HCID 86686176, compound → HCID 86686175, compound

HRID 1409768Notes

Reaction equation

HRID 1409768 reaction equation
[C:1]([N:3]1[CH2:8][CH2:7][CH:6]([N:9]([CH:23]2[CH2:25][CH2:24]2)[C:10]([C:12]2[CH:13]=[N:14][C:15]([N:18]3[CH:22]=[CH:21][N:20]=[CH:19]3)=[N:16][CH:17]=2)=[O:11])[CH2:5][CH2:4]1)#[N:2].[OH:26][NH:27][C:28](=N)[CH2:29][CH2:30][CH3:31]>C(OCC)(=O)C.O1CCCC1.[Cl-].[Zn+2].[Cl-]>[CH:23]1([N:9]([CH:6]2[CH2:5][CH2:4][N:3]([C:1]3[O:26][N:27]=[C:28]([CH2:29][CH2:30][CH3:31])[N:2]=3)[CH2:8][CH2:7]2)[C:10]([C:12]2[CH:17]=[N:16][C:15]([N:18]3[CH:22]=[CH:21][N:20]=[CH:19]3)=[N:14][CH:13]=2)=[O:11])[CH2:25][CH2:24]1

Participants

6

Reactant 2

HCID 86686176HCID 86686176, compound2×HCID 178449909HCID 178449909, compound2×

Product 1

HCID 86686175HCID 86686175, compound

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalyst2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 2-imidazol-1-yl-pyrimidine-5-carboxylic acid (1-cyano-piperidin-4-yl)-cyclopropyl-amide (50 mg, Intermediate 33) and N-hydroxy-butyramidine (30 mg) in ethyl acetate (12 mL) and tetrahydrofuran is added zinc chloride (0.64 mL, 0.7 M in tetrahydrofuran) and the mixture is stirred for two weeks. Again zinc chloride solution and N-hydroxy-butyramidine are added and stirring is continued at room temperature for 24 h. The solvents are removed in vacuo, ethanol (15 mL) and concentrated HCl solution (0.5 mL) are added and the mixture is stirred for 3 h under reflux. After removal of the solvent the residue is purified by HPLC (MeOH, H2O, ammonia) to yield the desired product. LC (method 3): tR=1.51 min; Mass spectrum (ESI+): m/z=423 [M+H]+.

Workup

  1. stirringstirring
  2. customThe solvents are removed in vacuo, ethanol (15 mL) and concentrated HCl solution (0.5 mL)
  3. additionare added
  4. stirringthe mixture is stirred for 3 h
  5. temperatureunder reflux
  6. customAfter removal of the solvent the residue
  7. customis purified by HPLC (MeOH, H2O, ammonia)

Sources & evidence

ORD record
ord-9ba2f77dcc704d918c07e52a1c4eba74
Source dataset
uspto-grants-2014_12
Patent number
US08921398B2

Reaction notes

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