Cesium carbonate → HCID 74220870, compound

HRID 1051410Notes

Reaction equation

HRID 1051410 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([C:28]1[S:32][N:31]=[CH:30][N:29]=1)[S:7]([C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][C:18]=1[F:19])[N:15]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1I)[N:14]=[CH:13]2)(=[O:9])=[O:8].CC1(C)C(C)(C)OB([CH2:47]/[CH:48]=[CH:49]/[NH:50]C(=O)OC(C)(C)C)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1>[NH2:50][CH2:49]/[CH:48]=[CH:47]/[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[CH2:20][N:15]1[C:16]2[C:12](=[CH:11][C:10]([S:7]([NH:6][C:28]3[S:32][N:31]=[CH:30][N:29]=3)(=[O:8])=[O:9])=[C:18]([F:19])[CH:17]=2)[CH:13]=[N:14]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 90110743HCID 90110743, compoundHCID 125500631HCID 125500631, compound

Product 1

HCID 74220870HCID 74220870, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-(2,4-dimethoxybenzyl)-6-fluoro-1-(2-iodobenzyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indazole-5-sulfonamide (2-3, 0.068 g, 0.103 mmol, 1.0 equiv) in THF (0.94 mL) was added (E)-tert-butyl (3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)prop-1-en-1-yl)carbamate (0.088 g, 0.310 mmol, 3.0 equiv) and Pd(Cl)2dppf (0.008 g, 10.34 μmol, 0.1 equiv) followed by 1M cesium carbonate (0.094 mL) and the system was irradiated at 120° C. for 10 min. The reaction contents were extracted with EtOAc and water and the organic phase was dried over Na2SO4, filtered and concentrated. To this residue was added DCM (0.69 mL) followed by TFA (0.17 mL) and the system was stirred at room temperature for 1 h. The reaction contents were then concentrated in vacuo and purified by reverse phase chromatography (10%→70% 0.1% TFA in ACN: 0.1% TFA in water) to yield compound Ex-5 as a mono TFA salt. 1H NMR (400 MHz, CDCl3) δ 8.30-8.43 (m, 3H), 8.00 (br s, 2H), 7.80 (m, 1H), 7.50 (m, 1H), 7.18-7.39 (m, 3H), 6.80 (m, 1H), 6.20 (m, 1H), 5.70 (s, 2H), 2.45 (m, 3H). HRMS [M+H] C19H17FN6O2S2 calc'd 445.0911. found 445.0910.

Workup

  1. customthe system was irradiated at 120° C. for 10 min
  2. customThe reaction contents
  3. extractionwere extracted with EtOAc and water
  4. dry with materialthe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionTo this residue was added DCM (0.69 mL)
  8. customThe reaction contents
  9. concentrationwere then concentrated in vacuo
  10. custompurified by reverse phase chromatography (10%→70% 0.1% TFA in ACN: 0.1% TFA in water)

Sources & evidence

ORD record
ord-ce794602501d4cbfab340068ce32bbd7
Source dataset
uspto-grants-2016_07
Patent number
US09388179B2

Reaction notes

Loading…