Hydrochloric Acid → N-(azetidin-1-ylsulfonyl)-5-chloro-2-fluoro-4-((1-(trifluoromethyl)-cyclopentyl)methoxy)benzamide

HRID 1849599ノート

反応式

HRID 1849599 の反応式
[Cl:1][C:2]1[C:3]([O:12][CH2:13][C:14]2([C:19]([F:22])([F:21])[F:20])[CH2:18][CH2:17][CH2:16][CH2:15]2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.Cl.C(N=C=NCCCN(C)C)C.[N:35]1([S:39]([NH2:42])(=[O:41])=[O:40])[CH2:38][CH2:37][CH2:36]1.Cl>ClCCl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[N:35]1([S:39]([NH:42][C:7](=[O:9])[C:6]2[CH:10]=[C:2]([Cl:1])[C:3]([O:12][CH2:13][C:14]3([C:19]([F:21])([F:22])[F:20])[CH2:18][CH2:17][CH2:16][CH2:15]3)=[CH:4][C:5]=2[F:11])(=[O:41])=[O:40])[CH2:38][CH2:37][CH2:36]1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 450805661-AzetidinesulfonamideHCID 867034525-Chloro-2-fluoro-4-((1-(trifluoromethyl)-cyclopentyl)methoxy)benzoic acid

生成物 1

HCID 86703454N-(azetidin-1-ylsulfonyl)-5-chloro-2-fluoro-4-((1-(trifluoromethyl)-cyclopentyl)methoxy)benzamide収率 47.9%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred solution of 5-chloro-2-fluoro-4-((1-(trifluoromethyl)cyclopentyl)-methoxy)benzoic acid (0.34 g, 1.00 mmol) in dichloromethane (20 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.29 g, 1.50 mmol) and 4-dimethylaminopyridine (0.28 g, 2.30 mmol). The reaction mixture was stirred at ambient temperature for 10 minutes, azetidine-1-sulfonamide (0.20 g, 1.50 mmol) was added and the stirring was continued at ambient temperature for 17 hours. 5% aqueous hydrochloric acid solution (10 mL) were added and diluted with ethyl acetate (100 mL), washed with water and brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (30% ethyl acetate in hexanes) afforded the title compound (0.22 g, 46%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.61 (br s, 1H), 8.11 (d, J=7.2 Hz, 1H), 6.69 (d, J=12.9 Hz, 1H), 4.22 (br s, 4H), 4.03 (s, 2H), 2.31-2.17 (m, 2H), 2.08-1.92 (m, 2H), 1.89-1.70 (m, 6H); MS (ES+) m/z 459.0, 461.0 (M+1); MS (ES−) m/z 457.1, 459.1 (M−1).

後処理

  1. waitthe stirring was continued at ambient temperature for 17 hours
  2. washwashed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by column chromatography (30% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-754e92d3bc194d75afdb1431b9248117
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

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