Trifluoroacetic acid → HCID 178425135, compound

HRID 2208776Notes

Reaction equation

HRID 2208776 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:25](=[O:37])[NH:26][CH2:27][C:28]2[C:29](=[O:36])[NH:30][C:31]([CH3:35])=[CH:32][C:33]=2[CH3:34])[C:5]([CH3:24])=[C:6]([N:8]([CH3:23])[C@H:9]2[CH2:14][CH2:13][C@H:12]([NH:15]C(=O)OC(C)(C)C)[CH2:11][CH2:10]2)[CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:15][C@H:12]1[CH2:11][CH2:10][C@H:9]([N:8]([CH3:23])[C:6]2[C:5]([CH3:24])=[C:4]([CH:3]=[C:2]([Br:1])[CH:7]=2)[C:25]([NH:26][CH2:27][C:28]2[C:29](=[O:36])[NH:30][C:31]([CH3:35])=[CH:32][C:33]=2[CH3:34])=[O:37])[CH2:14][CH2:13]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178425137HCID 178425137, compound

Product 1

HCID 178425135HCID 178425135, compoundYield 86.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirred solution of trans-tert-butyl (4-((5-bromo-3-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-2-methylphenyl)(methyl)amino)cyclohexyl)carbamate (0.7 g, 1.21 mmol) in DCM (8 mL) was cooled to 0° C. and TFA (2.5 mL) was added to it. Reaction mass was stirred at room temperature for 1 h. On completion, reaction was concentrated to dryness. Residue was basified with aqueous sodium bicarbonate till pH 8 and aqueous layer extracted with 20% MeOH/DCM. The combined organic layers were dried over sodium sulfate, filtered and concentrated to afford crude material which was then purified by solvent washings giving desired compound (0.5 g, 86%). LCMS: 475.20 (M+1)+; HPLC % 92.35 (@ 254 nm) (Rt; 4.416; Method: Column: YMC ODS-A 150 mm×4.6 mm×5μ; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 μL, Col. Temp.: 30° C.; Flow rate: 1.4 mL/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (DMSO-d6, 400 MHz) δ 8.21 (t, 1H), 7.18 (s, 1H), 7.01 (s, 1H), 5.85 (s, 1H), 4.23 (d, 2H), 2.63-2.66 (m, 2H), 2.55 (s, 3H), 2.17 (s, 3H), 2.10 (s, 6H), 1.79-1.82 (m, 2H), 1.60 (m, 2H), 1.46-1.49 (m, 2H), 1.06-1.09 (m, 2H).

Workup

  1. customReaction mass
  2. customOn completion, reaction
  3. concentrationwas concentrated to dryness
  4. extractionextracted with 20% MeOH/DCM
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford crude material which
  9. customwas then purified by solvent washings

Sources & evidence

ORD record
ord-8dda8538f3a841948151cbef553484b8
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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