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

HRID 1908613Notes

Reaction equation

HRID 1908613 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:38])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([OH:31])[N:28]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=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].[CH:39]1(O)[CH2:42][CH2:41][CH2:40]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:38])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][CH:39]3[CH2:42][CH2:41][CH2:40]3)[N:28]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=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

6

Reactant 4

HCID 11776TriphenylphosphineHCID 76218CyclobutanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 178473388HCID 178473388, compound

Product 1

HCID 441264054-{(S)-4-Carboxy-2-[(5-cyclobutoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]butyryl}-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 50 mg of 4-{(S)-4-tert-Butoxycarbonyl-2-[(5-hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester and 8 mg of Cyclobutanol in 2 ml of THF, 37 mg of polymerbound triphenyl phosphine (Fluka, 3 mmol triphenylphosphine/g resin) and 20 mg of Diethyl azodicarboxylate was added and stirred for 16 h. Then, the reaction mixture was filtered and the solvents were removed under reduced pressure. The residue was dissolved in 1 ml of DCM and 0.2 ml TFA. After 4 h 10 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. Yield: 2 mg MS (ES+): m/e=528.

Workup

  1. filtrationThen, the reaction mixture was filtered
  2. customthe solvents were removed under reduced pressure
  3. dissolutionThe residue was dissolved in 1 ml of DCM
  4. additionAfter 4 h 10 ml of toluene was added
  5. customthe solvents were removed under reduced pressure
  6. customThe residue was purified by preparative HPLC (
  7. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  8. additionThe fractions containing the product
  9. customwere evaporated
  10. customto yield a white solid

Sources & evidence

ORD record
ord-d9de045fbb2d4b668f5b1ce3b1c3287a
Source dataset
uspto-grants-2013_12
Patent number
US08598179B2

Reaction notes

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