Hydrazine hydrate (1:1) → HCID 86597693, compound

HRID 547796Notes

Reaction equation

HRID 547796 reaction equation
[F:1][C:2]([F:52])([F:51])[C:3]1[CH:4]=[C:5]([C:13]([CH3:50])([CH3:49])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:32]3[CH2:36][CH2:35][CH2:34][C@H:33]3[CH2:37][N:38]3C(=O)C4C(=CC=CC=4)C3=O)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O.NN>C(O)C.[OH-].[Na+]>[NH2:38][CH2:37][C@@H:33]1[CH2:34][CH2:35][CH2:36][N:32]1[C:21]1[N:20]=[CH:19][C:18]([N:16]([CH3:17])[C:14](=[O:15])[C:13]([C:5]2[CH:4]=[C:3]([C:2]([F:1])([F:51])[F:52])[CH:8]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:6]=2)([CH3:50])[CH3:49])=[C:23]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH:22]=1

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 86597692HCID 86597692, compound

Product 1

HCID 86597693HCID 86597693, compoundYield 103.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of 65 mg (0.089 mmol) (S)-2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-pyrrolidin-1-yl]-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide and 7.0 mg (0.14 mmol) hydrazine hydrate in 1 ml ethanol was stirred at room temperature over night. The reaction mixture was diluted with a 1 M aqueous sodium hydroxide solution and extracted with three portions of tert-butyl methyl ether. The combined organic extracts were dried over sodium sulphate and concentrated to give 55 mg of crude (S)-N-[6-(2-aminomethyl-pyrrolidin-1-yl)-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-isobutyramide. This material was dissolved in 2 ml dichloromethane, followed by the addition of 0.013 ml (0.092 mmol) triethylamine and 0.009 ml (0.09 mmol) acetic anhydride at 0° C. The cooling bath was removed 5 min. after completed addition, and stirring was continued at room temperature over night. The reaction mixture was diluted with a 0.5 M aqueous sodium hydroxide solution and extracted with three portions of tert-butyl methyl ether. The combined organic extracts were dried over sodium sulphate and concentrated. Flash chromatography gave 44 mg (77%) of the title compound as an off-white solid.

Workup

  1. extractionextracted with three portions of tert-butyl methyl ether
  2. dry with materialThe combined organic extracts were dried over sodium sulphate
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-577116db537d44ab84cb171e84056719
Source dataset
uspto-grants-2011_05
Patent number
US07939533B2

Reaction notes

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