Triethylamine → HCID 68228514, 화합물

HRID 2370338노트

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HRID 2370338 반응식
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([F:39])=[C:8]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][C:25]=4[C:27]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[O:28])[N:20]([CH2:35][CH2:36][O:37][CH3:38])[CH:19]=3)=[O:17])[CH2:12][CH2:11]2)[CH:9]=1.OC1C2N=NNC=2C=CC=1.[NH:50]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[C@H:51]([C:55]([NH:57][CH2:58][C:59](O)=[O:60])=[O:56])[CH:52]([CH3:54])[CH3:53].C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.C(OCC)(=O)C>[C:65]([O:64][C:62](=[O:63])[NH:50][CH:51]([C:55](=[O:56])[NH:57][CH2:58][C:59](=[O:60])[NH:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([F:39])=[C:8]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][C:25]=4[C:27]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[O:28])[N:20]([CH2:35][CH2:36][O:37][CH3:38])[CH:19]=3)=[O:17])[CH2:12][CH2:11]2)[CH:9]=1)[CH:52]([CH3:53])[CH3:54])([CH3:66])([CH3:68])[CH3:67]

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7014901BOC-VAL-GLY-OHHCID 67261087HCID 67261087, 화합물HCID 178418300HCID 178418300, 화합물

생성물 1

HCID 68228514HCID 68228514, 화합물수율 72%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

[4-(5-Aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-[1-(2-methoxy-ethyl)-4-(morpholine-4-carbonyl)-1H-indol-3-yl]-methanone hydrochloride (100 mg, 0.18 mmol) was dissolved in DMF (2.6 mL) under nitrogen and stirred at 0° C. for 5 min. To this was added sequentially hydroxybenzotriazole (77 mg, 0.57 mmol), BOC-Val-Gly-OH (59 mg, 0.21 mmol), triethylamine (0.05 mL, 0.36 mmol) followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (41 mg, 0.21 mmol). The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was diluted with ethyl acetate (30 mL) and washed with brine (30 mL). The brine was back extracted with ethyl acetate (2×30 mL) and the organic fractions were combined and washed with 10% citric acid (2×30 mL), sat sodium bicarbonate solution (2×30 mL) and brine (30 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give the crude product which was purified by SiO2 column chromatography using 5% MeOH/CH2Cl2 as the eluent to afford (1-{[(4-fluoro-3-{1-[1-(2-methoxy-ethyl)-4-(morpholine-4-carbonyl)-1H-indole-3-carbonyl]-piperidin-4-yl}-benzylcarbamoyl)-methyl]-carbamoyl}-2-methyl-propyl)-carbamic acid tert-butyl ester (100 mg, 72%). 1H NMR (300 MHz, CDCl3) δ 7.40-7.30 (m, 2H), 7.28-7.21 (m, 2H), 7.18-7.10 (m, 1H), 7.08-7.00 (m, 1H), 6.98-6.85 (m, 1H), 5.00-4.90 (br s, 1H), 4.30 (t, 2H), 3.85-3.70 (br m, 2H), 3.73 (t, 2H), 3.47 (s, 2H), 3.33 (s, 3H), 3.20-2.90 (br m, 2H), 1.90-1.60 (br m, 6H), 1.30-1.24 (m, 10H), 1.80-1.70 (br m, 6H); 19F NMR (282 MHz, CDCl3) δ −57.60 (s, 1F); MS m/z: [M+H]+=779.

후처리

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringstirred overnight
  3. washwashed with brine (30 mL)
  4. extractionThe brine was back extracted with ethyl acetate (2×30 mL)
  5. washwashed with 10% citric acid (2×30 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give the crude product which
  10. customwas purified by SiO2 column chromatography

출처 및 근거

ORD 기록
ord-e811c860f298484684cf147bd7128259
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08710080B2

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