p-Toluenesulfonic acid monohydrate → HCID 68685078, compound

HRID 2234294Notes

Reaction equation

HRID 2234294 reaction equation
Cl[C:2]1[N:12]=[C:11]2[C:5]([NH:6][C:7](=[O:18])[CH2:8][CH2:9][N:10]2[CH:13]([CH3:17])[CH2:14][O:15][CH3:16])=[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].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C.CO>[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)[NH:6][C:7](=[O:18])[CH2:8][CH2:9][N:10]2[CH:13]([CH3:17])[CH2:14][O:15][CH3:16])[C:24]([NH:26][CH:27]1[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]1)=[O:25]

Participants

6

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 86617547HCID 86617547, compound2×

Product 1

HCID 68685078HCID 68685078, compoundYield 20.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

10-chloro-2-(1-methoxypropan-2-yl)-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 137; 35 mg, 0.13 mmol)), 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (WO06/018220; 34 mg, 0.13 mmol) and p-toluenesulphonic acid monohydrate (61 mg, 0.32 mmol) were dissolved in 4-methyl-2-pentanol (2 mL) and heated at 100° C. for 18 hrs. The reaction mixture was cooled to room temperature dissolved in MeOH and added to a 2 g SCX-2 column pre wet with MeOH (2 column volumes). Flushed with MeOH (2 column volumes) and the product eluted with 2M ammonia in MeOH. Product containing fractions were evaporated and the resultant material purified by base modified reverse phase HPLC to yield the title compound as a cream coloured solid (13 mg, 20%)

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customFlushed with MeOH (2 column volumes)
  3. washthe product eluted with 2M ammonia in MeOH
  4. additionProduct containing fractions
  5. customwere evaporated
  6. customthe resultant material purified by base modified reverse phase HPLC

Sources & evidence

ORD record
ord-da3e425c924b4e67bb92940e2dddcba7
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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