Methyl 3-aminopropanoate hydrochloride → 3-(5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-benzylamino)-propionic Acid Methyl Ester

HRID 11636

Reaction equation

HRID 11636 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][CH2:11][C:12]([N:14]2[CH2:19][C@H:18]([CH3:20])[N:17]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH2:16][C@H:15]2[CH3:29])=[O:13])=[C:6]([CH:9]=1)[CH:7]=O.Cl.[CH3:31][O:32][C:33](=[O:37])[CH2:34][CH2:35][NH2:36].C([BH3-])#N.[Na+]>CO.C(OCC)(=O)C.C(N(CC)CC)C.C(O)(=O)C>[CH3:31][O:32][C:33](=[O:37])[CH2:34][CH2:35][NH:36][CH2:7][C:6]1[CH:9]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=1[O:10][CH2:11][C:12]([N:14]1[CH2:19][C@H:18]([CH3:20])[N:17]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)[CH2:16][C@H:15]1[CH3:29])=[O:13]

Participants

8

Reactant 3

HCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 53673807(2R,5S)-5-Chloro-2-{2-[4-(4-fluoro-benzyl)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-benzaldehyde

Product 1

HCID 696552703-(5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-benzylamino)-propionic Acid Methyl EsterYield 38.4%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolvent2×HCID 887MethanolSolventHCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-benzaldehyde (0.075 g, 0.18 mmol) in methanol (2 mL) was added 3-amino-propionic acid methyl ester hydrochloride salt (0.063 g, 0.45 mmol) and the pH of the solution was adjusted to 5–6 with triethylamine and acetic acid. The reaction mixture was stirred at ambient temperature for 1 hour. To the resulting reaction mixture was added sodium cyanoborohydride (0.023 g, 0.36 mmol), and the pH of the solution was again adjusted to pH 5 with acetic acid and triethylamine. The reaction mixture was stirred at ambient temperature overnight, diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography on silica gel to give the title compound (0.035 g).

Workup

  1. customTo the resulting reaction mixture
  2. stirringThe reaction mixture was stirred at ambient temperature overnight
  3. washwashed with saturated aqueous sodium hydrogen carbonate
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-bc7c522e78254b1bac83549a81ef66f7
Source dataset
uspto-grants-2006_08
Patent number
US07098212B2

Linked notes

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