Pyrrolidine → HCID 46918204, compound

HRID 1619836Notes

Reaction equation

HRID 1619836 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[CH2:42][CH2:41][CH2:40][CH2:39]1>O1CCOCC1>[F:37][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:11]=[C:10]([N:20]3[CH2:21][CH2:22][N:23]([S:26]([CH2:29][CH2:30][N:38]4[CH2:42][CH2:41][CH2:40][CH2:39]4)(=[O:28])=[O:27])[CH2:24][CH2:25]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

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 469174972-(difluoromethyl)-4-methoxy-1-{4-(4-morpholinyl)-6-[4-(vinylsulfonyl)-1-piperazinyl]-1,3,5-triazin-2-yl}-1H-benzimidazole

Product 1

HCID 46918204HCID 46918204, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

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) and pyrrolidine (0.23 mL, 2.80 mmol) in 1,4-dioxane (20 mL) was stirred at room temperature for 16 hrs and then refluxed for 3 hrs. The solvent was removed under vacuum, the residue was diluted with water and the resulting precipitate was dissolved in CH2Cl2. The organic layer was separated and dried (Na2SO4), and solvent was removed under vacuum. Chromatography on silica eluting with CH2Cl2/MeOH (98:2), followed by recrystallization from CH2Cl2/hexanes gave 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(4-{[2-(1-pyrrolidinyl)ethyl]sulfonyl}-1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (137 mg, 81%): mp 186-188° C.; 1H NMR (CDCl3) δ 7.86 (dd, J=8.4, 0.6 Hz, 1H), 7.44 (t, JHF=53.5 Hz, 1H), 7.35 (t, J=8.2 Hz, 1H), 6.82 (d, J=7.6 Hz, 1H), 4.05 (s, 3H), 3.99 (br s, 4H), 3.88 (br s, 4H), 3.79 (m, 4H), 3.39 (t, J=5.0 Hz, 4H), 3.16 (m, 2H), 2.93 (m, 2H), 2.53 (m, 4H), 1.76 (m, 4H); Anal. Calcd. for C26H35F2N9O4S: C, 51.4; H, 5.8; N, 20.7. Found: C, 51.3; H, 5.9; N, 20.5%.

Workup

  1. temperaturerefluxed for 3 hrs
  2. customThe solvent was removed under vacuum
  3. additionthe residue was diluted with water
  4. dissolutionthe resulting precipitate was dissolved in CH2Cl2
  5. customThe organic layer was separated
  6. dry with materialdried (Na2SO4), and solvent
  7. customwas removed under vacuum
  8. customChromatography on silica eluting with CH2Cl2/MeOH (98:2), followed by recrystallization from CH2Cl2/hexanes

Sources & evidence

ORD record
ord-8bd52a7a82744d1c95b6777d96c8cd22
Source dataset
uspto-grants-2014_07
Patent number
US08772287B2

Reaction notes

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