Pyridine → HCID 131719067, compound

HRID 1648491Notes

Reaction equation

HRID 1648491 reaction equation
[C:1]1([CH:7]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:19]=3[CH:20]=[C:21]([C:27]([NH2:29])=O)[NH:22]4)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C(Cl)[Cl:56]>O1CCOCC1.CCOCC>[ClH:56].[ClH:56].[C:27]([C:21]1[NH:22][C:23]2[C:19]([CH:20]=1)=[C:18]([O:17][CH2:16][CH2:15][CH2:14][N:11]1[CH2:10][CH2:9][N:8]([CH:7]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:13][CH2:12]1)[CH:26]=[CH:25][CH:24]=2)#[N:29]

Participants

7

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 9845Trifluoroacetic anhydrideHCID 19920072HCID 19920072, compound

Product 1

HCID 131719067HCID 131719067, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent2×

Procedure

4-[3-[4-(Diphenylmethyl)-1-piperazinyl]propoxy]indole-2-carboxamide (EXAMPLE 5, 1.45 g) and pyridine (1.18 ml) in dioxane (442) ml) is cooled to 12°. Trifluoroacetic anhydride (1.1 ml) in dioxane (8 ml) is added dropwise over 15 min (the reaction temperature remained between 12° and 14° ). The mixture is stirred for 2 hr at 20°-25°, diluted with methylene chloride and the mixture is washed with aqueous sodium bicarbonate, water and finally saline. The organic solution is dried over magnesium sulfate and concentrated to give a solid. The residue is dissolved in ether, filtered through magnesol, and the solution concentrated to give the free base of the title compound. The hydrochloride salt is prepared and recrystallized with an impurity. The solids and filtrates are combined, concentrated, and the residue partitioned between saturated sodium bicarbonate and methylene chloride to give the free base. This is chromatographed over silica gel (500 ml), eluting with methanol/methylene chloride (2.5/97.5). Twenty ml fractions are collected. Fractions 58-84 contained clean product. The hydrochloride salt is prepared from an ether solution by the addition of ethereal hydrochloric acid. Recrystallization from methanol/acetone/ether gives the title compound, mp 231°-2°. The proposed structure is supported by NMR, IR and mass spectra.

Workup

  1. customremained between 12° and 14°
  2. washthe mixture is washed with aqueous sodium bicarbonate, water and finally saline
  3. dry with materialThe organic solution is dried over magnesium sulfate
  4. concentrationconcentrated
  5. customto give a solid
  6. filtrationfiltered through magnesol
  7. concentrationthe solution concentrated

Sources & evidence

ORD record
ord-006ae846275a4f7b97dadeddf2837c8c
Source dataset
uspto-grants-1995_07
Patent number
US05436337

Reaction notes

Loading…