Dimethylformamide → HCID 86687675, compound

HRID 1473610Notes

Reaction equation

HRID 1473610 reaction equation
FC(F)(F)S(O[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([S:17](=[O:36])(=[O:35])[N:18](CC3C=CC(OC)=CC=3OC)[C:19]3[S:20][CH:21]=[CH:22][N:23]=3)[CH:15]=2)[C:10]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=2[O:44][CH3:45])=[N:9][CH:8]=1)(=O)=O.[CH3:48][N:49](C=O)C.C(O)(C(F)(F)F)=O>C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[C-]#N.[Zn+2].[C-]#N>[C:48]([C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([S:17]([NH:18][C:19]3[S:20][CH:21]=[CH:22][N:23]=3)(=[O:36])=[O:35])[CH:15]=2)[C:10]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=2[O:44][CH3:45])=[N:9][CH:8]=1)#[N:49]

Participants

8

Reactant 3

HCID 6228DimethylformamideHCID 6422Trifluoroacetic acidHCID 86687674HCID 86687674, compound

Product 1

HCID 86687675HCID 86687675, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A vial was charged with 6-(N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)sulfamoyl)-1-(4-fluoro-2-methoxyphenyl)isoquinolin-4-yl trifluoromethanesulfonate (0.140 g, 0.196 mmol), Pd2(dba)3 (0.018 g, 0.020 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.022 g, 0.039 mmol), and zinc cyanide (0.025 ml, 0.392 mmol). DMF (1.962 ml) was added, and the reaction was stirred at 80° C. for one hour. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-50% EtOAc:Heptane). The material was dissolved in DCM and TFA (0.1 ml, 1.298 mmol) was added. The reaction was stirred at room temperature for 30 minutes. The reaction was concentrated and purified via column chromatography (RediSep Gold 12 g, gradient elution 25-100% EtOAc:Heptane) to afford 4-cyano-1-(4-fluoro-2-methoxyphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=13.06 (br. s., 1H), 9.26 (s, 1H), 8.50 (d, J=1.5 Hz, 1H), 8.06 (dd, J=1.7, 8.9 Hz, 1H), 7.94 (d, J=8.9 Hz, 1H), 7.44 (dd, J=6.8, 8.4 Hz, 1H), 7.32 (d, J=4.6 Hz, 1H), 7.20 (dd, J=2.3, 11.4 Hz, 1H), 7.00 (dt, J=2.4, 8.4 Hz, 1H), 6.92 (d, J=4.6 Hz, 1H), 3.68 (s, 3H). m/z (ESI) 441.2 (M+H)+.

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-50% EtOAc:Heptane)
  8. dissolutionThe material was dissolved in DCM
  9. stirringThe reaction was stirred at room temperature for 30 minutes
  10. concentrationThe reaction was concentrated
  11. custompurified via column chromatography (RediSep Gold 12 g, gradient elution 25-100% EtOAc:Heptane)

Sources & evidence

ORD record
ord-dfdc36fa36bd4dd288a8854574c0eb17
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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