Water → HCID 11655371, compound

HRID 1373967Notes

Reaction equation

HRID 1373967 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:15]([NH:16][CH:17]([CH3:19])[CH3:18])[C:14]([CH2:20][CH2:21][CH3:22])=[N:13][C:7]=3[C:8]([NH2:12])=[N:9][C:10]=2[CH:11]=1.[CH3:23][S:24]([NH:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)(=[O:26])=[O:25].C(=O)([O-])[O-].[Na+].[Na+].O>C(O)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:12][C:8]1[C:7]2[N:13]=[C:14]([CH2:20][CH2:21][CH3:22])[N:15]([NH:16][CH:17]([CH3:19])[CH3:18])[C:6]=2[C:5]2[CH:4]=[CH:3][C:2]([C:32]3[CH:33]=[C:28]([NH:27][S:24]([CH3:23])(=[O:25])=[O:26])[CH:29]=[CH:30][CH:31]=3)=[CH:11][C:10]=2[N:9]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27735353-Methylsulfonylaminophenylboronic acidHCID 69177518HCID 69177518, compound

Product 1

HCID 11655371HCID 11655371, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 10311-PropanolSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 7-bromo-N1-isopropyl-2-propyl-1H-imidazo[4,5-c]quinoline-1,4-diamine (1.00 g, 2.76 mmol) in 20 mL of 1-propanol was treated with 3-(methanesulfonylamino)phenylboronic acid (0.653 g, 3.04 mmol). The headspace of the reaction flask was purged and back-filled with nitrogen (3×). The reaction mixture was then treated with triphenylphosphine (11 mg, 0.041 mmol), sodium carbonate (1.66 mL, 3.31 mmol, 2 M solution in H2O), H2O (2 mL) and palladium (II) acetate (3.1 mg, 0.014 mmol). Again the headspace of the reaction flask was purged and back-filled with nitrogen (3×). The reaction was heated to 100° C. After 17 h, the reaction was cooled to ambient temperature and concentrated under reduced pressure to yield a brown solid. The solid was partitioned between 15 mL of H2O and 15 mL of CHCl3 and then separated. The aqueous portion was extracted with CHCl3 (2×15 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to yield a tan foam. The material was purified by chromatography (SiO2, 50% (80:18:2 CHCl3:MeOH:NH4OH) in CHCl3) and then dissolved in boiling CHCl3 and slowly cooled to yield N-{3-[4-amino-1-(isopropylamino)-2-propyl-1H-imidazo[4,5-c]quinolin-7-yl]phenyl}methanesulfonamide (0.700 g) as a white solid. mp 217–227° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.85 (s, 1H), 8.54 (d, J=8.5 Hz, 1H), 7.79 (d, J=1.4 Hz, 1H), 7.60 (s, 1H), 7.52–7.42 (m, 3H), 7.22 (d, J=7.8 Hz, 1H), 7.01 (s, 1H), 6.55 (s, 2H), 3.55–3.51 (m, 1H), 3.06 (s, 3H), 2.92 (bs, 2H), 1.91–1.84 (m, 2H), 1.05–1.01 (m, 9H); 13C NMR (125 MHz, DMSO-d6) δ 155.4, 152.9, 145.8, 142.4, 139.9, 138.6, 133.1, 130.8, 124.9, 124.2, 123.1, 122.5, 120.2, 119.5, 118.7, 114.9, 51.8, 28.7, 21.6, 21.1, 14.8; MS (APCI) m/z 453 (M+H)+; Anal. Calcd for C23H28N6O2S: C, 61.04; H, 6.24; N, 18.57; Found: C, 60.66; H, 60.40; N, 18.47.

Workup

  1. customThe headspace of the reaction flask was purged
  2. additionback-filled with nitrogen (3×)
  3. customAgain the headspace of the reaction flask was purged
  4. additionback-filled with nitrogen (3×)
  5. temperaturethe reaction was cooled to ambient temperature
  6. concentrationconcentrated under reduced pressure
  7. customto yield a brown solid
  8. customThe solid was partitioned between 15 mL of H2O and 15 mL of CHCl3
  9. customseparated
  10. extractionThe aqueous portion was extracted with CHCl3 (2×15 mL)
  11. washThe combined organic extracts were washed with brine (15 mL)
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customto yield a tan foam
  16. customThe material was purified by chromatography (SiO2, 50% (80:18:2 CHCl3:MeOH:NH4OH) in CHCl3)
  17. dissolutiondissolved
  18. temperatureslowly cooled

Sources & evidence

ORD record
ord-24487cb6d959403e87f66a70ca9e9905
Source dataset
uspto-grants-2007_01
Patent number
US07163947B2

Reaction notes

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