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Triethylamine → (S)-ethyl N-({6-[(3-methyl-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}butyl)amino]pyridin-3-yl}carbonyl)-beta-alaninate

HRID 1427477
ノート
印刷プレビュー

反応式

HRID 1427477 の反応式
Cl.[NH2:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH3:10][CH:11]([CH3:40])[CH2:12][C@H:13]([NH:30][C:31]1[CH:39]=[CH:38][C:34]([C:35](O)=[O:36])=[CH:33][N:32]=1)[C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][N:21]=2)=[CH:16][CH:15]=1.O.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C>ClCCl.C(=O)(O)[O-].[Na+]>[CH3:10][CH:11]([CH3:40])[CH2:12][C@H:13]([NH:30][C:31]1[N:32]=[CH:33][C:34]([C:35]([NH:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])=[O:36])=[CH:38][CH:39]=1)[C:14]1[CH:15]=[CH:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:22][N:21]=2)=[CH:18][CH:19]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 8471TriethylamineHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67980958(S)-6-[(3-methyl-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}butyl)amino]nicotinic acidHCID 178526939HCID 178526939、化合物

生成物 1

HCID 68061979
(S)-ethyl N-({6-[(3-methyl-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}butyl)amino]pyridin-3-yl}carbonyl)-beta-alaninate
収率 86%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
40 °C

実験手順

To a mixture of ethyl 3-aminopropionate hydrochloride (41.1 g, 268 mmol), (S)-6-[(3-methyl-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}butyl)amino]nicotinic acid (57.51 g, 133.9 mmol), hydroxybenzotriazole hydrate (20.5 g, 134 mmol), and triethylamine (103 ml, 737 mmol) in dichloromethane (1.34 L) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (38.9 g, 201 mmol) at ambient temperature. The reaction was heated to 40° C. for 12 hours. The reaction was diluted with saturated aqueous sodium bicarbonate (1.5 L) and the organic layer was separated. The aqueous layer was extracted with dichloromethane (2×500 ml) and the combined organic layers were washed with brine (1 L), then dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified via ISCO MPLC (SiO2, 0-100% ethyl acetate in heptane) to yield the product (60.9 g, 86%) as a white foam. 1H NMR (400 MHz, CDCl3, δ): 8.93 (s, 1H), 8.51 (d, J=2.0 Hz, 1H), 7.95-8.02 (m, 3H), 7.81 (d, J=8.6 Hz, 1H), 7.78 (dd, J=9.1, 2.4 Hz, 1H), 7.47 (d, J=8.2 Hz, 2H), 6.73 (t, J=5.7 Hz, 1H), 6.29 (d, J=8.8 Hz, 1H), 5.81-5.91 (m, 1H), 4.76 (q, J=6.8 Hz, 1H), 4.10-4.16 (m, 2H), 3.67 (q, J=6.1 Hz, 2H), 2.60 (t, J=5.9 Hz, 2H), 1.77-1.87 (m, 1H), 1.65-1.77 (m, 2H), 1.23-1.28 (m, 3H), 1.01 (d, J=6.1 Hz, 3H), 0.97 (d, J=6.1 Hz, 3H). MS (M+1): 529.3.

後処理

  1. customthe organic layer was separated
  2. extractionThe aqueous layer was extracted with dichloromethane (2×500 ml)
  3. washthe combined organic layers were washed with brine (1 L)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified via ISCO MPLC (SiO2, 0-100% ethyl acetate in heptane)

出典と根拠

ORDレコード
ord-8b009a96c92740e6bcaa04506e1e061b
出典データセット
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08933104B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート