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

HRID 2234288ノート

反応式

HRID 2234288 の反応式
Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:21])[C:7](=[O:20])[CH2:8][CH2:9][N:10]2[CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:37]=[CH:36][C:26]([C:27]([NH:29][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)=[O:28])=[CH:25][C:24]=1[O:38][CH3:39].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C.CO>[CH:30]1([NH:29][C:27](=[O:28])[C:26]2[CH:36]=[CH:37][C:23]([NH:22][C:2]3[N:12]=[C:11]4[C:5](=[CH:4][N:3]=3)[N:6]([CH3:21])[C:7](=[O:20])[CH2:8][CH2:9][N:10]4[CH:13]3[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]3)=[C:24]([O:38][CH3:39])[CH:25]=2)[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1

参加物

6

反応物 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 672140984-amino-N-cyclohexyl-3-methoxy-benzamide2 回HCID 8661754610-Chloro-6-methyl-2-(1-methyl-4-piperidyl)-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one2 回

生成物 1

HCID 68683396N-cyclohexyl-3-methoxy-4-[[2-methyl-6-(1-methyl-4-piperidyl)-3-oxo-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl]amino]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-6-methyl-2-(1-methyl-4-piperidyl)-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 118; 39 mg, 0.13 mmol), 4-amino-N-cyclohexyl-3-methoxy-benzamide (Intermediate 119; 31 mg, 0.13 mmol) and p-toluenesulphonic acid monohydrate (60 mg, 0.31 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 and added to a 5 g SCX-3 column pre wet with MeOH (2 column volumes). Flushed with MeOH (2 column volumes) then crude product eluted with 2M ammonia in MeOH and solvents evaporated. The resultant material was dissolved in DCM and purified on silica eluting with a shallow (25 column volumes) gradient of 0-10% 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 white solid. (15 mg, 23%).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customFlushed with MeOH (2 column volumes)
  3. washcrude product eluted with 2M ammonia in MeOH and solvents
  4. customevaporated
  5. dissolutionThe resultant material was dissolved in DCM
  6. custompurified on silica eluting with a shallow (25 column volumes) gradient of 0-10% 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-0911d38519444c738a5d98725a64bf2a
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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