-grants-2015_03
Patent number
US08969346B2

Reaction notes

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