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Citric Acid → 2-(4-{6-[3-(4-tert-Butylbenzamido)-2-methylphenyl]-4-methyl-3-oxo-3,4-dihydropyrazin-2-ylamino}phenyl)-2-[isopropyl(methyl)amino]acetic Acid

HRID 888444
ノート
印刷プレビュー

反応式

HRID 888444 の反応式
[C:1]([C:5]1[CH:46]=[CH:45][C:8]([C:9]([NH:11][C:12]2[C:13]([CH3:44])=[C:14]([C:18]3[N:23]=[C:22]([NH:24][C:25]4[CH:30]=[CH:29][C:28]([CH:31]([N:37]([CH:39]([CH3:41])[CH3:40])[CH3:38])[C:32]([O:34]CC)=[O:33])=[CH:27][CH:26]=4)[C:21](=[O:42])[N:20]([CH3:43])[CH:19]=3)[CH:15]=[CH:16][CH:17]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C1COCC1.[OH-].[Li+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O.C(O)C>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:9]([NH:11][C:12]2[C:13]([CH3:44])=[C:14]([C:18]3[N:23]=[C:22]([NH:24][C:25]4[CH:30]=[CH:29][C:28]([CH:31]([N:37]([CH:39]([CH3:40])[CH3:41])[CH3:38])[C:32]([OH:34])=[O:33])=[CH:27][CH:26]=4)[C:21](=[O:42])[N:20]([CH3:43])[CH:19]=3)[CH:15]=[CH:16][CH:17]=2)=[O:10])=[CH:45][CH:46]=1)([CH3:2])([CH3:3])[CH3:4]
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

7

反応物 4

HCID 311Citric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 57625127Ethyl 2-(4-{6-[3-(4-tert-Butylbenzamido)-2-methylphenyl]-4-methyl-3-oxo-3,4-dihydropyrazin-2-ylamino}phenyl)-2-[isopropyl(methyl)amino]acetate

生成物 1

HCID 576251502-(4-{6-[3-(4-tert-Butylbenzamido)-2-methylphenyl]-4-methyl-3-oxo-3,4-dihydropyrazin-2-ylamino}phenyl)-2-[isopropyl(methyl)amino]acetic Acid
収率 55%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 962Water溶媒

反応条件

温度
60 °C

実験手順

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 28 (400 mg, 0.642 mmol), THF (5 mL) and ethanol (5 mL). A solution of lithium hydroxide (124 mg, 10.2 mmol) in water (5 mL) was added, and the mixture was heated at 60° C. for 48 h. After this time, the reaction was cooled to room temperature, and the mixture was slowly acidified to pH 4.0 with 10% aqueous citric acid. The resulting precipitate was filtered, and the filter cake was washed with water (20 mL), then triturated with a 1:10 mixture of methylene chloride/ethyl acetate (20 mL). The resulting residue was dried to a constant weight under vacuum at 45° C. to afford 29 in 55% yield (210 mg) as an off-white solid: mp 197-198° C.; 1H NMR (500 MHz, DMSO-d5) δ 9.91 (s, 1H), 9.29 (s, 1H), 7.99 (d, 2H, J=8.5 Hz), 7.95 (d, 2H, J=8.5 Hz), 7.55 (d, 2H, J=8.5 Hz), 7.39 (d, 2H, J=8.5 Hz), 7.35 (dd, 1H, J=7.0, 1.5 Hz), 7.32-7.28 (m, 2H), 7.24 (s, 1H), 4.23 (s, 1H), 3.56 (s, 3H), 3.30 (m, 1H), 2.30 (s, 3H), 2.23 (s, 3H), 1.33 (s, 9H), 1.13 (d, 3H, J=6.5 Hz), 1.10 (d, 3H, J=6.5 Hz); MS (ESI+) m/z 596 (M+H).

後処理

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. temperatureAfter this time, the reaction was cooled to room temperature
  4. filtrationThe resulting precipitate was filtered
  5. washthe filter cake was washed with water (20 mL)
  6. customtriturated with a 1:10 mixture of methylene chloride/ethyl acetate (20 mL)
  7. customThe resulting residue was dried to a constant weight under vacuum at 45° C.

出典と根拠

ORDレコード
ord-291b95e6ac0b4ba9b38f9a15076f61fd
出典データセット
uspto-grants-2012_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08247550B2

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