Pyridine-2-carbonitrile → HCID 178432372, compound

HRID 1915575Notes

Reaction equation

HRID 1915575 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][C:27]1[N:49]=[C:30]2[N:31]=[C:32]([C:41]3[CH:48]=[CH:47][C:44](C=O)=[CH:43][CH:42]=3)[C:33]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[CH:34][N:29]2[N:28]=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>[CH3:26][C:27]1[N:49]=[C:30]2[N:31]=[C:32]([C:41]3[CH:42]=[CH:43][C:44]([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:47][CH:48]=3)[C:33]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[CH:34][N:29]2[N:28]=1

Participants

9

Reactant 4

HCID 7522Pyridine-2-carbonitrileHCID 5049666Sodium triacetoxyborohydride2×HCID 22713165tert-Butyl 4-(hydrazinecarbonyl)piperidine-1-carboxylateHCID 866306814-(2-Methyl-6-phenyl[1,2,4]triazolo[1,5-a]pyrimidin-5-yl)benzaldehyde

Product 1

HCID 178432372HCID 178432372, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

8.03 ml triethylamine is added to a solution of 9.13 g 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 150 ml methanol. To this solution a solution of 7.90 g 4-(2-methyl-6-phenyl[1,2,4]triazolo[1,5-a]pyrimidin-5-yl)benzaldehyde in 150 ml DMF is added, followed by 4.14 ml glacial acetic acid and 10.65 g NaBH(OAc)3. The resulting mixture is stirred at room temperature. Five additional portions of 2 equivalents NaBH(OAc)3 are added after 1.5, 2.5, 3.5, 4.5 and 6 hours. The solvent is removed by evaporation after 8 hours and the residue is purified by chromatography on silica gel (dichloromethane/[dichloromethane+7M NH3 in methanol]). The solid residue is suspended in diethylether/methanol (9:1) and stirred at ambient temperature for 18 hours. The desired product is collected by filtration and dried.

Workup

  1. customThe solvent is removed by evaporation after 8 hours
  2. customthe residue is purified by chromatography on silica gel (dichloromethane/[dichloromethane+7M NH3 in methanol])
  3. stirringstirred at ambient temperature for 18 hours
  4. filtrationThe desired product is collected by filtration
  5. customdried

Sources & evidence

ORD record
ord-991f6d54df444182ac4fdadf928618b9
Source dataset
uspto-grants-2013_12
Patent number
US08614218B2

Reaction notes

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