4-Fluorobenzohydrazide → (R)-N'-(2-(4-cyano-2-methyl-3-(trifluoromethyl)phenylamino)-3-hydroxy-3-methylbutanoyl)-4-fluorobenzohydrazide

HRID 238562

反応式

HRID 238562 の反応式
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C@H:10]([C:14]([OH:17])([CH3:16])[CH3:15])[C:11]([OH:13])=O)=[C:5]([CH3:18])[C:4]=1[C:19]([F:22])([F:21])[F:20])#[N:2].[F:23][C:24]1[CH:33]=[CH:32][C:27]([C:28]([NH:30][NH2:31])=[O:29])=[CH:26][CH:25]=1.OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC>C1COCC1.C(OCC)(=O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C@H:10]([C:14]([OH:17])([CH3:15])[CH3:16])[C:11]([NH:31][NH:30][C:28](=[O:29])[C:27]2[CH:26]=[CH:25][C:24]([F:23])=[CH:33][CH:32]=2)=[O:13])=[C:5]([CH3:18])[C:4]=1[C:19]([F:20])([F:21])[F:22])#[N:2]

参加物

7

反応物 4

HCID 99724-FluorobenzohydrazideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66624722(R)-2-(4-cyano-2-methyl-3-(trifluoromethyl)phenylamino)-3-hydroxy-3-methylbutanoic acidHCID 178418300HCID 178418300、化合物

生成物 1

HCID 66625420(R)-N'-(2-(4-cyano-2-methyl-3-(trifluoromethyl)phenylamino)-3-hydroxy-3-methylbutanoyl)-4-fluorobenzohydrazide収率 92.3%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
-15 °C

実験手順

(R)-2-(4-cyano-2-methyl-3-(trifluoromethyl)phenylamino)-3-hydroxy-3-methylbutanoic acid (500 mg, 1.58 mmol) and 4-fluorobenzohydrazide (244 mg, 1.58 mmol) were mixed together in THF (20 mL) and cooled to −15° C. under N2 atmosphere. To the pre-cooled reaction mixture were added hydroxybenzotriazole (HOBT) (214 mg, 1.58 mmol), TEA (0.33 mL, 2.37 mmol) followed by N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI) (454 mg, 2.37 mmol). The reaction mixture was allowed to stir at −20° C. for 20 min and then at room temperature overnight. After the reaction was complete, ethyl acetate (50 mL) was added and the solution was washed with 5% citric acid (2×40 mL), 5% NaHCO3 (2×40 mL) followed by water (40 mL) and then dried (Na2SO4) to provide the crude product as a yellow solid (660 mg, 92%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 9.81 (br s, 1H), 8.02-7.95 (m, 2H), 7.69-7.63 (m, 1H), 7.27-7.21 (m, 2H), 7.01-6.95 (m, 1H), 5.54 (d, J=7 Hz, 1H), 4.14 (d, J=8 Hz, 1H), 2.38 (s, 3H), 1.47 (s, 3H) and 1.43 (s, 3H).

後処理

  1. customTo the pre-cooled reaction mixture
  2. customat room temperature
  3. customovernight
  4. washthe solution was washed with 5% citric acid (2×40 mL), 5% NaHCO3 (2×40 mL)
  5. dry with materialdried (Na2SO4)

出典と根拠

ORDレコード
ord-6f4a635a6a094ce8bcb5dee8181c43dd
出典データセット
uspto-grants-2014_02
特許番号
US08642632B2

関連ノート

読み込み中…