Cesium carbonate → [6-(5-Carbamoyl-pyrazin-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester

HRID 1798238Notes

Reaction equation

HRID 1798238 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([OH:19])[CH:14]=[C:15]([CH2:16]OC)[C:7]1=2)[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].Br[C:28]1[N:29]=[CH:30][C:31]([C:34]([NH2:36])=[O:35])=[N:32][CH:33]=1>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:20])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:19][C:28]3[CH:33]=[N:32][C:31]([C:34](=[O:35])[NH2:36])=[CH:30][N:29]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 582925675-Bromopyrazine-2-carboxamideHCID 58292640(1,6-Dihydroxy-4-methoxymethyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester

Product 1

HCID 58292848[6-(5-Carbamoyl-pyrazin-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl esterYield 49.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of (1,6-dihydroxy-4-methoxymethyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester (150 mg, 0.600 mmol) and Cs2CO3 (430 mg, 1.32 mmol) in DMF (4 mL) was treated with 5-bromo-pyrazine-2-carboxylic acid amide (158 mg, 0.780 mmol) at room temperature and the reaction was heated to 80° C. for 2 h. The reaction mixture was concentrated to dryness. The residue was diluted with water and adjusted to pH 2 with 1N HCl. The aqueous phase was extracted with ethyl acetate. The organic phase was separated, dried (Na2SO4), and concentrated. The residue was purified by the flash column chromatography (silica, hexanes/ethyl acetate=1:2 to DCM/MeOH=10:1) to afford the title compound as a white solid (110 mg). 1H NMR (300 MHz, CD3OD) δ 8.90 (s, 1H), 8.34 (s, 1H), 7.48 (s, 1H), 7.35 (s, 1H), 7.08 (s, 1H), 5.70 (s, 1H), 5.69-5.66 (m, 1H), 4.21 (q, 2H), 3.14-3.12 (m, 1H), 2.49-2.41 (m, 1H), 2.37 (s, 3H), 1.26 (t, 1H). MS found: (M+H)+: 372.2.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. additionThe residue was diluted with water
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. customThe organic phase was separated
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by the flash column chromatography (silica, hexanes/ethyl acetate=1:2 to DCM/MeOH=10:1)

Sources & evidence

ORD record
ord-189ee6d9fcc8484b8921c3106e3b7cdc
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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