Sodium Carbonate → HCID 53378976, compound

HRID 2360974Notes

Reaction equation

HRID 2360974 reaction equation
C(OC(=O)[NH:7][C@@H:8]([CH2:34][C:35]1[S:36][CH:37]=[CH:38][CH:39]=1)[C:9]([N:11]1[CH2:16][CH2:15][C:14]([C:25](=[O:33])[NH:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)([CH2:17][C:18]2[CH:23]=[CH:22][C:21](I)=[CH:20][CH:19]=2)[CH2:13][CH2:12]1)=[O:10])(C)(C)C.[CH3:41][O:42][C:43]1[CH:44]=[C:45](B(O)O)[CH:46]=[CH:47][CH:48]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[CH:27]1([NH:26][C:25]([C:14]2([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([C:45]4[CH:46]=[CH:47][CH:48]=[C:43]([O:42][CH3:41])[CH:44]=4)=[CH:22][CH:23]=3)[CH2:15][CH2:16][N:11]([C:9](=[O:10])[C@@H:8]([NH2:7])[CH2:34][C:35]3[S:36][CH:37]=[CH:38][CH:39]=3)[CH2:12][CH2:13]2)=[O:33])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734370(3-Methoxyphenyl)boronic acidHCID 67418449HCID 67418449, compound

Product 1

HCID 53378976HCID 53378976, compound

Reagents, catalysts & solvents 3

HCID 178454861HCID 178454861, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-{2-[4-cyclohexylcarbamoyl-4-(4-iodo-benzyl)-piperidin-1-yl]-2-oxo-1-thiophen-2-ylmethyl-ethyl}-carbamic acid tert-butyl ester 1d (0.221 mmol; 0.15 g) (prepared as described in Example 1 above, substituting 4-iodobenzylbromide for 4-biphenylmethyl bromide and cyclohexylamine for cyclohexylmethylamine) and 3-methoxyphenylboronic acid (0.265 mmol; 0.04 g) in dioxane (2 mL) was added a 10% solution of sodium carbonate in water (0.53 mL), followed by 1,1′-bis-(di-t-butylphosphino)-ferrocene palladium dichloride (0.011 mmol; 7.2 mg). The resulting mixture was heated in sealed tube at 100° C. for 3 hrs. The resulting mixture was allowed to cool to room temperature and then purified via reverse phase HPLC. The desired fractions were collected and lyophilized. The resulting residue was dissolved in a 4 M HCl solution in 1,4-dioxane (3 mL) and the resulting solution was stirred overnight at room temperature. The resulting solution was then evaporated, and the residue was triturated with diethyl ether and dried under vacuum to yield 1-(2-(S)-amino-3-thiophen-2-yl-propionyl)-4-(3′-methoxy-biphenyl-4-ylmethyl)-piperidine-4-carboxylic acid cyclohexylamide as a hydrochloride salt.

Workup

  1. temperatureto cool to room temperature
  2. custompurified via reverse phase HPLC
  3. customThe desired fractions were collected
  4. dissolutionThe resulting residue was dissolved in a 4 M HCl solution in 1,4-dioxane (3 mL)
  5. customThe resulting solution was then evaporated
  6. customthe residue was triturated with diethyl ether
  7. customdried under vacuum

Sources & evidence

ORD record
ord-53998d1887a1428fb4d993615f49dd25
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

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