Cesium carbonate → 6'-(3-(Cyclopropylamino)-6-methylbenzo[d]isoxazol-7-yl)spiro[cyclopentane-1,3'-indolin]-2'-one

HRID 2096989Notes

Reaction equation

HRID 2096989 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[C:16]3[C:12]([C:13]4([CH2:22][CH2:21][CH2:20][CH2:19]4)[C:14](=[O:18])[NH:15]3)=[CH:11][CH:10]=2)O1.[CH:24]1([NH:27][C:28]2[C:32]3[CH:33]=[CH:34][C:35]([CH3:38])=[C:36](I)[C:31]=3[O:30][N:29]=2)[CH2:26][CH2:25]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[CH:24]1([NH:27][C:28]2[C:32]3[CH:33]=[CH:34][C:35]([CH3:38])=[C:36]([C:9]4[CH:17]=[C:16]5[C:12]([C:13]6([CH2:19][CH2:20][CH2:21][CH2:22]6)[C:14](=[O:18])[NH:15]5)=[CH:11][CH:10]=4)[C:31]=3[O:30][N:29]=2)[CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 58702151N-cyclopropyl-7-iodo-6-methylbenzo[d]isoxazol-3-amineHCID 669537286'-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[cyclopentane-1,3'-indolin]-2'-one

Product 1

HCID 444773826'-(3-(Cyclopropylamino)-6-methylbenzo[d]isoxazol-7-yl)spiro[cyclopentane-1,3'-indolin]-2'-oneYield 28%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

An oven-dried resealable Schlenk tube was charged with 6′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[cyclopentane-1,3′-indolin]-2′-one (preparation 4, 0.060 g, 0.19 mmol), N-cyclopropyl-7-iodo-6-methylbenzo[d]isoxazol-3-amine (WO2006094187, 0.090 g, 0.29 mmol), 1,4-dioxane (1.2 mL) and a 2M aqueous caesium carbonate solution (0.29 mL, 0.58 mmol). The Schlenk tube was subjected to three cycles of evacuation-backfilling with argon, and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (0.015 g, 0.02 mmol) was added. After three further cycles of evacuation-backfilling with argon, the Schlenk tube was sealed and the mixture was stirred and heated in an oil bath to 100-110° C. After 20 hours, the mixture was cooled and partitioned between water and ethyl acetate. The organic extract was dried (MgSO4) and evaporated in vacuo. Purification of the residue by flash chromatography (98:2 dichloromethane/methanol) gave the title compound (0.017 g, 28%) as a yellow solid.

Workup

  1. additionwas added
  2. customAfter three further cycles of evacuation-backfilling with argon, the Schlenk tube was sealed
  3. temperaturethe mixture was cooled
  4. custompartitioned between water and ethyl acetate
  5. extractionThe organic extract
  6. dry with materialwas dried (MgSO4)
  7. customevaporated in vacuo
  8. customPurification of the residue by flash chromatography (98:2 dichloromethane/methanol)

Sources & evidence

ORD record
ord-9af6aa06bb5140f088b99066a7945096
Source dataset
uspto-grants-2013_05
Patent number
US08450341B2

Reaction notes

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