1,4-Dioxane → HCID 178468576, compound

HRID 2068281Notes

Reaction equation

HRID 2068281 reaction equation
[NH2:1][C:2]1[N:6]([C@H:7]2[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:9][CH2:8]2)[C:5]2[CH:21]=[CH:22][C:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:24][C:4]=2[N:3]=1.[Br:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[N:36]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[N:35]=[C:34]2I.O1CCOCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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]>[Br:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[N:36]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[N:35]=[C:34]2[NH:1][C:2]1[N:6]([C@H:7]2[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:15])[CH3:16])[CH2:9][CH2:8]2)[C:5]2[CH:21]=[CH:22][C:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:24][C:4]=2[N:3]=1

Participants

7

Reactant 5

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 583172565-Bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazoleHCID 178468579HCID 178468579, compound

Product 1

HCID 178468576HCID 178468576, compoundYield 54.7%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A mixture of ethyl 2-amino-1-(trans-4-(tert-butyldimethylsilyloxy)cyclohexyl)-1H-benzo[d]imidazole-5-carboxylate (102 mg, 0.000244 mol), 5-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (130 mg, 0.00029 mol), 1,4-dioxane (0.6 mL, 0.007 mol), potassium phosphate (78 mg, 0.00037 mol), xantphos (34 mg, 0.000059 mol) and tris(dibenzylideneacetone)dipalladium(0) (20 mg, 0.00002 mol) was placed in a microwave reaction vessel. The reaction mixture was stirred under nitrogen and the sides were washed down with additional 1,4-dioxane (0.5 mL). The reaction vessel was irradiated under microwave radiation for 60 minutes at 130° C. The reaction mixture was diluted with ethyl acetate and washed with aqueous saturated sodium bicarbonate and then brine. The organic phase was dried over sodium sulfate and concentrated to a brown residue which was purified by combiflash chromatography on a 40 g silica gel cartridge using an initial eluent of 10% ethyl acetate-90% hexanes for 5 minutes then a gradient to 30% ethyl acetate over the next 15 minutes. Concentration of the product fractions gave a yellow oil (99.1 mg).

Workup

  1. customwas placed in a microwave reaction vessel
  2. washthe sides were washed down with additional 1,4-dioxane (0.5 mL)
  3. customThe reaction vessel was irradiated under microwave radiation for 60 minutes at 130° C
  4. additionThe reaction mixture was diluted with ethyl acetate
  5. washwashed with aqueous saturated sodium bicarbonate
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. concentrationconcentrated to a brown residue which
  8. customwas purified by combiflash chromatography on a 40 g silica gel cartridge
  9. customfor 5 minutes
  10. customover the next 15 minutes

Sources & evidence

ORD record
ord-c7cde0bcffd840e09b861fee7d1753db
Source dataset
uspto-grants-2012_10
Patent number
US08293923B2

Reaction notes

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