Potassium Hydroxide → 3-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-amine

HRID 2178386Notes

Reaction equation

HRID 2178386 reaction equation
[CH:1]1([CH:4]([C:36]2[CH:37]=[N:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=2)[O:5][C:6]2[CH:33]=[CH:32][C:9]([CH2:10][N:11]3[C:15]4=[N:16][CH:17]=[C:18]([C:20]5[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=5)[CH:19]=[C:14]4[N:13]=[C:12]3[NH:26]C(=O)OCC)=[CH:8][C:7]=2[O:34][CH3:35])[CH2:3][CH2:2]1.[OH-].[K+]>C(O)CCC.O>[CH:1]1([CH:4]([C:36]2[CH:37]=[N:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=2)[O:5][C:6]2[CH:33]=[CH:32][C:9]([CH2:10][N:11]3[C:15]4=[N:16][CH:17]=[C:18]([C:20]5[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=5)[CH:19]=[C:14]4[N:13]=[C:12]3[NH2:26])=[CH:8][C:7]=2[O:34][CH3:35])[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 131733020ethyl (3-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)carbamate

Product 1

HCID 1180098333-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-amineYield 15.1%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
130 °C

Procedure

To a stirred solution of ethyl (3-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)carbamate (0.44 g, 0.75 mmol) in n-butanol (4 mL) and water (4 mL) was added potassium hydroxide (0.42 g, 7.49 mmol). The mixture was heated to 130° C. After 16 h, the mixture was allowed to cool to room temperature and was diluted with water (15 mL). The mixture was extracted with ethyl acetate (2×60 mL). The combined organic phases were dried over sodium sulfate, filtered, and concentrated. The residue was purified via prep-HPLC to provide 0.058 g (15%) of the product as a white solid: 1H NMR (500 MHz, CDCl3) δ 8.24 (d, J=1.5 Hz, 1H), 8.09 (d, J=3.0 Hz, 1H), 7.78 (s, 1H), 7.70-7.68 (m, 2H), 7.64 (s, 1H), 6.78-6.23 (m, 4H), 5.21 (s, 2H), 4.85 (s, 2H), 4.50 (d, J=8.5 Hz, 1H), 3.98 (s, 3H), 3.93 (s, 3H), 3.79 (s, 3H), 1.45-1.40 (m, 1H), 0.75-0.70 (m, 1H), 0.61-0.50 (m, 2H), 0.38-0.34 (m, 1H) ppm; (M+1)=512.

Workup

  1. temperatureto cool to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (2×60 mL)
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified via prep-HPLC

Sources & evidence

ORD record
ord-ae5babec017244f795be99015bca3df0
Source dataset
uspto-grants-2015_06
Patent number
US09067914B1

Reaction notes

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