tert-Butyl 2-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)-4-methyl-1,3-thiazole-5-carboxylate → 2-({6-[(2-{4-[(Biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)-4-methyl-1,3-thiazole-5-carboxylic acid

HRID 446622Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 446622
[C:1]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][N:19]([CH3:41])[C:20](=[O:40])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:27]2[S:28][C:29]([C:33]([O:35]C(C)(C)C)=[O:34])=[C:30]([CH3:32])[N:31]=2)[CH2:13][CH2:12]1)=[O:9]>Cl.O1CCOCC1>[C:1]1([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:12][CH2:13][N:14]([CH2:17][CH2:18][N:19]([CH3:41])[C:20](=[O:40])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:27]2[S:28][C:29]([C:33]([OH:35])=[O:34])=[C:30]([CH3:32])[N:31]=2)[CH2:15][CH2:16]1)=[O:9]

Komponenten

3

Edukt 1

HCID 86663486tert-Butyl 2-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)-4-methyl-1,3-thiazole-5-carboxylate

Produkt 1

HCID 866634852-({6-[(2-{4-[(Biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)-4-methyl-1,3-thiazole-5-carboxylic acidAusbeute 116,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 204431481,4-Dioxane hydrochlorideLösungsmittel

Versuchsvorschrift

A 4 N hydrochloric acid-dioxane solution (10 mL) was added to the compound (66 mg, 0.099 mmol) obtained in Example 105a, and the mixture was stirred at room temperature for 18 hours. The reaction mixture was evaporated to dryness to give crude 2-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)-4-methyl-1,3-thiazole-5-carboxylic acid (70 mg). The resulting crude carboxylic acid (70 mg) and the compound (98 mg, 0.126 mmol) obtained in Example 1k were dissolved in dichloromethane (4 mL), and triethylamine (30 μL, 0.218 mmol) was added. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (38 mg, 0.198 mmol) was added under ice cooling, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate, and the organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated sodium chloride solution. The organic layer was dried with anhydrous magnesium sulfate, then the solvent was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel chromatography (ethyl acetate:methanol, 100:0→90:10, v/v) and by reverse phase preparative chromatography (Waters Corporation; XBridge Prep C18 OBD column, 30 mm ID×150 mm, 5 μm; 0.1% [w/v] aqueous ammonium formate solution:acetonitrile, 50:50->30:70) to give a free form (56 mg; yield, 41%) of the title compound as a white solid.

Aufarbeitung

  1. customThe reaction mixture was evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-fbcc04edd558482cb7b65f29484cb79f
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08476253B2

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