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

HRID 2405254노트

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HRID 2405254 반응식
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]

참가 물질

11

반응물 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

생성물 1

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

시약·촉매·용매 5

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 1140Toluene용매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

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온도
100 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-28532d63a7c049279cfe173a4b37bbfe
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08802720B2

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