Morpholine → [8-Methyl-3-(1-{4-[5-(morpholin-4-ylcarbonyl)pyridin-2-yl]phenyl}cyclopropyl)-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl]methanol

HRID 1424120Notes

Reaction equation

HRID 1424120 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.[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:31][C:3]1([CH2:2][OH:1])[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:32]6[CH2:37][CH2:36][O:35][CH2:34][CH2:33]6)=[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 8083MorpholineHCID 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 86712967[8-Methyl-3-(1-{4-[5-(morpholin-4-ylcarbonyl)pyridin-2-yl]phenyl}cyclopropyl)-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl]methanolYield 29.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of the compound (200 mg, 0.458 mmol) obtained in Example 66, morpholine (200 μL, 2.29 mmol), N,N-dimethylaminopyridine (6 mg, 46 μmol), 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 (69 mg, 11%) 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. customThe residue was purified by preparative TLC (dichloromethane:methanol=9:1)

Sources & evidence

ORD record
ord-dd1ba778418b47feb54e7ca146e9bd38
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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