N-Methylethylamine → 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)-N-methyl nicotinamide

HRID 1424119Notes

Reaction equation

HRID 1424119 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]([OH:28])=O)=[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.[CH2:32]([NH:34][CH3:35])[CH3:33].Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH2:32]([N:34]([CH3:35])[C:26](=[O:28])[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)[CH3:33]

Participants

6

Reactant 4

HCID 12219N-MethylethylamineHCID 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 86712966N-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)-N-methyl nicotinamideYield 8.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of the compound (200 mg, 0.458 mmol) obtained in Example 66, ethylmethylamine (197 μL, 2.29 mmol), N,N-dimethylaminopyridine (6 mg, 46 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (264 mg, 1.37 mmol) in N,N-dimethylformamide (4.00 mL) was stirred at room temperature for 14 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. The residue was purified by preparative TLC (dichloromethane:methanol=9:1) to obtain the title compound (18 mg, 8%) as a brown 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. customThe residue was purified by preparative TLC (dichloromethane:methanol=9:1)

Sources & evidence

ORD record
ord-fedb12ebcad24dd0b783434e7d72f30e
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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