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

HRID 2360966Notes

Reaction equation

HRID 2360966 reaction equation
[CH:1]1([CH2:7][NH:8][C:9]([C:11]2([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:20][CH:19]=3)[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(OC([NH:37][C@@H:38]([CH2:42][C:43]1[S:44][CH:45]=[CH:46][CH:47]=1)[C:39](O)=[O:40])=O)(C)(C)C.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>[CH:1]1([CH2:7][NH:8][C:9]([C:11]2([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)=[CH:22][CH:23]=3)[CH2:16][CH2:15][N:14]([C:39](=[O:40])[C@@H:38]([NH2:37])[CH2:42][C:43]3[S:44][CH:45]=[CH:46][CH:47]=3)[CH2:13][CH2:12]2)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27344843-(Thien-2-yl)-L-alanine, N-BOC protectedHCID 673848954-Biphenyl-4-ylmethyl-piperidine-4-carboxylic acid cyclohexylmethylamide

Product 1

HCID 533788601-[2-(S)-amino-3-thiophen-2-yl-propionyl]-4-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid cyclohexylmethylamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid cyclohexylmethylamide (3.98 mmol; 1.7 g) in DMF (20 mL) was added (S)-2-tert-butoxycarbonylamino-3-thiophen-2-yl-propionic acid (4.63 mmol; 1.26 g), N,N-diisopropyl-N-ethylamine (13.9 mmol; 2.46 mL) and HBTU (6.02 mmol; 2.28 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 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 cyclohexylmethylamide as a hydrochloride salt.

Workup

  1. customThe resulting mixture was then purified via reverse phase HPLC
  2. dissolutionThe 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-7fb86c01118b4d35977ba3d41417241a
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

Loading…