Trifluoroacetic acid → HCID 67411907, compound

HRID 1949653Notes

Reaction equation

HRID 1949653 reaction equation
C(O[C:6](=O)[N:7]([CH:9]([C:11](=[O:43])[NH:12][CH:13]([C:17]([N:19]1[CH2:23][CH2:22][CH:21]2[N:24]([C:37]3[N:42]=[CH:41][CH:40]=[CH:39][N:38]=3)[CH2:25][CH:26]([C:27]3[C:35]4[C:30](=[CH:31][C:32]([F:36])=[CH:33][CH:34]=4)[NH:29][CH:28]=3)[CH:20]12)=[O:18])[CH:14]([CH3:16])[CH3:15])[CH3:10])C)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:36][C:32]1[CH:31]=[C:30]2[C:35]([C:27]([CH:26]3[CH:20]4[N:19]([C:17]([CH:13]([NH:12][C:11](=[O:43])[CH:9]([NH:7][CH3:6])[CH3:10])[CH:14]([CH3:15])[CH3:16])=[O:18])[CH2:23][CH2:22][CH:21]4[N:24]([C:37]4[N:42]=[CH:41][CH:40]=[CH:39][N:38]=4)[CH2:25]3)=[CH:28][NH:29]2)=[CH:34][CH:33]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67407129HCID 67407129, compound

Product 1

HCID 67411907HCID 67411907, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution containing 74 (202 mg, 0.33 mmol) in DCM (10 mL) was added TFA (4 mL) at 0° C. After 2 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, 10-70% ACN/water containing 0.1% HOAc over 30 min; Flow: 40 mL/min) to afford 125 mg (61%, 3 steps) of 75. 1H NMR (CDCl3, 300 MHz): δ8.37 (dd, J=6.0, 10.5 Hz, 2H), 8.19 (s, 1H), 8.11 (dd, J=5.4, 8.7 Hz, 1H), 7.82 (d, J=8.7 Hz, 1H), 6.99-6.88 (m, 2H), 6.74-6.68 (m 1H), 6.62-6.58 (m, 1H), 4.74-4.60 (m, 1H), 4.48-4.44 (m, 1H) 4.16-4.04 (m, 2H), 3.69 (dd, J=6.0, 11.4 Hz, 1H), 3.51-3.42 (m, 1H), 3.26 (dd, J=6.6, 13.5 Hz, 1H), 2.76 (br s, 4H), 2.53-2.47 (m, 1H), 2.44-2.39 (m, 3H), 2.21-2.01 (m, 3H), 1.39-1.32 (m, 3H), 1.06-0.96 (m, 6H) ppm. 13C NMR (CDCl3, 75 MHz) δ173.9, 170.8, 160.2 (JCF=237.4 Hz), 159.8, 136.2, 123.4, 120.9 (JCF=10.1 Hz), 116.6, 110.1, 108.5 (JCF=24.5 Hz), 97.2 (JCF=26.2 Hz), 68.2, 60.3, 59.7, 55.9, 51.4, 47.2, 38.9, 34.2, 31.5, 30.7, 19.4, 18.8, 18.0 ppm. Mass spectrum, m/z [508.3] (M)+.

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, 10-70% ACN/water containing 0.1% HOAc over 30 min

Sources & evidence

ORD record
ord-d5022831ce0e4cb98c360b6844228b95
Source dataset
uspto-grants-2013_03
Patent number
US08399683B2

Reaction notes

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