Trifluoroacetic acid → HCID 118009784, compound

HRID 706441Notes

Reaction equation

HRID 706441 reaction equation
C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:41]=[CH:40][C:17]3[N:18]([CH2:21][C:22]4[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]5[CH:31]=[N:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=5)=[C:24]([O:38][CH3:39])[CH:23]=4)[CH:19]=[N:20][C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:39][O:38][C:24]1[CH:23]=[C:22]([CH:27]=[CH:26][C:25]=1[O:28][CH2:29][C:30]1[CH:31]=[N:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=1)[CH2:21][N:18]1[C:17]2[CH:40]=[CH:41][C:14]([N:11]3[CH2:12][CH2:13][CH:8]([NH2:7])[CH2:9][CH2:10]3)=[CH:15][C:16]=2[N:20]=[CH:19]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131733010HCID 131733010, compound

Product 1

HCID 118009784HCID 118009784, compoundYield 69.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl(1-(1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazol-5-yl)piperidin-4-yl)carbamate (0.33 g, 0.58 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (5.0 mL. 64.90 mmol). The reaction mixture was allowed to stir at room temperature. After 2 h, the mixture was concentrated, and the residue partitioned between 3 M ammonium hydroxide solution and dichloromethane. The phases were separated, and the aqueous phase was extracted with dichloromethane. The combined organic phases were washed with brine, dried over magnesium sulfate, filtered, and concentrated. Chromatographic purification (Combi-Flash, 40 g SiO2 gold column, 1-15% methanol/dichloromethane elute) afforded 0.19 g (62%) of the product as a solid: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J=2.0 Hz, 1H), 7.83 (s, 1H), 7.65 (dd, J=8.5, 2.4 Hz, 1H), 7.36-7.26 (m, 1H), 7.15 (d, J=8.8 Hz, 1H), 7.01 (dd, J=8.8, 2.2 Hz, 1H), 6.89-6.82 (m, 1H), 6.78-6.67 (m, 3H), 5.21 (s, 2H), 5.01 (s, 2H), 3.93 (s, 3H), 3.76 (s, 3H), 3.60-3.52 (m, 2H), 2.85-2.72 (m, 3H), 1.98-1.90 (m, 2H), 1.80 (b, 2H), 1.62-1.50 (m, 2H) ppm; (M+1)=474.

Workup

  1. concentrationthe mixture was concentrated
  2. customthe residue partitioned between 3 M ammonium hydroxide solution and dichloromethane
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with dichloromethane
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customChromatographic purification (Combi-Flash, 40 g SiO2 gold column, 1-15% methanol/dichloromethane elute)

Sources & evidence

ORD record
ord-cb123ae3ebb44bc3b7b85b42066a806c
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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