Phenylboronic Acid → HCID 58345200, compound

HRID 1887995Notes

Reaction equation

HRID 1887995 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]1(B(O)O)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C1(C)C=CC=CC=1.C(O)C>[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]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 66827Phenylboronic 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 58345200HCID 58345200, 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 (20 g) in toluene (200 mL) and ethanol (200 mL) was added saturated aqueous sodium bicarbonate (150 mL) and phenyl boronic acid (9.9 g). The reaction was degassed for 5 minutes and the Pd (PPh3)4 (1.0 g) was added. The reaction was again degassed for 5 minutes and then heated to 100° C. for 2 days or until reaction is complete by LCMS. The reaction mixture was cooled to room temperature, and dichloromethane (250 ml×3) and water (100 mL) were added to the reaction. The organics were washed with saturated sodium bicarbonate (1×250 mL) and water (1×250 mL), dried over sodium sulfate and concentrated. Purification by column chromatography (10-100% ethyl acetate in hexanes) gave the product with some impurities. The solid was re-crystallized with ethyl acetate affording an off-white solid (7.2 g). 400 M Hz 1H NMR (DMSO-d6) δ: 8.23 (d, J=8.0 Hz, 1H), 8.04-7.98 (m, 3H), 7.94 (d, J=8.0 Hz, 1H), 7.55 (d, J=8.8 Hz, 2H), 7.46-7.35 (m, 6H), 7.18-7.14 (m, 1H), 6.90 (bs, 1H), 6.33 (dd, J=7.6 Hz and 4.4 Hz, 1H), 2.48-2.40 (m, 4H), 2.09-2.00 (m, 1H), 1.89-1.79 (m, 1H), 1.30 (m, 9H); LCMS: 533 [M+H].

Workup

  1. customThe reaction was degassed for 5 minutes
  2. additionthe Pd (PPh3)4 (1.0 g) was added
  3. customThe reaction was again degassed for 5 minutes
  4. temperatureThe reaction mixture was cooled to room temperature
  5. additiondichloromethane (250 ml×3) and water (100 mL) were added to the reaction
  6. washThe organics were washed with saturated sodium bicarbonate (1×250 mL) and water (1×250 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customPurification by column chromatography (10-100% ethyl acetate in hexanes)
  10. customgave the product with some impurities
  11. customThe solid was re-crystallized with ethyl acetate affording an off-white solid (7.2 g)

Sources & evidence

ORD record
ord-9a8f41d471db4de2bd628b5a00c7838c
Source dataset
uspto-grants-2013_08
Patent number
US08501770B2

Reaction notes

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