Dimethylamine, hydrochloride → 6-(4-{1-[(8R)-8-(Hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)-N,N-dimethylnicotinamide

HRID 1424104Notes

Reaction equation

HRID 1424104 reaction equation
[OH:1][CH2:2][C@:3]1([CH3:31])[S:9][CH2:8][CH2:7][N:6]2[C:10]([C:13]3([C:16]4[CH:21]=[CH:20][C:19]([C:22]5[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][N:23]=5)=[CH:18][CH:17]=4)[CH2:15][CH2:14]3)=[N:11][N:12]=[C:5]2[CH2:4]1.Cl.[CH3:33][NH:34][CH3:35].Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[OH:1][CH2:2][C@:3]1([CH3:31])[S:9][CH2:8][CH2:7][N:6]2[C:10]([C:13]3([C:16]4[CH:17]=[CH:18][C:19]([C:22]5[CH:30]=[CH:29][C:25]([C:26]([N:34]([CH3:35])[CH3:33])=[O:27])=[CH:24][N:23]=5)=[CH:20][CH:21]=4)[CH2:14][CH2:15]3)=[N:11][N:12]=[C:5]2[CH2:4]1

Participants

6

Reactant 4

HCID 10473Dimethylamine, hydrochlorideHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712952HCID 86712952, compound

Product 1

HCID 714659506-(4-{1-[(8R)-8-(Hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)-N,N-dimethylnicotinamideYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of the compound (124 mg, 0.284 mmol) obtained in Example 68-1), dimethylamine hydrochloride (116 mg, 1.42 mmol), N,N-dimethylaminopyridine (3 mg, 28 μmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (163 mg, 0.852 mmol) in N,N-dimethylformamide (2.48 mL) was stirred at room temperature for 5.5 h. Saturated aqueous sodium hydrogencarbonate was added to the reaction mixture, the mixture was extracted with dichloromethane/2-propanol (4/1), and the organic layer was washed with water and dried with anhydrous sodium sulfate. Then the solvent was distilled off under reduced pressure. The residue was purified by silica gel thin layer chromatography (ethyl acetate:methanol=2:1) to obtain the title compound (85 mg, 65%) as a white solid.

Workup

  1. extractionthe mixture was extracted with dichloromethane/2-propanol (4/1)
  2. washthe organic layer was washed with water
  3. dry with materialdried with anhydrous sodium sulfate
  4. distillationThen the solvent was distilled off under reduced pressure
  5. customThe residue was purified by silica gel thin layer chromatography (ethyl acetate:methanol=2:1)

Sources & evidence

ORD record
ord-ce9b31ac168a42b28e48aed530874f48
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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