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1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6,6-dimethyl-4-{3-methyl-2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl}-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide

HRID 552236
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HRID 552236 반응식
[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH:15][C:16]([CH:18]3[CH2:23][O:22][C:21]([CH3:25])([CH3:24])[CH2:20][N:19]3[CH2:26][CH:27]([NH2:31])[CH:28]([CH3:30])[CH3:29])=[O:17])[CH:14]=1)[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1.[CH3:32][C:33]1[N:41]=[CH:40][CH:39]=[CH:38][C:34]=1[C:35](O)=[O:36].CCN=C=NCCCN(C)C>N1C=CC=CC=1.O.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH:15][C:16]([CH:18]3[CH2:23][O:22][C:21]([CH3:24])([CH3:25])[CH2:20][N:19]3[CH2:26][CH:27]([NH:31][C:35]([C:34]3[C:33]([CH3:32])=[N:41][CH:40]=[CH:39][CH:38]=3)=[O:36])[CH:28]([CH3:29])[CH3:30])=[O:17])[CH:14]=1)[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1
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참가 물질

7

반응물 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 6433732-Methylnicotinic acidHCID 671651234-(2-amino-3-methyl-butyl)-6,6-dimethyl-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide

생성물 1

HCID 671657436,6-dimethyl-4-{3-methyl-2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl}-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide수율 77%

시약·촉매·용매 3

HCID 962Water용매2회
HCID 1049Pyridine용매
HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 4-(2-amino-3-methyl-butyl)-6,6-dimethyl-morpholine-3-carboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide (1.47 g, 3.31 mmol) in pyridine (35 mL) was added 2-methyl-nicotinic acid (544 mg, 3.97 mmol) and EDCI (1.02 g, 5.30 mmol). The solution was stirred 6.5 hours at room temperature, then diluted with water (100 mL). The mixture was poured into a separatory funnel and diluted further with water (50 mL) and EtOAc (150 mL). The layers were shaken and separated. The aqueous layer was extracted with EtOAc (3×50 mL), then the combined organic layers were washed with brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated to yield an orange semi-solid residue which was purified via column chromatography. The resulting yellow solid was placed on the high-vacuum pump overnight, after which 1.43 g of 6,6-dimethyl-4-{3-methyl-2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl}-morpholine-3-carboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide was obtained (77% yield). 1H-NMR (DMSO-d6, 300 MHz) δ 11.32 (s, 1); 10.08 (s, 1); 9.02 (s, 1); 8.46 (dd, 1); 8.38 (d, 1); 8.21-8.14 (m, 3); 7.97 (d, 1); 7.64 (dd, 1); 7.23 (dd, 1); 4.23-4.14 (m, 1); 3.99-3.87 (m, 2); 3.22-3.19 (m, 1): 3.02 (d, 1); 2.85 (dd, 1); 2.52 (s, 3); 2.30 (dd, 1); 2.11 (d, 1); 2.05-1.95 (m, 1); 1.32 (s, 3); 1.21 (s, 3); 0.93 (d, 3); 0.86 (d, 3). NH4OAc standard conditions. DAD Rf=1.67 min. M+H=563.

후처리

  1. additionThe mixture was poured into a separatory funnel
  2. stirringThe layers were shaken
  3. customseparated
  4. extractionThe aqueous layer was extracted with EtOAc (3×50 mL)
  5. washthe combined organic layers were washed with brine
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield an orange semi-solid residue which
  10. customwas purified via column chromatography
  11. customwas placed on the high-vacuum pump overnight

출처 및 근거

ORD 기록
ord-8945d91e0ef74c9bb54ab3a96c721281
출처 데이터셋
uspto-grants-2011_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07951801B2

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