Dichloromethane → HCID 86608527, compound

HRID 244141Notes

Reaction equation

HRID 244141 reaction equation
ClC1C([CH:8]([C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[N:26]=[CH:25][C:24]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[N:23]3)[N:9]2[C:17](=O)C3C(=CC=CC=3)C2=O)=NC=CN=1.NN.[CH2:38]([Cl:40])Cl>CCO>[Cl:40][C:38]1[C:17]([NH:9][CH2:8][C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[N:26]=[CH:25][C:24]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[N:23]3)=[N:23][CH:22]=[CH:27][N:26]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 9321HydrazineHCID 53629052HCID 53629052, compound

Product 1

HCID 86608527HCID 86608527, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A flask containing crude (3-chloropyrazin-2-yl)(3-phenylquinoxalin-6-yl)methanol (153 mg, 0.44 mmol) was flashed with Ar and charged with phthalimide (71 mg, 0.48 mmol) and triphenylphosphine (130 mg, 0.48 mmol) and anh. THF (10 mL). DIAD (0.1 mL, 0.48 mmol) was added slowly dropwise at rt and then the reaction was stirred at rt for 16 h. The reaction was concentrated under reduced pressure and purified by flash chromatography (silica gel, 5% EtOAc in DCM to 10%) affording 2-[(3-chloropyrazin-2-yl)(3-phenylquinoxalin-6-yl)methyl]-1H-isoindole-1,3(2H)-dione compound as a creamy solid. To stirred solution of the crude 2-[(3-chloropyrazin-2-yl)(3-phenylquinoxalin-6-yl)methyl]-1H-isoindole-1,3(2H)-dione (147 mg, 0.31 mmol) in anh. EtOH (12 mL) and anh. DCM (2 mL) under Ar was added anh. hydrazine (0.03 mL, 0.9 mmol). The reaction mixture was stirred at rt for 22 h. The 1:1 mixture of the product and a partially cleaved phthalimide was concentrated under reduced pressure at rt and dried under high vacuum overnight. The light yellow, solid residue was dissolved in anh. i-PrOH (6 mL) and anh. CHCl3 (3 mL) and heated under Ar at 50° C. for 16 h. Later the reaction was cooled to rt, evaporated to dryness and triturated with DCM. The DCM aliquots were filtered through a pad of Celite affording the title compound as a light yellow solid; 1H NMR (400 MHz, CD3OD/CDCl3) δ 9.37 (s, 1H), 8.71 (d, J=2.4 Hz, 1H), 8.39 (d, J=2.4 Hz, 1H), 8.23 (d, J=6.8 Hz, 2H), 8.12 (s, 1H), 8.06 (d, J=8.4 Hz, 1H), 7.88 (dd, J=0.8 Hz, 8.8 Hz, 1H), 7.62-7.52 (m, 3H), 5.81 (s, 1H). MS (ES+): m/z 348.0 (40) [MH+]; HPLC: tR=2.08 min (OpenLynx, polar—5 min).

Workup

  1. additionThe 1:1 mixture of the product
  2. concentrationa partially cleaved phthalimide was concentrated under reduced pressure at rt
  3. customdried under high vacuum overnight
  4. dissolutionThe light yellow, solid residue was dissolved in anh. i-PrOH (6 mL)
  5. temperatureanh. CHCl3 (3 mL) and heated under Ar at 50° C. for 16 h
  6. temperatureLater the reaction was cooled to rt
  7. customevaporated to dryness
  8. customtriturated with DCM
  9. filtrationThe DCM aliquots were filtered through a pad of Celite

Sources & evidence

ORD record
ord-47dab5a3621e49bbbd33b0c9cb35490b
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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