Oxalic Acid → HCID 66836012, compound

HRID 2404475Notes

Reaction equation

HRID 2404475 reaction equation
C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:21][CH2:22][CH2:23][NH:24][C:25](=O)[CH2:26][S:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([CH:34]([C:43]2[NH:47][C:46]3[CH:48]=[CH:49][CH:50]=[CH:51][C:45]=3[N:44]=2)[O:35][CH:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)[CH:29]=1.C(O)(=O)C(O)=O>C(Cl)Cl>[NH:24]1[CH2:23][CH2:22][N:21]=[C:25]1[CH2:26][S:27][C:28]1[CH:29]=[C:30]([CH:34]([O:35][CH:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)[C:43]2[NH:47][C:46]3[CH:48]=[CH:49][CH:50]=[CH:51][C:45]=3[N:44]=2)[CH:31]=[CH:32][CH:33]=1

Participants

5

Reactant 3

HCID 971Oxalic AcidHCID 13097Triphenylphosphine OxideHCID 66836013HCID 66836013, compound

Product 1

HCID 66836012HCID 66836012, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of triphenylphosphine oxide (2.2 mmoles) in 4 mL CH2Cl2 cooled at 0° C. is added dropwise trifluoromethanesulfonyl anhydride (310 mg, 1.1 mmoles). The reaction mixture is stirred at 0° C. for 30 minutes, then a solution of N-(2-aminoethyl)-2-{3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenylsulfanyl}acetamide (Example 436) (250 mg, 0.55 mmole) in 2 mL CH2Cl2 is added dropwise. The reaction mixture is allowed to reach room temperature and stirred for 1.5 h. The organic phase is washed with 1N sodium hydroxide solution, then dried over magnesium sulfate and concentrated. The residue is purified by chromatography on silica gel (gradient dichloromethane/methanol/ammonia from 100/0/0 to 80/20/2). The residue is then dissolved in acetone and one equivalent of oxalic acid is added. Acetone is removed under reduced pressure to afford 2-[[3-(4,5-dihydro-1H-imidazol-2-ylmethylsulfanyl)phenyl](1-methylpiperidin-4-yloxy)methyl]-1H-benzimidazole melting at 62° C. (déc.); MS, [M+H]+=436.1.

Workup

  1. customto reach room temperature
  2. stirringstirred for 1.5 h
  3. washThe organic phase is washed with 1N sodium hydroxide solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue is purified by chromatography on silica gel (gradient dichloromethane/methanol/ammonia from 100/0/0 to 80/20/2)
  7. dissolutionThe residue is then dissolved in acetone
  8. customAcetone is removed under reduced pressure

Sources & evidence

ORD record
ord-a0c970cab2ab404eb26af5801519d84d
Source dataset
uspto-grants-2014_08
Patent number
US08802664B2

Reaction notes

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