Diisopropylethylamine → HCID 53378864, compound

HRID 2360973Notes

Reaction equation

HRID 2360973 reaction equation
[CH:1]1([CH2:7][O:8][C:9]([C:11]2([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[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:33][C@@H:34]([CH2:38][C:39]1[S:40][CH:41]=[CH:42][CH:43]=1)[C:35](O)=[O:36])=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][O:8][C:9]([C:11]2([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([C:24]#[N:25])=[CH:22][CH:23]=3)[CH2:12][CH2:13][N:14]([C:35](=[O:36])[C@@H:34]([NH2:33])[CH2:38][C:39]3[S:40][CH:41]=[CH:42][CH:43]=3)[CH2:15][CH2:16]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 67384925HCID 67384925, compound

Product 1

HCID 53378864HCID 53378864, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(4-cyano-benzyl)-piperidine-4-carboxylic acid cyclohexylmethyl ester (0.377 mmol; 0.128 g) in DMF (2 mL) was added (S)-2-tert-butoxycarbonylamino-3-thiophen-2-yl-propionic acid (0.377 mmol; 0.102 g), N,N-diisopropyl-N-ethylamine (0.755 mmol; 0.134 mL) and HBTU (0.491 mmol; 0.186 g), and the resulting mixture was stirred at room temperature overnight. The resulting mixture was purified via reverse phase HPLC and the desired fractions were combined and lyophilized. The 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 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-(4-cyano-benzyl)-piperidine-4-carboxylic acid cyclohexylmethyl ester as a hydrochloride salt.

Workup

  1. customThe resulting mixture was purified via reverse phase HPLC
  2. dissolutionThe residue was dissolved in a 4 M HCl solution in 1,4-dioxane (3 mL)
  3. stirringthe resulting solution was stirred overnight at room temperature
  4. customThe solution was then evaporated
  5. customthe residue was triturated with diethyl ether
  6. customdried under vacuum

Sources & evidence

ORD record
ord-2197f868c94a4cfe848383d57f0da9ba
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

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