Water → (2R)-4-{4-[4-(4-methoxy-2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 1475889Notes

Reaction equation

HRID 1475889 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH3:7][O:8][C:9]1[CH:13]=[N:12][N:11]([C:14]2[CH:19]=[CH:18][C:17](B3OC(C)(C)C(C)(C)O3)=[CH:16][CH:15]=2)[N:10]=1.I[C:30]1[CH:35]=[CH:34][N:33]([CH2:36][CH2:37][C@@:38]([CH3:53])([S:49]([CH3:52])(=[O:51])=[O:50])[C:39]([NH:41][O:42][CH:43]2[CH2:48][CH2:47][CH2:46][CH2:45][O:44]2)=[O:40])[C:32](=[O:54])[CH:31]=1.O>O1CCOCC1.[Pd]>[CH3:7][O:8][C:9]1[CH:13]=[N:12][N:11]([C:14]2[CH:15]=[CH:16][C:17]([C:30]3[CH:35]=[CH:34][N:33]([CH2:36][CH2:37][C@@:38]([CH3:53])([S:49]([CH3:52])(=[O:51])=[O:50])[C:39]([NH:41][O:42][CH:43]4[CH2:48][CH2:47][CH2:46][CH2:45][O:44]4)=[O:40])[C:32](=[O:54])[CH:31]=3)=[CH:18][CH:19]=2)[N:10]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 57326595(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideHCID 672500254-Methoxy-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2H-1,2,3-triazole

Product 1

HCID 86671958(2R)-4-{4-[4-(4-methoxy-2H-1,2,3-triazol-2-yl)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

Pd EnCat (98 mg, 0.03 mmol) was added to a mixture of potassium carbonate (171 mg, 1.24 mmol), 4-methoxy-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2H-1,2,3-triazole (138 mg, 0.457 mmol) and (2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide which may be produced as in Preparation 2B(T6) (190 mg, 0.381 mmol) in dioxane:water (6 ml, 5:1 mix) in a 20 ml vial. The reaction was cooled and filtered through celite (approx 1 inch). The celite was washed with additional methanol (100 ml). The filtrate was concentrated in vacuo and the crude material was purified by chromatography on silica gel (4:1 heptane:EtOAc to 100% EtOAc to 85% EtOAc:15% methanol) to furnish a light tan gum (120 mg, 58% TY). MS (LC/MS) m/z 546.2 (M+1). 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.28 (s, 1H) 1.57-1.70 (m, 2H) 1.68-1.81 (m, 3H) 1.78-1.92 (m, 3H) 2.36-2.50 (m, 1H) 2.55-2.72 (m, 1H) 3.09-3.21 (m, 3H) 3.56-3.70 (m, 1H) 4.07 (s, 3H) 4.12 (d, J=7.22 Hz, 2H) 4.15-4.25 (m, 1H) 4.25-4.42 (m, 1H) 5.01-5.14 (m, 1H) 6.76-6.85 (m, 1H) 6.87 (s, 1H) 7.49 (s, 1H) 7.68-7.80 (m, 1H) 7.85 (d, J=9.17 Hz, 2H) 8.08 (d, J=8.98 Hz, 2H)

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered through celite (approx 1 inch)
  3. washThe celite was washed with additional methanol (100 ml)
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe crude material was purified by chromatography on silica gel (4:1 heptane:EtOAc to 100% EtOAc to 85% EtOAc:15% methanol)
  6. customto furnish a light tan gum (120 mg, 58% TY)

Sources & evidence

ORD record
ord-9d25df598ece401db180613fe36a8f79
Source dataset
uspto-grants-2015_04
Patent number
US09018384B2

Reaction notes

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