Lithium Hydroxide → 4-(1-{[2-Oxo-1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indole-7-carbonyl]-amino}-cyclopropyl)-benzoic acid

HRID 1951653ノート

反応式

HRID 1951653 の反応式
[O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[C:5]([C:11]([OH:13])=O)[CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1.C[O:26][C:27](=[O:37])[C:28]1[CH:33]=[CH:32][C:31]([CH:34]([NH2:36])[CH3:35])=[CH:30][CH:29]=1.Cl.[CH2:39](N=C=NCCCN(C)C)C.CN1CCOCC1.[Li+].[OH-]>CN(C=O)C.C1COCC1.CO>[O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[C:5]([C:11]([NH:36][C:34]3([C:31]4[CH:32]=[CH:33][C:28]([C:27]([OH:26])=[O:37])=[CH:29][CH:30]=4)[CH2:39][CH2:35]3)=[O:13])[CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:14][C:15]1[CH:16]=[CH:17][C:18]([C:21]([F:23])([F:24])[F:22])=[CH:19][CH:20]=1

参加物

9

反応物 5

HCID 3939Lithium HydroxideHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 20134240Methyl 4-(1-aminoethyl)benzoateHCID 582977002-Oxo-1-(4-trifluoromethyl-benzyl)-2,3-dihydro-1H-indole-7-carboxylic acid

生成物 1

HCID 582976764-(1-{[2-Oxo-1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indole-7-carbonyl]-amino}-cyclopropyl)-benzoic acid収率 42.4%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of 0.40 g of 2-oxo-1-(4-trifluoromethyl-benzyl)-2,3-dihydro-1H-indole-7-carboxylic acid, 0.29 g of (±)4-(1-amino-ethyl)-benzoic acid methyl ester, 0.19 g of HOBT-hydrate, 0.30 g of ethyl-dimethylaminopropyl-carbodiimide hydrochloride (EDC1) and 0.150 ml of N-methylmorpholine in 7 ml of DMF was stirred at room temperature for 16 h. The reaction was then quenched with 10 ml of water and 5 ml of sat. NaHCO3 solution. The resulting mixture extracted with 25 ml of EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated to give the crude methyl ester (0.3 g) which was dissolved in 5 ml THF, 5 mL MeOH and treated with 4 mL of 1N LiOH solution. After stirring at 50° C. for 12 h, the reaction mixture was concentrated under reduced pressure to remove THF and MeOH. The residue was diluted with 8 mL of water and treated with 1 mL of AcOH with vigorous stirring. After stirring for 2 h, the solid was collected by filtration and air-dried to give 0.25 g of the title compound as a white powder.

後処理

  1. customThe reaction was then quenched with 10 ml of water and 5 ml of sat. NaHCO3 solution
  2. extractionThe resulting mixture extracted with 25 ml of EtOAc
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude methyl ester (0.3 g) which
  7. stirringAfter stirring at 50° C. for 12 h
  8. concentrationthe reaction mixture was concentrated under reduced pressure
  9. customto remove THF and MeOH
  10. additionThe residue was diluted with 8 mL of water
  11. additiontreated with 1 mL of AcOH with vigorous stirring
  12. stirringAfter stirring for 2 h
  13. filtrationthe solid was collected by filtration
  14. customair-dried

出典と根拠

ORDレコード
ord-1c79f4f10c994344b4aca2e4c0d471ae
出典データセット
uspto-grants-2013_03
特許番号
US08404736B2

反応ノート

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