Toluene → HCID 12051844, compound

HRID 991785Notes

Reaction equation

HRID 991785 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]2[C:11](=[O:22])[C:12](=[O:21])[C:13]=2[NH:14][CH:15]([CH3:20])[C:16]([CH3:19])([CH3:18])[CH3:17])=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.[CH3:30][N:31](C=O)C>[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[O:21]=[C:12]1[C:11](=[O:22])[C:10](/[CH:9]=[CH:8]/[C:5]2[CH:6]=[CH:7][C:2]([C:30]#[N:31])=[CH:3][CH:4]=2)=[C:13]1[NH:14][CH:15]([CH3:20])[C:16]([CH3:19])([CH3:18])[CH3:17]

Participants

6

Reactant 3

HCID 1140TolueneHCID 6228DimethylformamideHCID 12051843HCID 12051843, compound

Product 1

HCID 12051844HCID 12051844, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

The title compound was prepared via cyano-debromination (Tschaen, Synth. Comm. 1994, 24, 887) of the title compound of Example 26. To a mixture of 3-[(E)-2-(4-bromo-phenyl)-vinyl]-4-(1,2,2-trimethyl-propylamino)-cyclobut-3-ene-1,2-dione (400 mg, 1.10 mmol) and zinc (II) cyanide (77.8 mg, 0.662 mmol) in DMF (1.20 mL) was added tetrakis(triphenylphosphine) palladium (0) (76.6 mg, 0.0662) under an atmosphere of Argon. The reaction mixture was heated to 100° C., stirred 18 hours, then worked up by dilution with toluene (150 mL), followed by consecutive extraction with ammonium hydroxide (3×50 mL) and brine (50 mL). The organic phase was further diluted with ethyl acetate (300 mL), dried over MgSO4, filtered through a short pad of diatomaceous earth, and then concentrated onto silica gel. Submission to flash chromatography (multiple gradient elution with ether-petroleum ether) afforded a yellow solid which was triturated with ether-hexanes. Drying under high vacuum at 60° C. yielded the title compound (248 mg, 73%) as a hydroscopic yellow solid (1H NMR in DMSO-d6 suggested the presence of amide rotamers in a ratio of approximately 4:1): m.p. 240.2-241.0° C.; 1H NMR (DMSO-d6) δ8.96(d,1H), 7.83(m,4H), 7.64(d,1H), 7.48(d,1H), 4.03(dq,1H), 1.20(d,3H), 0.90(s,9H); IR (KBr) 3450, 3250, 3290, 2960, 1770, 1725, 1620, 1600, 1500, 1480, 1440, 1405, 1170, 1140, 1080, 980, 825, 755; MS (m/z) 309 [(M+H)+], 331 [(M+Na)+].

Workup

  1. customThe title compound was prepared via cyano-debromination (Tschaen, Synth. Comm. 1994, 24, 887) of the title compound of Example 26
  2. extractionfollowed by consecutive extraction with ammonium hydroxide (3×50 mL) and brine (50 mL)
  3. additionThe organic phase was further diluted with ethyl acetate (300 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered through a short pad of diatomaceous earth
  6. concentrationconcentrated onto silica gel
  7. washSubmission to flash chromatography (multiple gradient elution with ether-petroleum ether)
  8. customafforded a yellow solid which
  9. customwas triturated with ether-hexanes
  10. customDrying under high vacuum at 60° C.

Sources & evidence

ORD record
ord-fa38c7cbd4f04554afe0d0fa2f207c52
Source dataset
uspto-grants-2002_10
Patent number
US06465523B1

Reaction notes

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