Hydrochloric Acid → (R)-2-((3-(3-aminopiperidin-1-yl)-6-methyl-5-oxo-1,2,4-triazin-4(5H)-yl)methyl)benzonitrile

HRID 524105

Reaction equation

HRID 524105 reaction equation
[C:1]([C:3]1[CH:31]=[CH:30][CH:29]=[CH:28][C:4]=1[CH2:5][N:6]1[C:11](=[O:12])[C:10]([CH3:13])=[N:9][N:8]=[C:7]1[N:14]1[CH2:19][CH2:18][CH2:17][C@@H:16]([NH:20]C(=O)OC(C)(C)C)[CH2:15]1)#[N:2].Cl.C([O-])(O)=O.[Na+]>ClCCl.CO>[NH2:20][C@@H:16]1[CH2:17][CH2:18][CH2:19][N:14]([C:7]2[N:6]([CH2:5][C:4]3[CH:28]=[CH:29][CH:30]=[CH:31][C:3]=3[C:1]#[N:2])[C:11](=[O:12])[C:10]([CH3:13])=[N:9][N:8]=2)[CH2:15]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 58328532(R)-tert-butyl 1-(4-(2-cyanobenzyl)-6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)piperidin-3-ylcarbamate

Product 1

HCID 53258442(R)-2-((3-(3-aminopiperidin-1-yl)-6-methyl-5-oxo-1,2,4-triazin-4(5H)-yl)methyl)benzonitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-tert-butyl 1-(4-(2-cyanobenzyl)-6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)piperidin-3-ylcarbamate (7, 13 mg) in dichloromethane (0.5 mL) was added HCl in methanol (20%) (1 mL) and the mixture was stirred at RT for 2 h. The mixture was carefully neutralized with NaHCO3 (aq, saturated), and extracted with CH2Cl2 (50 mL×3). The combined extracts were dried over Na2SO4 and concentrated to give the crude product. This was purified by column chromatography on silica gel, eluted with 92:6:2 dichloromethane-methanol-ammonia to provide (R)-2-((3-(3-aminopiperidin-1-yl)-6-methyl-5-oxo-1,2,4-triazin-4(5H)-yl)methyl)benzonitrile (8). MS: m/z, 325 (100%, M+1).

Workup

  1. extractionextracted with CH2Cl2 (50 mL×3)
  2. dry with materialThe combined extracts were dried over Na2SO4
  3. concentrationconcentrated
  4. customto give the crude product
  5. customThis was purified by column chromatography on silica gel
  6. washeluted with 92:6:2 dichloromethane-methanol-ammonia

Sources & evidence

ORD record
ord-e0423379aca04820bc6bfb5eaa778d1f
Source dataset
uspto-grants-2016_05
Patent number
US09340523B2

Linked notes

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