Water → Alvelestat

HRID 1517471ノート

反応式

HRID 1517471 の反応式
[CH3:1][C:2]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[C:6](=[O:18])[C:5]([C:19]([OH:21])=O)=[CH:4][C:3]=1[C:22]1[N:26]([CH3:27])[N:25]=[CH:24][CH:23]=1.Cl.[CH3:29][S:30]([C:33]1[CH:34]=[CH:35][C:36]([CH2:39][NH2:40])=[N:37][CH:38]=1)(=[O:32])=[O:31].O>C(#N)C>[CH3:1][C:2]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:16])([F:15])[F:17])[CH:9]=2)[C:6](=[O:18])[C:5]([C:19]([NH:40][CH2:39][C:36]2[CH:35]=[CH:34][C:33]([S:30]([CH3:29])(=[O:32])=[O:31])=[CH:38][N:37]=2)=[O:21])=[CH:4][C:3]=1[C:22]1[N:26]([CH3:27])[N:25]=[CH:24][CH:23]=1

参加物

5

反応物 3

HCID 962WaterHCID 594558756-Methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylic acidHCID 66725223[5-(Methanesulfonyl)pyridin-2-yl]methanaminium chloride

生成物 1

HCID 46861623Alvelestat収率 96%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒2 回

反応条件

温度
50 °C

実験手順

6-Methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylic acid (52.0 kg, 1 mol eq, limiting reagent) and acetonitrile (208 L, 4 rel vol,) were charged. The reaction mixture was heated to 50° C. 1,1′-s carbonyldiimidazole as a solution in acetonitrile (208 L, 4 rel vol) is charged to the reaction until the reaction is complete as judged by HPLC. C-(5-(Methanesulfonyl)pyridine-2-yl)methylamine monohydrochloride (33.8 kg, 1.1 mol eq) was charged and the reaction maintained at 50° C. until the reaction was deemed complete as judged by HPLC. Water (780 L, 15 rel vol) was charged. The reaction mixture was stirred, cooled and further stirred. The solid was collected by filtration and washed twice with water (2×104 L, 2×2 rel vol) and dried to constant weight to yield the title compound (96.0 kg, 176.0 mol, 96%); 1H NMR (d6-DMSO): δ 1.83 (s, 3H); 3.29 (s, 3H); 3.72 (s, 3H); 4.73 (d, 2H, J 5.8 Hz); 6.33 (d, 1H, J=1.9 Hz); 7.53 (d, 1H, J=1.9 Hz); 7.57 (d, 1H, J 8.3 Hz); 7.81-7.88 (m, 2H); 7.92-7.94 (m, 1H); 8.03 (s, 1H); 8.21 (s, 1H); 8.27 (dd, 1H, J 2.3, 7.9 Hz); 8.99 (d, 1H, J=2.3 Hz); 10.06 (t, 1H, J 6.0 Hz); LCMS: m/z 546.3 (MH+).

後処理

  1. additionwere charged
  2. temperaturethe reaction maintained at 50° C. until the reaction
  3. temperaturecooled
  4. stirringfurther stirred
  5. filtrationThe solid was collected by filtration
  6. washwashed twice with water (2×104 L, 2×2 rel vol)
  7. customdried to constant weight

出典と根拠

ORDレコード
ord-3df95681d663401dbcd622c7b4d1f491
出典データセット
uspto-grants-2012_07
特許番号
US08232296B2

反応ノート

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