Water → HCID 46917285, compound

HRID 1256540Notes

Reaction equation

HRID 1256540 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][NH+:52]=[CH:51][CH: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:50]=[CH:51][N:52]=[CH:53][CH:54]=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 178527441HCID 178527441, compound2×

Product 1

HCID 46917285HCID 46917285, compoundYield 65%

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 4-[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 3 hrs. Additional 4-[2-(chlorosulfonyl)ethyl]pyridinium chloride (41 mg, 0.169 mmol) was added and the mixture stirred for another 21 hrs. Water was added and the phases were separated. The aqueous phase was extracted with CH2Cl2 (1×), the combined organic extracts were dried (Na2SO4), and the solvent was removed under vacuum. Chromatography on silica eluting with CH2Cl2/MeOH (100:0 to 98:2) followed by recrystallization from CH2Cl2/MeOH gave 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(4-{[2-(4-pyridinyl)ethyl]sulfonyl}-1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (134 mg, 65%).

Workup

  1. stirringthe mixture stirred for another 21 hrs
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted with CH2Cl2 (1×)
  4. dry with materialthe combined organic extracts were dried (Na2SO4)
  5. customthe solvent was removed under vacuum
  6. customChromatography on silica eluting with CH2Cl2/MeOH (100:0 to 98:2) followed by recrystallization from CH2Cl2/MeOH

Sources & evidence

ORD record
ord-13db00d68a8c41edbe2dd8dc6f3b3b5e
Source dataset
uspto-grants-2013_06
Patent number
US08461158B2

Reaction notes

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