Imidazole → HCID 46917283, compound

HRID 1619850Notes

Reaction equation

HRID 1619850 reaction equation
[F:1][CH:2]([F:37])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([N:20]3[CH2:25][CH2:24][N:23]([S:26]([CH:29]=[CH2:30])(=[O:28])=[O:27])[CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:31]=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:5]=2[N:4]=1.[NH:38]1[CH:42]=[CH:41][N:40]=[CH:39]1>N1C=CC=CC=1.CS(C)=O>[F:37][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:9]=[C:10]([N:20]3[CH2:21][CH2:22][N:23]([S:26]([CH2:29][CH2:30][N:38]4[CH:42]=[CH:41][N:40]=[CH:39]4)(=[O:28])=[O:27])[CH2:24][CH2:25]3)[N:11]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:13]=2)[C:6]2[CH:31]=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:5]=2[N:4]=1

Participants

5

Reactant 2

HCID 795ImidazoleHCID 469174972-(difluoromethyl)-4-methoxy-1-{4-(4-morpholinyl)-6-[4-(vinylsulfonyl)-1-piperazinyl]-1,3,5-triazin-2-yl}-1H-benzimidazole

Product 1

HCID 46917283HCID 46917283, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 1049PyridineCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
137.5 °C

Procedure

A mixture of 2-(difluoromethyl)-4-methoxy-1-{4-(4-morpholinyl)-6-[4-(vinylsulfonyl)-1-piperazinyl]-1,3,5-triazin-2-yl}-1H-benzimidazole (Example 3) (150 mg, 0.280 mmol), imidazole (38 mg, 0.558 mmol), and pyridine (2 drops) in DMSO (5 mL) was heated at 135-140° C. for 5 days. The mixture was then poured over ice and extracted with CH2Cl2 (3×). The combined organic extracts were washed with H2O (1×), dried (Na2SO4) and concentrated. Chromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 95:5), followed by recrystallization from CH2Cl2/hexanes gave 2-(difluoromethyl)-1-[4-(4-{[2-(1H-imidazol-1-yl)ethyl]sulfonyl}-1-piperazinyl)-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole (45 mg, 27%): mp 188-191° C.; 1H NMR (CDCl3) δ 7.84 (dd, J=8.4, 0.6 Hz, 1H), 7.55 (s, 1H), 7.41 (t, JHF=53.5 Hz, 1H), 7.35 (t, J=8.2 Hz, 1H), 7.10 (t, J=1.0 Hz, 1H), 6.96 (t, J=1.3 Hz, 1H), 6.82 (d, J=7.7 Hz, 1H), 4.46 (t, J=7.0 Hz, 2H), 4.05 (s, 3H), 3.94 (br s, 4H), 3.87 (br s, 4H), 3.78 (m, 4H), 3.35 (t, J=7.1 Hz, 2H), 3.29 (br s, 4H); Anal. Calcd. for C25H30F2N10O4S: C, 49.7; H, 5.0; N, 23.2. Found: C, 49.3; H, 4.9; N, 23.2%.

Workup

  1. additionThe mixture was then poured over ice
  2. extractionextracted with CH2Cl2 (3×)
  3. washThe combined organic extracts were washed with H2O (1×)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. washChromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 95:5)
  7. customfollowed by recrystallization from CH2Cl2/hexanes

Sources & evidence

ORD record
ord-d673c66496f04230a592fb90d4bb03a4
Source dataset
uspto-grants-2014_07
Patent number
US08772287B2

Reaction notes

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