(3-Acetamidophenyl)boronic acid → HCID 58344994, compound

HRID 1887996Notes

Reaction equation

HRID 1887996 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[N:17]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:11]3=[N:12][C:13](Cl)=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.C(=O)(O)[O-].[Na+].[C:41]([NH:44][C:45]1[CH:46]=[C:47](B(O)O)[CH:48]=[CH:49][CH:50]=1)(=[O:43])[CH3:42]>C1(C)C=CC=CC=1.C(O)C>[C:41]([NH:44][C:45]1[CH:50]=[C:49]([C:13]2[N:12]=[C:11]3[N:17]([C:18]4[CH:19]=[CH:20][C:21]([C:24]5([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:34])[CH3:33])[CH2:27][CH2:26][CH2:25]5)=[CH:22][CH:23]=4)[C:8]([C:7]4[C:2]([NH2:1])=[N:3][CH:4]=[CH:5][CH:6]=4)=[N:9][C:10]3=[CH:15][CH:14]=2)[CH:48]=[CH:47][CH:46]=1)(=[O:43])[CH3:42]

Participants

6

Reactant 3

HCID 157274(3-Acetamidophenyl)boronic acidHCID 516892Sodium BicarbonateHCID 86675348tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)cyclobutyl)carbamate

Product 1

HCID 58344994HCID 58344994, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)cyclobutyl)carbamate (3.0 g) in toluene (100 mL) and ethanol (100 mL) was added saturated aqueous sodium bicarbonate (15 ml) and (3-acetamidophenyl) boronic acid (2.18 g). The reaction was degassed for 5 minutes and Pd(PPh3)4 (0.300 g) was added. The reaction was again degassed for 5 minutes with nitrogen and then heated to 100° C. overnight. The reaction mixture was cooled to room temperature, dichloromethane (250 ml) and water (100 ml) were added to the reaction. The organics were separated, the aqueous washed with dichloromethane (1×100 ml) and the organics combined. The organics were washed with saturated sodium bicarbonate (1×100 ml) and brine (1×100 ml). The organics were dried over sodium sulfate and concentrated under reduced pressure. Purification by column chromatography (0-10% methanol in dichloromethane) gave the product as a brown solid with some co-eluting impurities. The fractions with the product were combined and concentrated to give a dark brown solid. The solid was triturated with ethyl acetate to give a tan solid (2.6 g, 70%). 400 M Hz 1H NMR (DMSO-d6) δ: 10.08 (s, 1H), 8.28 (d, J=8.0 Hz, 1H), 8.11 (bs, 1H), 7.99 (dd, J=5.2 Hz and 2.0 Hz, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.72-7.63 (m, 3H), 7.55-7.51 (m, 2H), 7.46-7.42 (m, 6H), 7.39-7.34 (m, 1H), 7.14-7.06 (m, 1H), 7.02 (s, 2H), 6.32 (dd, J=7.6 Hz and 4.8 Hz 1H), 2.48-2.40 (m, 4H), 2.07-1.98 (m, 4H), 1.89-1.79 (m, 1H), 1.38-1.12 (m, 9H); LCMS: 590 [M+H].

Workup

  1. customThe reaction was degassed for 5 minutes
  2. additionPd(PPh3)4 (0.300 g) was added
  3. customThe reaction was again degassed for 5 minutes with nitrogen
  4. temperatureThe reaction mixture was cooled to room temperature
  5. additiondichloromethane (250 ml) and water (100 ml) were added to the reaction
  6. customThe organics were separated
  7. washthe aqueous washed with dichloromethane (1×100 ml)
  8. washThe organics were washed with saturated sodium bicarbonate (1×100 ml) and brine (1×100 ml)
  9. dry with materialThe organics were dried over sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customPurification by column chromatography (0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-2d23c1521c184e00a2c4b578f055b219
Source dataset
uspto-grants-2013_08
Patent number
US08501770B2

Reaction notes

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