Hydrazine hydrate (1:1) → ((2S,3R)-2-(Aminomethyl)-3-methylpiperidin-1-yl)(5-fluoro-2-(pyrimidin-2-yl)phenyl)methanone

HRID 61177Notes

Reaction equation

HRID 61177 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:29]2[N:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[C:6]([CH:28]=1)[C:7]([N:9]1[CH2:14][CH2:13][CH2:12][C@@H:11]([CH3:15])[C@H:10]1[CH2:16][N:17]1C(=O)C2C(=CC=CC=2)C1=O)=[O:8].NN.O>CO>[NH2:17][CH2:16][C@@H:10]1[C@H:11]([CH3:15])[CH2:12][CH2:13][CH2:14][N:9]1[C:7]([C:6]1[CH:28]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[C:29]1[N:30]=[CH:31][CH:32]=[CH:33][N:34]=1)=[O:8]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 1177279542-(((2S,3R)-1-(5-Fluoro-2-(pyrimidin-2-yl)benzoyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione

Product 1

HCID 117728469((2S,3R)-2-(Aminomethyl)-3-methylpiperidin-1-yl)(5-fluoro-2-(pyrimidin-2-yl)phenyl)methanoneYield 93.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A stirred solution of the product of Step 228b (274 mg, 0.590 mmol) and NH2NH2.H2O (114 mg, 2.27 mmol) in MeOH (10 mL) was heated to reflux for 2.5 h. After this time, the reaction mixture was cooled to rt then concentrated under reduced pressure. The resulting residue was triturated with a mixture of CH2Cl2/hexanes (1:1) and the solid was filtered off. The filtrate was concentrated under reduced pressure and dried under high vacuum to afford the title compound as a white foam (182 mg, 93%). ESI MS (M+H) 329.

Workup

  1. temperatureto reflux for 2.5 h
  2. concentrationthen concentrated under reduced pressure
  3. customThe resulting residue was triturated with a mixture of CH2Cl2/hexanes (1:1)
  4. filtrationthe solid was filtered off
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-486e596bb6654cde8e9e284c04c417e2
Source dataset
uspto-grants-2016_09
Patent number
US09440982B2

Reaction notes

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