5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole → HCID 46205231, compound

HRID 1408472Notes

Reaction equation

HRID 1408472 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]2[O:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[C:6]=2[N:7]=1.[NH:21]1[C:29]2[C:24](=[CH:25][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:27][CH:28]=2)[CH:23]=[CH:22]1>COCCOC.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>[NH:21]1[C:29]2[C:24](=[CH:25][C:26]([C:2]3[N:3]=[C:4]([N:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:5]4[O:10][C:9]5[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=5[C:6]=4[N:7]=3)=[CH:27][CH:28]=2)[CH:23]=[CH:22]1

Participants

6

Reactant 2

HCID 27347725-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 58508038HCID 58508038, compound

Product 1

HCID 46205231HCID 46205231, compoundYield 34.2%

Reagents, catalysts & solvents 3

HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
90 °C

Procedure

Argon gas was bubbled through a mixture of 2-chloro-4-morpholinobenzofuro[3,2-d]pyrimidine (ASA75) (80 mg, 0.276 mmol, 1.0 eq) and Indole-5-boronic acid pinacol ester (MW 243) (267 mg, 1.10 mmol, 4.0 eq) in 1,2 dimethoxyethan and 2 M Na2CO3 (3:1) (6 mL) for 5 min. dichloro 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloromethane complex (MW 732) (5.05 mg, 0.00690 mmol, 0.025 eq) was added and the reaction mixture was heated to reflux (90° C.) for 15 h, cooled and diluted with EtOAc (20 mL). The organic solution was washed with a mixture of H2O:Na2CO3:NH4OH (conc. 32 (% in water)=5:4:1 (9 mL), then NH4Cl (sat.) and brine (2×), dried over Na2CO3, filtered and concentrated. Purification by silica gel chromatography (gradient from 100% hexane in EtOAc to 70% hexane) gave a colorless solid (35 mg, 34%).

Workup

  1. additionwas added
  2. temperaturethe reaction mixture was heated
  3. temperaturecooled
  4. washThe organic solution was washed with a mixture of H2O
  5. dry with materialNa2CO3:NH4OH (conc. 32 (% in water)=5:4:1 (9 mL), then NH4Cl (sat.) and brine (2×), dried over Na2CO3
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (gradient from 100% hexane in EtOAc to 70% hexane)

Sources & evidence

ORD record
ord-955dfeb1b5fa448ea4893a942095df65
Source dataset
uspto-grants-2014_12
Patent number
US08921361B2

Reaction notes

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