Water → HCID 46918130, compound

HRID 1619829Notes

Reaction equation

HRID 1619829 reaction equation
[O-][Mn](=O)(=O)=O.[K+].[F:7][CH:8]([F:49])[C:9]1[N:13]([C:14]2[N:19]=[C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:17]=[C:16]([N:26]3[CH2:31][CH2:30][N:29]([S:32]([CH2:35][CH2:36][N:37]4[CH2:42][CH2:41]S[CH2:39][CH2:38]4)(=O)=[O:33])[CH2:28][CH2:27]3)[N:15]=2)[C:12]2[CH:43]=[CH:44][CH:45]=[C:46]([O:47][CH3:48])[C:11]=2[N:10]=1.[O-:50][S:51]([O-:53])=O.[Na+].[Na+].[OH2:56]>CC(C)=O.C(O)(=O)C.C(Cl)Cl>[F:49][CH:8]([F:7])[C:9]1[N:13]([C:14]2[N:15]=[C:16]([N:26]3[CH2:31][CH2:30][N:29]([S:32]([CH2:35][CH2:36][N:37]4[CH2:38][CH2:39][S:51](=[O:53])(=[O:50])[CH2:41][CH2:42]4)(=[O:33])=[O:56])[CH2:28][CH2:27]3)[N:17]=[C:18]([N:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)[N:19]=2)[C:12]2[CH:43]=[CH:44][CH:45]=[C:46]([O:47][CH3:48])[C:11]=2[N:10]=1

Participants

8

Reactant 4

HCID 962Water2×HCID 24437Sodium SulfiteHCID 516875Potassium PermanganateHCID 67543789HCID 67543789, compound

Product 1

HCID 46918130HCID 46918130, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of KMnO4 (88 mg, 0.559 mmol) in water (6 mL) was added dropwise to a stirred solution of 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(4-{[2-(4-thiomorpholinyl)ethyl]sulfonyl}-1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (170 mg, 0.266 mmol) in acetone (50 mL) and acetic acid (7.5 mL) at room temperature. After 2.5 hrs the reaction was diluted with water, decolourized with Na2SO3 and the acetone removed under vacuum. The mixture was neutralized with conc. aq. NH3 to give a precipitate, which was dissolved in CH2Cl2 and dried (Na2SO4). The solvent was then removed under vacuum. Chromatography on silica, eluting with CH2Cl2/MeOH (98.5:1.5) gave 117 mg (65% yield) of 2-(difluoromethyl)-1-[4-(4-{[2-(1,1-dioxido-4-thiomorpholinyl)ethyl]sulfonyl}-1-piperazinyl)-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole: mp 258-261° C.; 1H NMR (CDCl3) δ 7.85 (d, J=8.3 Hz, 1H), 7.42 (t, JHF=53.5 Hz, 1H), 7.35 (t, J=8.2 Hz, 1H), 6.82 (d, J=8.0 Hz, 1H), 4.05 (s, 3H), 4.01 (br s, 4H), 3.88 (br s, 4H), 3.79 (m, 4H), 3.37 (t, J=5.0 Hz, 4H), 3.07 (m, 4H), 3.05 (s, 8H); HRMS Calcd. for C26H36F2N9O6S2: MH+ m/z 672.2198. Found: m/z 672.2184.

Workup

  1. customthe acetone removed under vacuum
  2. customto give a precipitate, which
  3. dry with materialdried (Na2SO4)
  4. customThe solvent was then removed under vacuum
  5. washChromatography on silica, eluting with CH2Cl2/MeOH (98.5:1.5)

Sources & evidence

ORD record
ord-9c00c83df54a42488a5c61619a1730b3
Source dataset
uspto-grants-2014_07
Patent number
US08772287B2

Reaction notes

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