Cesium carbonate → 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-5-(tert-butyl-dimethyl-silanoxy)-indole-1-carboxylic acid tert-butyl ester

HRID 2111162Notes

Reaction equation

HRID 2111162 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][S:15][C:11]=2[C:10](I)=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17]([Si:21]([CH3:43])([CH3:42])[O:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:27](B(O)O)=[CH:26]2)([CH3:20])([CH3:19])[CH3:18].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C(OCC)(=O)C>[C:35]([O:34][C:32]([N:28]1[C:29]2[C:25](=[CH:24][C:23]([O:22][Si:21]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:42])[CH3:43])=[CH:31][CH:30]=2)[CH:26]=[C:27]1[C:10]1[C:11]2[S:15][CH:14]=[CH:13][C:12]=2[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[N:9]=1)=[O:33])([CH3:38])([CH3:37])[CH3:36]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 22285134[1-(tert-Butoxycarbonyl)-5-{[tert-butyl(dimethyl)silyl]oxy}-1H-indol-2-yl]boronic acidHCID 576372991,1-Dimethylethyl 3-iodo-1H-thieno[3,2-c]pyrazole-1-carboxylate

Product 1

HCID 113076212-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-5-(tert-butyl-dimethyl-silanoxy)-indole-1-carboxylic acid tert-butyl esterYield 61%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3-iodo-thieno[3,2-c]pyrazole-1-carboxylic acid tert-butyl ester (200 mg, 0.57 mmol, Example 5B) and bis-(diphenylphosphinoferrocene)-dichloro palladium (complex with dichloromethane 1:1, 21 mg, 0.03 mmol) in 1,4-dioxane (5 mL) is added 5-(tert-butyl-dimethyl-silanoxy)-1-(tert-butoxycarbonyl)-1H-indole-2-boronic acid (335 mg, 0.86 mmol, prepared as described in Example 4-6 of International Patent Application Publication No. WO 02/32861) followed by a solution of cesium carbonate (741 mg, 2.28 mmol) in water (2 mL). The mixture is stirred at reflux for 15 minutes. Then it is diluted with ethyl acetate and washed with water and brine. The organic layer is dried over magnesium sulfate and concentrated. The residue is chromatographed through silica gel (n-heptane-ethyl acetate, 95:05 as eluant) to afford 200 mg (61%) of 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-5-(tert-butyl-dimethyl-silanoxy)-indole-1-carboxylic acid tert-butyl ester as a white foam. LC/MS: RT=4.29 minutes, 570.1 m/e.

Workup

  1. customprepared
  2. temperatureat reflux for 15 minutes
  3. washwashed with water and brine
  4. dry with materialThe organic layer is dried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue is chromatographed through silica gel (n-heptane-ethyl acetate, 95:05 as eluant)

Sources & evidence

ORD record
ord-fc4232aa9bf04dd2a4111b070671206a
Source dataset
uspto-grants-2009_04
Patent number
US07518000B2

Reaction notes

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