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

HRID 1424105Notes

Reaction equation

HRID 1424105 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.[CH2:33]([NH2:35])[CH3:34].Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH2:33]([NH:35][C:26](=[O:27])[C:25]1[CH:29]=[CH:30][C:22]([C:19]2[CH:18]=[CH:17][C:16]([C:13]3([C:10]4[N:6]5[CH2:7][CH2:8][S:9][C:3]([CH2:2][OH:1])([CH3:31])[CH2:4][C:5]5=[N:12][N:11]=4)[CH2:14][CH2:15]3)=[CH:21][CH:20]=2)=[N:23][CH:24]=1)[CH3:34]

Participants

6

Reactant 4

HCID 11198Ethylamine hydrochlorideHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 867129516-(4-{1-[8-(Hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)nicotinic acid

Product 1

HCID 86712953N-ethyl-6-(4-{1-[8-(Hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)nicotinamideYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of the compound (150 mg, 0.344 mmol) obtained in Example 66, ethylamine hydrochloride (140 mg, 1.72 mmol), N,N-dimethylaminopyridine (4 mg, 34 μmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (198 mg, 1.03 mmol) in N,N-dimethylformamide (3.00 mL) was stirred at room temperature for 5 h. Saturated aqueous sodium hydrogencarbonate (100 mL) was added to the reaction mixture, the mixture was extracted with dichloromethane, and the organic layer was washed with water and dried with anhydrous sodium sulfate. Then the solvent was distilled off under reduced pressure. Diisopropyl ether was added to the residue, and the precipitate was collected by filtration and dried under reduced pressure to obtain the title compound (76 mg, 48%) as a white solid.

Workup

  1. extractionthe mixture was extracted with dichloromethane
  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. additionDiisopropyl ether was added to the residue
  6. filtrationthe precipitate was collected by filtration
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-63100136e3764e2284b7430c3582e747
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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