Trifluoroacetic acid → 3-(3-Methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

HRID 706453Notes

Reaction equation

HRID 706453 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:34]=[CH:35][C:36]=1[O:37][CH2:38][C:39]1[CH:40]=[N:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=1)[CH2:6][N:7]1[C:11]2=[N:12][CH:13]=[C:14]([C:16]3[CH:17]=[N:18][N:19]([CH:21]4[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]4)[CH:20]=3)[CH:15]=[C:10]2[N:9]=[CH:8]1.FC(F)(F)C(O)=O>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:34]=[CH:35][C:36]=1[O:37][CH2:38][C:39]1[CH:40]=[N:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=1)[CH2:6][N:7]1[C:11]2=[N:12][CH:13]=[C:14]([C:16]3[CH:17]=[N:18][N:19]([CH:21]4[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]4)[CH:20]=3)[CH:15]=[C:10]2[N:9]=[CH:8]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118114193tert-butyl 4-(4-(3-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-3H-imidazo[4,5-b]pyridin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Product 1

HCID 1180097973-(3-Methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridineYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl 4-(4-(3-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-3H-imidazo[4,5-b]pyridin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.15 g, 0.24 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (0.5 mL). The resulting mixture was stirred at room temperature. After 1 h, the reaction mixture was concentrated, and the residue was diluted with 1M potassium carbonate solution (20 mL) and extracted with dichloromethane (3×10 mL). The combined organic phases were washed with brine (3×20 mL), dried over sodium sulfate, filtered, and concentrated. The residue was purified by Prep-HPLC to afford 0.065 g (52%) of the product as a white solid: 1H NMR (500 MHz, CDCl3) δ 8.59 (s, 1H), 8.19 (s, 1H), 8.13 (s, 1H), 8.02 (s, 1H), 7.83 (s, 1H), 7.75 (s, 1H), 7.67 (d, J=8.0 Hz, 1H), 6.93 (s, 1H), 6.89 (d, J=8.0 Hz, 1H), 6.85 (d, J=8.5 Hz, 1H), 6.75 (d, J=8.5 Hz, 1H), 5.40 (s, 2H), 5.03 (s, 2H), 4.30 (m, 1H), 3.94 (s, 3H), 3.82 (s, 3H), 3.31-3.28 (m, 2H), 2.84-2.80 (m, 2H), 2.24-2.22 (m, 2H), 2.04-1.97 (m, 2H) ppm; (M+1)=526.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. additionthe residue was diluted with 1M potassium carbonate solution (20 mL)
  3. extractionextracted with dichloromethane (3×10 mL)
  4. washThe combined organic phases were washed with brine (3×20 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by Prep-HPLC

Sources & evidence

ORD record
ord-5fa88fdae4d844bc8668d83358c0d6b9
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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