Cyclopropylamine → N-Cyclopropyl-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 1424106Notes

Reaction equation

HRID 1424106 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.[CH:32]1([NH2:35])[CH2:34][CH2:33]1.Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH:32]1([NH:35][C:26](=[O:28])[C:25]2[CH:29]=[CH:30][C:22]([C:19]3[CH:18]=[CH:17][C:16]([C:13]4([C:10]5[N:6]6[CH2:7][CH2:8][S:9][C:3]([CH2:2][OH:1])([CH3:31])[CH2:4][C:5]6=[N:12][N:11]=5)[CH2:14][CH2:15]4)=[CH:21][CH:20]=3)=[N:23][CH:24]=2)[CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 69828CyclopropylamineHCID 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 86712954N-Cyclopropyl-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 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of the compound (150 mg, 0.344 mmol) obtained in Example 66, cyclopropylamine (119 μL, 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 purified by silica gel column chromatography (ethyl acetate:methanol=1:4) to obtain the title compound (29 mg, 18%) 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. custompurified by silica gel column chromatography (ethyl acetate:methanol=1:4)

Sources & evidence

ORD record
ord-99cbb6eb92d04bd6b6552f82b2f76e31
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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