Iodoethane → 4-[4-(2,4-Difluorophenoxy)-1-methyl-1H-benzimidazol-5-yl]-6-ethyl-1-[(4-methylphenyl)sulfonyl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one

HRID 1056995Notes

Reaction equation

HRID 1056995 reaction equation
[F:1][C:2]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:3]=1[O:4][C:5]1[C:13]2[N:12]=[CH:11][N:10]([CH3:14])[C:9]=2[CH:8]=[CH:7][C:6]=1[C:15]1[C:16]2[CH:24]=[CH:23][N:22]([S:25]([C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[C:17]=2[C:18](=[O:21])[NH:19][CH:20]=1.[CH3:40][C:41](C)([O-])C.[K+].ICC>O1CCCC1>[F:1][C:2]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:3]=1[O:4][C:5]1[C:13]2[N:12]=[CH:11][N:10]([CH3:14])[C:9]=2[CH:8]=[CH:7][C:6]=1[C:15]1[C:16]2[CH:24]=[CH:23][N:22]([S:25]([C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[C:17]=2[C:18](=[O:21])[N:19]([CH2:40][CH3:41])[CH:20]=1

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 23665647Potassium tert-butoxideHCID 1180938474-[4-(2,4-Difluorophenoxy)-1-methyl-1H-benzimidazol-5-yl]-1-[(4-methylphenyl)sulfonyl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one

Product 1

HCID 1180938854-[4-(2,4-Difluorophenoxy)-1-methyl-1H-benzimidazol-5-yl]-6-ethyl-1-[(4-methylphenyl)sulfonyl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-oneYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of 4-[4-(2,4-difluorophenoxy)-1-methyl-1H-benzimidazol-5-yl]-1-[(4-methylphenyl)sulfonyl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (33.2 mg, 0.0607 mmol) in tetrahydrofuran (1.0 mL) at 0° C. was treated with 1.0 M solution of potassium tert-butoxide in THF (0.0850 mL, 0.0850 mmol) and the resultant reaction mixture was stirred at 0° C. for 30 min, after which time the reaction mixture was treated with iodoethane (0.00680 mL, 0.0850 mmol), warmed to RT and stirred at RT for 19 h. The reaction mixture was quenched with saturated ammonium chloride solution, diluted with water, and extracted with ethyl acetate. Layers were separated and the organic layer was washed with brine, dried with sodium sulfate, filtered, and concentrated in vacuo to give a crude residue. Purification via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min) gave the desired product (15.4 mg, 44%). LCMS calculated for C30H25F2N4O4S (M+H)+: m/z=575.2. found: 575.1.

Workup

  1. customthe resultant reaction mixture
  2. temperaturewarmed to RT
  3. stirringstirred at RT for 19 h
  4. customThe reaction mixture was quenched with saturated ammonium chloride solution
  5. additiondiluted with water
  6. extractionextracted with ethyl acetate
  7. customLayers were separated
  8. washthe organic layer was washed with brine
  9. dry with materialdried with sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give a crude residue
  13. customPurification via preparative LCMS (XBridge C18 column
  14. washeluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-82a985cb972b4cce97b86921ca75d758
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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