Acetonitrile → 1-(4-chloro-5-cyano-2-methoxyphenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473552Notes

Reaction equation

HRID 1473552 reaction equation
[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([C:10]2[C:19]3[C:14](=[CH:15][C:16]([S:20](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:22])=[O:21])=[CH:17][CH:18]=3)[CH:13]=[CH:12][N:11]=2)=[C:4]([O:35][CH3:36])[CH:3]=1.[S:37]1[CH:41]=[N:40][N:39]=[C:38]1[NH2:42].C(=O)([O-])[O-].[Cs+].[Cs+].C(#N)C>CCOC(C)=O.Cl>[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([C:10]2[C:19]3[C:14](=[CH:15][C:16]([S:20]([NH:42][C:38]4[S:37][CH:41]=[N:40][N:39]=4)(=[O:21])=[O:22])=[CH:17][CH:18]=3)[CH:13]=[CH:12][N:11]=2)=[C:4]([O:35][CH3:36])[CH:3]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 199091,3,4-Thiadiazol-2-amineHCID 86687608Perfluorophenyl 1-(4-chloro-5-cyano-2-methoxyphenyl)isoquinoline-6-sulfonate

Product 1

HCID 866876101-(4-chloro-5-cyano-2-methoxyphenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamideYield 53.7%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A vial was charged with perfluorophenyl 1-(4-chloro-5-cyano-2-methoxyphenyl)isoquinoline-6-sulfonate (INTERMEDIATE VVVV, 145.2 mg, 0.268 mmol). 1,3,4-thiadiazol-2-amine (32.6 mg, 0.322 mmol), and cesium carbonate (262 mg, 0.805 mmol). Acetonitrile (1342 μl) was added, and the mixture was stirred for 2 h. The mixture was diluted with EtOAc and 0.5 N aq. HCl. The layers were separated, and the aq. layer was extracted with 10% MeOH/EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was concentrated from MeOH, then the mixture was filtered through a membrane filter. The collected solid was washed with MeOH (3×), dried under a stream of N2 (g), then dried under vacuum to give 1-(4-chloro-5-cyano-2-methoxyphenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide (65.89 mg, 0.144 mmol, 53.6% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=14.51 (br. s., 1H), 8.80 (s, 1H), 8.70 (d, J=5.7 Hz, 1H), 8.58 (d, J=1.6 Hz, 1H), 8.16 (d, J=5.7 Hz, 1H), 7.98 (s, 1H), 7.89-7.82 (m, 1H), 7.80-7.72 (m, 1H), 7.65 (s, 1H), 3.78 (s, 3H). m/z (ESI) 458.2 (M+H)+.

Workup

  1. customThe layers were separated
  2. extractionthe aq. layer was extracted with 10% MeOH/EtOAc (2×)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. concentrationThe residue was concentrated from MeOH
  7. filtrationthe mixture was filtered through a membrane
  8. filtrationfilter
  9. washThe collected solid was washed with MeOH (3×)
  10. dry with materialdried under a stream of N2 (g)
  11. customdried under vacuum

Sources & evidence

ORD record
ord-d5e86923a62c42d78ac1ad29d2de8092
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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