Acetic Acid → HCID 118417117, compound

HRID 1483046Notes

Reaction equation

HRID 1483046 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][N:3]1[CH2:12][CH2:13][NH:14][C:15](=O)OC(C)(C)C.FC(F)(F)C(O)=O.[F:29][C:30]([F:46])([F:45])[C@@H:31]([NH:40][S:41]([CH3:44])(=[O:43])=[O:42])[C:32]1[CH:37]=[CH:36][C:35](C=O)=[CH:34][CH:33]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[ClH:65]>C(Cl)Cl.CO>[ClH:65].[F:46][C:30]([F:29])([F:45])[C@@H:31]([NH:40][S:41]([CH3:44])(=[O:43])=[O:42])[C:32]1[CH:33]=[CH:34][C:35]([CH2:15][NH:14][CH2:13][CH2:12][N:3]2[CH2:4][CH2:5][C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:2]2=[O:1])=[CH:36][CH:37]=1

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 86691246HCID 86691246, compoundHCID 90135616HCID 90135616, compound

Product 1

HCID 118417117HCID 118417117, compoundYield 4.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Dissolve tert-butyl 2-(1-oxo-3,4-dihydroisoquinolin-2(1H)-yl)ethylcarbamate (220 mg, 0.76 mmol) in DCM (3 mL) and add trifluoroacetic acid (1 mL, 13.23 mmol). Stir at ambient temperature for 30 minutes. Concentrate the mixture under reduced pressure, then dissolve in 1,2-dichloroethane (20 mL). Add N-[(1S)-2,2,2-trifluoro-1-(4-formylphenyl)-ethyl]-methanesulfonamide (150 mg, 0.53 mmol), acetic acid (0.05 mL, 0.87 mmol), and sodium triacetoxyborohydride (642.3 mg, 3.03 mmol). Stir the mixture at ambient temperature overnight. Concentrate under reduced pressure to give a residue and dilute the residue with MeOH (2 mL). Purify the residue via preparatory TLC using 10% MeOH in DCM to give a colorless oil. Dissolve the oil in MeOH (3 mL) and add HCl (1M in diethyl ether; 0.5 mL, 0.5 mmol) and stir for 30 minutes. Concentrate under reduced pressure to give the title compound as a white solid (10 mg, 3.7%). MS (m/z): 456 (M-Cl).

Workup

  1. concentrationConcentrate the mixture under reduced pressure
  2. dissolutiondissolve in 1,2-dichloroethane (20 mL)
  3. stirringStir the mixture at ambient temperature overnight
  4. concentrationConcentrate under reduced pressure
  5. customto give a residue
  6. customPurify the residue via preparatory TLC
  7. customto give a colorless oil
  8. stirringstir for 30 minutes
  9. concentrationConcentrate under reduced pressure

Sources & evidence

ORD record
ord-43debd9f465440859e30a3aec58f84cc
Source dataset
uspto-grants-2016_08
Patent number
US09416138B2

Reaction notes

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