Diethanolamine → 4-(4-(3-Cyano-4-(ethylsulfonyl)phenylamino)-4-oxobutyl)phenylboronic acid

HRID 735503Notes

Reaction equation

HRID 735503 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])=[C:16]([C:25]#[N:26])[CH:15]=2)=[O:12])=[CH:4][CH:3]=1.CC1(C)C[O:32][B:31](B2OCC(C)(C)CO2)[O:30]C1.C([O-])(=O)C.[K+].N(CCO)CCO>C(O)(C)C.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[C:25]([C:16]1[CH:15]=[C:14]([NH:13][C:11](=[O:12])[CH2:10][CH2:9][CH2:8][C:5]2[CH:6]=[CH:7][C:2]([B:31]([OH:32])[OH:30])=[CH:3][CH:4]=2)[CH:19]=[CH:18][C:17]=1[S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])#[N:26]

Participants

7

Reactant 4

HCID 8113DiethanolamineHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 578426674-(4-Bromophenyl)-N-(3-cyano-4-(ethylsulfonyl)phenyl)butanamide

Product 1

HCID 578426844-(4-(3-Cyano-4-(ethylsulfonyl)phenylamino)-4-oxobutyl)phenylboronic acidYield 57.9%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

A flask containing 6C (83 mg, 0.19 mmol), 5,5,5′,5′-tetramethyl-[2,2′]bi[[1,3,2]dioxaborinanyl] (47.6 mg, 0.211 mmol), potassium acetate (83 mg, 0.84 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (4.4 mg, 0.0060 mmol) was purged with argon. DMSO (1 mL) was added, and the reaction mixture was degassed with three cycles of vacuum followed by argon backfill. The reaction mixture was heated for 2 h at 80° C., cooled to rt, and diluted with water (100 mL). The aqueous solution was extracted with diethyl ether (3×25 mL), dried (MgSO4), and concentrated under reduced pressure. The residue was dissolved in a mixture of diethyl ether (1 mL), DCM (˜0.1 mL), and EtOAc (˜0.1 mL). Diethanolamine (22 mg, 0.21 mmol) in isopropanol (0.5 mL) was added, and the reaction mixture was stirred overnight at rt. The reaction mixture was concentrated, and the residue was purified by reverse phase HPLC (under the standard acidic conditions) to give 6D (44 mg, 57%) as a clear oil. MS (ESI) m/z 425.4 (M+CH3OH—H2O+H)+.

Workup

  1. customwas purged with argon
  2. additionDMSO (1 mL) was added
  3. customthe reaction mixture was degassed with three cycles of vacuum
  4. temperaturecooled to rt
  5. additiondiluted with water (100 mL)
  6. extractionThe aqueous solution was extracted with diethyl ether (3×25 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe residue was dissolved in a mixture of diethyl ether (1 mL), DCM (˜0.1 mL), and EtOAc (˜0.1 mL)
  10. concentrationThe reaction mixture was concentrated
  11. customthe residue was purified by reverse phase HPLC (under the standard acidic conditions)

Sources & evidence

ORD record
ord-dbf33763284642fc828585fa8e4469ba
Source dataset
uspto-grants-2009_09
Patent number
US07592331B2

Reaction notes

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