Triethylamine → Ethyl 3-(4-((3,3-dimethylcyclobutyl)(quinolin-3-ylamino)methyl)benzamido)propanoate

HRID 2281144ノート

反応式

HRID 2281144 の反応式
[CH3:1][C:2]1([CH3:27])[CH2:5][CH:4]([CH:6]([NH:16][C:17]2[CH:18]=[N:19][C:20]3[C:25]([CH:26]=2)=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:7]2[CH:15]=[CH:14][C:10]([C:11](O)=[O:12])=[CH:9][CH:8]=2)[CH2:3]1.[CH2:28]([O:30][C:31](=[O:35])[CH2:32][CH2:33][NH2:34])[CH3:29].ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>C(Cl)Cl>[CH3:27][C:2]1([CH3:1])[CH2:5][CH:4]([CH:6]([NH:16][C:17]2[CH:18]=[N:19][C:20]3[C:21]([CH:26]=2)=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:7]2[CH:15]=[CH:14][C:10]([C:11]([NH:34][CH2:33][CH2:32][C:31]([O:30][CH2:28][CH3:29])=[O:35])=[O:12])=[CH:9][CH:8]=2)[CH2:3]1

参加物

7

反応物 5

HCID 8471TriethylamineHCID 181649HOAtHCID 419889Ethyl 3-aminopropanoateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 712393444-((3,3-Dimethylcyclobutyl)(quinolin-3-ylamino)methyl)benzoic acid

生成物 1

HCID 71239304Ethyl 3-(4-((3,3-dimethylcyclobutyl)(quinolin-3-ylamino)methyl)benzamido)propanoate収率 66.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a vial containing 4-((3,3-dimethylcyclobutyl)(quinolin-3-ylamino)methyl)benzoic acid (14.0 mg, 0.0390 mmol) was added 3-aminopropionic acid ethyl ester hydrochloric (6.60 mg, 0.0430 mmol), 1-Hydroxy-7-azabenzotriazole (6.40 mg, 0.0470 mmol) and 1-ethyl-3-(3-dimethylamino propyl)carbodiimide hydrochloride (9.00 mg, 0.0470 mmol). Anhydrous methylene chloride (0.390 mL) was added followed by triethylamine (0.007 mL, 0.0510 mmol). After 18 h, the reaction was diluted with methylene chloride and quenched with a saturated solution of ammonium chloride. The aqueous layer was extracted three times with methylene chloride. The combined organic layers were dried with sodium sulfate, filtered, and concentrated to give 26.0 mg of crude material. Purification by column chromatography (0-70% ethyl acetate in heptane) provided ethyl 3-(4-((3,3-dimethylcyclobutyl)(quinolin-3-ylamino)methyl)benzamido)propanoate (11.9 mg, 66% yield) as an oil. 1H NMR (400 MHz, CDCl3) δ: 8.48 (d, J=2.7 Hz, 1H), 7.88 (dd, J=8.3, 1.3 Hz, 1H), 7.74-7.67 (m, 2H), 7.46-7.41 (m, 2H), 7.41-7.29 (m, 3H), 6.81 (t, J=6.1 Hz, 1H), 6.69 (d, J=2.7 Hz, 1H), 4.42 (br. s., 1H), 4.25 (dd, J=9.3, 4.4 Hz, 1H), 4.19-4.08 (m, 2H), 3.70 (q, J=6.0 Hz, 2H), 2.61 (t, J=5.7 Hz, 2H), 2.59-2.45 (m, 1H), 2.07-1.97 (m, 1H), 1.76-1.67 (m, 2H), 1.66-1.55 (m, 1H), 1.28-1.21 (m, 3H), 1.13 (s, 3H), 1.09 (m, 3H). MS (M+1): 460.4.

後処理

  1. customquenched with a saturated solution of ammonium chloride
  2. extractionThe aqueous layer was extracted three times with methylene chloride
  3. dry with materialThe combined organic layers were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give 26.0 mg of crude material
  7. customPurification by column chromatography (0-70% ethyl acetate in heptane)

出典と根拠

ORDレコード
ord-70c388923bbb42369a5882ded04d546b
出典データセット
uspto-grants-2015_09
特許番号
US09139538B2

反応ノート

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