Sodium Carbonate → N-(4-{(E)-2-[3-tert-butyl-5-(2,6-dimethoxy-pyridin-3-yl)-2-methoxy-phenyl]-vinyl}-3-methoxymethyl-phenyl) methanesulfonamide

HRID 2390856Notes

Reaction equation

HRID 2390856 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:26]([CH3:29])([CH3:28])[CH3:27])[C:5]([O:24][CH3:25])=[C:6](/[CH:8]=[CH:9]/[C:10]2[CH:15]=[CH:14][C:13]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])=[CH:12][C:11]=2[CH2:21][O:22][CH3:23])[CH:7]=1.[CH3:30][O:31][C:32]1[C:37](B(O)O)=[CH:36][CH:35]=[C:34]([O:41][CH3:42])[N:33]=1.C([O-])([O-])=O.[Na+].[Na+]>CO.C(Cl)Cl.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>[C:26]([C:4]1[C:5]([O:24][CH3:25])=[C:6](/[CH:8]=[CH:9]/[C:10]2[CH:15]=[CH:14][C:13]([NH:16][S:17]([CH3:20])(=[O:18])=[O:19])=[CH:12][C:11]=2[CH2:21][O:22][CH3:23])[CH:7]=[C:2]([C:37]2[C:32]([O:31][CH3:30])=[N:33][C:34]([O:41][CH3:42])=[CH:35][CH:36]=2)[CH:3]=1)([CH3:27])([CH3:28])[CH3:29]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2762707(2,6-Dimethoxypyridin-3-yl)boronic acidHCID 67286866N-{4-[(E)-2-(5-bromo-3-tert-butyl-2-methoxy-phenyl)-vinyl]-3-methoxymethyl-phenyl}-methanesulfonamide

Product 1

HCID 68537390N-(4-{(E)-2-[3-tert-butyl-5-(2,6-dimethoxy-pyridin-3-yl)-2-methoxy-phenyl]-vinyl}-3-methoxymethyl-phenyl) methanesulfonamideYield 79.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

step 1—A sealed tube containing 315 (117 mg, 0.243 mmol), 2,6-dimethoxy-pyridin-3-yl boronic acid (53 mg, 0.290 mmol, CASRN 221006-70-8), Pd(PPh3)4 (28 mg, 0.024 mmol), Na2CO3 (76 mg, 0.717 mmol) in a mixture of MeOH (3 mL) and DCM (1 mL) was irradiated in a microwave reactor at 115° C. for 30 minutes. The reaction mixture was concentrated, diluted with EtOAc, washed with brine and dried (Na2SO4), filtered and concentrated. The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (20% to 30% EtOAc) to afford 104 mg (79%) of N-(4-{(E)-2-[3-tert-butyl-5-(2,6-dimethoxy-pyridin-3-yl)-2-methoxy-phenyl]-vinyl}-3-methoxymethyl-phenyl) methanesulfonamide (322) as a colorless oil.

Workup

  1. customstep 1—A sealed tube
  2. customwas irradiated in a microwave reactor at 115° C. for 30 minutes
  3. concentrationThe reaction mixture was concentrated
  4. additiondiluted with EtOAc
  5. washwashed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by SiO2 chromatography
  10. washeluting with an EtOAc/hexane gradient (20% to 30% EtOAc)

Sources & evidence

ORD record
ord-3feb1da521004014be8e809ee5a57147
Source dataset
uspto-grants-2012_09
Patent number
US08273773B2

Reaction notes

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