Dichloromethane → HCID 25070421, compound

HRID 1893443Notes

Reaction equation

HRID 1893443 reaction equation
Br[C:2]1[CH:3]=[C:4]([S:8]([NH2:11])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].C(Cl)Cl.I[C:39]1[N:43]2[C:44]3[C:49]([N:50]=[C:51]([NH:52][CH2:53][CH2:54][CH2:55][OH:56])[C:42]2=[N:41][CH:40]=1)=[CH:48][C:47]([C:57]([F:60])([F:59])[F:58])=[CH:46][CH:45]=3.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.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].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:56][CH2:55][CH2:54][CH2:53][NH:52][C:51]1[C:42]2[N:43]([C:39]([C:2]3[CH:3]=[C:4]([S:8]([NH2:11])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=3)=[CH:40][N:41]=2)[C:44]2[C:49]([N:50]=1)=[CH:48][C:47]([C:57]([F:60])([F:59])[F:58])=[CH:46][CH:45]=2

Participants

11

Reactant 6

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 27347653-Bromobenzene-1-sulfonamideHCID 593332953-{[1-Iodo-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4-yl]amino}propan-1-ol

Product 1

HCID 25070421HCID 25070421, compoundYield 28.6%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 3-bromobenzenesulfonamide (50 mg, 0.21 mmol), bis(pinacolato)diboron (54 mg, 0.21 mmol), potassium acetate (78 mg, 0.80 mmol) and Pd(dppf)Cl2.DCM (9 mg, 0.0105 mmol) in anhydrous dimethylformamide (1 mL) was degassed under argon for 10 minutes and then stirred at 80° C. for 2 h. The reaction mixture was allowed to cool to room temperature and 3-{[1-iodo-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4-yl]amino}propan-1-ol (46 mg, 0.105 mmol), an aqueous solution of sodium carbonate 2M (367 μL, 0.735 mmol) and Pd(PPh3)4 (5 mg, 0.0042 mmol) was added. The mixture was stirred under argon at 80° C. overnight and then cooled to room temperature, diluted with cold water and extracted four times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and evaporated. The crude product was purified by preparative TLC (silica gel, dichloromethane/methanol 90/10) to afford 3-{4-[(3-hydroxypropyl)amino]-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-1-yl}benzenesulfonamide (14 mg, 28%) as a white solid.

Workup

  1. temperatureto cool to room temperature
  2. stirringThe mixture was stirred under argon at 80° C. overnight
  3. temperaturecooled to room temperature
  4. extractionextracted four times with ethyl acetate
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by preparative TLC (silica gel, dichloromethane/methanol 90/10)

Sources & evidence

ORD record
ord-59312357f6994823b302cb3dbbd63e90
Source dataset
uspto-grants-2013_08
Patent number
US08513250B2

Reaction notes

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