Water → HCID 11583672, compound

HRID 1373969Notes

Reaction equation

HRID 1373969 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.[N:23]1([C:29]([C:31]2[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=2)=[O:30])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]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:35]4[CH:34]=[CH:33][CH:32]=[C:31]([C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)=[O:30])[CH:36]=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 36029163-(Morpholine-4-carbonyl)phenylboronic acidHCID 69177518HCID 69177518, compound

Product 1

HCID 11583672HCID 11583672, compoundYield 52.4%

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 the 3-(morpholine-4-carbonyl)phenylboronic acid (0.715 g, 3.04 mmol). 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 purified by chromatography (SiO2, 95:5 CHCl3: MeOH) to yield a light yellow foam. The foam was crystallized from 1:1 acetonitrile (MeCN):MeOH to give N1-isopropyl-7-[3-(morpholin-4-ylcarbonyl)phenyl]-2-propyl-1H-imidazo[4,5-c]quinoline-1,4-diamine (0.683 g) as light yellow crystals. mp 274–276° C.; 1H NMR (300 MHz, DMSO-d6, 350 K) δ 8.56 (d, J=8.5 Hz, 1H), 7.86–7.81 (m, 2H), 7.74 (s, 1H), 7.57–7.52 (m, 2H), 7.38 (d, J=7.6 Hz, 1H), 6.81 (s, 1H), 6.21 (s, 2H), 3.65–3.62 (m, 4H), 3.58–3.54 (m, 5H), 2.93 (t, J=7.5 Hz, 2H), 1.96–1.83 (m, 2H), 1.07–1.02 (m, 9H); 13C NMR (75 MHz, DMSO-d6, 350 K) δ 169.5, 154.9, 152.3, 145.4, 141.1, 137.8, 136.9, 132.8, 129.4, 128.1, 126.1, 125.5, 124.6, 124.1, 122.0, 119.9, 114.7, 66.5, 51.4, 45.4, 28.3, 20.9, 20.6, 14.1; MS (APCI) m/z 473 (M+H)+; Anal. Calcd for C27H32N6O2: C, 68.62; H, 6.83; N, 17.78; Found: C, 68.73; H, 6.71; N, 17.85.

Workup

  1. customThe headspace of the flask was purged
  2. additionback-filled with nitrogen (3×)
  3. customAgain the headspace of the flask was purged
  4. additionback filled with nitrogen (3×)
  5. concentrationthe reaction mixture was concentrated under reduced pressure
  6. customto yield a brown solid
  7. customThe solid was partitioned between CHCl3 (45 mL) and H2O (15 mL)
  8. customseparated
  9. washThe organic portion was washed again with H2O (15 mL) and brine (15 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto yield a tan solid
  14. customThe solid was purified by chromatography (SiO2, 95:5 CHCl3: MeOH)
  15. customto yield a light yellow foam
  16. customThe foam was crystallized from 1:1 acetonitrile (MeCN)

Sources & evidence

ORD record
ord-579b1c4eadef4b309eb2d7cf4c6f7b0d
Source dataset
uspto-grants-2007_01
Patent number
US07163947B2

Reaction notes

Loading…