Diisopropylethylamine → 1-[2-(S)-amino-3-thiophen-2-yl-propionyl]-4-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid(tetrahydro-pyran-4-ylmethyl)-amide

HRID 2360969Notes

Reaction equation

HRID 2360969 reaction equation
[C:1]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:6]=[CH:5][C:4]([CH2:7][C:8]2([C:31]([OH:33])=O)[CH2:13][CH2:12][N:11]([C:14](=[O:30])[C@@H:15]([NH:22]C(OC(C)(C)C)=O)[CH2:16][C:17]3[S:18][CH:19]=[CH:20][CH:21]=3)[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.[O:40]1[CH2:45][CH2:44][CH:43]([CH2:46][NH2:47])[CH2:42][CH2:41]1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[O:40]1[CH2:45][CH2:44][CH:43]([CH2:46][NH:47][C:31]([C:8]2([CH2:7][C:4]3[CH:3]=[CH:2][C:1]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[CH:6][CH:5]=3)[CH2:13][CH2:12][N:11]([C:14](=[O:30])[C@@H:15]([NH2:22])[CH2:16][C:17]3[S:18][CH:19]=[CH:20][CH:21]=3)[CH2:10][CH2:9]2)=[O:33])[CH2:42][CH2:41]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27732104-AminomethyltetrahydropyranHCID 673846684-biphenyl-4-ylmethyl-1-[2-(S)-tert-butoxycarbonylamino-3-thiophen-2-yl-propionyl]-piperidine-4-carboxylic acid

Product 1

HCID 533788621-[2-(S)-amino-3-thiophen-2-yl-propionyl]-4-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid(tetrahydro-pyran-4-ylmethyl)-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-biphenyl-4-ylmethyl-1-[2-(S)-tert-butoxycarbonylamino-3-thiophen-2-yl-propionyl]-piperidine-4-carboxylic acid (0.24 mmol; 0.13 g) in DMF (5 mL) was added C-(tetrahydro-pyran-4-yl)-methylamine (0.28 mmol; 0.027 g), N,N-diisopropyl-N-ethylamine (0.48 mmol; 0.084 mL) and HBTU (0.28 mmol; 0.108 g), and the resulting mixture was stirred at room temperature overnight. The resulting mixture was then purified via reverse phase HPLC and the desired fractions were combined and lyophilized. The resulting residue was dissolved in THF (5 mL) and a 4N HCl solution in 1,4-dioxane (15 mL) was added. The resulting solution was stirred for 7 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-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid(tetrahydro-pyran-4-ylmethyl)-amide as a hydrochloride salt.

Workup

  1. customThe resulting mixture was then purified via reverse phase HPLC
  2. dissolutionThe resulting residue was dissolved in THF (5 mL)
  3. additiona 4N HCl solution in 1,4-dioxane (15 mL) was added
  4. stirringThe resulting solution was stirred for 7 hours at room temperature
  5. customevaporated
  6. customThe residue was triturated with diethyl ether
  7. customdried under vacuum

Sources & evidence

ORD record
ord-49d7f68a454344bdb0405c8d37e53f3d
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

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