Trifluoroacetic acid → HCID 67444100, compound

HRID 1400817Notes

Reaction equation

HRID 1400817 reaction equation
C(OC([NH:8][C@@H:9]([CH:52]([CH3:54])[CH3:53])[C:10]([O:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[CH:23]=[N:24][C:25]([C:28]3[S:36][C:35]4[C:30](=[N:31][CH:32]=[CH:33][C:34]=4[O:37][C:38]4[CH:43]=[CH:42][C:41]([NH:44][C:45]([NH:47][CH:48]5[CH2:50][CH2:49]5)=[O:46])=[CH:40][C:39]=4[F:51])[CH:29]=3)=[CH:26][CH:27]=2)[CH2:17][CH2:16]1)=[O:11])=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C@@H:9]([CH:52]([CH3:54])[CH3:53])[C:10]([O:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[CH:23]=[N:24][C:25]([C:28]3[S:36][C:35]4[C:30](=[N:31][CH:32]=[CH:33][C:34]=4[O:37][C:38]4[CH:43]=[CH:42][C:41]([NH:44][C:45]([NH:47][CH:48]5[CH2:49][CH2:50]5)=[O:46])=[CH:40][C:39]=4[F:51])[CH:29]=3)=[CH:26][CH:27]=2)[CH2:17][CH2:16]1)=[O:11]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67444254HCID 67444254, compound

Product 1

HCID 67444100HCID 67444100, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 78 (115 mg. 0.15 mmol) and TFA (2 mL) in DCM (10 mL) was stirred at RT for 3 h. The TFA was removed by co-evaporation with DCM, diluted with a minimum of water, and the pH was adjusted to around 9 with a saturated aqueous solution of sodium bicarbonate (and few drops of 1N NaOH at the end). The aqueous solution was extracted with DCM containing traces of methanol. The organic extract was dried over anhydrous magnesium sulfate, filtered and concentrated. The crude product was purified by Biotage (SNAP 10 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 5/95 to 20/80 over 20 CV), to afford the title compound 79 (36 mg, 0.05 mmol, 36% yield) as a white sticky solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.72 (s, 1H), 8.54 (d, J=1.4 Hz, 1H), 8.52 (d, J=5.3 Hz, 1H), 8.32 (s, 1H), 8.24 (d, J=8.0 Hz, 1H), 7.85 (dd, J=8.0, 2.0 Hz, 1H), 7.73 (dd, J=13.4, 2.4 Hz, 1H), 7.38 (t, J=9.1 Hz, 1H), 7.20 (bd, J=10.4 Hz, 1H), 6.64 (d, J=5.3 Hz, 1H), 6.58 (bd, J=2.2 Hz, 1H), 4.26-4.18 (m, 1H), 4.11-4.03 (m, 1H), 3.54 (s, 2H), 3.10 (d, J=5.3 Hz, 1H), 2.59-2.30 (m, 11H), 1.88-1.78 (m, 1H), 0.87 (d, J=6.8 Hz, 3H), 0.83 (d, J=6.7 Hz, 3H), 0.69-0.62 (m, 2H), 0.46-0.40 (m, 2H), NH2 is missing. MS (m/z): 662.7 (M+H).

Workup

  1. customThe TFA was removed by co-evaporation with DCM
  2. additiondiluted with a minimum of water
  3. extractionThe aqueous solution was extracted with DCM containing traces of methanol
  4. extractionThe organic extract
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by Biotage (SNAP 10 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 5/95 to 20/80 over 20 CV)

Sources & evidence

ORD record
ord-1f538b84e66e4ea9a8739fa4be6b7a74
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

Loading…