Potassium Phosphate, Tribasic → 2-(3-(2,4-difluorophenyl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole

HRID 634163Notes

Reaction equation

HRID 634163 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1B1OC(C)(C)C(C)(C)O1.I[C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:36]3[S:37][C:38]([S:41]([CH3:44])(=[O:43])=[O:42])=[N:39][N:40]=3)[CH:34]=2)[N:29]([S:45]([C:48]2[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=2)(=[O:47])=[O:46])[CH:28]=1>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.CC(O)C.O>[F:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:36]3[S:37][C:38]([S:41]([CH3:44])(=[O:43])=[O:42])=[N:39][N:40]=3)[CH:34]=2)[N:29]([S:45]([C:48]2[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=2)(=[O:47])=[O:46])[CH:28]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 162176522-(2,4-Difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 683282122-(3-iodo-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole

Product 1

HCID 683286122-(3-(2,4-difluorophenyl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazoleYield 37.5%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 21889133Propan-2-ol--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

A mixture of potassium phosphate tribasic (1.309 g, 6.17 mmol, Aldrich), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.044 g, 0.062 mmol, Aldrich), 2,4-difluorophenylboronic acid pinacol ester (0.740 g, 3.08 mmol, Aldrich), 2-(3-iodo-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole (1.15 g, 2.056 mmol), and IPA/H2O (70%, 10 mL) was heated at 80° C. for 2 h. The mixture was partially concentrated to remove most IPA, and the aq. layer was extracted with DCM. The aq. layer was acidified with 2M HCl and extracted again with DCM. The combined DCM fractions were evaporated and purified by prep HPLC (50-95% AcCN/H2O/0.1% TFA) to give 2-(3-(2,4-difluorophenyl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole (0.42 g, 0.770 mmol, 37.4%) as a light yellow solid. MS (ESI, pos. ion) m/z 546 (M+1).

Workup

  1. concentrationThe mixture was partially concentrated
  2. customto remove most IPA
  3. extractionthe aq. layer was extracted with DCM
  4. extractionextracted again with DCM
  5. customThe combined DCM fractions were evaporated
  6. custompurified by prep HPLC (50-95% AcCN/H2O/0.1% TFA)

Sources & evidence

ORD record
ord-865d605dfff24052b33096189df91e88
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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