Potassium Carbonate → 4-(3'-fluoro-4-methoxy-[1,1'-biphenyl]-3-yl)-N-(pyrimidin-4-yl)quinoline-7-sulfonamide

HRID 1473517Notes

Reaction equation

HRID 1473517 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]3[CH:21]=[CH:20][N:19]=[CH:18][N:17]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.ClC1C=CC=CC=1B(O)O.C(=O)([O-])[O-].[K+].[K+].[F:38][C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[CH:43][CH:44]=1.[CH3:48][O:49][C:50]1[CH:51]=[CH:52][CH:53]=[C:54](OC)[C:55]=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[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>[F:38][C:39]1[CH:40]=[C:41]([C:53]2[CH:52]=[CH:51][C:50]([O:49][CH3:48])=[C:55]([C:2]3[C:11]4[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]5[CH:21]=[CH:20][N:19]=[CH:18][N:17]=5)(=[O:14])=[O:13])=[CH:9][CH:10]=4)[N:5]=[CH:4][CH:3]=3)[CH:54]=2)[CH:42]=[CH:43][CH:44]=1

Participants

8

Reactant 6

HCID 11430Potassium CarbonateHCID 62657Potassium Phosphate, TribasicHCID 27339863-Fluorophenylboronic acidHCID 27343222-Chlorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl2×HCID 866874614-chloro-N-(pyrimidin-4-yl)quinoline-7-sulfonamide

Product 1

HCID 866875724-(3'-fluoro-4-methoxy-[1,1'-biphenyl]-3-yl)-N-(pyrimidin-4-yl)quinoline-7-sulfonamideYield 13.98%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

A vial was charged with 4-chloro-N-(pyrimidin-4-yl)quinoline-7-sulfonamide (INTERMEDIATE OOOO, 103.75 mg, 0.323 mmol), (2-chlorophenyl)boronic acid (53.1 mg, 0.340 mmol), potassium carbonate (134 mg, 0.970 mmol), and Pd(Ph3P)4 (18.69 mg, 0.016 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (1213 μl) and water (404 μl) were added. The vial was sealed and heated in a Biotage Initiator microwave reactor for 1 h at 100° C. LCMS showed about 5% starting material remaining. (3-fluorophenyl)boronic acid (100 mg, 0.712 mmol), S-Phos Precatalyst (Strem Chemical, Newburyport, Mass., 24.50 mg, 0.032 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (6.64 mg, 0.016 mmol), and potassium phosphate (206 mg, 0.970 mmol) were added. The vial was heated in the microwave at 100° C. for 1 h. The mixture was extracted with EtOAc (3×). The combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (25-g Interchim 15-micron column, 3.5% MeOH/DCM). Several mixed fractions were discarded. Those fractions containing clean product were combined and concentrated to give 4-(3′-fluoro-4-methoxy-[1,1′-biphenyl]-3-yl)-N-(pyrimidin-4-yl)quinoline-7-sulfonamide (22 mg, 0.045 mmol, 13.98% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=13.30-12.39 (m, 1H), 9.13-9.07 (m, 1H), 8.63-8.53 (m, 2H), 8.28 (d, J=5.4 Hz, 1H), 7.93 (ddd, J=2.2, 8.8, 17.8 Hz, 2H), 7.74 (d, J=8.8 Hz, 1H), 7.69-7.62 (m, 2H), 7.59-7.52 (m, 2H), 7.50-7.41 (m, 1H), 7.34 (d, J=8.7 Hz, 1H), 7.17-7.11 (m, 1H), 7.06 (d, J=5.5 Hz, 1H), 3.72 (s, 3H). m/z (ESI) 487.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (1213 μl) and water (404 μl) were added
  3. customThe vial was sealed
  4. temperatureThe vial was heated in the microwave at 100° C. for 1 h
  5. extractionThe mixture was extracted with EtOAc (3×)
  6. concentrationThe combined organic extracts were concentrated
  7. customThe residue was purified by chromatography on silica gel (25-g Interchim 15-micron column, 3.5% MeOH/DCM)
  8. additionSeveral mixed fractions
  9. additionThose fractions containing clean product
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-76f27f2a36c7454fa502514fb341650b
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…