Hydrochloric Acid → 3-((1H-indol-3-yl)methyl)-5-chloro-2-oxo-1-propylindolin-3-yl benzoate

HRID 1523098ノート

反応式

HRID 1523098 の反応式
[C:1]([O:9][CH:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([Cl:19])[CH:17]=2)[N:12]([CH2:20][CH2:21][CH3:22])[C:11]1=[O:23])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C(O[CH2:43][C:44]1[C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[N:46](C(=O)C2C=CC=CC=2)[CH:45]=1)(=O)C1C=CC=CC=1.Cl>C(OCC)(=O)C>[C:1]([O:9][C:10]1([CH2:43][C:44]2[C:52]3[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=3)[NH:46][CH:45]=2)[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([Cl:19])[CH:17]=2)[N:12]([CH2:20][CH2:21][CH3:22])[C:11]1=[O:23])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 3251421Potassium bis(trimethylsilyl)amideHCID 90411032HCID 90411032、化合物HCID 904179755-Chloro-2-oxo-1-propylindolin-3-yl benzoate

生成物 1

HCID 863014383-((1H-indol-3-yl)methyl)-5-chloro-2-oxo-1-propylindolin-3-yl benzoate収率 43%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

To an oven dried flask cooled under argon equipped with a stir bar was added 5-chloro-2-oxo-1-propylindolin-3-yl benzoate (0.08 grams, 0.24 mmol, 0.2 M in toluene). While stirring at 0° C. KHMDS (0.3 mL, 0.26 mmol, 0.87 M, purchased from Fisher Scientific) was added. After approximately fifteen minutes a solution of (1-benzoyl-1H-indol-3-yl)methyl benzoate (0.02 grams, 0.06 mmol, 0.3 M in anhydrous DMF (purchased from Fisher Scientific)) was added. The reaction continued to stir overnight. The next day the reaction was acidified with 0.1M HCl, diluted with ethyl acetate and the two layers were separated. The aqueous layer was salted out and washed twice more with ethyl acetate. The combined organic solution was dried with sodium sulfate, filtered and concentrated. Purification was done on a Teledyne ISCO with silica gel using a hexanes ethyl acetate gradient. This was followed by a subsequent reverse phase purification using Teledyne ISCO with a C18 column and a water with 0.1% formic acid, acetonitrile gradient. 43% yield. 1H-NMR δ 8.05 (bs, NH), 8.00 (d, 2H), 7.57 (t, 1H), 7.50 (d, 1H), 7.42 (t, 2H), 7.30 (d, 1H), 7.18 (m, 2H), 7.08 (m, 2H), 6.78 (d, 1H), 6.61 (d, 1H), 3.71 (d, 1H), 3.60 (m, 1H), 3.51 (d, 1H), 3.40 (m, 1H), 1.35 (m, 2H), 0.74 (t, 3H). Calculated mass for C27H23ClN2O3, 458.14. Observed 481.1 (M+Na).

後処理

  1. customTo an oven dried flask
  2. temperaturecooled under argon
  3. customequipped with a stir bar
  4. stirringto stir overnight
  5. customthe two layers were separated
  6. washwashed twice more with ethyl acetate
  7. dry with materialThe combined organic solution was dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification
  11. customThis was followed by a subsequent reverse phase purification

出典と根拠

ORDレコード
ord-13f7ff63cfec4cf88835243781cbf41b
出典データセット
uspto-grants-2015_07
特許番号
US09079853B2

反応ノート

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