Acetonitrile → HCID 86687648, compound

HRID 1473586Notes

Reaction equation

HRID 1473586 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:24]4[C:19](=[CH:20][C:21]([S:25](OC5C(F)=C(F)C(F)=C(F)C=5F)(=[O:27])=[O:26])=[CH:22][CH:23]=4)[CH:18]=[CH:17][N:16]=3)=[C:11]([O:40][CH3:41])[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.[O:42]1[CH:46]=[N:45][N:44]=[C:43]1[NH2:47].C(=O)([O-])[O-].[Cs+].[Cs+].C(#N)C>Cl>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:24]4[C:19](=[CH:20][C:21]([S:25]([NH:47][C:43]5[O:42][CH:46]=[N:45][N:44]=5)(=[O:27])=[O:26])=[CH:22][CH:23]=4)[CH:18]=[CH:17][N:16]=3)=[C:11]([O:40][CH3:41])[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 2397872-Amino-1,3,4-oxadiazoleHCID 86687644HCID 86687644, compound

Product 1

HCID 86687648HCID 86687648, compoundYield 46.4%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A vial was charged with perfluorophenyl 1-(3′,5′-difluoro-3-methoxy-[1,1′-biphenyl]-4-yl)isoquinoline-6-sulfonate (INTERMEDIATE KKKKK; 50.05 mg, 0.084 mmol), 1,3,4-oxadiazol-2-amine (7.89 mg, 0.093 mmol), cesium carbonate (82 mg, 0.253 mmol), and acetonitrile (0.42 mL). After 3 h or stirring, the mixture was diluted with 0.5 N aq. HCl, then extracted with EtOAc (3×), 20% MeOH/EtOAc (2×), and DCM (1×). The combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-7% MeOH/DCM) to give 1-(3′,5′-difluoro-3-methoxy-[1,1′-biphenyl]-4-yl)-N-(1,3,4-oxadiazol-2-yl)isoquinoline-6-sulfonamide (19.1 mg, 0.039 mmol, 45.8% yield) as a white foam. 1H NMR (400 MHz, DMSO-d6) δ=12.24 (br. s., 1H), 8.82 (d, J=2.0 Hz, 1H), 8.78 (d, J=5.7 Hz, 1H), 8.23 (d, J=5.3 Hz, 1H), 8.17 (s, 1H), 8.00-7.94 (m, 1H), 7.92-7.84 (m, 1H), 7.68-7.60 (m, 2H), 7.58-7.49 (m, 2H), 7.47-7.41 (m, 1H), 7.30 (tt, J=2.3, 9.3 Hz, 1H), 3.78 (s, 3H). m/z (ESI) 495.1 (M+H)+.

Workup

  1. extractionextracted with EtOAc (3×), 20% MeOH/EtOAc (2×), and DCM (1×)
  2. concentrationThe combined organic extracts were concentrated
  3. customThe residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-7% MeOH/DCM)

Sources & evidence

ORD record
ord-59e295ac21284a5ea7a4bd88341c374a
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…