Pyridine → n-{6-[({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}amino)sulfonyl]-2-naphthyl}acetamide

HRID 2224939ノート

反応式

HRID 2224939 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.[C:39]([NH:42][C:43]1[CH:44]=[C:45]2[C:50](=[CH:51][CH:52]=1)[CH:49]=[C:48]([S:53](Cl)(=[O:55])=[O:54])[CH:47]=[CH:46]2)(=[O:41])[CH3:40]>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:53]([C:48]3[CH:49]=[C:50]4[C:45](=[CH:46][CH:47]=3)[CH:44]=[C:43]([NH:42][C:39](=[O:41])[CH3:40])[CH:52]=[CH:51]4)(=[O:55])=[O:54])=[CH:4][C:5]=2[S:10](=[O:12])(=[O:11])[N:9]=1

参加物

5

反応物 3

HCID 1049PyridineHCID 1198272-Naphthalenesulfonyl chloride, 6-(acetylamino)-HCID 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 136384631n-{6-[({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}amino)sulfonyl]-2-naphthyl}acetamide収率 61%

試薬・触媒・溶媒 1

HCID 180Acetone溶媒

実験手順

A mixture of Example 39H (23.8 mg, 0.050 mmol), pyridine (31.6 mg, 0.40 mmol) and 6-acetylamino-2-naphthalenesulfonyl chloride (56.7 mg, 0.20 mmol, prepared by the procedure as described in J. Med. Chem., 1995, 38, 8, p. 1344-1354) in acetone (1.5 mL) was stirred at rt for 18 h. The reaction mixture was evaporated in vacuo and partitioned between ethyl acetate and 1 N HCl. 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 (20.8 mg, 61% yield). 1H NMR (300 MHz, DMSO-d6) δ 0.38 m, 1 H) 0.66 (d, J=7.35 Hz, 3 H) 0.68 (d, J=6.99 Hz, 3H) 0.80 m, 1 H) 1.30 m, 1 H) 1.53 (s, 3 H) 2.02 m, 1 H) 2.10 (s, 3 H) 2.18 (m, 1 H) 7.52 m, 4 H) 7.69 m, 4 H) 7.99 (d, J=8.82 Hz, 1 H) 8.07 (d, J=8.82 Hz, 1 H) 8.11 (d, J=8.09 Hz, 1H) 8.38 (s, 2 H) 10.32 (s, 1 H) 10.87 (s, 1 H) 13.72 (s, 1 H).

後処理

  1. customThe reaction mixture was evaporated in vacuo
  2. custompartitioned between ethyl acetate and 1 N HCl
  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-e4eaa3693d324abd81e254526fe60235
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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