2-(4-Fluoro-phenyl)-7,10-bis-methanesulfonyl-5-methylene-5,6,7,8,9,10-hexahydro-1-oxa-7,10,11-triaza-cycloocta[f]indene-3-carboxylic acid methylamide → 2-(4-Fluoro-phenyl)-7,10-bis-methanesulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-1-oxa-7,10,11-triaza-cycloocta[f]indene-3-carboxylic acid methylamide

HRID 2190186Notes

Reaction equation

HRID 2190186 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:13]2[CH:12]=[C:11]3[C:14](=[CH2:28])[CH2:15][N:16]([S:24]([CH3:27])(=[O:26])=[O:25])[CH2:17][CH2:18][N:19]([S:20]([CH3:23])(=[O:22])=[O:21])[C:10]3=[N:9][C:8]=2[O:7][C:6]=1[C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)=[O:4]>CO.CCOC(C)=O.O[Pd]O>[CH3:1][NH:2][C:3]([C:5]1[C:13]2[CH:12]=[C:11]3[CH:14]([CH3:28])[CH2:15][N:16]([S:24]([CH3:27])(=[O:26])=[O:25])[CH2:17][CH2:18][N:19]([S:20]([CH3:23])(=[O:21])=[O:22])[C:10]3=[N:9][C:8]=2[O:7][C:6]=1[C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)=[O:4]

Participants

4

Reactant 1

HCID 666642522-(4-Fluoro-phenyl)-7,10-bis-methanesulfonyl-5-methylene-5,6,7,8,9,10-hexahydro-1-oxa-7,10,11-triaza-cycloocta[f]indene-3-carboxylic acid methylamide

Product 1

HCID 545756722-(4-Fluoro-phenyl)-7,10-bis-methanesulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-1-oxa-7,10,11-triaza-cycloocta[f]indene-3-carboxylic acid methylamideYield 4.6%

Reagents, catalysts & solvents 2

HCID 178526213HCID 178526213, compoundCatalystHCID 21584119Ethylacetate methanolSolvent

Procedure

To 2-(4-Fluoro-phenyl)-7,10-bis-methanesulfonyl-5-methylene-5,6,7,8,9,10-hexahydro-1-oxa-7,10,11-triaza-cycloocta[f]indene-3-carboxylic acid methylamide (3 mg, 5.74 umol) dissolved in MeOH:EtOAc (1:1 1 mL) was added Dihydroxypalladium (0.5 mg, 2.87 umol). The reaction was fitted with a balloon of H2 and then stirred overnight. The mixture was filtered through a bed of celite and washed with additional MeOH (10 mL) and EtOAc (10 mL) and then concentrated and purified by HPLC CH3CN/H2O/0.1% TFA) to provide 2-(4-Fluoro-phenyl)-7,10-bis-methanesulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-1-oxa-7,10,11-triaza-cycloocta[f]indene-3-carboxylic acid methylamide (140 ug, 3%). MS-ES [M+H]+=525.2.

Workup

  1. customThe reaction was fitted with a balloon of H2
  2. filtrationThe mixture was filtered through a bed of celite
  3. washwashed with additional MeOH (10 mL) and EtOAc (10 mL)
  4. concentrationconcentrated
  5. custompurified by HPLC CH3CN/H2O/0.1% TFA)

Sources & evidence

ORD record
ord-6374e62802c74578b64d6128e3e0b0ea
Source dataset
uspto-grants-2012_12
Patent number
US08324239B2

Reaction notes

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