Triethylamine → (S)-2-Methyl-4-[4-(2-oxa-7-aza-spiro[3.5]non-7-yl)-4-oxo-butyl]-3-oxo-piperazine-1-carboxylic acid (3-chloro-phenyl)-amide

HRID 2095567Notes

Reaction equation

HRID 2095567 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][C:20]([OH:22])=O)[C:13](=[O:23])[C@@H:12]2[CH3:24])=[O:10])[CH:5]=[CH:6][CH:7]=1.ON1C=CC=CC1=O.CCN=C=NCCCN(C)C.FC(F)(F)C(O)=O.[CH2:51]1[C:54]2([CH2:59][CH2:58][NH:57][CH2:56][CH2:55]2)[CH2:53][O:52]1.C(N(CC)CC)C.OS([O-])(=O)=O.[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][C:20]([N:57]3[CH2:58][CH2:59][C:54]4([CH2:51][O:52][CH2:53]4)[CH2:55][CH2:56]3)=[O:22])[C:13](=[O:23])[C@@H:12]2[CH3:24])=[O:10])[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69975HydroxypyridinoneHCID 516920Potassium bisulfateHCID 670741184-[(S)-4-(3-chloro-phenylcarbamoyl)-3-methyl-2-oxo-piperazin-1-yl]-butyric acid2×HCID 670747192-Oxa-7-azaspiro[3.5]nonane 2,2,2-trifluoroacetate2×

Product 1

HCID 58232147(S)-2-Methyl-4-[4-(2-oxa-7-aza-spiro[3.5]non-7-yl)-4-oxo-butyl]-3-oxo-piperazine-1-carboxylic acid (3-chloro-phenyl)-amideYield 28.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A suspension of 0.035 g (0.10 mmol) of 4-[(S)-4-(3-chloro-phenylcarbamoyl)-3-methyl-2-oxo-piperazin-1-yl]-butyric acid (intermediate 19) and 0.012 g (0.11 mmol) N-hydroxy-2-pyridon in 1.5 ml of DMF was treated at 0° C. with 0.021 g (0.11 mmol) of EDCI and was naturally warmed to RT over night. A solution of 0.035 g (0.10 mmol) of 2-oxa-7-aza-spiro[3.5]nonane trifluoro-acetic acid salt (1:2) (intermediate 20) and 0.030 ml (0.30 mmol) of triethylamine in 1.5 ml of DMF was then added and the reaction was stirred for 1 h at RT. The solution was poured on aqueous 10% KHSO4 solution and extracted with Et2O (3×). The organic phases were washed with aqueous saturated NaHCO3 and aqueous 10% NaCl, dried (Na2SO4) and evaporated to give 0.013 g of the titled compound with maximal 60% purity. The aqueous phases were reextracted with EtOAc (3×), the organic phases were dried (NaSO4), evaporated and dried under reduced pressure to give 0.029 g (62%) of the titled compound as light yellow foam. MS: 463.21 (MH+, Cl).

Workup

  1. extractionextracted with Et2O (3×)
  2. washThe organic phases were washed with aqueous saturated NaHCO3 and aqueous 10% NaCl
  3. dry with materialdried (Na2SO4)
  4. customevaporated

Sources & evidence

ORD record
ord-00ef6c97ecee4e6ab956d26472ae96f0
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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