Hydrochloric Acid → 2-({5-[(Azetidin-3-yloxy)methyl]-6-methylpyridin-2-yl}amino)-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide

HRID 385985Notes

Reaction equation

HRID 385985 reaction equation
[NH2:1][C:2]([C:4]1[CH:8]=[C:7]([C:9]2[C:14]([F:15])=[CH:13][C:12]([C:16]([OH:19])([CH3:18])[CH3:17])=[CH:11][C:10]=2[F:20])[S:6][C:5]=1[NH:21][C:22]1[N:27]=[C:26]([CH3:28])[C:25]([CH2:29][O:30][CH:31]2[CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32]2)=[CH:24][CH:23]=1)=[O:3].Cl.[OH-].[Na+]>C(#N)C>[NH:33]1[CH2:32][CH:31]([O:30][CH2:29][C:25]2[CH:24]=[CH:23][C:22]([NH:21][C:5]3[S:6][C:7]([C:9]4[C:10]([F:20])=[CH:11][C:12]([C:16]([OH:19])([CH3:18])[CH3:17])=[CH:13][C:14]=4[F:15])=[CH:8][C:4]=3[C:2]([NH2:1])=[O:3])=[N:27][C:26]=2[CH3:28])[CH2:34]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59525770tert-Butyl 3-{[6-({3-(aminocarbonyl)-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-thienyl}amino)-2-methylpyridin-3-yl]methoxy}azetidine-1-carboxylate

Product 1

HCID 595261642-({5-[(Azetidin-3-yloxy)methyl]-6-methylpyridin-2-yl}amino)-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

tert-Butyl 3-{[6-({3-(aminocarbonyl)-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-thienyl}amino)-2-methylpyridin-3-yl]methoxy}azetidine-1-carboxylate (146 mg, 0.248 mmol) was suspended in acetonitrile (4 mL). Aqueous hydrochloric acid (3.7 mL of 1N, 3.7 mmol) was added, and the reaction was allowed to react at room temperature overnight. It was then heated to 50° C. for 5 hours. The mixture was cooled to room temperature, neutralized with 1 N aqueous sodium hydroxide and extracted with ethyl acetate (3×). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford the title compound.

Workup

  1. customto react at room temperature overnight
  2. temperatureThe mixture was cooled to room temperature
  3. extractionextracted with ethyl acetate (3×)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-69e1e6cf2a6e40b1b1a12dff171ed2f5
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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