p-Toluenesulfonic acid → HCID 51348850, compound

HRID 2234278Notes

Reaction equation

HRID 2234278 reaction equation
Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:15])[C:7](=[O:14])[CH2:8][CH2:9][N:10]2[CH3:13])=[CH:4][N:3]=1.[NH2:16][C:17]1[CH:32]=[CH:31][C:20]([C:21]([NH:23][CH:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]2)=[O:22])=[CH:19][C:18]=1[O:33][CH3:34].C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C>[CH3:13][N:10]1[CH2:9][CH2:8][C:7](=[O:14])[N:6]([CH3:15])[C:5]2[C:11]1=[N:12][C:2]([NH:16][C:17]1[CH:32]=[CH:31][C:20]([C:21]([NH:23][CH:24]3[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]3)=[O:22])=[CH:19][C:18]=1[O:33][CH3:34])=[N:3][CH:4]=2

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 86617542HCID 86617542, compound2×

Product 1

HCID 51348850HCID 51348850, compoundYield 48.4%

Reagents, catalysts & solvents 1

HCID 79104-Methyl-2-PentanolSolvent

Procedure

10-Chloro-2,6-dimethyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 9; 185 mg, 0.82 mmol), 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (215 mg, 0.82 mmol) and p-toluenesulphonic acid (389 mg, 2.05 mmol) in (R/S)-4-methyl-2-pentanol (6 mL) were heated at 115° C. for 5 h. The reaction mixture was cooled to ambient temperature then passed through a SCX-2 cartridge and washed with MeOH (40 mL). The crude product was eluted off the SCX-2 cartridge with NH3 (40 mL, 7M in MeOH). Purification by preparative HPLC (Gemini RP C18 30×100 mm, gradient mobile phase: 10-80% MeCN/water+0.5% NH3) afforded the title compound (180 mg, 48%) as a foam.

Workup

  1. washwashed with MeOH (40 mL)
  2. washThe crude product was eluted off the SCX-2 cartridge with NH3 (40 mL, 7M in MeOH)
  3. customPurification by preparative HPLC (Gemini RP C18 30×100 mm, gradient mobile phase: 10-80% MeCN/water+0.5% NH3)

Sources & evidence

ORD record
ord-cc31f10a8d1d44bba436a9d06a8cef3c
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

Loading…