1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 4-(1-(5-(5-Ethyl-4H-1,2,4-triazol-3-yl)-4-fluoro-2-methylbenzoyl)piperidin-4-yl)benzonitrile

HRID 541407Notes

Reaction equation

HRID 541407 reaction equation
[CH2:1]([C:3]1[NH:4][C:5]([C:8]2[C:9]([F:18])=[CH:10][C:11]([CH3:17])=[C:12]([CH:16]=2)[C:13]([OH:15])=O)=[N:6][N:7]=1)[CH3:2].CCN=C=NCCCN(C)C.Cl.Cl.[NH:32]1[CH2:37][CH2:36][CH:35]([C:38]2[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][CH:39]=2)[CH2:34][CH2:33]1>CN(C=O)C.CN(C)C1C=CN=CC=1>[CH2:1]([C:3]1[NH:4][C:5]([C:8]2[C:9]([F:18])=[CH:10][C:11]([CH3:17])=[C:12]([CH:16]=2)[C:13]([N:32]2[CH2:37][CH2:36][CH:35]([C:38]3[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][CH:39]=3)[CH2:34][CH2:33]2)=[O:15])=[N:6][N:7]=1)[CH3:2]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 178437948HCID 178437948, compound2×

Product 1

HCID 1784379414-(1-(5-(5-Ethyl-4H-1,2,4-triazol-3-yl)-4-fluoro-2-methylbenzoyl)piperidin-4-yl)benzonitrile

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a round-bottom flask was added a solution of 5-(5-ethyl-4H-1,2,4-triazol-3-yl)-4-fluoro-2-methylbenzoic acid (compound 258.1, 125 mg, 0.500 mmol, 1.00 equiv) in DMF (10 mL). EDC.HCl (143 mg, 0.750 mmol, 1.50 equiv), 4-(piperidin-4-yl)benzonitrile hydrochloride (compound 1.5, 122 mg, 0.550 mmol, 1.10 equiv), and 4-dimethylaminopyridine (183 mg, 1.50 mmol, 3.00 equiv) were added in portions. The resulting solution was stirred for 1 h at 40° C. in an oil bath, then quenched with 50 mL of NH4Cl (aq.sat.). The mixture was extracted with 40 mL of ethyl acetate and the combined organic layers were washed with 3×30 mL of NH4Cl (aq.sat.), dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 180 mg (86%) of 4-(1-(5-(5-ethyl-4H-1,2,4-triazol-3-yl)-4-fluoro-2-methylbenzoyl)piperidin-4-yl)benzonitrile as a white solid.

Workup

  1. customquenched with 50 mL of NH4Cl (aq.sat.)
  2. extractionThe mixture was extracted with 40 mL of ethyl acetate
  3. washthe combined organic layers were washed with 3×30 mL of NH4Cl (aq.sat.)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThis resulted in 180 mg (86%) of 4-(1-(5-(5-ethyl-4H-1,2,4-triazol-3-yl)-4-fluoro-2-methylbenzoyl)piperidin-4-yl)benzonitrile as a white solid

Sources & evidence

ORD record
ord-eb7fc0e0ced84087b2b4dc5f28234367
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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