1,2-Dichloroethane → HCID 178428539, 화합물

HRID 12248

반응식

HRID 12248 반응식
[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

참가 물질

7

반응물 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, 화합물

생성물 1

HCID 178428539HCID 178428539, 화합물수율 60%

시약·촉매·용매 2

HCID 962Water용매HCID 1049Pyridine용매

실험 절차

[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.

후처리

  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)

출처 및 근거

ORD 기록
ord-8b72ff95936842d0a95d831f3c3c8d3b
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727985B2

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