Triethyl phosphite → tert-butyl(1-(4-(2-methyl-8-phenyl-4,5-dihydro-3H-imidazo[4,5-f]quinolin-7-yl)phenyl)cyclobutyl)carbamate

HRID 1509093Notes

Reaction equation

HRID 1509093 reaction equation
[C:1]([O:5][C:6](=[O:39])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:26][C:25]4[C:24]5[N:34]=[C:35]([CH3:38])[N:36](O)[C:23]=5[CH2:22][CH2:21][C:20]=4[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].P(OCC)(OCC)OCC>CN(C=O)C.O>[C:1]([O:5][C:6](=[O:39])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:27]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[CH:26][C:25]4[C:24]5[N:34]=[C:35]([CH3:38])[NH:36][C:23]=5[CH2:22][CH2:21][C:20]=4[N:19]=3)=[CH:16][CH:17]=2)[CH2:9][CH2:10][CH2:11]1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 31215Triethyl phosphiteHCID 123557753tert-butyl(1-(4-(3-hydroxy-2-methyl-8-phenyl-4,5-dihydro-3H-imidazo[4,5-f]quinolin-7-yl)phenyl)cyclobutyl)carbamate

Product 1

HCID 131734397tert-butyl(1-(4-(2-methyl-8-phenyl-4,5-dihydro-3H-imidazo[4,5-f]quinolin-7-yl)phenyl)cyclobutyl)carbamateYield 37.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl(1-(4-(3-hydroxy-2-methyl-8-phenyl-4,5-dihydro-3H-imidazo[4,5-f]quinolin-7-yl)phenyl)cyclobutyl)carbamate (276 mg, 0.528 mmol) in anhydrous DMF (1.4 mL) was added triethyl phosphite (181 μl, 1.056 mmol) and heated to 100° C. under a nitrogen atmosphere overnight. The reaction mixture was allowed to cool to room temperature, diluted with 50:50 water:brine (10 mL) and extracted into ethyl acetate (3×5 mL). The combined organic phases were washed with 50:50 water:brine (2×10 mL), brine (10 mL) dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The residue was purified via Biotage chromatography (silica, DCM:MeOH, gradient elution from 100:0 to 90:10) to give the desired product as a pale brown solid (100 mg, 37% yield). 1H-NMR (500 MHz, CDCl3) δ 7.74 (1H, s), 7.28 (2H, d), 7.23 (2H, d), 7.13-7.17 (3H, m), 7.06-7.11 (2H, m), 5.09 (1H, br s), 3.25 (2H, t), 2.92 (2H, t), 2.16-2.59 (4H, br m), 2.41 (3H, s), 1.95-2.08 (1H, m), 1.70-1.82 (1H, m), 1.05-1.47 (9H, br m). LCMS (Method A) RT=4.66 min, M+H+=507.20.

Workup

  1. temperatureto cool to room temperature
  2. extractionbrine (10 mL) and extracted into ethyl acetate (3×5 mL)
  3. washThe combined organic phases were washed with 50:50 water
  4. dry with materialbrine (2×10 mL), brine (10 mL) dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe residue was purified via Biotage chromatography (silica, DCM:MeOH, gradient elution from 100:0 to 90:10)

Sources & evidence

ORD record
ord-47a0a60ac1ff426185f3ef2e5c4c37fe
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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