Hydrochloric Acid → (2R)-5-[4-(2-Hydroxy-4-pyridin-3-ylbutoxy)phenyl]thiophene-2-sulfonic acid amide

HRID 1856698Notes

Reaction equation

HRID 1856698 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[Si]([O:14][C@H:15]([CH2:27][CH2:28][C:29]1[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=1)[CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)(C(C)(C)C)(C)C.Br[C:36]1[S:40][C:39]([S:41]([NH2:44])(=[O:43])=[O:42])=[CH:38][CH:37]=1.Cl>C(O)C.CO.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>[OH:14][C@H:15]([CH2:27][CH2:28][C:29]1[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=1)[CH2:16][O:17][C:18]1[CH:19]=[CH:20][C:21]([C:36]2[S:40][C:39]([S:41]([NH2:44])(=[O:43])=[O:42])=[CH:38][CH:37]=2)=[CH:22][CH:23]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 12413045-Bromo-2-thiophenesulfonamideHCID 11200434(2R)-4-[2-(tert-butyldimethylsilanyloxy)-4-pyridin-3-yl-butoxy]benzeneboronic acid

Product 1

HCID 53641749(2R)-5-[4-(2-Hydroxy-4-pyridin-3-ylbutoxy)phenyl]thiophene-2-sulfonic acid amide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolvent

Conditions

Temperature
90 °C

Procedure

2M Aqueous sodium carbonate (2.5 ml), (2R)-4-[2-(tert-butyldimethylsilanyloxy)-4-pyridin-3-yl-butoxy]benzeneboronic acid (Example 7b)), 1.0 g), and tetrakis(triphenylphosphine)palladium(0) (0.1 g) were added to a solution of 5-bromothiophene-2-sulfonic acid amide (1.21 g) in ethanol (25 ml). The mixture was heated at 90° C. for 4 hours. The mixture was cooled to room temperature and solvents were evaporated under reduced pressure. The reaction mixture was triturated with acetone (10 ml) and filtered through a short silica gel column. The column was eluted with a further 10 ml of acetone. The filtrate was evaporated before purification by normal-phase HPLC, eluting with a gradient of 0-10% ethanol in dichloromethane. The oil obtained was dissolved in methanol (25 ml), 2M hydrochloric acid (10 ml) was added and the solution stirred overnight at room temperature. The solid was filtered off, washed with methanol, water, and then diethyl ether. The product was liberated from its hydrochloride salt by stirring in 2M sodium hydrogencarbonate for 30 minutes. The resulting solid was collected by filtration and washed sequentially with water and diethyl ether to afford the title compound as a solid (0.56 g).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customsolvents were evaporated under reduced pressure
  3. customThe reaction mixture was triturated with acetone (10 ml)
  4. filtrationfiltered through a short silica gel column
  5. washThe column was eluted with a further 10 ml of acetone
  6. customThe filtrate was evaporated before purification by normal-phase HPLC
  7. washeluting with a gradient of 0-10% ethanol in dichloromethane
  8. customThe oil obtained
  9. filtrationThe solid was filtered off
  10. washwashed with methanol, water
  11. stirringby stirring in 2M sodium hydrogencarbonate for 30 minutes
  12. filtrationThe resulting solid was collected by filtration
  13. washwashed sequentially with water and diethyl ether

Sources & evidence

ORD record
ord-e8e0a9f73eb845eba40487c90d548dc1
Source dataset
uspto-grants-2000_11
Patent number
US06143751

Reaction notes

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