Pyridine-2-carbonitrile → N,N,2-trimethyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine

HRID 1915607Notes

Reaction equation

HRID 1915607 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].[CH3:26][N:27]([CH3:52])[C:28]1[N:33]2[N:34]=[C:35]([CH3:37])[N:36]=[C:32]2[N:31]=[C:30]([C:38]2[CH:45]=[CH:44][C:41](C=O)=[CH:40][CH:39]=2)[C:29]=1[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=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>[CH3:52][N:27]([CH3:26])[C:28]1[N:33]2[N:34]=[C:35]([CH3:37])[N:36]=[C:32]2[N:31]=[C:30]([C:38]2[CH:45]=[CH:44][C:41]([CH2:11][N:8]3[CH2:7][CH2:6][CH:5]([C:3]4[N:25]=[C:24]([C:19]5[CH:20]=[CH:21][CH:22]=[CH:23][N:18]=5)[NH:2][N:1]=4)[CH2:10][CH2:9]3)=[CH:40][CH:39]=2)[C:29]=1[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Participants

9

Reactant 4

HCID 7522Pyridine-2-carbonitrileHCID 5049666Sodium triacetoxyborohydride2×HCID 22713165tert-Butyl 4-(hydrazinecarbonyl)piperidine-1-carboxylateHCID 866306984-[7-(Dimethylamino)-2-methyl-6-phenyl[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]benzaldehyde

Product 1

HCID 178432374N,N,2-trimethyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

0.28 ml triethylamine are added to a solution of 317 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 390 mg 4-[7-(dimethylamino)-2-methyl-6-phenyl[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]benzaldehyde in 5 ml DMF is added, followed by 0.13 ml glacial acetic acid and 445 mg NaBH(OAc)3. The resulting mixture is stirred at room temperature. Additional portions of 2 equivalents NaBH(OAc)3 are added after 1 and 2 hours. The solvent is removed by evaporation after 3 h 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 3 h
  2. customthe residue is purified by chromatography on silica gel (dichloromethane/[dichloromethane+7M NH3 in methanol])

Sources & evidence

ORD record
ord-d232693a775d4d6ca12b20dd4a9e0e7f
Source dataset
uspto-grants-2013_12
Patent number
US08614218B2

Reaction notes

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