Dichloromethane → HCID 86700204, compound

HRID 879397Notes

Reaction equation

HRID 879397 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH3:17])[N:12]=[CH:11]3)[N:5]=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.ClCCl.C([O-])(=O)C.[K+].Br[C:45]1[S:46][C:47]2[C:53]([C:54]3[CH:59]=[CH:58][C:57]([Cl:60])=[CH:56][CH:55]=3)=[C:52]([C@H:61]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])[C:62]([O:64][CH2:65][CH3:66])=[O:63])[C:51]([CH3:72])=[CH:50][C:48]=2[N:49]=1.C([O-])([O-])=O.[K+].[K+]>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:68]([O:67][C@@H:61]([C:52]1[C:51]([CH3:72])=[CH:50][C:48]2[N:49]=[C:45]([C:2]3[CH:3]=[C:4]([C:8]4[CH:9]=[C:10]5[C:14](=[CH:15][CH:16]=4)[N:13]([CH3:17])[N:12]=[CH:11]5)[N:5]=[N:6][CH:7]=3)[S:46][C:47]=2[C:53]=1[C:54]1[CH:55]=[CH:56][C:57]([Cl:60])=[CH:58][CH:59]=1)[C:62]([O:64][CH2:65][CH3:66])=[O:63])([CH3:69])([CH3:70])[CH3:71]

Participants

8

Reactant 6

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 86700141(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetateHCID 867002035-(5-chloropyridazin-3-yl)-1-methyl-1H-indazole

Product 1

HCID 86700204HCID 86700204, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

5-(5-chloropyridazin-3-yl)-1-methyl-1H-indazole (75.0 mg, 0.307 mmol), bis(pinacolato)diboron (101.2 mg, 0.398 mmol), [1,1′Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (37.5 mg, 0.046 mmol), and potassium acetate (90.2 mg, 0.920 mmol) were taken in a microwave vial, and the vial was vacuum pumped and flushed with argon three times. To this mixture was added degassed DMF (3 mL). The reaction mixture was heated at 110° C. for 2 h then cooled. To the cooled reaction mixture was added (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (180.0 mg, 0.368 mmol), tetrakis(triphenylphosphine)palladium(0) (53.1 mg, 0.046 mmol), K2CO3 (127.1 mg, 0.920 mmol) and degassed water (0.5 mL). The reaction mixture was heated to 110° C. for 2 h, cooled, filtered through Celite (ethyl acetate eluent), and concentrated. Purification by flash column chromatography on silica gel (hexanes/ethyl acetate eluent) provided the product. LCMS-ESI+ calc'd for C34H33ClN5O3S (M+H+): 626.2; Found: 625.5 (M+H+).

Workup

  1. customflushed with argon three times
  2. additionTo this mixture was added
  3. customdegassed DMF (3 mL)
  4. temperaturethen cooled
  5. customTo the cooled reaction mixture
  6. customdegassed water (0.5 mL)
  7. temperatureThe reaction mixture was heated to 110° C. for 2 h
  8. temperaturecooled
  9. filtrationfiltered through Celite (ethyl acetate eluent)
  10. concentrationconcentrated
  11. customPurification by flash column chromatography on silica gel (hexanes/ethyl acetate eluent)
  12. customprovided the product

Sources & evidence

ORD record
ord-e9012eb478414b22ab142c8b44f47236
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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