Acetonitrile → HCID 44541045, compound

HRID 1695799Notes

Reaction equation

HRID 1695799 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[CH:18]=[C:17]([Sn](C)(C)C)[CH:16]=[C:15]3[C:11]=2[CH:12]=[N:13][N:14]3S(C2C=CC=CC=2)(=O)=O)=[O:8])[N:6]=1.Br[C:33]1[CH:38]=[CH:37][C:36]([S:39]([NH2:42])(=[O:41])=[O:40])=[CH:35][CH:34]=1.CC#N>CN(C=O)C.Cl[Pd]C1C=CC=CC=1C1C=CC=CC=1N(C)C.[C@H]12C[C@H](CC1)CC2PC1C[C@H]2C[C@@H]1CC2>[NH2:42][S:39]([C:36]1[CH:37]=[CH:38][C:33]([C:17]2[CH:16]=[C:15]3[C:11]([CH:12]=[N:13][NH:14]3)=[C:10]([NH:9][C:7]([C:5]3[N:6]=[C:2]([CH3:1])[S:3][CH:4]=3)=[O:8])[CH:18]=2)=[CH:34][CH:35]=1)(=[O:41])=[O:40]

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 696964-BromobenzenesulfonamideHCID 582558202-Methyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

Product 1

HCID 44541045HCID 44541045, compoundYield 6.7%

Reagents, catalysts & solvents 2

HCID 178420574HCID 178420574, compoundCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
135 °C

Procedure

2-Methyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide (101 mg) was dissolved in DMF (0.4 ml) and added to 4-bromobenzenesulfonamide (42.5 mg) in DMF (0.4 ml). Chloro[2′-(dimethylamino)-2-biphenylyl]palladium-(1R,4S)-bicyclo[2.2.1]hept-2-yl[(1S,4R)-bicyclo[2.2.1]hept-2-yl]phosphane (1:1) (4 mg, heaped microspatula) was added to the reaction which was then heated under microwave irradiation at 135° C. for 20 min. The reaction was loaded onto a C18 SPE pre-conditioned with MeCN:0.1% TFA (aq), eluted with 3 ml MeCN:0.1% TFA (aq) then evaporated to dryness. The residue was dissolved in DMSO (0.5 ml) and purified by MDAP (method C). The residue was then dissolved in IPA (0.3 ml) and 2M NaOH (0.3 ml) was added. The reaction was stirred at RT for 18 h then diluted with DMSO (0.6 ml) and purified by MDAP (method D) to give the title compound (5 mg).

Workup

  1. wash0.1% TFA (aq), eluted with 3 ml MeCN
  2. custom0.1% TFA (aq) then evaporated to dryness
  3. dissolutionThe residue was dissolved in DMSO (0.5 ml)
  4. custompurified by MDAP (method C)
  5. dissolutionThe residue was then dissolved in IPA (0.3 ml)
  6. addition2M NaOH (0.3 ml) was added
  7. additionthen diluted with DMSO (0.6 ml)
  8. custompurified by MDAP (method D)

Sources & evidence

ORD record
ord-ba20874753b447578a64ab00d82fbeb0
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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