Pyridine 4-methylbenzene-1-sulfonate → Azd-8835

HRID 1749045ノート

反応式

HRID 1749045 の反応式
CC1C=CC(S(O)(=O)=O)=CC=1.N1C=CC=CC=1.[NH2:18][C:19]1[N:20]=[CH:21][C:22]([C:34]2[N:38]([CH2:39][CH3:40])[N:37]=[C:36]([CH:41]3[CH2:46][CH2:45][N:44]([C:47](=[O:57])[CH2:48][CH2:49][O:50]C4CCCCO4)[CH2:43][CH2:42]3)[N:35]=2)=[N:23][C:24]=1[C:25]1[O:26][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[N:28][N:29]=1>CO>[NH2:18][C:19]1[N:20]=[CH:21][C:22]([C:34]2[N:38]([CH2:39][CH3:40])[N:37]=[C:36]([CH:41]3[CH2:42][CH2:43][N:44]([C:47](=[O:57])[CH2:48][CH2:49][OH:50])[CH2:45][CH2:46]3)[N:35]=2)=[N:23][C:24]=1[C:25]1[O:26][C:27]([C:30]([CH3:33])([CH3:31])[CH3:32])=[N:28][N:29]=1

参加物

4

反応物 2

HCID 161440Pyridine 4-methylbenzene-1-sulfonateHCID 867276661-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propan-1-one

生成物 1

HCID 76685059Azd-8835収率 85%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
60 °C

実験手順

Pyridine 4-methylbenzenesulfonate (11.62 g, 46.24 mmol) was added to a suspension of 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propan-1-one (128 g, 231.19 mmol) in methanol (1 L) under nitrogen. The mixture was stirred at 60° C. for 1.5 hours. The mixture was soluble after 5 minutes. The mixture was held at 50° C. overnight during which time a precipitate formed. The solid material was isolated by filtration and washed with water and acetonitrile. This material still contained minor impurities from the previous stage and required further purification. The material was dissolved in dichloromethane and purified by flash chromatography on silica gel (0% methanol/DCM to 10% methanol/DCM). The desired product, 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-hydroxypropan-1-one (Reference Example 1) (92 g, 85%), was thus isolated as a cream solid (Form A): 1H NMR Spectrum: (DMSO-d6) 1.4-1.51 (12H, m), 1.51-1.78 (2H, m), 1.89-2.05 (2H, n), 72-2.86 (1H, m), 2.91-3.05 (1H, m), 3.12-3.24 (1H, m), 3.64 (2H, q), 3.83-4.01 (1H, m), 4.29-4.41 (1H, m), 4.47 (1H, t), 4.58 (2H, q), 8.26 (2H, s), 8.85 (1H, s): Mass Spectrum [M+H]+=470.

後処理

  1. waitThe mixture was soluble after 5 minutes
  2. waitThe mixture was held at 50° C. overnight during which time
  3. customa precipitate formed
  4. customThe solid material was isolated by filtration
  5. washwashed with water and acetonitrile
  6. customThis material still contained minor impurities from the previous stage and required further purification
  7. dissolutionThe material was dissolved in dichloromethane
  8. custompurified by flash chromatography on silica gel (0% methanol/DCM to 10% methanol/DCM)

出典と根拠

ORDレコード
ord-c444e4c9538440e4aec6263ef097a9f7
出典データセット
uspto-grants-2015_10
特許番号
US09155727B2

反応ノート

読み込み中…