5-(Trifluoromethyl)dibenzothiophen-5-ium-3-sulfonate → 2-[(S)-1-Phenylethylamino]-4-[4-trifluoromethyl-5-aminobenzimidazol-1-yl]pyrimidine

HRID 2300797Notes

Reaction equation

HRID 2300797 reaction equation
[C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[CH:22][C:23]([NH2:25])=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:26][C:27]([F:46])([F:45])[S+]1C2C=CC=CC=2C2C=CC(S([O-])(=O)=O)=CC1=2>CN(C=O)C>[C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[CH:22][C:23]([NH2:25])=[C:24]([C:27]([F:46])([F:45])[F:26])[C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 27774995-(Trifluoromethyl)dibenzothiophen-5-ium-3-sulfonateHCID 98839772-[(S)-1-phenylethylamino]-4-[5-aminobenzimidazol-1-yl]pyrimidine

Product 1

HCID 599249592-[(S)-1-Phenylethylamino]-4-[4-trifluoromethyl-5-aminobenzimidazol-1-yl]pyrimidineYield 23.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 2-[(S)-1-phenylethylamino]-4-[5-amino-benzimidazol-1-yl]pyrimidine (330 mg, 1 mmol, 1 eq) in DMF (2 mL) was added S-(trifluoromethyl)-dibenzothiophenium-3-sulfonate (166 mg, 0.5 mmol, 0.5 eq) and the mixture was heated to 80° C. for 7 hours. The reaction was cooled and the DMF was removed under reduced pressure. The residue was diluted with water and extracted wth CH2Cl2. The organic extracts were combined, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The product was purified by column chromatography (eluted with 3.5% MeOH/CH2Cl2) followed by preparative thin layer chromatography (eluted 2× with 3.5% MeOH/CH2Cl2) to give 46 mg of the title compound. 1H NMR (500 MHz, CDCl3): δ 1.63 (3H, d, J=7 Hz), 4.32 (3H, s), 5.13 (1H, br s), 5.80 (1H, br s), 6.62 (1H, br), 6.70 (1H, d, J=5.5 Hz), 7.29 (1H, m), 7.39 (2H, t, J=7.5 Hz), 7.43 (2H, d, J=7 Hz), 7.62 (1H, br), 8.38 (1H, d, J=5.5 Hz), 8.40 (1H, br). Mass spectrum (ESI) 398.14 (M+1).

Workup

  1. temperatureThe reaction was cooled
  2. customthe DMF was removed under reduced pressure
  3. additionThe residue was diluted with water
  4. extractionextracted wth CH2Cl2
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe product was purified by column chromatography (eluted with 3.5% MeOH/CH2Cl2)
  9. washfollowed by preparative thin layer chromatography (eluted 2× with 3.5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ced5a082381d4a2abb92cf2ff2df1a61
Source dataset
uspto-grants-2002_12
Patent number
US06498165B1

Reaction notes

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