Water → (2R)-N-hydroxy-2-methyl-4-[4-(2-methyl-1H-indol-5-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamide

HRID 84244Notes

Reaction equation

HRID 84244 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH3:7][C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[CH:14][C:13](B1OC(C)(C)C(C)(C)O1)=[CH:12][CH:11]=2.[OH:26][NH:27][C:28](=[O:45])[C@:29]([CH3:44])([S:40]([CH3:43])(=[O:42])=[O:41])[CH2:30][CH2:31][N:32]1[CH:37]=[CH:36][C:35](I)=[CH:34][C:33]1=[O:39].O>O1CCOCC1.[Pd]>[OH:26][NH:27][C:28](=[O:45])[C@:29]([CH3:44])([S:40]([CH3:43])(=[O:42])=[O:41])[CH2:30][CH2:31][N:32]1[CH:37]=[CH:36][C:35]([C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[NH:9][C:8]([CH3:7])=[CH:16]3)=[CH:34][C:33]1=[O:39]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 184506482-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-indoleHCID 86671930(2R)-N-hydroxy-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanamide

Product 1

HCID 86671929(2R)-N-hydroxy-2-methyl-4-[4-(2-methyl-1H-indol-5-yl)-2-oxopyridin-1(2H)-yl]-2-(methylsulfonyl)butanamideYield 22%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Pd EnCat™ (93 mg, 0.03 mmol) was added to a mixture of potassium carbonate (115 mg, 0.83 mmol), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (86 mg, 0.33 mmol), and (2R)-N-hydroxy-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanamide (115 mg, 0.28 mmol) in dioxane:water (2.5 mL, 5:1 mixture). The reaction mixture was heated overnight at 80° C. The reaction was cooled to ambient temperature, filtered through a nylon filter and concentrated. The material was dissolved in a minimal amount of DMSO and loaded onto a 13g c18 column. The gradient was run from 25-45% acetonitrile in water. The desired material was concentrated yielding 25 mg (22%) of a light brown solid. LCMS m/z 418.5 (M+1) 1H NMR (400 MHz, DMSO-d6) δ ppm 1.58 (s, 3 H) 2.13-2.24 (m, 1 H) 2.32-2.46 (m, 1 H) 2.39 (s, 3 H) 3.12 (s, 3 H) 3.69-3.78 (m, 1 H) 4.06-4.16 (m, 1 H) 6.20 (s, 1 H) 6.65 (d, J=1.95 Hz, 1 H) 6.70 (dd, J=7.22, 1.95 Hz, 1 H) 7.31-7.39 (m, 2 H) 7.70 (d, J=7.22 Hz, 1 H) 7.79 (s, 1 H) 9.25 (br. s., 1 H) 11.11 (br. s., 1 H) 11.23 (br. s., 1 H)

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. filtrationfiltered through a nylon
  3. filtrationfilter
  4. concentrationconcentrated
  5. dissolutionThe material was dissolved in a minimal amount of DMSO
  6. concentrationThe desired material was concentrated

Sources & evidence

ORD record
ord-c41bd8d323f24cafb52412319aa768ac
Source dataset
uspto-grants-2014_09
Patent number
US08846933B2

Reaction notes

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