Trifluoroacetic acid → 1-(3-Methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-5-(piperidin-4-yl)-1H-benzo[d]imidazole

HRID 706435Notes

Reaction equation

HRID 706435 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][C:31]=1[O:32][CH2:33][C:34]1[CH:35]=[N:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=1)[CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][C:14]([CH:16]3[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]3)=[CH:15][C:10]=2[N:9]=[CH:8]1.FC(F)(F)C(O)=O.[OH-].[Na+]>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][C:31]=1[O:32][CH2:33][C:34]1[CH:35]=[N:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=1)[CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][C:14]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:15][C:10]=2[N:9]=[CH:8]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 118113962tert-butyl 4-(1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 1180097801-(3-Methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-5-(piperidin-4-yl)-1H-benzo[d]imidazoleYield 8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred and cooled (5° C.) solution of tert-butyl 4-(1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazol-5-yl)piperidine-1-carboxylate (0.28 g, 0.51 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (1 mL). The resulting mixture was allowed to warm room temperature and stir. After 2 h, the mixture was treated with 1 N sodium hydroxide solution to achieve a pH ˜10 and was extracted with dichloromethane (3×10 mL). The combined organic layers were washed with brine (3×10 mL), dried over sodium sulfate, concentrated. The residue was purified by prep-HPLC to afford 0.018 g (8%) of the product as a white solid: 1H NMR (500 MHz, MeOD-d4) δ 8.25 (s, 1H), 8.16 (d, J=2.5 Hz, 1H), 7.76 (dd, J=8.5, 2.5 Hz, 1H), 7.55 (s, 1H), 7.40 (d, J=8.5 Hz, 1H), 7.20 (dd, J=8.5, 1.0 Hz, 1H), 7.00-6.97 (m, 2H), 6.82-6.79 (m, 2H), 5.41 (s, 2H), 5.01 (s, 2H), 3.91 (s, 3H), 3.79 (s, 3H), 3.24-3.21 (m, 2H), 2.86-2.81 (m, 3H), 1.93-1.90 (m, 2H), 1.78-1.75 (m, 2H) ppm; (M+1)=459.

Workup

  1. stirringstir
  2. extractionwas extracted with dichloromethane (3×10 mL)
  3. washThe combined organic layers were washed with brine (3×10 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-2ac0f922c3d44048b5a4778557ea000c
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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