Trifluoroacetic acid → HCID 71737376, compound

HRID 1481067Notes

Reaction equation

HRID 1481067 reaction equation
C([O:5][C:6](=[O:39])[CH2:7][C@@H:8]([NH:16][C:17]([C:19]1[N:20]=[C:21]([C:37]#[N:38])[C:22]2[C:27]([C:28]=1[OH:29])=[CH:26][CH:25]=[C:24]([O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH:23]=2)=[O:18])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[C:37]([C:21]1[C:22]2[C:27](=[CH:26][CH:25]=[C:24]([O:30][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH:23]=2)[C:28]([OH:29])=[C:19]([C:17]([NH:16][C@@H:8]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:7][C:6]([OH:39])=[O:5])=[O:18])[N:20]=1)#[N:38]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89815835HCID 89815835, compound

Product 1

HCID 71737376HCID 71737376, compoundYield 44.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-3-[(1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-4-phenyl-butyric acid tert-butyl ester (50 mg, 0.096 mmol) was dissolved in CH2Cl2 (4 mL) and cooled in an ice bath. Trifluoroacetic acid (4 mL) was added, and the mixture was stirred at r.t. for 2 h. The solvent was evaporated in vacuo, and the residue was partitioned between saturated NaHCO3 and EtOAc. Hydrochloric acid (1 M) was added with vigorous stirring until pH was ˜2. The organic layer was dried over MgSO4 and concentrated. The crude product was first purified by column chromatography (0-40% EtOAc/hexanes+2% AcOH), then by preparative TLC (60% EtOAc/hexanes+2% AcOH) to give 20 mg of the title compound as a pale brown solid. MS: (+) m/z 468.14 (M+1).

Workup

  1. temperaturecooled in an ice bath
  2. customThe solvent was evaporated in vacuo
  3. customthe residue was partitioned between saturated NaHCO3 and EtOAc
  4. additionHydrochloric acid (1 M) was added
  5. stirringwith vigorous stirring until pH was ˜2
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was first purified by column chromatography (0-40% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-8f29fc9c520f497db2314f07be985387
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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