p-Toluenesulfonic acid monohydrate → 4-[[2-(2-fluoroethyl)-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl]amino]-3-methoxy-N-(1-methyl-4-piperidyl)benzamide

HRID 2234298Notes

Reaction equation

HRID 2234298 reaction equation
Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:17])[C:7](=[O:16])[CH2:8][CH2:9][N:10]2[CH2:13][CH2:14][F:15])=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:34]=[CH:33][C:22]([C:23]([NH:25][CH:26]2[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]2)=[O:24])=[CH:21][C:20]=1[O:35][CH3:36].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C.O.CO>[F:15][CH2:14][CH2:13][N:10]1[CH2:9][CH2:8][C:7](=[O:16])[N:6]([CH3:17])[C:5]2[C:11]1=[N:12][C:2]([NH:18][C:19]1[CH:34]=[CH:33][C:22]([C:23]([NH:25][CH:26]3[CH2:27][CH2:28][N:29]([CH3:32])[CH2:30][CH2:31]3)=[O:24])=[CH:21][C:20]=1[O:35][CH3:36])=[N:3][CH:4]=2

Participants

7

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 8661755310-Chloro-2-(2-fluoroethyl)-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one2×

Product 1

HCID 866175524-[[2-(2-fluoroethyl)-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl]amino]-3-methoxy-N-(1-methyl-4-piperidyl)benzamideYield 37.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 79104-Methyl-2-PentanolSolvent

Procedure

10-chloro-2-(2-fluoroethyl)-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 157; 86 mg, 0.33 mmol), 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (WO06/018220; 104 mg, 0.40 mmol) and p-toluenesulphonic acid monohydrate (126 mg, 0.66 mmol) were heated together in 4-methyl-2-pentanol (4 mL) at 100° C. for 24 hours. The reaction mixture was diluted with water and methanol and the solution loaded onto an SCX-2 (5 g) column pre-wet with methanol. The column was washed with methanol (×2) and the product eluted with 2M NH3/MeOH. Product containing fractions were combined and evaporated. The resultant material was purified by base modified reverse phase preparative HPLC to yield the title compound as a yellow solid (60 mg, 37%).

Workup

  1. washThe column was washed with methanol (×2)
  2. washthe product eluted with 2M NH3/MeOH
  3. additionProduct containing fractions
  4. customevaporated
  5. customThe resultant material was purified by base modified reverse phase preparative HPLC

Sources & evidence

ORD record
ord-2158296aa8044306b30a7646799b8b79
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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