Formic Acid → 6-[4-(3,6-Dihydro-4-phenyl-1(2H)-pyridinyl)-1-butynyl]-N-methyl-3-pyridinamine

HRID 128956Notes

Reaction equation

HRID 128956 reaction equation
[C:1](OC(=O)C)(=O)C.C(O)=O.[C:11]1([C:17]2[CH2:18][CH2:19][N:20]([CH2:23][CH2:24][C:25]#[C:26][C:27]3[N:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=3)[CH2:21][CH:22]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[C:11]1([C:17]2[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][C:25]#[C:26][C:27]3[N:32]=[CH:31][C:30]([NH:33][CH3:1])=[CH:29][CH:28]=3)[CH2:19][CH:18]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 284Formic AcidHCID 7918Acetic AnhydrideHCID 100863486-[4-(3,6-Dihydro-4-phenyl-1(2H)-pyridinyl)-1-butynyl]-3-pyridinamineHCID 21226445Aluminium lithium hydride

Product 1

HCID 199601296-[4-(3,6-Dihydro-4-phenyl-1(2H)-pyridinyl)-1-butynyl]-N-methyl-3-pyridinamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
50 °C

Procedure

To 0.50 mL (6.8 mmol) of acetic anhydride is added 0.32 mL (8.4 mmol) of 88% formic acid dropwise under nitrogen. Anhydrous tetrahydrofuran (10 mL) is added, and the solution is heated at 50° C. for 2 hours. To the cooled solution is added a suspension of 6-[4-(3,6-dihydro-4-phenyl-1(2H)-pyridinyl)-1-butynyl]-3-pyridinamine (Example 20) (0.8 g, 2.6 mmol) in 10 mL of tetrahydrofuran, and the solution is stirred at room temperature for 18 hours. The mixture is concentrated in vacuo, and the residue is partitioned between dichloromethane and 5% ammonium hydroxide. The organic layer is dried and concentrated in vacuo. The residue, in 10 mL of tetrahydrofuran, is added dropwise under nitrogen to a suspension of 0.14 g (3.9 mmol) of lithium aluminum hydride in 20 mL of dry tetrahydrofuran at 0° C. The reaction mixture is stirred at 0° C. for 5 hours. The reaction is quenched by sequential addition of 0.52 mL of 10% hydrochloric acid solution, 0.52 mL of 30% sodium hydroxide solution, and 0.52 mL of water. The resulting mixture is filtered through diatomaceous earth (Celite), evaporated in vacuo, and chromatographed (silica gel, 1% methanol/99% dichloromethane) to give the title compound, containing 0.5 mol of water; mp 164.5°-165.5° C.

Workup

  1. additionTo the cooled solution is added
  2. concentrationThe mixture is concentrated in vacuo
  3. customthe residue is partitioned between dichloromethane and 5% ammonium hydroxide
  4. customThe organic layer is dried
  5. concentrationconcentrated in vacuo
  6. stirringThe reaction mixture is stirred at 0° C. for 5 hours
  7. customThe reaction is quenched by sequential addition of 0.52 mL of 10% hydrochloric acid solution, 0.52 mL of 30% sodium hydroxide solution, and 0.52 mL of water
  8. filtrationThe resulting mixture is filtered through diatomaceous earth (Celite)
  9. customevaporated in vacuo
  10. customchromatographed (silica gel, 1% methanol/99% dichloromethane)

Sources & evidence

ORD record
ord-a3aed0e3d4f74b86891cc88f37552b7d
Source dataset
uspto-grants-1995_11
Patent number
US05466698

Reaction notes

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