Sodium Carbonate → N-(2-Chloro-5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)pyridin-3-yl)-4-methoxybenzenesulfonamide

HRID 1963795Notes

Reaction equation

HRID 1963795 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:9][S:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=1.[O:21]1[CH2:26][CH2:25][O:24][C:23]2[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][C:22]1=2.C(=O)([O-])[O-].[Na+].[Na+]>CCO.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:8][C:5]1[C:4]([NH:9][S:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)(=[O:12])=[O:11])=[CH:3][C:2]([C:28]2[CH:29]=[CH:30][C:22]3[O:21][CH2:26][CH2:25][O:24][C:23]=3[CH:27]=2)=[CH:7][N:6]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2776178(2,3-Dihydro-1,4-benzodioxin-6-yl)boronic acidHCID 51355175HCID 51355175, compound

Product 1

HCID 58229519N-(2-Chloro-5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)pyridin-3-yl)-4-methoxybenzenesulfonamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

A 15 mL sealed pressure tube was charged with N-(5-bromo-2-chloropyridin-3-yl)-4-methoxybenzenesulfonamide (190 mg, 0.503 mmol), 2,3-dihydrobenzo[b][1,4]dioxin-6-ylboronic acid (100 mg, 0.553 mmol) in EtOH (1.5 ml). Pd(PPh3)4 (29 mg, 0.025 mmol) was added, followed by sodium carbonate (2M, 0.629 mL). The tube was purged with argon, backfilled with argon, sealed and stirred at 85° C. for 1.5 hours. The crude was partitioned between water and methylene chloride and extracted with methylene chloride (3×, 10 ml). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo. The solid was purified by ISCO with a 20-50% gradient of EtOAc in hexanes to afford desired product. MS (ESI pos. ion) m/z calcd for C20H12ClN2O5S: 432.8; found 433.3 1H NMR (400 MHz, DMSO-d6) δ ppm 3.83 (s, 3 H), 4.30 (s, 4 H), 6.99 (d, J=8.3 Hz, 1 H), 7.06-7.15 (m, 4 H), 7.61-7.72 (m, 2 H), 7.78 (d, J=2.3 Hz, 1 H), 8.47 (s, 1 H), 10.21 (s, 1 H).

Workup

  1. customA 15 mL sealed pressure tube
  2. customThe tube was purged with argon
  3. customsealed
  4. customThe crude was partitioned between water and methylene chloride
  5. extractionextracted with methylene chloride (3×, 10 ml)
  6. dry with materialThe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe solid was purified by ISCO with a 20-50% gradient of EtOAc in hexanes

Sources & evidence

ORD record
ord-a7b5ef18add048eab39cd255800af012
Source dataset
uspto-grants-2013_04
Patent number
US08415376B2

Reaction notes

Loading…