p-Toluenesulfonic acid monohydrate → 3-methoxy-4-[[6-(1-methoxypropan-2-yl)-2-methyl-3-oxo-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl]amino]-N-(1-methyl-4-piperidyl)benzamide

HRID 2234287ノート

反応式

HRID 2234287 の反応式
Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:19])[C:7](=[O:18])[CH2:8][CH2:9][N:10]2[CH:13]([CH3:17])[CH2:14][O:15][CH3:16])=[CH:4][N:3]=1.[NH2:20][C:21]1[CH:36]=[CH:35][C:24]([C:25]([NH:27][CH:28]2[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]2)=[O:26])=[CH:23][C:22]=1[O:37][CH3:38].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C.CO>[CH3:38][O:37][C:22]1[CH:23]=[C:24]([CH:35]=[CH:36][C:21]=1[NH:20][C:2]1[N:12]=[C:11]2[C:5](=[CH:4][N:3]=1)[N:6]([CH3:19])[C:7](=[O:18])[CH2:8][CH2:9][N:10]2[CH:13]([CH3:17])[CH2:14][O:15][CH3:16])[C:25]([NH:27][CH:28]1[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]1)=[O:26]

参加物

6

反応物 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 8661754510-Chloro-2-(1-methoxypropan-2-yl)-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one2 回

生成物 1

HCID 686835153-methoxy-4-[[6-(1-methoxypropan-2-yl)-2-methyl-3-oxo-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl]amino]-N-(1-methyl-4-piperidyl)benzamide

試薬・触媒・溶媒 2

HCID 887Methanol溶媒2 回HCID 79104-Methyl-2-Pentanol溶媒

反応条件

温度
100 °C

実験手順

10-chloro-2-(1-methoxypropan-2-yl)-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 112 60 mg, 0.21 mmol), 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (WO06/018220; 56 mg, 0.21 mmol), and p-toluenesulphonic acid monohydrate (100 mg, 0.53 mmol) were combined in 4-Methyl-2-pentanol (2 mL) and heated at 100° C. for 16 hrs. The reaction mixture was cooled to room temperature and dissolved in Methanol. The resultant solution was added to a 5 g SCX-3 column pre wet with MeOH (2 column volumes). Flushed with MeOH (2 column volumes) and crude product eluted with 2M ammonia in MeOH and solvents evaporated. The resultant residue was dissolved in DCM and purified on silica eluting with a gradient of 5-15% MeOH/DCM. Product containing fractions were combined and evaporated to a yellow gum which was purified by base modified reverse phase HPLC to give the title compound as a beige solid. (35 mg, 32%)

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customFlushed with MeOH (2 column volumes) and crude product
  3. washeluted with 2M ammonia in MeOH and solvents
  4. customevaporated
  5. dissolutionThe resultant residue was dissolved in DCM
  6. custompurified on silica eluting with a gradient of 5-15% MeOH/DCM
  7. additionProduct containing fractions
  8. customevaporated to a yellow gum which
  9. customwas purified by base modified reverse phase HPLC

出典と根拠

ORDレコード
ord-4ea80e9d1ca141259182dea6cf84e18a
出典データセット
uspto-grants-2010_05
特許番号
US07709471B2

反応ノート

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