Pyridine-2-carbonitrile → HCID 178483024, compound

HRID 1915604Notes

Reaction equation

HRID 1915604 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]([CH3:51])[C:28]1[N:50]=[C:31]2[N:32]=[C:33]([C:42]3[CH:49]=[CH:48][C:45](C=O)=[CH:44][CH:43]=3)[C:34]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[CH:35][N:30]2[N:29]=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][N:27]([CH3:51])[C:28]1[N:50]=[C:31]2[N:32]=[C:33]([C:42]3[CH:43]=[CH:44][C:45]([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:48][CH:49]=3)[C:34]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[CH:35][N:30]2[N:29]=1

Participants

9

Reactant 4

HCID 7522Pyridine-2-carbonitrileHCID 5049666Sodium triacetoxyborohydride2×HCID 22713165tert-Butyl 4-(hydrazinecarbonyl)piperidine-1-carboxylateHCID 86630696HCID 86630696, compound

Product 1

HCID 178483024HCID 178483024, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

0.138 ml triethylamine are added to a solution of 207 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 10 ml methanol. To this solution a solution of 196 mg 4-[2-(dimethylamino)-6-phenyl[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]benzaldehyde in 10 ml DMF is added, followed by 0.09 ml glacial acetic acid and 242 mg NaBH(OAc)3. The resulting mixture is stirred at room temperature. Two 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 dissolved in dichloromethane and water. The phases are separated and the water phase is extracted with dichloromethane. The combined organic layers are dried over Na2SO4 and the solvent is evaporated. The crude product is purified by RP HPLC (water, 10 mM NH4COOH, pH 3.7/ACN) to yield the desired compound.

Workup

  1. customThe solvent is removed by evaporation after 3 h
  2. dissolutionthe residue is dissolved in dichloromethane
  3. customThe phases are separated
  4. extractionthe water phase is extracted with dichloromethane
  5. dry with materialThe combined organic layers are dried over Na2SO4
  6. customthe solvent is evaporated
  7. customThe crude product is purified by RP HPLC (water, 10 mM NH4COOH, pH 3.7/ACN)

Sources & evidence

ORD record
ord-f212ea07d5bc454d98e9884a53e3c707
Source dataset
uspto-grants-2013_12
Patent number
US08614218B2

Reaction notes

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