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 446622Notes

Reaction equation

HRID 446622 reaction equation
[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]

Participants

3

Reactant 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

Product 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 acidYield 116.3%

Reagents, catalysts & solvents 1

HCID 204431481,4-Dioxane hydrochlorideSolvent

Procedure

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.

Workup

  1. customThe reaction mixture was evaporated to dryness

Sources & evidence

ORD record
ord-fbcc04edd558482cb7b65f29484cb79f
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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