Dichloromethane → (S)-ethyl 2-(2-(3-amino-1-methyl-1H-indazol-6-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

HRID 879489Notes

Reaction equation

HRID 879489 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([NH2:12])=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.C(Cl)Cl.CC([O-])=O.[K+].Br[C:22]1[S:23][C:24]2[C:30]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=3)=[C:29]([C@H:38]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[C:39]([O:41][CH2:42][CH3:43])=[O:40])[C:28]([CH3:49])=[CH:27][C:25]=2[N:26]=1.C([O-])([O-])=O.[K+].[K+]>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.O1CCOCC1>[NH2:12][C:6]1[C:5]2[C:9](=[CH:10][C:2]([C:22]3[S:23][C:24]4[C:30]([C:31]5[CH:32]=[CH:33][C:34]([Cl:37])=[CH:35][CH:36]=5)=[C:29]([C@H:38]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[C:39]([O:41][CH2:42][CH3:43])=[O:40])[C:28]([CH3:49])=[CH:27][C:25]=4[N:26]=3)=[CH:3][CH:4]=2)[N:8]([CH3:11])[N:7]=1

Participants

10

Reactant 5

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 468355496-Bromo-1-methyl-1H-indazol-3-amineHCID 86700141(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

Product 1

HCID 86700305(S)-ethyl 2-(2-(3-amino-1-methyl-1H-indazol-6-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A vessel was charged with 6-bromo-1-methyl-1H-indazol-3-amine (191 mg, 0.846 mmol), bis-pinacolatodiboron (236 mg, 0.930 mmol), PdCl2(dppf).DCM (69 mg, 85 μmol), glacial KOAc (273 mg, 2.79 mmol), and dioxane (3.2 mL). The reaction was heated to 100° C. for 1 h. To this reaction was added (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (420 mg, 0.846 mmol), 2 M aq K2CO3 (800 μL), and Pd(PPh3)4 (98 mg, 85 mmol). The reaction was heated for another 1 h at 100° C. The reaction was diluted with water and extracted with EtOAc (3×). Combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was treated with benzene and purification by flash column chromatography on silica gel (hexanes/ethyl acetate eluent) gave the title compound in semi-pure form. The mixture was treated with DCM and purification by flash column chromatography on silica gel (DCM/MeOH eluent) giving the title compound. LCMS-ESI+: calc'd for C30H31ClN4O3S: 563.2, 565.2 (M+H+); Found: 563.3, 565.3 (M+H+).

Workup

  1. temperatureThe reaction was heated for another 1 h at 100° C
  2. extractionextracted with EtOAc (3×)
  3. dry with materialCombined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe residue was treated with benzene and purification by flash column chromatography on silica gel (hexanes/ethyl acetate eluent)

Sources & evidence

ORD record
ord-363008c7f93d491a9c3a6ce407e56296
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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