Phenylboronic Acid → HCID 118292615, compound

HRID 1486130Notes

Reaction equation

HRID 1486130 reaction equation
[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:25])[C@@H:14]([N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH3:15])[C:8](=[O:26])[N:7]([CH2:27][C:28]2[CH:33]=[C:32](Br)[CH:31]=[CH:30][C:29]=2[O:35][CH3:36])[C:6]2[CH:37]=[CH:38][C:39]([C:41]#[N:42])=[CH:40][C:5]1=2)(=[O:3])[CH3:2].[C:43]1(B(O)O)[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:25])[C@@H:14]([N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH3:15])[C:8](=[O:26])[N:7]([CH2:27][C:28]2[CH:33]=[C:32]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH:31]=[CH:30][C:29]=2[O:35][CH3:36])[C:6]2[CH:37]=[CH:38][C:39]([C:41]#[N:42])=[CH:40][C:5]1=2)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 66827Phenylboronic AcidHCID 516892Sodium BicarbonateHCID 118292635HCID 118292635, compound

Product 1

HCID 118292615HCID 118292615, compoundYield 75.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A rt suspension of tert-butyl(S)-1-((3S,4S)-5-acetyl-1-(5-bromo-2-methoxybenzyl)-7-cyano-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (24 mg, 37.4 μmol), phenylboronic acid (6.83 mg, 56.0 μmol), and sodium bicarbonate (7.84 mg, 93.4 μmol) in 1,4-dioxane (280 μl) was sparged with Ar for 5 min, then [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (3.05 mg, 3.74 μmol) was added. The reaction was sparged with Ar for an additional minute, then sealed and stirred at 80° C. for 2 h, then cooled to rt, diluted with EtOAc, washed with H2O and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl(S)-1-((3S,4S)-5-acetyl-7-cyano-1-((4-methoxybiphenyl-3-yl)methyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (18 mg, 75%) as a white solid. MS m/z 662 (MNa)+.

Workup

  1. customwas sparged with Ar for 5 min
  2. addition[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (3.05 mg, 3.74 μmol) was added
  3. customThe reaction was sparged with Ar for an additional minute
  4. customsealed
  5. temperaturecooled to rt
  6. additiondiluted with EtOAc
  7. washwashed with H2O and sat. aq. NaCl
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-fb28b01560f243e0b36b9dbd60477d71
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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