Isopropylamine → 4-((S)-4-Carboxy-2-{[5-(1-isopropylcarbamoyl-cyclobutoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester

HRID 1908615Notes

Reaction equation

HRID 1908615 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:45])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][C:32]3([C:36](O)=[O:37])[CH2:35][CH2:34][CH2:33]3)[N:28]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18]C(C)(C)C)=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2].[B-](F)(F)(F)F.CCO[C:54]([C:56]([C:66]#N)=[N:57]OC(N(C)C)=[N+](C)C)=O.C(N)(C)C.C(O)(C(F)(F)F)=O>CN(C=O)C.O.C(Cl)Cl.C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:45])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][C:32]3([C:36](=[O:37])[NH:57][CH:56]([CH3:66])[CH3:54])[CH2:35][CH2:34][CH2:33]3)[N:28]([C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([OH:18])=[O:17])[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

9

Reactant 4

HCID 6363IsopropylamineHCID 6422Trifluoroacetic acidHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669200494-((S)-4-tert-Butoxycarbonyl-2-{[5-(1-carboxy-cyclobutoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester

Product 1

HCID 669202074-((S)-4-Carboxy-2-{[5-(1-isopropylcarbamoyl-cyclobutoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 50 mg of 4-((S)-4-tert-Butoxycarbonyl-2-{[5-(1-carboxy-cyclobutoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester in 0.3 ml of DMF, 28 mg of TOTU, 36 mg of NEM and 10 mg of isopropylamine was added. The reaction mixture was allowed to stir at RT for 16 h. Then, the reaction mixture was diluted with water and filtered through a Chem Elut® cartridge by eluting with ethyl acetate. 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. This 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 dissolved in 3 ml of water and lyophilized to yield a white solid.

Workup

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

Sources & evidence

ORD record
ord-8bb234312abc489ca2b565ef7da2c7a3
Source dataset
uspto-grants-2013_12
Patent number
US08598179B2

Reaction notes

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