Hydrochloric Acid → HCID 67110273, compound

HRID 1481131Notes

Reaction equation

HRID 1481131 reaction equation
[CH2:1]([O:5][C:6]([C:8]1[N:9]=[CH:10][C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([S:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].CC1C=C(C)[N:30]=[C:29](C)C=1.CC1C([IH+])=C(C)N=C(C)C=1.F[P-](F)(F)(F)(F)F.C([Cu])#N.Cl>C(Cl)Cl.O.CN(C=O)C>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([C:29]#[N:30])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([S:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 46863890C16H22F6IN2PHCID 667130924-Hydroxy-7-phenylsulfanyl-isoquinoline-3-carboxylic acid butyl esterHCID 178418546HCID 178418546, compound

Product 1

HCID 67110273HCID 67110273, compoundYield 85.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

A mixture of 4-hydroxy-7-phenylsulfanyl-isoquinoline-3-carboxylic acid butyl ester (300 mg, 0.85 mmol) (prepared according to WO 2004108681) and bis(2,4,6-trimethylpyridine)iodine(I) hexafluorophosphate (1.09 g, 2.12 mmol) in CH2Cl2 (10 mL) was stirred at r.t. for 16 h, then diluted with CH2Cl2 (50 mL). The resulting mixture was washed with 5% sodium thiosulfate and 1 M HCl. The organic layer was dried over MgSO4 and concentrated. To the residue were added CuCN (152 mg, 1.70 mmol) and anhydrous DMF (10 mL), and the resulting mixture was refluxed for 20 min. The reaction mixture was poured into a mixture of CH2Cl2 and water. 4 M HCl was added with vigorous stirring until no solid was observed. The aqueous layer was extracted with additional CH2Cl2, and the organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by column chromatography (0-30% EtOAc/hexanes) to give 274 mg of the title compound as a white solid. MS: (+) m/z 379.09 (M+1).

Workup

  1. washThe resulting mixture was washed with 5% sodium thiosulfate and 1 M HCl
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated
  4. temperaturethe resulting mixture was refluxed for 20 min
  5. stirringwith vigorous stirring until no solid
  6. extractionThe aqueous layer was extracted with additional CH2Cl2
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography (0-30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-23aa9949406442a9b882be717c6bfd51
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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