Acetic Anhydride → HCID 18663644, compound

HRID 1956719Notes

Reaction equation

HRID 1956719 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH2:10][NH:11][C:12]1[C:15](=[O:16])[C:14](=[O:17])[C:13]=1[NH:18][C:19]([CH3:23])([CH3:22])[CH2:20][CH3:21])[C:5]#[N:6].[H-].[Na+].[C:26](OC(=O)C)(=[O:28])[CH3:27]>O1CCCC1.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]#[N:6])[CH:7]=[CH:8][C:9]=1[CH2:10][N:11]([C:12]1[C:15](=[O:16])[C:14](=[O:17])[C:13]=1[NH:18][C:19]([CH3:22])([CH3:23])[CH2:20][CH3:21])[C:26](=[O:28])[CH3:27]

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 24758Sodium hydrideHCID 10687975HCID 10687975, compound

Product 1

HCID 18663644HCID 18663644, compoundYield 54.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-chloro-4-{[2-(1,1-dimethyl-propylamino)-3,4-dioxo-cyclobut-1-enylamino]-methyl}-benzonitrile (0.829 g, 2.50 mmol, Example 76) in tetrahydrofuran (10 mL) and N,N-dimethylformamide (5 mL) was treated with sodium hydride (0.066 g, 2.75 mmol) and stirring was continued for 15 minutes. Acetic anhydride (0.281 g, 2.75 mmol) was added. After stirring 40 minutes at room temperature, solvent was removed and the residue was partitioned between ethyl acetate and brine, and the brine fraction was extracted with ethyl acetate. The combined ethyl acetate fractions were washed with dilute, aqueous sodium carbonate solution, with brine and dried (anhydrous sodium sulfate). Removal of solvent gave a yellow solid that was chromatographed (gravity, chloroform) on silica. The appropriate fractions were freed of solvent and the foamy residue was solidified by addition-rotoevaporation of hexane (twice). Recrystallization (twice) of the solid from acetone-hexane gave 513 mg of the title compound as a white solid: mp 150.5°-151.0° C. (softens 149.5° C.); 1H NMR (DMSO-d6) δ7.90-9.22 (broad hump, 1H), 8.10 (s, 1H), 7.84 (m, 1H), 7.51 (d, 1H), 5.29 (br s, 2H), 2.16 (s, 3H), 1.71 (q, 2H), 1.35 (s, 6H), 0.85 (t, 3H) ppm. IR (KBr): 3300, 3080, 2230, 1790, 1720, 1680 cm-1. MS (m/z) 373/375 (M+). HPLC indicates a major component (>99%).

Workup

  1. stirringAfter stirring 40 minutes at room temperature
  2. customsolvent was removed
  3. customthe residue was partitioned between ethyl acetate and brine
  4. extractionthe brine fraction was extracted with ethyl acetate
  5. washThe combined ethyl acetate fractions were washed
  6. additionwith dilute
  7. dry with materialaqueous sodium carbonate solution, with brine and dried (anhydrous sodium sulfate)
  8. customRemoval of solvent
  9. customgave a yellow solid
  10. customthat was chromatographed (gravity, chloroform) on silica
  11. additionthe foamy residue was solidified by addition-rotoevaporation of hexane (twice)
  12. customRecrystallization (twice) of the solid from acetone-hexane

Sources & evidence

ORD record
ord-ec0122b873e248a68d7e8785071142cb
Source dataset
uspto-grants-1998_07
Patent number
US05780505

Reaction notes

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