Potassium Carbonate → 1-methylethyl ((2S,4R)-1-acetyl-6-{1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-imidazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

HRID 2366875ノート

反応式

HRID 2366875 の反応式
[CH3:1][CH:2]([O:4][C:5](=[O:30])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](B3OC(C)(C)C(C)(C)O3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[CH3:3].CC([N:35]([CH2:39][CH2:40][N:41]1[CH:45]=[C:44](I)[N:43]=[CH:42]1)[C:36](=[O:38])[O-:37])(C)C.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.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>[CH3:1][CH:2]([O:4][C:5](=[O:30])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:44]3[N:43]=[CH:42][N:41]([CH2:40][CH2:39][NH:35][C:36]([O:37][C:16]([CH3:11])([CH3:7])[CH3:15])=[O:38])[CH:45]=3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[CH3:3]

参加物

7

反応物 3

HCID 11430Potassium Carbonate2 回HCID 681853941-Methylethyl [(cis)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamateHCID 1317313251,1-dimethylethyl[2-(4-iodo-1H-imidazol-1-yl)ethyl]carbamate

生成物 1

HCID 681854051-methylethyl ((2S,4R)-1-acetyl-6-{1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-imidazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate収率 12%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒2 回HCID 702Ethanol溶媒HCID 1140Toluene溶媒

実験手順

A mixture of 1-methylethyl[(2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 52) (333 mg, 0.80 mmol), 1,1-dimethylethyl[2-(4-iodo-1H-imidazol-1-yl)ethyl]carbamate (for a preparation see Intermediate 80) (270 mg, 0.8 mmol), potassium carbonate (443 mg, 3.2 mmol) and tetrakis(triphenylphosphine)palladium(0) (46 mg, 0.040 mmol) in toluene (10 ml) and ethanol (10 ml) was refluxed under nitrogen for 16 h then cooled to room temperature and the insoluble were filtered off. Potassium carbonate (443 mg, 3.2 mmol) and tetrakis(triphenylphosphine)palladium(0) (46 mg, 0.040 mmol) were added to the filtrate and the resulting mixture refluxed for 7 h then cooled to room temperature and the insoluble filtered off. The resulting solution was concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 0 to 6% MeOH in DCM) gave 1-methylethyl((2S,4R)-1-acetyl-6-{1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-imidazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (47 mg, 0.094 mmol, 12%) as a light brown solid.

後処理

  1. temperaturewas refluxed under nitrogen for 16 h
  2. filtrationthe insoluble were filtered off
  3. temperaturethe resulting mixture refluxed for 7 h
  4. temperaturethen cooled to room temperature
  5. concentrationThe resulting solution was concentrated in vacuo
  6. customPurification of the residue by flash chromatography on silica gel (gradient: 0 to 6% MeOH in DCM)

出典と根拠

ORDレコード
ord-d58d5a6c4db1414795bb17103fd7084a
出典データセット
uspto-grants-2014_04
特許番号
US08697725B2

反応ノート

読み込み中…