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

HRID 521486

反応式

HRID 521486 の反応式
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]

参加物

11

反応物 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

生成物 1

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

試薬・触媒・溶媒 5

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-a9719b708ac1479889384ec2455c4bf9
出典データセット
uspto-grants-2016_05
特許番号
US09328071B2

関連ノート

読み込み中…