1H-Indazole → (S)-ethyl 2-(2-(2-(1H-indazol-1-yl)pyridin-4-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

HRID 879370Notes

Reaction equation

HRID 879370 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:27]([CH3:28])=[CH:26][C:15]2[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][N:22]=[C:21](Cl)[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[NH:36]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:38]=[N:37]1.C([O-])([O-])=O.[K+].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C=O)C.CCOC(C)=O>[N:36]1([C:21]2[CH:20]=[C:19]([C:17]3[S:18][C:14]4[C:13]([C:29]5[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=5)=[C:12]([C@H:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:7]([O:9][CH2:10][CH3:11])=[O:8])[C:27]([CH3:28])=[CH:26][C:15]=4[N:16]=3)[CH:24]=[CH:23][N:22]=2)[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:38]=[N:37]1

Participants

7

Reactant 4

HCID 92211H-IndazoleHCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 86700142(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-chloropyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate

Product 1

HCID 86700177(S)-ethyl 2-(2-(2-(1H-indazol-1-yl)pyridin-4-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-chloropyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate (30 mg, 0.057 mmol) and 1H-indazole (6.0 mg, 0.052 mmol) in DMF (0.5 mL) was added K2CO3 (16.0 mg, 0.117 mmol) and 18-crown-6 (0.1 mg, 5.1×10−4 mmol). The reaction mixture was heated in a microwave at 160° C. for 1 h. After cooling, the reaction mixture was diluted with EtOAc, extracted with H2O, brine, dried over Na2SO4, filtered and concentrated and purified by flash column chromatography (silica gel, 0 to 60% ethyl acetate/hexanes) and then purified by reverse phase HPLC, eluting by 0-100% acetonitrile in H2O with 0.1% TFA to give the desired product. LCMS-ESI+ (m/z): [M+H]+ calcd for C34H32ClN4O3S: 611.2; found: 611.3.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with H2O, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash column chromatography (silica gel, 0 to 60% ethyl acetate/hexanes)
  7. custompurified by reverse phase HPLC
  8. washeluting by 0-100% acetonitrile in H2O with 0.1% TFA

Sources & evidence

ORD record
ord-a2c6036ded6541b89c89cb2c6e55593b
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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