1,2-Dimethoxyethane → 2-[(3'-Ethanesulfonyl-5-fluoro-6-methoxy-biphenyl-3-carbonyl)-amino]-indane-2-carboxylic acid

HRID 521538Notes

Reaction equation

HRID 521538 reaction equation
C[O:2][C:3]([C:5]1([NH:14][C:15](=[O:26])[C:16]2[CH:21]=[C:20]([F:22])[C:19]([O:23][CH3:24])=[C:18](Br)[CH:17]=2)[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6]1)=[O:4].[CH2:27]([S:29]([C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1)(=[O:31])=[O:30])[CH3:28].COCCOC.[F-].[Cs+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:27]([S:29]([C:32]1[CH:37]=[C:36]([C:18]2[C:19]([O:23][CH3:24])=[C:20]([F:22])[CH:21]=[C:16]([C:15]([NH:14][C:5]3([C:3]([OH:2])=[O:4])[CH2:13][C:12]4[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=4)[CH2:6]3)=[O:26])[CH:17]=2)[CH:35]=[CH:34][CH:33]=1)(=[O:30])=[O:31])[CH3:28]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 25953Cesium fluorideHCID 164271023-Ethylsulfonylphenylboronic acidHCID 670766342-(3-Bromo-5-fluoro-4-methoxy-benzoylamino)-indane-2-carboxylic acid methyl ester

Product 1

HCID 670766932-[(3'-Ethanesulfonyl-5-fluoro-6-methoxy-biphenyl-3-carbonyl)-amino]-indane-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

300 mg (0.71 mmol) of the compound of step 4 and 175 mg (1.07 mmol) of 3-ethanesulfonylphenylboronic acid were dissolved in 4 ml of DMF and 4 ml of 1,2-dimethoxyethane under an argon atmosphere. 216 mg (1.42 mmol) of cesium fluoride and 41.08 mg (0.04 mmol) of tetrakis(triphenylphosphine)palladium(0) were added, and the mixture was heated to 130° C. in a microwave reactor for 15 min. After cooling, the solvent was evaporated and the residue purified by preparative RP HPLC (water/ACN gradient) to yield the methyl ester of the title compound. 135.1 mg (0.26 mmol) methyl ester were dissolved in 5 ml of a mixture of THF and water (9:1), 12.65 mg (0.53 mmol) of lithium hydroxide were added and the mixture was stirred for 3 days. The solvent was evaporated and the residue was purified by preparative RP HPLC (water/ACN gradient). 123 mg of the title compound were obtained.

Workup

  1. temperatureAfter cooling
  2. customthe solvent was evaporated
  3. customthe residue purified by preparative RP HPLC (water/ACN gradient)

Sources & evidence

ORD record
ord-ecc97610398547bcaf7a831a407e945e
Source dataset
uspto-grants-2016_05
Patent number
US09328071B2

Reaction notes

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