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 2234288Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2234288
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

Komponenten

6

Edukt 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 672140984-amino-N-cyclohexyl-3-methoxy-benzamide2×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×

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittel2×HCID 79104-Methyl-2-PentanolLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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%).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-0911d38519444c738a5d98725a64bf2a
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07709471B2

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