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

HRID 2190183Notes

Reaction equation

HRID 2190183 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:13]2[C:8](=[N:9][C:10]([N:15]([CH2:20][CH2:21][N:22]([CH2:35][CH:36]=[CH2:37])[S:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[N+:32]([O-:34])=[O:33])(=[O:25])=[O:24])[S:16]([CH3:19])(=[O:18])=[O:17])=[C:11](I)[CH:12]=2)[O:7][C:6]=1[C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=1)=[O:4].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.C(O[Pd]OC(=O)C)(=O)C>[CH3:1][NH:2][C:3]([C:5]1[C:13]2[CH:12]=[C:11]3[C:36](=[CH2:37])[CH2:35][N:22]([S:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[N+:32]([O-:34])=[O:33])(=[O:25])=[O:24])[CH2:21][CH2:20][N:15]([S:16]([CH3:19])(=[O:18])=[O:17])[C:10]3=[N:9][C:8]=2[O:7][C:6]=1[C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=1)=[O:4]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 666637406-({2-[Allyl-(2-nitro-benzenesulfonyl)-amino]-ethyl}-methanesulfonyl-amino)-2-(4-fluoro-phenyl)-5-iodo-furo[2,3-b]pyridine-3-carboxylic acid methylamide

Product 1

HCID 666635422-(4-Fluoro-phenyl)-10-methanesulfonyl-5-methylene-7-(2-nitro-benzenesulfonyl)-5,6,7,8,9,10-hexahydro-1-oxa-7,10,11-triaza-cycloocta[f]indene-3-carboxylic acid methylamideYield 27%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
122 °C

Procedure

6-({2-[Allyl-(2-nitro-benzenesulfonyl)-amino]-ethyl}-methanesulfonyl-amino)-2-(4-fluoro-phenyl)-5-iodo-furo[2,3-b]pyridine-3-carboxylic acid methylamide (50 mg, 0.07 mmol) is dissolved in DMF/H2O (10:1, 2 mL: 0.2 mL) and diacetoxypalladium (0.5 mg, 2.64 umol), 1,3-bis(diphenylphosphino)propane (8.17 mg, 0.02 mmol) and potassium carbonate (13.7 mg, 0.10 mmol) are added together then heated in the microwave for 20 min at 122° C. The mixture is then filtered through a bed of celite and the solid is washed with EtOAc (25 mL). The combined organic is then washed with H2O (10 mL), Brine (10 mL) and dried over Na2SO4, followed by evaporation of the solvent. HPLC (CH3CN/H2O/0.1% TFA) provides 2-(4-Fluoro-phenyl)-10-methanesulfonyl-5-methylene-7-(2-nitro-benzenesulfonyl)-5,6,7,8,9,10-hexahydro-1-oxa-7,10,11-triaza-cycloocta[f]indene-3-carboxylic acid methylamide (10 mg, 27%). MS-ES [M+H]+=632.3 and 2-(4-Fluoro-phenyl)-5-iodo-6-{methanesulfonyl-[2-(2-nitro-benzenesulfonylamino)-ethyl]-amino}-furo[2,3-b]pyridine-3-carboxylic acid methylamide (3 mg, 7%). MS-ES [M+H]+=718.0.

Workup

  1. filtrationThe mixture is then filtered through a bed of celite
  2. washthe solid is washed with EtOAc (25 mL)
  3. washThe combined organic is then washed with H2O (10 mL), Brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. customfollowed by evaporation of the solvent

Sources & evidence

ORD record
ord-1c6b493bfa834615b68cb3f8eeab6096
Source dataset
uspto-grants-2012_12
Patent number
US08324239B2

Reaction notes

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