Water → HCID 11595634, compound

HRID 1373972Notes

Reaction equation

HRID 1373972 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.[C:23]1(B(O)O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.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>[CH:17]([NH:16][N:15]1[C:6]2[C:5]3[CH:4]=[CH:3][C:2]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:11][C:10]=3[N:9]=[C:8]([NH2:12])[C:7]=2[N:13]=[C:14]1[CH2:20][CH2:21][CH3:22])([CH3:19])[CH3:18]

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 69177518HCID 69177518, compound

Product 1

HCID 11595634HCID 11595634, compoundYield 40.4%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A solution 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 1-propanol was treated with phenylboronic acid (0.371 g, 3.04 mmol) giving a suspension. The headspace of the 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 flask was purged and back-filled with nitrogen (3×). The reaction mixture was heated to 100° C. After 16 h, the reaction mixture was concentrated under reduced pressure to yield a brown solid. The solid was partitioned between CHCl3 (45 mL) and H2O (15 mL) and separated. The organic portion was washed again with H2O (15 mL) and brine (15 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to yield a tan solid. The solid was recrystallized from MeCN to yield N1-isopropyl-7-phenyl-2-propyl-1H-imidazo[4,5-c]quinoline-1,4-diamine (0.401 g) as light yellow crystals. mp 217–220° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.53 (d, J=8.5 Hz, 1H), 7.83 (d, J=1.8 Hz, 1H), 7.78–7.76 (m, 2H), 7.55 (dd, J=7.5, 1.9 Hz, 1H), 7.52–7.47 (m, 2H), 7.40–7.35 (m, 1H), 7.01 (s, 1H), 6.53 (s, 2H), 3.57–3.49 (m, 1H), 2.92 (bs, 2H), 1.94–1.81 (m, 2H), 1.06–1.01 (m, 9H); 13C NMR (75 MHz, DMSO-d6) δ 154.2, 151.9, 144.9, 140.3, 138.1, 132.1, 128.9, 127.2, 126.7, 123.9, 123.2, 121.4, 119.4, 113.8, 50.8, 27.8, 20.7, 20.2, 13.9; MS (ESI) m/z 360 (M+H)+; Anal. Calcd for C22H25N5: C, 73.51; H, 7.01; N, 19.48; Found: C, 73.39; H, 7.20; N, 19.36.

Workup

  1. customgiving a suspension
  2. customThe headspace of the flask was purged
  3. additionback-filled with nitrogen (3×)
  4. customAgain the headspace of the flask was purged
  5. additionback-filled with nitrogen (3×)
  6. concentrationthe reaction mixture was concentrated under reduced pressure
  7. customto yield a brown solid
  8. customThe solid was partitioned between CHCl3 (45 mL) and H2O (15 mL)
  9. customseparated
  10. washThe organic portion was washed again with H2O (15 mL) and brine (15 mL)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customto yield a tan solid
  15. customThe solid was recrystallized from MeCN

Sources & evidence

ORD record
ord-94503ed9de234787a8e71afcb3beb18b
Source dataset
uspto-grants-2007_01
Patent number
US07163947B2

Reaction notes

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