1-Piperazinecarboxylic acid, ethyl ester → HCID 178473382, compound

HRID 2403999Notes

Reaction equation

HRID 2403999 reaction equation
[NH:1]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C@H:2]([C:27](O)=[O:28])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:26])[NH:8][S:9]([C:12]1[C:24]([CH3:25])=[C:23]2[C:17]([O:18][C:19]([CH2:22]2)([CH3:21])[CH3:20])=[C:15]([CH3:16])[C:13]=1[CH3:14])(=[O:11])=[O:10].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:70]([O:72][C:73]([N:75]1[CH2:80][CH2:79][NH:78][CH2:77][CH2:76]1)=[O:74])[CH3:71]>CN(C=O)C.CCOC(C)=O.O>[CH2:70]([O:72][C:73]([N:75]1[CH2:76][CH2:77][N:78]([C:27](=[O:28])[C@@H:2]([NH:1][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:3][CH2:4][CH2:5][NH:6]/[C:7](/[NH2:26])=[N:8]/[S:9]([C:12]2[C:13]([CH3:14])=[C:15]([CH3:16])[C:17]3[O:18][C:19]([CH3:20])([CH3:21])[CH2:22][C:23]=3[C:24]=2[CH3:25])(=[O:10])=[O:11])[CH2:79][CH2:80]1)=[O:74])[CH3:71]

Participants

8

Reactant 4

HCID 84311-Piperazinecarboxylic acid, ethyl esterHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178427604HCID 178427604, compound

Product 1

HCID 178473382HCID 178473382, compoundYield 96.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of Boc-Arg(Pbf)-OH (13.3 g, 25.3 mmol) in DMF (10 mL) was added DIEA (22.0 mL, 126.5 mmol) at room temperature and stirred for 15 min The reaction mixture was then cooled to ˜5° C. and HATU (11.5 g, 30.3 mmol) was added in portions and stirred for 30 min, followed by the dropwise addition of ethyl-1-piperazine carboxylate (4.0 g, 25.3 mmol) in DMF (30 mL). After 40 min, the reaction mixture was diluted with EtOAc (400 mL) and poured in to H2O (1 L). Extracted with EtOAc (2×400 mL) and washed with H2O (800 mL), 2% H2SO4 (500 mL), H2O (2×800 mL) and brine (800 mL). Organic layer was separated, dried over MgSO4 and solvent removed in vacuo. The resultant oily residue was dried in vacuo to afford compound Y (16.4 g, 24.5 mmol) as foamy solid. LC-MS [M+H] 667.2 (C31H50N6O8S+H, calc: 667.8). Compound Y was used without further purification.

Workup

  1. stirringstirred for 30 min
  2. waitAfter 40 min
  3. extractionExtracted with EtOAc (2×400 mL)
  4. washwashed with H2O (800 mL), 2% H2SO4 (500 mL), H2O (2×800 mL) and brine (800 mL)
  5. customOrganic layer was separated
  6. dry with materialdried over MgSO4 and solvent
  7. customremoved in vacuo
  8. customThe resultant oily residue was dried in vacuo

Sources & evidence

ORD record
ord-0d13185e94f04041bf3d6ce9a076fd02
Source dataset
uspto-grants-2014_08
Patent number
US08802681B2

Reaction notes

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