Trifluoroacetic acid → HCID 67451760, compound

HRID 869160Notes

Reaction equation

HRID 869160 reaction equation
[CH3:1][C:2]1[N:3]([C:8]2[CH:9]=[CH:10][C:11]([C:14]3[N:19]=[N:18][C:17]([N:20]([CH2:28][C:29]4([C:33]5[C:38]([F:39])=[CH:37][CH:36]=[CH:35][N:34]=5)[CH2:32][CH2:31][CH2:30]4)C(=O)OC(C)(C)C)=[CH:16][CH:15]=3)=[N:12][CH:13]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:7][C:4]1[N:3]([C:8]2[CH:9]=[CH:10][C:11]([C:14]3[N:19]=[N:18][C:17]([NH:20][CH2:28][C:29]4([C:33]5[C:38]([F:39])=[CH:37][CH:36]=[CH:35][N:34]=5)[CH2:30][CH2:31][CH2:32]4)=[CH:16][CH:15]=3)=[N:12][CH:13]=2)[C:2]([CH3:1])=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67451763HCID 67451763, compound

Product 1

HCID 67451760HCID 67451760, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 20 dram vial was added tert-butyl 6-(5-(2,5-dimethyl-1H-pyrrol-1-yl)pyridin-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (245 mg, 0.5 mmol) and a 5 mL of a 50% mixture of TFA and CH2Cl2. The reaction was stirred for 15 min, concentrated, and then diluted with sodium bicarbonate (20 mL) and extracted with ethyl acetate (40 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography (60% EtOAc/hexanes) to give 91 mg (46%) of 6-(5-(2,5-dimethyl-1H-pyrrol-1-yl)pyridin-2-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine. This product was transferred to a 100 mL round bottom flask to which was added hydroxylamine hydrochloride (270 mg), triethylamine (5 mL), and ethanol (20 mL). The reaction mixture was heated to reflux overnight and then concentrated, diluted with sodium bicarbonate (20 mL) and extracted with ethyl acetate (40 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to give a crude solid that was purified by reverse phase column chromatography to afford 28 mg of 6-(5-aminopyridin-2-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine, m/z=351.2 [M+H].

Workup

  1. concentrationconcentrated
  2. additiondiluted with sodium bicarbonate (20 mL)
  3. extractionextracted with ethyl acetate (40 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude solid that
  8. customwas purified by silica gel column chromatography (60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-3610403559fc47d794e8ec24ec85ea0c
Source dataset
uspto-grants-2015_03
Patent number
US08969346B2

Reaction notes

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