Water → HCID 46917284, compound

HRID 1256539Notes

Reaction equation

HRID 1256539 reaction equation
CCN(C(C)C)C(C)C.[F:10][CH:11]([F:41])[C:12]1[N:16]([C:17]2[N:22]=[C:21]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[N:20]=[C:19]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)[N:18]=2)[C:15]2[CH:35]=[CH:36][CH:37]=[C:38]([O:39][CH3:40])[C:14]=2[N:13]=1.[Cl-].Cl[S:44]([CH2:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][NH+:50]=1)(=[O:46])=[O:45].O>C(Cl)Cl>[F:41][CH:11]([F:10])[C:12]1[N:16]([C:17]2[N:22]=[C:21]([N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[N:20]=[C:19]([N:29]3[CH2:34][CH2:33][N:32]([S:44]([CH2:47][CH2:48][C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][N:50]=4)(=[O:45])=[O:46])[CH2:31][CH2:30]3)[N:18]=2)[C:15]2[CH:35]=[CH:36][CH:37]=[C:38]([O:39][CH3:40])[C:14]=2[N:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 666980472-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazoleHCID 87113963HCID 87113963, compound2×

Product 1

HCID 46917284HCID 46917284, compoundYield 71.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIPEA (0.29 mL, 1.66 mmol) was added to a suspension of 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (Example 2) (150 mg, 0.336 mmol) and 2-[2-(chlorosulfonyl)ethyl]pyridinium chloride (122 mg, 0.504 mmol) in CH2Cl2 (10 mL) at room temperature under nitrogen, and the mixture was stirred for 4 hrs. Additional 2-[2-(chlorosulfonyl)ethyl]pyridinium chloride (41 mg, 0.169 mmol) was added and the reaction mixture was stirred for another 20 hrs. Water was added and the phases were separated. The aqueous phase was extracted with CH2Cl2, the combined organic extracts were dried (Na2SO4), and the solvent was removed under vacuum. Chromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 98.5:1.5), gave 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(4-{[2-(2-pyridinyl)ethyl]sulfonyl}-1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (148 mg, 71%).

Workup

  1. stirringthe reaction mixture was stirred for another 20 hrs
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted with CH2Cl2
  4. dry with materialthe combined organic extracts were dried (Na2SO4)
  5. customthe solvent was removed under vacuum
  6. washChromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 98.5:1.5)

Sources & evidence

ORD record
ord-409bac9b5ca2435bab2036af94e0e760
Source dataset
uspto-grants-2013_06
Patent number
US08461158B2

Reaction notes

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