1,2-Dichloroethane → HCID 178428539、化合物

HRID 12248

反応式

HRID 12248 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH:15][C:16]([CH:18]3[N:23]([CH2:24][C:25]([OH:27])=O)[CH2:22][C:21]([CH3:29])([CH3:28])[O:20][CH2:19]3)=[O:17])[CH:14]=1)[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1.Cl.[NH2:31][C@H:32]1[CH2:37][CH2:36][C@H:35]([OH:38])[CH2:34][CH2:33]1.C(N(C(C)C)CC)(C)C.C(Cl)CCl>N1C=CC=CC=1.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH:15][C:16]([CH:18]3[CH2:19][O:20][C:21]([CH3:29])([CH3:28])[CH2:22][N:23]3[CH2:24][C:25](=[O:27])[NH:31][C@H:32]3[CH2:37][CH2:36][C@H:35]([OH:38])[CH2:34][CH2:33]3)=[O:17])[CH:14]=1)[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1

参加物

7

反応物 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 59337527[5-(6-Chloro-9H-beta-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholin-4-yl]-acetic acidHCID 178479278HCID 178479278、化合物

生成物 1

HCID 178428539HCID 178428539、化合物収率 60%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 1049Pyridine溶媒

実験手順

[5-(6-Chloro-9H-beta-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholin-4-yl]-acetic acid (200 mg, 0.48 mmol), trans-4-aminocyclohexanol hydrochloride (145 mg, 0.96 mmol) and diisopropylethylamine (124 mg, 167 uL, 0.96 mmol) were dissolved in pyridine (4 mL) and stirred at room temperature10 min. EDC (184 mg) was added and the reaction was stirred at room temperature over night (16 h). Water (2 mL) was added and the resulting mixture was concentrated under reduced pressure. The resulting residue was diluted with 50 mL 1 M aqueous potassium carbonate and extracted with ethyl acetate (75+2×50 mL). The combined extracts were washed with water and brine, dried over sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (methanol/methylene chloride gradient) to afford pure 4-[(trans-4-hydroxy-cyclohexylcarbamoyl)-methyl]-6,6-dimethyl-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide (148 mg, 59%) as a yellow foam. The bis-HCl salt was prepared by adding 2 equivalents of conc. HCl to an ethanolic solution of the freebase. Concentration, followed by ether trituration afforded the salt as a free-flowing, yellow powder.

後処理

  1. stirringthe reaction was stirred at room temperature over night (16 h)
  2. concentrationthe resulting mixture was concentrated under reduced pressure
  3. additionThe resulting residue was diluted with 50 mL 1 M aqueous potassium carbonate
  4. extractionextracted with ethyl acetate (75+2×50 mL)
  5. washThe combined extracts were washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica gel chromatography (methanol/methylene chloride gradient)

出典と根拠

ORDレコード
ord-8b72ff95936842d0a95d831f3c3c8d3b
出典データセット
uspto-grants-2010_06
特許番号
US07727985B2

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