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

HRID 1849599노트

반응식

HRID 1849599 반응식
[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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-754e92d3bc194d75afdb1431b9248117
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952169B2

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