Hydrazine hydrate (1:1) → ((2S,3R)-2-(Aminomethyl)-3-methylpiperidin-1-yl)(2-fluoro-6-(pyrimidin-2-yl)phenyl)methanone

HRID 61200Notes

Reaction equation

HRID 61200 reaction equation
[F:1][C:2]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]2[N:34]=[CH:33][CH:32]=[CH:31][N:30]=2)[C:3]=1[C:4]([N:6]1[CH2:11][CH2:10][CH2:9][C@@H:8]([CH3:12])[C@H:7]1[CH2:13][N:14]1C(=O)C2C(=CC=CC=2)C1=O)=[O:5].NN.O>CO>[NH4+:6].[OH-:5].[NH2:14][CH2:13][C@@H:7]1[C@H:8]([CH3:12])[CH2:9][CH2:10][CH2:11][N:6]1[C:4]([C:3]1[C:25]([C:29]2[N:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[CH:26][CH:27]=[CH:28][C:2]=1[F:1])=[O:5]

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 1177278022-(((2S,3R)-1-(2-Fluoro-6-(pyrimidin-2-yl)benzoyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione

Product 2

HCID 14923Ammonium HydroxideHCID 117727763((2S,3R)-2-(Aminomethyl)-3-methylpiperidin-1-yl)(2-fluoro-6-(pyrimidin-2-yl)phenyl)methanoneYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A stirred solution of the product of Step 240a (99 mg, 0.216 mmol) and NH2NH2.H2O (43 mg, 0.864 mmol) in MeOH (10 mL) was heated to reflux for 2 h. The reaction mixture was cooled to rt then concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel eluting with CH2Cl2/MeOH/conc. NH4OH (100:0:0 to 90:9:1) to afford the title compound as a white foam (33 mg, 45%). ESI MS (M+H) 329.

Workup

  1. temperatureto reflux for 2 h
  2. concentrationthen concentrated under reduced pressure
  3. customThe resulting residue was purified by flash column chromatography on silica gel eluting with CH2Cl2/MeOH/conc

Sources & evidence

ORD record
ord-dce39c3cbfd548f19bea37aba194ae39
Source dataset
uspto-grants-2016_09
Patent number
US09440982B2

Reaction notes

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