Sodium hydride → HCID 44247543, compound

HRID 1621273Notes

Reaction equation

HRID 1621273 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([S:10]([CH2:12][C:13]([NH:15][C:16]2[CH:20]=[C:19]([CH3:21])[O:18][N:17]=2)=[O:14])=[O:11])=[CH:2]1.[H-].[Na+].[Cl:24][C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH2:28]Br>CN(C=O)C>[Cl:24][C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH2:28][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([S:10]([CH2:12][C:13]([NH:15][C:16]2[CH:20]=[C:19]([CH3:21])[O:18][N:17]=2)=[O:14])=[O:11])=[CH:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 698381-(Bromomethyl)-3-chlorobenzeneHCID 68003850HCID 68003850, compound

Product 1

HCID 44247543HCID 44247543, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

In a 10 mL vial, 2-((1H-indol-3-yl)sulfinyl)-N-(5-methylisoxazol-3-yl)acetamide (50.0 mg, 0.165 mmol) from Step D was dissolved in DMF (5 mL) and cooled to 0° C. Sodium hydride (60% by weight, 13.0 mg, 0.330 mmol) was then added in one portion and the reaction mixture vigorously stirred at 0° C. for 15 minutes. 3-chloro-benzylbromide (21.6 μL, 0.165 mmol) was added in one portion and the reaction mixture was stirred while being allowed to warm to ambient temperature over 3 hours. The reaction mixture was quenched with water (2 mL) and the solution was extracted with ethyl acetate (3×2 mL). The combined organics were dried over magnesium sulfate and concentrated in vacuo to give an oily residue which was purified on a silica gel column (0-50% ethyl acetate:hexanes over 19 min) to yield the title compound (24 mg, 0.056 mmol, 34% yield). LCMS>98% 220 nm, RT=1.26 min, m/z=428 (m+1). 1H NMR (400 MHz, DMSOD6) 11.32 (s, 1H), 8.19 (s, 1H), 8.00 (d, J=7.8 Hz, 1H), 7.61 (d, J=8.2 Hz, 1H), 7.38 (s, 1H), 7.21-7.36 (m, 4H), 7.15 (d, J=7.2 Hz, 1H), 6.61 (s, 1H), 5.52 (s, 2H), 4.58 (d, J=13.1 Hz, 1H), 4.14 (d, J=13.1 Hz, 1H), 2.38 (s, 3H).

Workup

  1. stirringthe reaction mixture was stirred
  2. temperatureto warm to ambient temperature over 3 hours
  3. customThe reaction mixture was quenched with water (2 mL)
  4. extractionthe solution was extracted with ethyl acetate (3×2 mL)
  5. dry with materialThe combined organics were dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give an oily residue which
  8. customwas purified on a silica gel column (0-50% ethyl acetate:hexanes over 19 min)

Sources & evidence

ORD record
ord-ab47260077b74175b493836068e664b3
Source dataset
uspto-grants-2014_07
Patent number
US08772509B2

Reaction notes

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