Cesium carbonate → 4-((S)-5-Carboxy-2-{[5-(1-ethoxycarbonyl-cyclobutoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-pentanoyl)-piperazine-1-carboxylic acid ethyl ester

HRID 1908624Notes

Reaction equation

HRID 1908624 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:39])[C@@H:13]([NH:24][C:25]([C:27]2[CH:31]=[C:30]([OH:32])[N:29]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[N:28]=2)=[O:26])[CH2:14][CH2:15][CH2:16][C:17]([O:19]C(C)(C)C)=[O:18])[CH2:8][CH2:7]1)=[O:5])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:46]([O:48][C:49]([C:51]1(Br)[CH2:54][CH2:53][CH2:52]1)=[O:50])[CH3:47]>CN(C=O)C.O>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:39])[C@@H:13]([NH:24][C:25]([C:27]2[CH:31]=[C:30]([O:32][C:51]3([C:49]([O:48][CH2:46][CH3:47])=[O:50])[CH2:54][CH2:53][CH2:52]3)[N:29]([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[N:28]=2)=[O:26])[CH2:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18])[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 97595Ethyl 1-bromocyclobutanecarboxylateHCID 178473381HCID 178473381, compound

Product 1

HCID 441258634-((S)-5-Carboxy-2-{[5-(1-ethoxycarbonyl-cyclobutoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-pentanoyl)-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 100 mg of 4-{(S)-5-tert-Butoxycarbonyl-2-[(5-hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-pentanoyl}-piperazine-1-carboxylic acid ethyl ester in 2 ml of DMF, 119 mg of cesium carbonate and 76 mg of 1-Bromo-cyclobutanecarboxylic acid ethyl ester was added and heated to 100° C. for 2 h. Then, the reaction mixture was diluted with water and filtered through a Chem Elut® cartridge by eluting with DCM. The solvents were removed under reduced pressure and the residue was dissolved in 1 ml of DCM, 0.2 ml of TFA was added at RT. After 4 h 20 ml of toluene was added and the solvents were removed under reduced pressure. The residue was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid.

Workup

  1. filtrationfiltered through a Chem Elut® cartridge
  2. washby eluting with DCM
  3. customThe solvents were removed under reduced pressure
  4. dissolutionthe residue was dissolved in 1 ml of DCM
  5. addition0.2 ml of TFA was added at RT
  6. additionAfter 4 h 20 ml of toluene was added
  7. customthe solvents were removed under reduced pressure
  8. customThe residue was purified by preparative HPLC (
  9. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  10. additionThe fractions containing the product
  11. customwere evaporated
  12. customto yield a white solid

Sources & evidence

ORD record
ord-c36b0736c7bb43ea9d51ba5e3821decc
Source dataset
uspto-grants-2013_12
Patent number
US08598179B2

Reaction notes

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