Trifluoroacetic acid → HCID 10166820, compound

HRID 1814376Notes

Reaction equation

HRID 1814376 reaction equation
C([O:5][C:6](=[O:49])[CH2:7][CH:8]([NH:16][S:17]([C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:29])[CH3:28])=[CH:22][C:21]=1[O:30][CH2:31][CH2:32][C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]([C:43]([NH:45][N:46]([CH3:48])[CH3:47])=[O:44])=[CH:35][CH:34]=1)(=[O:19])=[O:18])[CH:9](OCC)[O:10]CC)(C)(C)C.C(O)(C(F)(F)F)=O.C(#N)C.O>C(Cl)Cl.O>[C:27]([NH:26][C:23]1[CH:24]=[CH:25][C:20]([S:17]([NH:16][CH:8]([CH:9]=[O:10])[CH2:7][C:6]([OH:49])=[O:5])(=[O:19])=[O:18])=[C:21]([O:30][CH2:31][CH2:32][C:33]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[C:36]([C:43]([NH:45][N:46]([CH3:48])[CH3:47])=[O:44])=[CH:35][CH:34]=2)[CH:22]=1)(=[O:29])[CH3:28]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 18373917Acetonitrile--water (1/1)HCID 131724824HCID 131724824, compound

Product 1

HCID 10166820HCID 10166820, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

3-(4-Acetylamino-2-{2-[4-(N′,N′-dimethyl-hydrazinocarbonyl)-naphthalen-1-yl]-ethoxy}-benzenesulfonylamino)-4,4-diethyoxy-butyric acid tert-butyl ester (0.12 g, 0.17 mmol) was stirred in 12 mL of a solution of 17% TFA in CH2Cl2 at room temperature for 2 h. Analytical HPLC indicated the reaction was complete. The reaction mixture was concentrated. Residual TFA was azeotroped with toluene. Half of the product was lyophilized to give (0.06 g, 54%). The second half of the crude product was stirred with 22 mL of a solution of 10% TFA in 1:1 acetonitrile/water for 16 h. Analytical HPLC indicated that reaction was complete. The reaction mixture was diluted with H2O and lyopholyzed. The crude product was purified by preparative-scale reverse phase HPLC (0 to 30% acetonitrile in H2O with 0.1% TFA over 2 h at 15 mL/min on Vydac #218TP152022-2.5×25 cm C18 column) and then lyophilized to give (0.035 g, 0.06 mmol, 36%) of 3-(4-Acetylamino-2-{2-[4-(N′,N′-dimethyl-hydrazinocarbonyl)-naphthalen-1-yl]-ethoxy}-benzenesulfonylamino)-4-oxo-butyric acid as a fluffy white solid. MS m/z 571 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customResidual TFA was azeotroped with toluene
  3. customto give (0.06 g, 54%)
  4. customAnalytical HPLC indicated that reaction
  5. customThe crude product was purified by preparative-scale reverse phase HPLC (0 to 30% acetonitrile in H2O with 0.1% TFA over 2 h at 15 mL/min on Vydac #218TP152022-2.5×25 cm C18 column)

Sources & evidence

ORD record
ord-ce775dd7d2514be1b894a5fc753a5516
Source dataset
uspto-grants-2005_04
Patent number
US06875765B2

Reaction notes

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