Dibutyltin oxide → HCID 178511774, compound

HRID 2360988Notes

Reaction equation

HRID 2360988 reaction equation
C(OC(=O)[NH:7][CH: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]2[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][CH:28]=2)([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.C[Si]([N:46]=[N+:47]=[N-:48])(C)C.C([Sn](=O)CCCC)CCC>C(COC)OC>[CH:19]1([NH:18][C:17]([C:14]2([CH2:26][C:27]3[CH:28]=[CH:29][C:30]([C:33]4[NH:34][N:48]=[N:47][N:46]=4)=[CH:31][CH:32]=3)[CH2:15][CH2:16][N:11]([C:9](=[O:10])[C@@H:8]([NH2:7])[CH2:35][C:36]3[S:37][CH:38]=[CH:39][CH:40]=3)[CH2:12][CH2:13]2)=[O:25])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1

Participants

5

Reactant 3

HCID 61221Dibutyltin oxideHCID 78378AzidotrimethylsilaneHCID 67384606HCID 67384606, compound

Product 1

HCID 178511774HCID 178511774, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of {2-[4-(4-cyanobenzyl)-4-cyclohexylcarbamoyl-piperidin-1-yl]-2-oxo-1-thiophen-2-ylmethyl-ethyl}-carbamic acid tert-butyl ester (9.77 mmol; 5.85 g) (prepared as in Example 1, substituting 4-cyanobenzylbromide for 4-biphenylmethyl bromide and cyclohexylamine for cyclohexylmethylamine), in dimethoxyethane (3 mL) was added trimethylsilyl azide (0.67 mmol; 0.088 mL) and dibutyltin oxide (0.201 mmol; 53.15 mg). The resulting mixture was heated at 100° C. for 18 hours and then purified via reverse phase HPLC. The desired fractions were collected and lyophilized, and the residue was dissolved in THF (2 mL) and a 4N HCl solution in 1,4-dioxane (4 mL) was added. The resulting solution was stirred for 5 hours at room temperature and evaporated. The residue was triturated with diethyl ether and dried under vacuum to yield 1-(2-(S)-amino-3-thiophen-2-yl-propionyl)-4-[4-(1H-tetrazol-5-yl)-benzyl]-piperidine-4-carboxylic acid cyclohexylamide as a hydrochloride salt.

Workup

  1. custompurified via reverse phase HPLC
  2. customThe desired fractions were collected
  3. dissolutionthe residue was dissolved in THF (2 mL)
  4. additiona 4N HCl solution in 1,4-dioxane (4 mL) was added
  5. customevaporated
  6. customThe residue was triturated with diethyl ether
  7. customdried under vacuum

Sources & evidence

ORD record
ord-f3a2cd00bd0040048df7206e208d5a52
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

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