Sodium hydride → HCID 10141230, compound

HRID 989685Notes

Reaction equation

HRID 989685 reaction equation
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].[H-].[Na+].[C:8]([C:10]1[CH:11]=[CH:12][C:13]2[N:19]([CH2:20][CH2:21]S)[CH2:18][C@@H:17]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[N:16]([S:30]([CH2:33][CH2:34][CH3:35])(=[O:32])=[O:31])[CH2:15][C:14]=2[CH:36]=1)#[N:9]>C1COCC1.C(Cl)Cl>[C:8]([C:10]1[CH:11]=[CH:12][C:13]2[N:19]([CH2:20][CH2:21][NH:5][S:2]([CH3:1])(=[O:4])=[O:3])[CH2:18][C@@H:17]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[N:16]([S:30]([CH2:33][CH2:34][CH3:35])(=[O:31])=[O:32])[CH2:15][C:14]=2[CH:36]=1)#[N:9]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 72879MethanesulfonamideHCID 10296290HCID 10296290, compound

Product 1

HCID 10141230HCID 10141230, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methanesulfonamide (23.8 mg, 0.25 mmol) was added to a suspension of sodium hydride (10 mg, 0.25 mmol, 60% in oil, washed with hexanes) in THF (1.5 mL). The mixture was stirred at rt for 30 min. and Compound B of Example 27 (47.6 mg, 0.1 mmol) was added. The resulting mixture was stirred at reflux temperature for 16 hours. The reaction mixture was cooled to rt, diluted with DCM (10 mL) and washed with water. The DCM solution was dried over Na2SO4 and concentrated. The residue was purified by preparative HPLC (Column: YMC S-5 ODS 100×20 mm; UV: 220 nm; Flow rate: 20 mL/min; solvent: gradient from 50-90% MeOH in water containing 0.1% TFA in 10 min.). The fractions containing the desired products were pooled and concentrated to afford the title compound as a colorless foam, 5.2 mg (10.6%) MS m/e 491 (M+H)+; 489(M−H)−.

Workup

  1. stirringThe resulting mixture was stirred
  2. temperatureat reflux temperature for 16 hours
  3. temperatureThe reaction mixture was cooled to rt
  4. washwashed with water
  5. dry with materialThe DCM solution was dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC (Column: YMC S-5 ODS 100×20 mm; UV: 220 nm; Flow rate: 20 mL/min; solvent: gradient from 50-90% MeOH in water containing 0.1% TFA in 10 min.)
  8. additionThe fractions containing the desired products
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c3fb7c1bd6204b2886e97045ee93c2aa
Source dataset
uspto-grants-2002_10
Patent number
US06458783B1

Reaction notes

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