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

HRID 446619Notes

Reaction equation

HRID 446619 reaction equation
[CH2:1](O)[CH2:2]CC.Cl.Cl.[C:8]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15](=[O:35])[O:16][CH:17]1[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][N:25]([C:27](=[O:34])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][NH2:33])[CH3:26])[CH2:19][CH2:18]1.Br[C:43]1[S:44][C:45]([C:48]([O:50]CC)=[O:49])=[CH:46][N:47]=1.C(N(CC)CC)C>C(OCC)(=O)C>[CH2:1]([C:46]1[N:47]=[C:43]([NH:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][C:27]([N:25]([CH2:24][CH2:23][N:20]2[CH2:19][CH2:18][CH:17]([O:16][C:15](=[O:35])[NH:14][C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=3[C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH2:22][CH2:21]2)[CH3:26])=[O:34])[S:44][C:45]=1[C:48]([OH:50])=[O:49])[CH3:2]

Participants

6

Reactant 4

HCID 2631-ButanolHCID 8471TriethylamineHCID 3614103Ethyl 2-bromothiazole-5-carboxylateHCID 666717251-{2-[(6-Aminohexanoyl)(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate dihydrochloride

Product 1

HCID 86663484Ethyl 2-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)-1,3-thiazole-5-carboxylic acidYield 79%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

1-Butanol (3.0 mL) was added to the compound (205 mg, 0.380 mmol) obtained in Example 11c, ethyl 2-bromo-1,3-thiazole-5-carboxylate (179 mg, 0.760 mmol) and triethylamine (212 μL, 1.52 mmol), and the mixture was stirred at 160° C. for 23 hours. The mixture was left to stand for cooling, then ethyl acetate was added to dilute the mixture, and the organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution. The organic layer was dried with anhydrous magnesium sulfate, and then solvent was evaporated under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (n-hexane:ethyl acetate, 50:50→0:100, v/v) to give the title compound (186 mg; 79%) as a colorless oily substance.

Workup

  1. waitThe mixture was left
  2. temperaturefor cooling
  3. additionto dilute the mixture
  4. washthe organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution
  5. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  6. customsolvent was evaporated under reduced pressure
  7. customThe resulting residue was purified by NH silica gel column chromatography (n-hexane:ethyl acetate, 50:50→0:100, v/v)

Sources & evidence

ORD record
ord-9d893f65946e41db963ec4beee89e19b
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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