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 2224943ノート

反応式

HRID 2224943 の反応式
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

参加物

5

反応物 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

生成物 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-sulfonamide収率 45%

試薬・触媒・溶媒 1

HCID 180Acetone溶媒

実験手順

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)−.

後処理

  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

出典と根拠

ORDレコード
ord-5545f7f541a24ac8a675f70a9014a666
出典データセット
uspto-grants-2008_05
特許番号
US07378414B2

反応ノート

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