Cesium carbonate → 7-(3,5-Dimethylisoxazol-4-yl)-4-phenyl-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one

HRID 589093Notes

Reaction equation

HRID 589093 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[NH:12][C:13](=[O:14])[N:7]3[C:8]=2[C:3]=1[CH2:4][CH2:5][CH:6]3[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.BrC1C=C2C3=C(NC(=O)N3C(C3C=CC=CC=3)CC2)C=1.[CH3:41][C:42]1[C:46](B(O)O)=[C:45]([CH3:50])[O:44][N:43]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.O>[CH3:41][C:42]1[C:46]([C:2]2[CH:11]=[CH:10][C:9]3[NH:12][C:13](=[O:14])[N:7]4[C:8]=3[C:3]=2[CH2:4][CH2:5][CH:6]4[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:45]([CH3:50])[O:44][N:43]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 904091427-Bromo-4-phenyl-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-oneHCID 904098178-bromo-4-phenyl-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one

Product 1

HCID 904098527-(3,5-Dimethylisoxazol-4-yl)-4-phenyl-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-oneYield 56.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 7-bromo-4-phenyl-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (0.050 g, 0.15 mmol) (4.4:1 mixture of isomers with 8-bromo-4-phenyl-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one as the minor isomer), (3,5-dimethylisoxazol-4-yl)boronic acid (10.7 mg, 0.0759 mmol), and cesium carbonate (99.0 mg, 0.304 mmol) in 1,2-dimethoxyethane (1.21 mL) and water (0.303 mL) was degassed with nitrogen for 5 min. The reaction mixture was treated with PEPPSI-IPr (5.2 mg, 0.0076 mmol) [Aldrich, cat. #669032], degassed with nitrogen for 5 min, and heated at 90° C. for 1 h. The reaction mixture was then diluted with ethyl acetate (25 mL) and water (20 mL). The organic layer was separated, washed with brine, dried over sodium sulfate, filtered, and concentrated to give a crude residue. Purification via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at flow rate of 60 mL/min) gave the desired product (14.7 mg, 28%) as a racemic mixture. 1H NMR (500 MHz, CDCl3) δ 10.00 (s, 1H), 7.34-7.20 (m, 3H), 7.08-6.95 (m, 3H), 6.88-6.76 (m, 1H), 5.54 (s, 1H), 2.45-1.96 (m, 10H); LCMS calculated for C21H20N3O2 (M+H)+: m/z=346.2. found: 346.1.

Workup

  1. customwas degassed with nitrogen for 5 min
  2. customdegassed with nitrogen for 5 min
  3. additionThe reaction mixture was then diluted with ethyl acetate (25 mL) and water (20 mL)
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a crude residue
  10. customPurification via preparative LCMS (XBridge C18 column
  11. washeluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-c4169bb0319d47f59557675aef61d145
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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