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 494623ノート

反応式

HRID 494623 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, 1H) 0.67 (d, J=6.62 Hz, 3H) 0.70 (d, J=6.62 Hz, 3H) 0.77 (m, 1H) 1.29 (m, 1H) 1.54 (s, 3H) 2.04 (m, 1H) 2.19 (m, 1H) 7.35 (dd, J=6.25, 2.94 Hz, 2H) 7.51 (m, 1H) 7.64 (m, 8H) 8.13 (d, J=7.72 Hz, 1H) 11.51 (s, 1H) 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-5776d230ca294790b11bb83128a89f69
出典データセット
uspto-grants-2009_05
特許番号
US07538105B2

反応ノート

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