Trifluoroacetic acid → HCID 44229836, compound

HRID 1026814Notes

Reaction equation

HRID 1026814 reaction equation
[CH:1]1([NH:4][C:5](=[O:46])[NH:6][C:7]2[CH:44]=[CH:43][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:26]=[CH:25][C:24]([CH2:27][N:28]([CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH3:42])C(=O)OC(C)(C)C)=[CH:23][CH:22]=5)[S:20][C:13]=34)=[C:9]([F:45])[CH:8]=2)[CH2:3][CH2:2]1.FC(F)(F)C(O)=O.[OH-].[Na+]>ClCCl>[CH:1]1([NH:4][C:5]([NH:6][C:7]2[CH:44]=[CH:43][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[CH:22]=[CH:23][C:24]([CH2:27][NH:28][CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH3:42])=[CH:25][N:26]=5)[S:20][C:13]=34)=[C:9]([F:45])[CH:8]=2)=[O:46])[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 58236625HCID 58236625, compound

Product 1

HCID 44229836HCID 44229836, compoundYield 86.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Compound 330 (0.15 g, 0.23 mmol) was dissolved in dichloromethane (20 mL) and trifluoroacetic acid (0.9 mL) and the reaction mixture was stirred for 12 h at r.t. The mixture was concentrated and the residue was purified by Gilson reverse phase HPLC (40-80% MeOH/H2O, Aquasil C18, 30 min) and lyophilized. The purified product (containing some formic acid from the HPLC) was partitioned between warm dichloromethane and 1M NaOH. The organic phase was dried (MgSO4), filtered and concentrated to give title compound 331 (0.110 g, 72% yield) (a mono-TFA salt despite the treatment with NaOH). 1H NMR (DMSO-d6) δ (ppm) 1H: 8.84 (s, 1H); 8.65 (d, J=1.3, 1H); 8.53 (d, J=5.5, 1H); 8.37 (s, 1H); 8.30 (d, J=8.2, 1H); 7.99 (dd, J=8.2, 2.0, 1H); 7.73 (dd, J=13.7, 2.5, 1H); 7.38 (t, 1H); 7.22-7.18 (m, 1H); 6.68-6.64 (m, 2H); 4.03 (s, 2H); 3.60-3.52 (m, 4H); 3.48-3.44 (m, 2H); 3.25 (s, 3H); 2.92-2.88 (m, 2H); 2.55 (septet, J=3.1, 1H); 0.69-0.62 (m, 2H); 0.44-0.40 (m, 2H). LRMS: (M+H): 552.5.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by Gilson reverse phase HPLC (40-80% MeOH/H2O, Aquasil C18, 30 min)
  3. additionThe purified product (containing some formic acid from the HPLC)
  4. customwas partitioned
  5. temperaturebetween warm dichloromethane and 1M NaOH
  6. dry with materialThe organic phase was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-774060442f7a472faf8d23f251fccbaf
Source dataset
uspto-grants-2014_05
Patent number
US08729268B2

Reaction notes

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