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

HRID 1424288Notes

Reaction equation

HRID 1424288 reaction equation
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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(+/−)-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, 2H), 7.66-7.57 (m, 2H), 7.56-7.48 (m, 3H), 7.44 (t, J=7.4 Hz, 1H), 7.16 (t, J=7.4 Hz, 1H), 6.81-6.73 (m, 1H), 5.60-5.52 (m, 1H), 4.73 (d, J=6.8 Hz, 1H), 4.16 (q, J=7.0 Hz, 2H), 3.71 (q, J=6.0 Hz, 2H), 2.62 (t, J=5.9 Hz, 2H), 2.28 (s, 3H), 1.93-1.82 (m, 1H), 1.81-1.70 (m, 1H), 1.69-1.60 (m, 1H), 1.26 (t, J=7.1 Hz, 3H), 1.04 (d, J=6.4 Hz, 3H), 0.97 (d, J=6.2 Hz, 3H). Methyl ester: 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J=8.2 Hz, 2H), 7.66-7.57 (m, 2H), 7.56-7.48 (m, 3H), 7.44 (t, J=7.4 Hz, 1H), 7.16 (t, J=7.3 Hz, 1H), 6.81-6.71 (m, 1H), 5.60-5.52 (m, 1H), 4.77-4.69 (m, 1H), 3.76-3.66 (m, 5H), 2.66-2.59 (m, 2H), 2.28 (s, 3H), 1.93-1.82 (m, 1H), 1.81-1.70 (m, 1H), 1.69-1.60 (m, 1H), 1.04 (d, J=6.4 Hz, 3H), 0.97 (d, J=6.4 Hz, 3H).

Workup

  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)

Sources & evidence

ORD record
ord-6cb8bc69ef5a44ff94f705bf62cd85e9
Source dataset
uspto-grants-2015_01
Patent number
US08927577B2

Reaction notes

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