Potassium Carbonate → 1-(5-chloro-6-(3-fluorophenyl)-2-methoxypyridin-3-yl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473645Notes

Reaction equation

HRID 1473645 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:11]2[C:20]3[C:15](=[CH:16][C:17]([S:21]([NH:24][C:25]4[S:26][CH:27]=[N:28][N:29]=4)(=[O:23])=[O:22])=[CH:18][CH:19]=3)[CH:14]=[CH:13][N:12]=2)[C:5]([O:9][CH3:10])=[N:6][C:7]=1Cl.[F:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:11]2[C:20]3[C:15](=[CH:16][C:17]([S:21]([NH:24][C:25]4[S:26][CH:27]=[N:28][N:29]=4)(=[O:23])=[O:22])=[CH:18][CH:19]=3)[CH:14]=[CH:13][N:12]=2)[C:5]([O:9][CH3:10])=[N:6][C:7]=1[C:35]1[CH:34]=[CH:33][CH:32]=[C:31]([F:30])[CH:36]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 866877161-(5,6-dichloro-2-methoxypyridin-3-yl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide

Product 1

HCID 866877171-(5-chloro-6-(3-fluorophenyl)-2-methoxypyridin-3-yl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A microwave vial was charged with 1-(5,6-dichloro-2-methoxypyridin-3-yl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide (0.032 g, 0.068 mmol), (3-fluorophenyl)boronic acid (0.014 g, 0.102 mmol), potassium carbonate (0.028 g, 0.205 mmol), and Pd(Ph3P)4 (7.90 mg, 6.83 μmol). The vial was flushed with Ar (g), then Dioxane (0.512 ml) and Water (0.171 ml) were added. The reaction was microwaved at 90° 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 dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-10% MeOH:DCM) to afford 1-(5-chloro-6-(3-fluorophenyl)-2-methoxypyridin-3-yl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ=8.80 (s, 1H), 8.74 (d, J=5.7 Hz, 1H), 8.60 (s, 1H), 8.19 (d, J=5.9 Hz, 1H), 8.12 (s, 1H), 7.91 (s, 2H), 7.74 (d, J=8.0 Hz, 1H), 7.72-7.67 (m, J=2.2, 9.7 Hz, 1H), 7.61 (dt, J=6.1, 7.9 Hz, 1H), 7.37 (dt, J=2.2, 8.5 Hz, 1H), 3.82 (s, 3H). m/z (ESI) 528.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. additionDioxane (0.512 ml) and Water (0.171 ml) were added
  3. customThe reaction was microwaved at 90° C. for one hour
  4. additionThe reaction was diluted with ethyl acetate
  5. washwashed with water
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. dry with materialthe combined organic layers were dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-10% MeOH:DCM)

Sources & evidence

ORD record
ord-8896672c050540f2b8699b3336ddf822
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…