Sodium Carbonate → HCID 44609857, compound

HRID 1963782Notes

Reaction equation

HRID 1963782 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.[Cl:12][C:13]1[C:18]([NH:19][S:20]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)(=[O:22])=[O:21])=[CH:17][C:16](B2OC(C)(C)C(C)(C)O2)=[CH:15][N:14]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[Cl:12][C:13]1[C:18]([NH:19][S:20]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)(=[O:22])=[O:21])=[CH:17][C:16]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH:8]=[N:7][CH:6]=[CH:5]3)=[CH:15][N:14]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 3136816-BromoisoquinolineHCID 218864351,4-Dioxane--water (1/1)HCID 53363355n-[2-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]-4-fluorobenzene-1-sulfonamide

Product 1

HCID 44609857HCID 44609857, compoundYield 8.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

(Some starting materials may be obtained from Kalexsyn, Kalamazoo, Mich.) A glass microwave reaction vessel was charged with 6-bromoisoquinoline (120 mg, 0.58 mmol), N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide (262 mg, 0.6 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (32 mg, 0.04 mmol), sodium carbonate (183 mg, 1.730 mmol), and dioxane-H2O (2:1, 3 mL). The reaction mixture was sealed and heated at 100° C. for 1 h. Water was added in, and the suspension was filtered, the solid was air-dry. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 2% to 5% MeOH in CH2Cl2 to provide N-(2-chloro-5-(isoquinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide (20 mg, 8.4% yield) as a white solid. MS (ESI pos. ion) m/z: calc'd for C20H13ClFN3O2S:413.0; found: 414.0(MH+). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.44(t,J=8.80 Hz, 2 H) 7.82-7.85 (m, 2 H) 7.93 (d, J=5.87 Hz, 1 H) 8.00 (dd, J=8.61, 1.37 Hz, 1 H) 8.16 (d, J=2.15 Hz, 1 H) 8.29 (d, J=8.61 Hz, 1 H) 8.33 (s, 1 H) 8.58 (d, J=5.67 Hz, 1 H) 8.75 (s, 1 H) 9.40 (s, 1 H) 10.58 (s, 1 H).

Workup

  1. custom) A glass microwave reaction vessel
  2. customThe reaction mixture was sealed
  3. filtrationwas filtered
  4. customthe solid was air-dry
  5. customThe crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
  6. washeluting with a gradient of 2% to 5% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-78f373411b474fc9b48c8b3de87aa23c
Source dataset
uspto-grants-2013_04
Patent number
US08415376B2

Reaction notes

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