p-Toluenesulfonic acid → 3-methoxy-4-[[2-methyl-6-(2-methylpropyl)-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 2234282Notes

Reaction equation

HRID 2234282 reaction equation
Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:18])[C:7](=[O:17])[CH2:8][CH2:9][N:10]2[CH2:13][CH:14]([CH3:16])[CH3:15])=[CH:4][N:3]=1.[NH2:19][C:20]1[CH:35]=[CH:34][C:23]([C:24]([NH:26][CH:27]2[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]2)=[O:25])=[CH:22][C:21]=1[O:36][CH3:37].C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C.CO.O>[CH3:37][O:36][C:21]1[CH:22]=[C:23]([CH:34]=[CH:35][C:20]=1[NH:19][C:2]1[N:12]=[C:11]2[C:5](=[CH:4][N:3]=1)[N:6]([CH3:18])[C:7](=[O:17])[CH2:8][CH2:9][N:10]2[CH2:13][CH:14]([CH3:16])[CH3:15])[C:24]([NH:26][CH:27]1[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]1)=[O:25]

Participants

7

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 8661754410-Chloro-6-methyl-2-(2-methylpropyl)-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one2×

Product 1

HCID 426103033-methoxy-4-[[2-methyl-6-(2-methylpropyl)-3-oxo-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl]amino]-N-(1-methyl-4-piperidyl)benzamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 79104-Methyl-2-PentanolSolvent

Conditions

Temperature
160 °C

Procedure

10-chloro-6-methyl-2-(2-methylpropyl)-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 84; 65 mg, 0.24 mmol), 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (WO06/018220, 57 mg, 0.24 mmol) and p-toluene sulphonic acid (110 mg, 0.58 mmol) were taken up in 4-methyl-2-pentanol (1 mL) and heated to 160° C. by microwave irradiation for 1 hour. The reaction mixture was diluted with methanol (5 mL) and water (2 mL) and resultant solution poured onto an SCX-3 cartridge (2 g). The cartridge was washed with methanol (˜30 mL) before eluting products with 2M ammonia methanol (20 mL). The Ammoniacal fraction was evaporated to give an amber gum which was purified by reverse phase HPLC to yield the title compound as a colourless glass (scratches down to a white solid) (80 mg, 75%).

Workup

  1. additionpoured onto an SCX-3 cartridge (2 g)
  2. washThe cartridge was washed with methanol (˜30 mL)
  3. washbefore eluting products with 2M ammonia methanol (20 mL)
  4. customThe Ammoniacal fraction was evaporated
  5. customto give an amber gum which
  6. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-a800a06474a0467fa047fec8166d8b42
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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