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 706505Notes

Reaction equation

HRID 706505 reaction equation
C(OC(=O)[NH:5][C:6]1[N:20]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH:29]([CH:38]3[CH2:40][CH2:39]3)[C:30]3[CH:31]=[N:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=3)=[C:24]([O:41][CH3:42])[CH:23]=2)[C:9]2=[N:10][CH:11]=[C:12]([C:14]3[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=3)[CH:13]=[C:8]2[N:7]=1)C.[OH-].[K+]>C(O)CCC.O>[CH:38]1([CH:29]([C:30]2[CH:31]=[N:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=2)[O:28][C:25]2[CH:26]=[CH:27][C:22]([CH2:21][N:20]3[C:9]4=[N:10][CH:11]=[C:12]([C:14]5[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=5)[CH:13]=[C:8]4[N:7]=[C:6]3[NH2:5])=[CH:23][C:24]=2[O:41][CH3:42])[CH2:40][CH2:39]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-57d45d5b161b40229b51edefc3318e07
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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