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 2234288노트

반응식

HRID 2234288 반응식
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

참가 물질

6

반응물 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 672140984-amino-N-cyclohexyl-3-methoxy-benzamide2회HCID 8661754610-Chloro-6-methyl-2-(1-methyl-4-piperidyl)-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one2회

생성물 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

시약·촉매·용매 2

HCID 887Methanol용매2회HCID 79104-Methyl-2-Pentanol용매

반응 조건

온도
100 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-0911d38519444c738a5d98725a64bf2a
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07709471B2

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