Pyridine-2-carbonitrile → HCID 178437545, compound

HRID 1915602Notes

Reaction equation

HRID 1915602 reaction equation
[NH:1]([C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11](OC(C)(C)C)=O)[CH2:7][CH2:6]1)=O)[NH2:2].[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[C:24]#[N:25].[C:26]1([C:32]2[C:33]([C:47]3[CH:54]=[CH:53][C:50](C=O)=[CH:49][CH:48]=3)=[N:34][C:35]3[N:36]([N:38]=[C:39]([C:41]#[C:42][Si](C)(C)C)[N:40]=3)[CH:37]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO.CN(C=O)C.C(O)(=O)C.C(N(CC)CC)C>[C:41]([C:39]1[N:40]=[C:35]2[N:34]=[C:33]([C:47]3[CH:54]=[CH:53][C:50]([CH2:11][N:8]4[CH2:7][CH2:6][CH:5]([C:3]5[N:25]=[C:24]([C:19]6[CH:20]=[CH:21][CH:22]=[CH:23][N:18]=6)[NH:2][N:1]=5)[CH2:10][CH2:9]4)=[CH:49][CH:48]=3)[C:32]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:37][N:36]2[N:38]=1)#[CH:42]

Participants

9

Reactant 4

HCID 7522Pyridine-2-carbonitrileHCID 5049666Sodium triacetoxyborohydride2×HCID 22713165tert-Butyl 4-(hydrazinecarbonyl)piperidine-1-carboxylateHCID 86630695HCID 86630695, compound

Product 1

HCID 178437545HCID 178437545, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

0.12 ml triethylamine are added to a solution of 137 mg 2-(5-piperidin-4H[1,2,4]triazol-3-yl)-pyridine*2HCl (prepared from tert-butyl 4-(hydrazinocarbonyl)piperidine-1-carboxylate and pyridine-2-carbonitrile according to a procedure described in U.S. Pat. No. 4,011,218 or WO2005100344) in 5 ml methanol. To this solution a solution of 150 mg 4-{6-phenyl-2-[(trimethylsilyl)ethynyl][1,2,4]triazolo[1,5-a]pyrimidin-5-yl}benzaldehyde in 5 ml DMF is added, followed by 0.057 ml glacial acetic acid and 161 mg NaBH(OAc)3. The resulting mixture is stirred at room temperature. Additional portions of 2 equivalents NaBH(OAc)3 are added after 1, 2, 4 and 6 hours. The solvent is removed by evaporation after 22 h. The residue is dissolved in methanol and potassium carbonate is added. The mixture is stirred over night. The solvent is evaporated and the residue is purified by chromatography on silica gel (dichloromethane/[dichloromethane+7M NH3 in methanol]) to yield the desired compound.

Workup

  1. customThe solvent is removed by evaporation after 22 h
  2. dissolutionThe residue is dissolved in methanol
  3. additionpotassium carbonate is added
  4. stirringThe mixture is stirred over night
  5. customThe solvent is evaporated
  6. customthe residue is purified by chromatography on silica gel (dichloromethane/[dichloromethane+7M NH3 in methanol])

Sources & evidence

ORD record
ord-fcc818abbe3f4a66ae2503329b6086df
Source dataset
uspto-grants-2013_12
Patent number
US08614218B2

Reaction notes

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