Potassium Phosphate, Tribasic → 2-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-5-phenyl-1,3,4-thiadiazole

HRID 634240Notes

Reaction equation

HRID 634240 reaction equation
[C:1]1([C:7]2[S:11][C:10]([C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][CH:20]=3)[N:17]([S:21]([C:24]3[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:16]=[C:15]4B(O)O)=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:35]1[CH:40]=[N:39][CH:38]=[C:37]([CH:41]2[CH2:43][CH2:42]2)[N:36]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>[CH:41]1([C:37]2[N:36]=[C:35]([C:15]3[C:14]4[C:18](=[CH:19][CH:20]=[C:12]([C:10]5[S:11][C:7]([C:1]6[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=6)=[N:8][N:9]=5)[CH:13]=4)[N:17]([S:21]([C:24]4[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=4)(=[O:23])=[O:22])[CH:16]=3)[CH:40]=[N:39][CH:38]=2)[CH2:43][CH2:42]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 457883052-Bromo-6-cyclopropylpyrazineHCID 683286685-(5-phenyl-1,3,4-thiadiazol-2-yl)-1-tosyl-1H-indol-3-ylboronic acid

Product 1

HCID 683281772-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-5-phenyl-1,3,4-thiadiazoleYield 67.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalyst

Conditions

Temperature
130 °C

Procedure

To a 20 mL microwave vial was added 5-(5-phenyl-1,3,4-thiadiazol-2-yl)-1-tosyl-1H-indol-3-ylboronic acid (245 mg, 0.515 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (14.7 mg, 0.031 mmol), Pd2(dba)3 (14.2 mg, 0.015 mmol), 2-bromo-6-cyclopropylpyrazine (118 mg, 0.593 mmol) (CombiPhos Catalysts Inc.) and potassium phosphate (328 mg, 1.55 mmol) followed by purging with argon. The solids were treated with dioxane (4.0 mL) and H2O (0.4 mL) and heated in the microwave at 130° C. for 20 min. The mixture was treated with H2O and extracted with EtOAc, dried over MgSO4, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 10-80% EtOAc in Hex) to give 2-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-5-phenyl-1,3,4-thiadiazole (191 mg, 67%) as a light yellow amorphous solid. (ESI, pos. ion) m/z: 550.1 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 9.01 (1H, s), 8.77 (1H, s), 8.43 (1H, s), 8.17-8.22 (2H, m), 8.11-8.16 (1H, m), 8.03 (2H, dd, J=6.6, 2.8 Hz), 7.86 (2H, d, J=8.4 Hz), 7.48-7.55 (3H, m), 7.28 (2H, d, J=8.4 Hz), 2.36 (3H, s), 2.14-2.22 (1H, m), 1.29-1.34 (2H, m), 1.17-1.24 (2H, m).

Workup

  1. customby purging with argon
  2. additionThe solids were treated with dioxane (4.0 mL) and H2O (0.4 mL)
  3. additionThe mixture was treated with H2O
  4. extractionextracted with EtOAc
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified with silica gel chromatography (eluting with 10-80% EtOAc in Hex)

Sources & evidence

ORD record
ord-5b293c9f64894887b4c990c996bdc515
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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