Lithium Hydroxide → 2-[(3'-Isopropyl-6-methoxy-biphenyl-3-carbonyl)-amino]-indane-2-carboxylic acid

HRID 521486Notes

Reaction equation

HRID 521486 reaction equation
COC(C1(NC(=O)C2C=CC(OC)=C(Br)C=2)CC2C(=CC=CC=2)C1)=O.C(C1C=C(B(O)O)C=CC=1)(C)C.[F-].[Cs+].C[O:41][C:42]([C:44]1([NH:53][C:54]([C:56]2[CH:57]=[C:58]([C:64]3[CH:69]=[CH:68][CH:67]=[C:66]([CH:70]([CH3:72])[CH3:71])[CH:65]=3)[C:59]([O:62][CH3:63])=[CH:60][CH:61]=2)=[O:55])[CH2:52][C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH2:45]1)=[O:43].[OH-].[Li+]>CN(C=O)C.C1COCC1.O.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.C1(C)C=CC=CC=1>[CH:70]([C:66]1[CH:65]=[C:64]([C:58]2[C:59]([O:62][CH3:63])=[CH:60][CH:61]=[C:56]([C:54]([NH:53][C:44]3([C:42]([OH:43])=[O:41])[CH2:52][C:51]4[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=4)[CH2:45]3)=[O:55])[CH:57]=2)[CH:69]=[CH:68][CH:67]=1)([CH3:72])[CH3:71]

Participants

11

Reactant 5

HCID 3939Lithium HydroxideHCID 25953Cesium fluorideHCID 27734783-Isopropylbenzeneboronic acidHCID 670763302-(3-Bromo-4-methoxy-benzoylamino)-indane-2-carboxylic acid methyl esterHCID 670766992-[(3'-Isopropyl-6-methoxy-biphenyl-3-carbonyl)-amino]-indane-2-carboxylic acid methyl ester

Product 1

HCID 444787752-[(3'-Isopropyl-6-methoxy-biphenyl-3-carbonyl)-amino]-indane-2-carboxylic acid

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

250 mg (0.62 mmol) of the compound of example 194, step 1, and 152.1 mg (0.93 mmol) of 3-isopropylphenylboronic acid were dissolved in 5 ml of DMF and 5 ml of toluene under an argon atmosphere. 187.9 mg (1.24 mmol) of cesium fluoride and 35.73 mg (0.05 mmol) of tetrakis(triphenylphosphine)palladium(0) were added, and the mixture was stirred overnight at 100° C. After cooling, the mixture was filtered and the solvent was evaporated. The obtained 2-[(3′-isopropyl-6-methoxy-biphenyl-3-carbonyl)-amino]-indane-2-carboxylic acid methyl ester was dissolved in 10 ml of a mixture of THF and water (9:1), 42.2 mg (1.80 mmol) of lithium hydroxide were added and the mixture was stirred overnight. The solvent was evaporated and the residue was purified by preparative RP HPLC (water/ACN gradient). 71 mg of the title compound were obtained.

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered
  3. customthe solvent was evaporated
  4. additionwere added
  5. stirringthe mixture was stirred overnight
  6. customThe solvent was evaporated
  7. customthe residue was purified by preparative RP HPLC (water/ACN gradient)

Sources & evidence

ORD record
ord-a9719b708ac1479889384ec2455c4bf9
Source dataset
uspto-grants-2016_05
Patent number
US09328071B2

Reaction notes

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