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

HRID 521486

Reaktionsgleichung

Reaktionsgleichung von HRID 521486
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]

Komponenten

11

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-a9719b708ac1479889384ec2455c4bf9
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09328071B2

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