HCID 66919042, compound → HCID 66919006, compound

HRID 2354188Notes

Reaction equation

HRID 2354188 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:39])=[C:11]([NH:13][C:14]([C:16]3[CH:17]=[C:18]([CH:33]=[CH:34][C:35]=3[N+:36]([O-])=O)[O:19][CH:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]3)=[O:15])[CH:12]=2)=[O:6])[CH2:3][CH2:2]1>[Pd].C(O)C>[NH2:36][C:35]1[CH:34]=[CH:33][C:18]([O:19][CH:20]2[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:30])([CH3:31])[CH3:32])=[O:27])[CH2:24][CH2:25]2)=[CH:17][C:16]=1[C:14]([NH:13][C:11]1[CH:12]=[C:7]([C:5]([NH:4][CH:1]2[CH2:2][CH2:3]2)=[O:6])[CH:8]=[CH:9][C:10]=1[CH3:39])=[O:15]

Participants

4

Reactant 1

HCID 66919042HCID 66919042, compound

Product 1

HCID 66919006HCID 66919006, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

tert-Butyl 4-{3-[({5-[(cyclopropylamino)carbonyl]-2-methylphenyl}amino)carbonyl]-4-nitrophenoxy}piperidine-1-carboxylate (4.03 g) and 10% Palladium on carbon (0.4 g) were stirred in ethanol (90 ml) under an atmosphere of hydrogen gas. After cessation of hydrogen uptake, the catalyst was removed by filtration through diatomaceous earth (Celite®). The filtrate was concentrated under reduced pressure to provide the crude tert-butyl 4-{4-amino-3-[({5-[(cyclopropylamino)carbonyl]-2-methylphenyl}amino)carbonyl]phenoxy}piperidine-1-carboxylate (3.50 g) which was used without further purification; NMR Spectrum: (DMSOd6) 0.59 (m, 2H), 0.70 (m, 2H), 1.40 (s, 9H), 1.52 (m, 2H), 1.38 (m, 2H), 2.24 (s, 3H), 2.84 (m, 1H), 3.18 (m, 2H), 3.64 (m, 2H), 4.36 (m, 1H), 6.03 (s, 21, 6.71 (d, 1H), 6.96 (d, 1H), 7.31 (d, 1H), 7.34 (s, 1H), 7.62 (d, 1H), 7.79 (s, 1H), 8.37 (d, 1H), 9.72 (s, 1H); Mass Spectrum: M+Na+ 531. C) Triethyl orthoformate (1.0 ml) was added to a stirred mixture of tert-butyl 4-{4-amino-3-[({5-[(cyclopropylamino)carbonyl]-2-methylphenyl}amino)carbonyl]phenoxy}piperidine-1-carboxylate (1.02 g) and glacial acetic acid (0.057 ml) in ethanol (15 ml). The mixture was heated to 80° C. and stirred for 2 hours and then concentrated. The residue was diluted with ethyl acetate and washed with saturated aqueous NaHCO3 solution, brine, dried (magnesium sulfate) and concentrated to provide tert-butyl 4-[(3-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-4-oxo-3,4-dihydroquinazolin-6-yl)oxy]piperidine-1-carboxylate (0.994 g) as a light brown solid; NMR Spectrum: (DMSOd6) 0.58 (m, 2H), 0.70 (m, 2H), 1.42 (s, 9H), 1.58 (m, 2H), 1.94 (m, 2H), 2.13 (s, 3H), 2.85 (m, 1H), 3.23 (m, 2H), 3.65 (m, 2H), 4.77 (m, 1H), 7.52 (d, 1H), 7.55 (d, 1H), 7.63 (s, 1H), 7.72 (d, 1H), 7.82 (s, 1H), 7.90 (d, 1H), 8.18 (s, 1H), 8.43 (d, 1H); Mass Spectrum: M+H+ 519.

Workup

  1. customAfter cessation of hydrogen uptake, the catalyst was removed by filtration through diatomaceous earth (Celite®)
  2. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-bf33b61c291f44b1a2d6c1a4c4d0f067
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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