Pyridine → n-{3-[(4r)-1-Hydroxy-4-methyl-4-(3-methylbutyl)-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-1,2,4-benzothiadiazin-7-yl}-1h-benzimidazole-2-sulfonamide

HRID 2224943노트

반응식

HRID 2224943 반응식
Cl.[NH2:2][C:3]1[CH:32]=[CH:31][C:6]2[NH:7][C:8]([C:13]3[C:14](=[O:30])[C@:15]([CH3:29])([CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27])[C:16]4[C:21]([C:22]=3[OH:23])=[CH:20][CH:19]=[CH:18][CH:17]=4)=[N:9][S:10](=[O:12])(=[O:11])[C:5]=2[CH:4]=1.N1C=CC=CC=1.[N:39]1[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=2[NH:41][C:40]=1[S:48](Cl)(=[O:50])=[O:49]>CC(C)=O>[OH:23][C:22]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C@@:15]([CH3:29])([CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27])[C:14](=[O:30])[C:13]=1[C:8]1[NH:7][C:6]2[CH:31]=[CH:32][C:3]([NH:2][S:48]([C:40]3[NH:39][C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=4[N:41]=3)(=[O:49])=[O:50])=[CH:4][C:5]=2[S:10](=[O:12])(=[O:11])[N:9]=1

참가 물질

5

반응물 3

HCID 1049PyridineHCID 110638611H-Benzo[d]imidazole-2-sulfonyl chlorideHCID 135869462(1R)-3-(7-amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-methyl-1-(3-methylbutyl)naphthalen-2(1 H)-one hydrochloride

생성물 1

HCID 136384791n-{3-[(4r)-1-Hydroxy-4-methyl-4-(3-methylbutyl)-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-1,2,4-benzothiadiazin-7-yl}-1h-benzimidazole-2-sulfonamide수율 45%

시약·촉매·용매 1

HCID 180Acetone용매

실험 절차

A mixture of Example 39H (47.6 mg, 0.10 mmol), pyridine (64 mg, 0.80 mmol), and 2-benzimidazole sulfonyl chloride (87 mg, 0.40 mmol, prepared according to the procedure reported by S. M. Deshpande et al, J. Med. Chem. 1970, 13, 143-144) in acetone (2 mL) was stirred at rt for 16 h. The reaction mixture was evaporated in vacuo and partitioned between ethyl acetate and water. The organic phase was separated, dried (MgSO4), filtered, and evaporated in vacuo. The residue was purified by chromatography on silica gel eluting with 99:1 dichloromethane/methanol to provide the title compound (28.0 mg, 45% yield). 1H NMR (300 MHz, DMSO-d6) δ 0.39 m, 1 H) 0.67 (d, J=6.62 Hz, 3 H) 0.70 (d, J=6.62 Hz, 3H) 0.77 m, 1 H) 1.29 m, 1 H) 1.54 (s, 3 H) 2.04 m, 1 H) 2.19 m, 1 H) 7.35 (dd, J=6.25, 2.94 Hz, 2 H) 7.51 m, 1 H) 7.64 m, 8 H) 8.13 (d, J=7.72 Hz, 1 H) 11.51 (s, 1 H) 13.77 (s, 1H). MS (ESI+) m/z 620.0 (M+H)+, 641.9 (M+H—Na)+, (ESI−) m/z 618.0 (M−H)−.

후처리

  1. customThe reaction mixture was evaporated in vacuo
  2. custompartitioned between ethyl acetate and water
  3. customThe organic phase was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by chromatography on silica gel eluting with 99:1 dichloromethane/methanol

출처 및 근거

ORD 기록
ord-5545f7f541a24ac8a675f70a9014a666
출처 데이터셋
uspto-grants-2008_05
특허 번호
US07378414B2

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