Hydrazine hydrate (1:1) → (1S,2S,5R)-(2-aminomethyl-7,7-difluoro-3-aza-bicyclo[3.3.0]-oct-3-yl)-(2-methyl-5-m-tolyl-thiazol-4-yl)-methanone

HRID 425807

Reaction equation

HRID 425807 reaction equation
[CH3:1][C:2]1[S:3][C:4]([C:31]2[CH:32]=[C:33]([CH3:37])[CH:34]=[CH:35][CH:36]=2)=[C:5]([C:7]([N:9]2[CH2:16][C@H:15]3[C@H:11]([CH2:12][C:13]([F:18])([F:17])[CH2:14]3)[C@H:10]2[CH2:19][N:20]2C(=O)C3C(=CC=CC=3)C2=O)=[O:8])[N:6]=1.O.NN>CCO>[NH2:20][CH2:19][C@H:10]1[N:9]([C:7]([C:5]2[N:6]=[C:2]([CH3:1])[S:3][C:4]=2[C:31]2[CH:32]=[C:33]([CH3:37])[CH:34]=[CH:35][CH:36]=2)=[O:8])[CH2:16][C@H:15]2[C@@H:11]1[CH2:12][C:13]([F:18])([F:17])[CH2:14]2

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 66703707(1S,2S,5R)-2-[3-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-7,7-difluoro-3-azabicyclo[3.3.0]oct-2-ylmethyl)-isoindole-1,3-dione

Product 1

HCID 59411607(1S,2S,5R)-(2-aminomethyl-7,7-difluoro-3-aza-bicyclo[3.3.0]-oct-3-yl)-(2-methyl-5-m-tolyl-thiazol-4-yl)-methanoneYield 92.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of (1S,2S,5R)-2-[3-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-7,7-difluoro-3-azabicyclo[3.3.0]oct-2-ylmethyl)-isoindole-1,3-dione (130 mg), hydrazine monohydrate (0.078 mL) in EtOH (10 mL) was stirred at reflux for 1 h 45. After cooling to RT, the reaction mixture was concentrated in vacuo, dissolved in DCM, washed twice with water, brine, dried (MgSO4), filtered and concentrated to yield the title compound (90 mg, 92%) as a colorless oil which was used for the next step without further purification. LC-MS: tR=0.79 min; [M+H]+=392

Workup

  1. temperatureat reflux for 1 h 45
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. dissolutiondissolved in DCM
  4. washwashed twice with water, brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-7591001438a54518a6eb4305f0d71b60
Source dataset
uspto-grants-2012_01
Patent number
US08106215B2

Linked notes

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