Methanol → HCID 178511775, compound

HRID 2360989Notes

Reaction equation

HRID 2360989 reaction equation
C(OC(=O)[NH:7][C@@H:8]([CH2:35][C:36]1[S:37][CH:38]=[CH:39][CH:40]=1)[C:9]([N:11]1[CH2:16][CH2:15][C:14]([CH2:26][C:27]2C=[CH:31][CH:30]=[CH:29][C:28]=2C#N)([C:17](=[O:25])[NH:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:13][CH2:12]1)=[O:10])(C)(C)C.[CH3:42][OH:43].[OH-:44].[Na+]>O1CCCC1>[NH2:7][C@@H:8]([CH2:35][C:36]1[S:37][CH:38]=[CH:39][CH:40]=1)[C:9]([N:11]1[CH2:12][CH2:13][C:14]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)([C:17]([NH:18][C@H:19]2[CH2:20][CH2:21][C@H:22]([C:42]([OH:44])=[O:43])[CH2:23][CH2:24]2)=[O:25])[CH2:15][CH2:16]1)=[O:10]

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 67384827HCID 67384827, compound

Product 1

HCID 178511775HCID 178511775, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-{2-[4-(2-cyanobenzyl)-4-cyclohexylcarbamoyl-piperidin-1-yl]-2-oxo-1-thiophen-2-ylmethyl-ethyl}-carbamic acid tert-butyl ester (0.346 mmol; 200 mg) (prepared by reacting trans-4-amino-cyclohexanecarboxylic acid methyl ester with (S)-2-tert-butoxycarbonylamino-3-thiophen-2-yl-propionic acid), in tetrahydrofuran (1 mL) and methanol (1 mL) was added a 1M NaOH solution (0.376 mmol; 0.376 mL). The resulting mixture was stirred overnight at room temperature. The mixture was then purified via reverse phase HPLC. The desired fractions were combined and lyophilized. The resulting residue was dissolved in tetrahydrofuran (3 mL) and a 4N HCl in dioxane solution (4 mL) was added. The resulting mixture was stirred for 4 hours at room temperature and evaporated. The residue was triturated with diethyl ether to yield 4-{[1-(2-(S)-amino-3-thiophen-2-yl-propionyl)-4-phenyl-piperidine-4-carbonyl]-amino}-trans-cyclohexanecarboxylic acid as a hydrochloride salt.

Workup

  1. customThe mixture was then purified via reverse phase HPLC
  2. dissolutionThe resulting residue was dissolved in tetrahydrofuran (3 mL)
  3. additiona 4N HCl in dioxane solution (4 mL) was added
  4. stirringThe resulting mixture was stirred for 4 hours at room temperature
  5. customevaporated
  6. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-38030cb65aab420d99a4b455c912bd52
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

Loading…