Methyl iodide → HCID 71285981, compound

HRID 246192Notes

Reaction equation

HRID 246192 reaction equation
[OH:1][CH2:2][C@@H:3]([NH:10][C:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:22]3[C:30]4[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=4)[N:24]([CH3:32])[N:23]=3)[N:20]=2)[N:15]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[CH:14]=1)=[O:12])[CH2:4][CH2:5][S:6]([CH3:9])(=[O:8])=[O:7].[OH-].[K+].[CH2:43]1OCCOCCOCCOCCOCCOC1.IC>C1COCC1>[CH3:43][O:1][CH2:2][C@@H:3]([NH:10][C:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:22]3[C:30]4[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=4)[N:24]([CH3:32])[N:23]=3)[N:20]=2)[N:15]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:39])([CH3:38])[CH3:40])[CH:14]=1)=[O:12])[CH2:4][CH2:5][S:6]([CH3:9])(=[O:7])=[O:8]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 2855718-Crown-6HCID 71286101HCID 71286101, compound

Product 1

HCID 71285981HCID 71285981, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a 10 mL round-bottomed flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-hydroxymethyl-3-methanesulfonyl-propyl)-amide (102 mg, 0.173 mmol) was dissolved in THF (1.9 ml) to give a colorless solution. The reaction was cooled in an ice bath and crushed KOH (97 mg, 1.73 mmol), 18-crown-6 (46 mg, 0.173 mmol), and iodomethane (11 μl, 0.173 mmol) were added successively. The reaction mixture was stirred at 0° C. for 1 h after which the ice bath was removed. The reaction mixture was stirred at room temperature for 2 h then diluted with dichloromethane (10 mL) and washed with aqueous ammonium chloride (10 mL), water (10 mL), and saturated sodium bicarbonate (10 mL). The organic layer was dried over Na2SO4 and concentrated. The crude material was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 0%-60% EtOAc) to afford 30 mg (29%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-methoxymethyl-3-methanesulfonyl-propyl)-amide as an off-white solid. MS: [M+Na]+=627).

Workup

  1. customto give a colorless solution
  2. temperatureThe reaction was cooled in an ice bath
  3. additionwere added successively
  4. customwas removed
  5. additionthen diluted with dichloromethane (10 mL)
  6. washwashed with aqueous ammonium chloride (10 mL), water (10 mL), and saturated sodium bicarbonate (10 mL)
  7. dry with materialThe organic layer was dried over Na2SO4
  8. concentrationconcentrated
  9. customThe crude material was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 0%-60% EtOAc)

Sources & evidence

ORD record
ord-f84d92ec9f1c47cab0109905da144682
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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