Dimethylformamide → HCID 66731351, compound

HRID 1028018Notes

Reaction equation

HRID 1028018 reaction equation
[C:1]([NH:5][S:6]([C:9]1[CH:10]=[N:11][C:12]([C:15]2[NH:16][C:17]3[C:22]([C:23]=2[S:24]([CH3:27])(=[O:26])=[O:25])=[CH:21][C:20]([F:28])=[C:19]([CH2:29][CH3:30])[CH:18]=3)=[CH:13][CH:14]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:32]1[N:37]=[CH:36][CH:35]=[CH:34][N:33]=1.C([O-])([O-])=O.[K+].[K+].CN(C=O)C>O.[Cu]I>[C:1]([NH:5][S:6]([C:9]1[CH:10]=[N:11][C:12]([C:15]2[N:16]([C:32]3[N:37]=[CH:36][CH:35]=[CH:34][N:33]=3)[C:17]3[C:22]([C:23]=2[S:24]([CH3:27])(=[O:26])=[O:25])=[CH:21][C:20]([F:28])=[C:19]([CH2:29][CH3:30])[CH:18]=3)=[CH:13][CH:14]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 783452-BromopyrimidineHCID 66730887HCID 66730887, compound

Product 1

HCID 66731351HCID 66731351, compoundYield 91%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of N-tert-butyl-6-(6-ethyl-5-fluoro-3-(methylsulfonyl)-1H-indol-2-yl)pyridine-3-sulfonamide (115 mg, 0.25 mmol), 2-bromopyrimidine (88 mg, 0.55 mmol), CuI (28 mg, 0.15 mmol), K2CO3 (160 mg, 1.15 mmol), and DMF (0.5 mL) was heated at 110° C. for 15 hours. The reaction mixture was diluted in water and extracted into ethyl acetate. The organic layer was washed with water and then with brine. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. Purification by silica gel chromatography (40% ethyl acetate in hexanes) yielded N-tert-butyl-6-(6-ethyl-5-fluoro-3-(methylsulfonyl)-1-(pyrimidin-2-yl)-1H-indol-2-yl)pyridine-3-sulfonamide (121 mg, 91%) as a white solid. Melting point: 244-248° C.; MS m/z 532.2 M+H+; 1H NMR (DMSO-d6, 500 MHz): δ 8.82 (d, 1H, J=2 Hz), 8.73 (d, 2H, 5.0 Hz), 8.23 (dd, 1H, J=8.0 Hz, 2 Hz), 8.05 (d, 1H, J=6.5 Hz), 7.96 (d, 1H, J=8 Hz), 7.87 (s, 1H), 7.76 (d, 1H, 10.5 Hz), 7.51 (t, 1H, J=5 Hz), 3.38 (s, 3H), 2.78 (q, 2H, J=7.5 Hz), 1.23 (t, 3H, 3.75 Hz), 1.13 (s, 9H).

Workup

  1. extractionextracted into ethyl acetate
  2. washThe organic layer was washed with water
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by silica gel chromatography (40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a472aa32644f47de9dc0207510d62648
Source dataset
uspto-grants-2014_05
Patent number
US08735414B2

Reaction notes

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