Triethylamine → Ethyl 3-(4-(1-((3-methylquinolin-2-yl)amino)butyl)benzamido)propanoate

HRID 2281159노트

반응식

HRID 2281159 반응식
FC(F)(F)C(O)=O.[CH3:8][CH:9](C)[CH2:10][CH:11]([C:24]1[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=1)[NH:12][C:13]1[C:22]([CH3:23])=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=1.Cl.[CH2:35]([O:37][C:38](=[O:42])[CH2:39][CH2:40][NH2:41])[CH3:36].O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>ClCCl>[CH3:23][C:22]1[C:13]([NH:12][CH:11]([C:24]2[CH:25]=[CH:26][C:27]([C:28]([NH:41][CH2:40][CH2:39][C:38]([O:37][CH2:35][CH3:36])=[O:42])=[O:29])=[CH:31][CH:32]=2)[CH2:10][CH2:9][CH3:8])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[CH:17][CH:16]=2

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86718841(+/-)-4-(3-Methyl-1-((3-methylquinolin-2-yl)amino)butyl)benzoic acid trifluoroacetic acid salt

생성물 1

HCID 71239522Ethyl 3-(4-(1-((3-methylquinolin-2-yl)amino)butyl)benzamido)propanoate

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

(+/−)-4-(3-methyl-1-((3-methylquinolin-2-yl)amino)butyl)benzoic acid trifluoroacetic acid salt (461 mg, 1.00 mmol), β-alanine ethyl ester hydrochloride (645 mg, 3.99 mmol), and 1-hydroxybenzotriazole hydrate (80%, 20 wt % water, 674 mg, 3.99 mmol) were suspended in dichloromethane (10.0 mL). Triethylamine (1.40 mL, 9.97 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (776 mg, 3.99 mmol) were added, and the solution was stirred at room temperature for 66 hours. The reaction mixture was diluted with dichloromethane (40 mL), washed with water (3×30 mL) and sat. aq NaCl (20 mL), dried over Na2SO4, and filtered, and the filtrate was concentrated under reduced pressure. Purification by silica gel flash chromatography (ethyl acetate/heptane) followed by chiral SFC (Chiralpak AD-H column, 10 mm×250 cm, 25% methanol/carbon dioxide eluent, 0.2% isopropylamine modifier) gave ethyl 3-(4-(1-((3-methylquinolin-2-yl)amino)butyl)benzamido)propanoate, isomer 1 (analytical chiral SFC 6.1 min retention) and 3-(4-(1-((3-methylquinolin-2-yl)amino)butyl)benzamido) propanoate as a mixture of methyl and ethyl esters, isomer 2 (analytical chiral SFC 6.7 min retention). Ethyl ester: 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J=8.2 Hz, 2 H), 7.66-7.57 (m, 2 H), 7.56-7.48 (m, 3 H), 7.44 (t, J=7.4 Hz, 1 H), 7.16 (t, J=7.4 Hz, 1 H), 6.81-6.73 (m, 1 H), 5.60-5.52 (m, 1 H), 4.73 (d, J=6.8 Hz, 1 H), 4.16 (q, J=7.0 Hz, 2 H), 3.71 (q, J=6.0 Hz, 2 H), 2.62 (t, J=5.9 Hz, 2 H), 2.28 (s, 3 H), 1.93-1.82 (m, 1 H), 1.81-1.70 (m, 1 H), 1.69-1.60 (m, 1 H), 1.26 (t, J=7.1 Hz, 3 H), 1.04 (d, J=6.4 Hz, 3 H), 0.97 (d, J=6.2 Hz, 3 H). Methyl ester: 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J=8.2 Hz, 2 H), 7.66-7.57 (m, 2 H), 7.56-7.48 (m, 3 H), 7.44 (t, J=7.4 Hz, 1 H), 7.16 (t, J=7.3 Hz, 1 H), 6.81-6.71 (m, 1 H), 5.60-5.52 (m, 1 H), 4.77-4.69 (m, 1 H), 3.76-3.66 (m, 5 H), 2.66-2.59 (m, 2 H), 2.28 (s, 3 H), 1.93-1.82 (m, 1 H), 1.81-1.70 (m, 1 H), 1.69-1.60 (m, 1 H), 1.04 (d, J=6.4 Hz, 3 H), 0.97 (d, J=6.4 Hz, 3 H).

후처리

  1. additionwere added
  2. washwashed with water (3×30 mL) and sat. aq NaCl (20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customPurification by silica gel flash chromatography (ethyl acetate/heptane)

출처 및 근거

ORD 기록
ord-6587e89bbf034aa1835524b58d543eed
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09139538B2

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