Methanol → HCID 66918775, compound

HRID 2354223Notes

Reaction equation

HRID 2354223 reaction equation
Cl.[CH:2]1([NH:5][C:6]([C:8]2[CH:9]=[CH:10][C:11]([CH3:33])=[C:12]([NH:14][C:15](=[O:32])[C:16]3[CH:21]=[C:20]([O:22][CH2:23][C@H:24]4[CH2:28][CH2:27][CH2:26][NH:25]4)[CH:19]=[CH:18][C:17]=3[N+:29]([O-])=O)[CH:13]=2)=[O:7])[CH2:4][CH2:3]1.[CH3:34]O>[Pd].C(O)C>[CH:2]1([NH:5][C:6](=[O:7])[C:8]2[CH:9]=[CH:10][C:11]([CH3:33])=[C:12]([N:14]3[C:15](=[O:32])[C:16]4[C:17](=[CH:18][CH:19]=[C:20]([O:22][CH2:23][C@H:24]5[CH2:28][CH2:27][CH2:26][NH:25]5)[CH:21]=4)[N:29]=[CH:34]3)[CH:13]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 2

HCID 887MethanolHCID 66918801HCID 66918801, compound

Product 1

HCID 66918775HCID 66918775, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

N-{5-[(Cyclopropylamino)carbonyl]-2-methylphenyl}-2-nitro-5-[(2R)-pyrrolidin-2-ylmethoxy]benzamide hydrochloride salt (3.32 g) and 10% Palladium on carbon (0.332 g) were stirred in ethanol (65 ml) and methanol (40 ml) under an atmosphere of hydrogen gas for 2 hours at room temperature. The catalyst was removed by filtration through diatomaceous earth (Celite®) and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethanol (65 ml) and stirred with triethylorthoformate (3.14 ml) and glacial acetic acid (0.18 ml) at 80° C. for 1.5 hours and then concentrated. The residue was diluted with ethyl acetate and washed with saturated aqueous NaHCO3 solution, brine, dried (magnesium sulfate) and concentrated. Purification by column chromatography on a silica column eluting with 20% methanol/ethyl acetate followed by 20% methanol/ethyl acetate+1% aqueous ammonia solution to give N-cyclopropyl-4-methyl-3-[4-oxo-6-[(2R)-pyrrolidin-2-ylmethoxy]quinazolin-3(4H)-yl]benzamide (AZ12304521) (0.763 g) as a yellow/brown foam solid; NMR Spectrum: (DMSOd6) 0.57 (m, 2H), 0.70 (m, 2H), 1.49 (m, 1H), 1.68 (m, 2H), 1.86 (m, 1H), 2.14 (s, 3H), 2.85 (m, 3H), 3.44 (m, 1H), 3.94 (d, 2H), 7.53 (m, 2H), 7.59 (s, 1H), 7.72 (d, 1H), 7.83 (s, 1H), 7.91 (d, 1H), 8.19 (s, 1H), 8.44 (d, 1H); Mass Spectrum: M+H+ 419.

Workup

  1. customThe catalyst was removed by filtration through diatomaceous earth (Celite®)
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethanol (65 ml)
  4. concentrationconcentrated
  5. additionThe residue was diluted with ethyl acetate
  6. washwashed with saturated aqueous NaHCO3 solution, brine
  7. dry with materialdried (magnesium sulfate)
  8. concentrationconcentrated
  9. customPurification by column chromatography on a silica column
  10. washeluting with 20% methanol/ethyl acetate

Sources & evidence

ORD record
ord-878aaccb85b94e41b45cced6884a2734
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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