Trifluoroacetic acid → HCID 67408332, compound

HRID 1949646Notes

Reaction equation

HRID 1949646 reaction equation
C(O[C:6](=O)[N:7]([CH:9]([C:11](=[O:40])[NH:12][CH:13]([C:16]([N:18]1[CH2:22][CH2:21][CH:20]2[N:23]([S:36]([CH3:39])(=[O:38])=[O:37])[CH2:24][CH:25]([C:26]3[C:34]4[C:29](=[CH:30][C:31]([F:35])=[CH:32][CH:33]=4)[NH:28][CH:27]=3)[CH:19]12)=[O:17])[CH2:14][CH3:15])[CH3:10])C)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:35][C:31]1[CH:30]=[C:29]2[C:34]([C:26]([CH:25]3[CH:19]4[N:18]([C:16]([CH:13]([NH:12][C:11](=[O:40])[CH:9]([NH:7][CH3:6])[CH3:10])[CH2:14][CH3:15])=[O:17])[CH2:22][CH2:21][CH:20]4[N:23]([S:36]([CH3:39])(=[O:38])=[O:37])[CH2:24]3)=[CH:27][NH:28]2)=[CH:33][CH:32]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67408599HCID 67408599, compound

Product 1

HCID 67408332HCID 67408332, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution containing 66 (160 mg, 0.27 mmol) in DCM (3 mL) was added TFA (3 mL) at 0° C. After 1 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in EtOAc and the resultant organic solution was washed successively with saturated aqueous NaHCO3 and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by RP-HPLC (2″ Dynamax C18, 5-40% ACN/water containing 0.1% HOAc over 30 min; Flow: 40 mL/min) to afford 100 mg (38%, 3 steps) of 67. 1H NMR (300 MHz, CDCl3/d4-MeOH), mixture of amide rotamers: δ10.34 (br s, 0.1H), 9.76 (br s, 0.3H), 7.92 (br d, 0.3H), 7.55 (dd, J=8.9, 5.3 Hz, 0.7H), 7.38 (m, 0.3H), 7.35 (s, 0.3H), 7.25 (m, 0.3H), 7.22 (s, 0.7H), 7.02 (m, 1H), 6.82 (dt, J=9.2, 2.0 Hz, 0.7H), 5.11 (t, J=7.8 Hz, 0.7H), 4.79 (m, 0.3H), 4.30 (br s, 2H), 4.24 (m, 1.7H), 4.14 (m, 1.3H), 4.00 (m, 1H), 3.82 (m, 1H), 3.71 (m, 2H), 3.51 (q, J=6.9 Hz, 0.7H), 3.38 (m, 0.3H), 3.29 (m, 0.3H), 3.15 (app q, J=9.0 Hz, 0.7H), 3.01 (s, 0.7H), 2.98 (s, 2.3H), 2.44 (s, 2.3H), 2.34 (s, 0.7H), 2.20 (m, 0.7H), 2.00 (br s, 3.3H), 1.57 (m, 0.3H), 1.35 (d, J=6.9 Hz, 2.3H), 1.17 (d, J=6.9 Hz, 0.7H), 0.71 (m, 1.5H), 0.47 (m, 1.5H) ppm. 13C NMR (75 MHz, CDCl3/d4-MeOH), mixture of amide rotamers: δ176.6, 171.3, 171.2, 170.7, 170.5, 169.1, 161.6, 158.4, 136.2, 136.0, 135.9, 124.3, 122.9, 122.8, 122.7(2), 120.2, 120.1, 108.3, 108.1, 107.8, 97.6, 97.5, 97.2, 65.0, 64.9, 62.3, 57.9, 57.5, 55.4, 53.4, 52.3, 52.2, 51.7, 47.4, 46.8, 43.1, 38.5, 37.6, 34.4, 33.9, 33.2, 32.2, 32.0, 25.9, 24.2, 22.1, 17.1, 16.8, 10.0, 9.1 ppm. Mass spectrum, m/z [494.2] (M+H)+.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in EtOAc
  3. washthe resultant organic solution was washed successively with saturated aqueous NaHCO3 and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by RP-HPLC (2″ Dynamax C18, 5-40% ACN/water containing 0.1% HOAc over 30 min

Sources & evidence

ORD record
ord-e4b18f0b99b04b5a917c996989b79c8e
Source dataset
uspto-grants-2013_03
Patent number
US08399683B2

Reaction notes

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