Potassium Carbonate → HCID 66731056, compound

HRID 1028031Notes

Reaction equation

HRID 1028031 reaction equation
[C:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([CH2:13][CH3:14])=[C:9]([F:12])[CH:10]=2)[NH:5][C:4]=1[C:15]1[N:20]=[CH:19][C:18]([S:21]([NH:24][C@@H:25]([CH3:30])[C:26]([F:29])([F:28])[F:27])(=[O:23])=[O:22])=[CH:17][CH:16]=1)#[N:2].Br[C:32]1[N:37]=[CH:36][CH:35]=[CH:34][N:33]=1.C(=O)([O-])[O-].[K+].[K+]>[Cu]I.CN(C=O)C>[C:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([CH2:13][CH3:14])=[C:9]([F:12])[CH:10]=2)[N:5]([C:32]2[N:37]=[CH:36][CH:35]=[CH:34][N:33]=2)[C:4]=1[C:15]1[N:20]=[CH:19][C:18]([S:21]([NH:24][C@@H:25]([CH3:30])[C:26]([F:29])([F:27])[F:28])(=[O:22])=[O:23])=[CH:17][CH:16]=1)#[N:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 783452-BromopyrimidineHCID 66730841HCID 66730841, compound

Product 1

HCID 66731056HCID 66731056, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of (S)-6-(3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (0.22 g, 0.5 mmol), prepared as above, 2-bromopyrimidine (0.167 g, 1.0 mmol), potassium carbonate (0.212 g, 1.5 mmol) and copper (I) iodide (20 mg, 0.1 mmol) were mixed with DMF (2.5 mL). The system was evacuated and replaced with an argon atmosphere. The reaction mixture was stirred at 110° C. for 70 hr, then cooled to 0° C., diluted with ethyl acetate and neutralized with 1N HCl. The ethyl acetate layer was washed with water, brine, dried over Na2SO4, filtrated through silica gel pad and evaporated. The crude product was triturated with CH2Cl2 and hexane and was further recrystallized from ethyl acetate and hexane. After air drying, the off-white solid (S)-6-(3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide was obtained. Melting point: 195-198° C.; MS m/z 519.1 M-1-H+; 1H NMR (500 MHz, acetone-d6): □ 8.90 (1H, dd, J=2.5, 1.0 Hz), 8.83 (2H, d, J=4.5 Hz), 8.49 (1H, dd, J=8.0, 2.5 Hz), 8.16 (1 H, t, J=6.5 Hz), 8.15 (1 H, d, J=9.0 Hz), 7.68 (1 H, br s), 7.57-7.54 (2H, m), 4.32 (1 H, br s), 2.85 (2 H, q, J=7.5 Hz), 1.29 (3 H, t, J=7.5 Hz), 1.28 (3 H, d, J=7.2 Hz).

Workup

  1. customThe system was evacuated
  2. temperaturecooled to 0° C.
  3. additiondiluted with ethyl acetate and neutralized with 1N HCl
  4. washThe ethyl acetate layer was washed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltrated through silica gel pad
  7. customevaporated
  8. customThe crude product was triturated with CH2Cl2 and hexane
  9. customwas further recrystallized from ethyl acetate and hexane
  10. customAfter air drying

Sources & evidence

ORD record
ord-15fae54828e24ada8db7ae2fd9f8b688
Source dataset
uspto-grants-2014_05
Patent number
US08735414B2

Reaction notes

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