1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-((1-benzoylazetidin-3-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide

HRID 1849893노트

반응식

HRID 1849893 반응식
[C:1]([N:9]1[CH2:12][CH:11]([CH2:13][O:14][C:15]2[C:23]([CH:24]3[CH2:26][CH2:25]3)=[CH:22][C:18]([C:19](O)=[O:20])=[C:17]([F:27])[CH:16]=2)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.[CH3:39][S:40]([NH2:43])(=[O:42])=[O:41]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([N:9]1[CH2:12][CH:11]([CH2:13][O:14][C:15]2[C:23]([CH:24]3[CH2:26][CH2:25]3)=[CH:22][C:18]([C:19]([NH:43][S:40]([CH3:39])(=[O:42])=[O:41])=[O:20])=[C:17]([F:27])[CH:16]=2)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

6

반응물 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 72879MethanesulfonamideHCID 867037714-((1-Benzoylazetidin-3-yl)methoxy)-5-cyclopropyl-2-fluorobenzoic acid

생성물 1

HCID 725493564-((1-benzoylazetidin-3-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide수율 17.9%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매2회

실험 절차

A mixture of 4-((1-benzoylazetidin-3-yl)methoxy)-5-cyclopropyl-2-fluorobenzoic acid (20 mg, 0.05 mmol), EDCI (21 mg, 0.10 mmol), DMAP (12 mg, 0.10 mmol) and methanesulfonamide (9 mg, 0.10 mmol) in DCM (5 mL) was stirred at room temperature for 18 h. The mixture was diluted with DCM (10 mL) and washed with HCl (2 N, 15 mL×2). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by HPLC (20%-30% CH3CN in 0.1% NH4HCO3) to give target compound (4 mg, 17%) as a pale yellow solid. LCMS (ESI) Method A: RT=3.86 min, m/z: 446.5 [M+H]+. 1H-NMR (500 MHz, MeOH-d4,): δ 7.67-7.31 (m, 5H), 7.30 (d, J=8.5 Hz, 1H), 6.89 (d, J=13.0 Hz, 1H), 4.65-3.62 (m, 1H), 4.61-4.22 (m, 5H), 3.36 (s, 3H), 3.25-3.23 (m, 1H), 1.99-1.95 (m, 1H), 0.94-0.61 (m, 4H).

후처리

  1. washwashed with HCl (2 N, 15 mL×2)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by HPLC (20%-30% CH3CN in 0.1% NH4HCO3)

출처 및 근거

ORD 기록
ord-f93f6b6c6134431bb4cb2534c4bea48d
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952169B2

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