Triethylamine → (+/-)-3-{4-[(3,3-Di methyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid ethyl ester

HRID 1424258ノート

反応式

HRID 1424258 の反応式
[CH3:1][C:2]1([CH3:28])[CH2:5][CH:4]([CH:6]([NH:16][C:17]2[C:26]([CH3:27])=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=2)[C:7]2[CH:15]=[CH:14][C:10]([C:11](O)=[O:12])=[CH:9][CH:8]=2)[CH2:3]1.Cl.[CH2:30]([O:32][C:33](=[O:37])[CH2:34][CH2:35][NH2:36])[CH3:31].C(N(CC)CC)C>ClCCl>[CH2:30]([O:32][C:33](=[O:37])[CH2:34][CH2:35][NH:36][C:11](=[O:12])[C:10]1[CH:14]=[CH:15][C:7]([CH:6]([CH:4]2[CH2:3][C:2]([CH3:1])([CH3:28])[CH2:5]2)[NH:16][C:17]2[C:26]([CH3:27])=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=2)=[CH:8][CH:9]=1)[CH3:31]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 71243837(+/-)-4-[(3,3-Dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid2 回

生成物 1

HCID 71239546(+/-)-3-{4-[(3,3-Di methyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid ethyl ester収率 80.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

(+/−)-4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid (Intermediate 26) (37 mg, 0.099 mmol) was combined with 1-hydrobenzotriazole hydrate (23.0 mg, 0.149 mmol), N-(3-dimethylaminopropyl)-W-ethylcarbodiimide hydrochloride (29.0 mg, 0.149 mmol), and beta-alanine ethyl ester hydrochloride (18.0 mg, 0.119 mmol). Anhydrous dichloromethane (5 mL) was added followed by triethylamine (0.027 mL, 0.198 mmol). The solution was stirred at room temperature for 3 d before partitioning between ethyl acetate and aq. sat. ammonium chloride. The separated aqueous layer was extracted with ethyl acetate and the combined organics dried over MgSO4. Purification by silica gel flash chromatography (ethyl acetate/heptane) gave (+/−)-3-{4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid ethyl ester (37.9 mg) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J=8.2 Hz, 2H) 7.59 (t, J=3.9 Hz, 2H) 7.46-7.52 (m, 3H) 7.37-7.45 (m, 1H) 7.11-7.19 (m, 1H) 6.75 (t, J=5.8 Hz, 1H) 5.32 (dd, J=9.7, 6.7 Hz, 1H) 4.75 (d, J=6.6 Hz, 1H) 4.10-4.21 (m, 2H) 3.70 (q, J=6.0 Hz, 2H) 2.55-2.74 (m, 3H) 2.29 (s, 3H) 1.96 (ddd, J=11.1, 8.2, 2.9 Hz, 1H) 1.75-1.84 (m, 1H) 1.64-1.73 (m, 2H) 1.26 (m, 3H) 1.16 (s, 3H) 1.09 (s, 3H); MS (M+1): 474.7.

後処理

  1. custombefore partitioning between ethyl acetate and aq. sat. ammonium chloride
  2. extractionThe separated aqueous layer was extracted with ethyl acetate
  3. dry with materialthe combined organics dried over MgSO4
  4. customPurification by silica gel flash chromatography (ethyl acetate/heptane)

出典と根拠

ORDレコード
ord-727990c21e384f7da5e4bb3322c45cef
出典データセット
uspto-grants-2015_01
特許番号
US08927577B2

反応ノート

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