Methyl pyruvate → 4-sec-butyl-8-(2-chloro-4-difluoromethoxy-phenyl)-2-methyl-4H-pyrido[2,3-b]pyrazin-3-one

HRID 1831553Notes

Reaction equation

HRID 1831553 reaction equation
[CH:1]([NH:5][CH:6]1[CH:11]([N+:12]([O-])=O)[C:10]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH:22]([F:24])[F:23])=[CH:17][C:16]=2[Cl:25])=[CH:9][CH:8]=[N:7]1)([CH2:3][CH3:4])[CH3:2].[C:26](OC)(=[O:30])[C:27]([CH3:29])=O>C1(C)C=CC=CC=1>[CH:1]([N:5]1[C:26](=[O:30])[C:27]([CH3:29])=[N:12][C:11]2[C:10]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH:22]([F:24])[F:23])=[CH:17][C:16]=3[Cl:25])=[CH:9][CH:8]=[N:7][C:6]1=2)([CH2:3][CH3:4])[CH3:2]

Participants

4

Reactant 2

HCID 11748Methyl pyruvateHCID 22052136Sec-butyl-[4-(chloro-4-difluoromethoxy-phenyl)-3-nitro-2,3-dihydro-pyridin-2-yl]-amine

Product 1

HCID 220521554-sec-butyl-8-(2-chloro-4-difluoromethoxy-phenyl)-2-methyl-4H-pyrido[2,3-b]pyrazin-3-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Sec-butyl-[4-(chloro-4-difluoromethoxy-phenyl)-3-nitro-2,3-dihydro-pyridin-2-yl]-amine (0.145 g, 0.43 mmol) was dissolved in toluene (20 mL), followed by methyl pyruvate (77 μL, 0.86 mmol) and heated to reflux overnight. The reaction was concentrated in vacuo and purified by reverse phase prep HPLC giving 4-sec-butyl-8-(2-chloro-4-difluoromethoxy-phenyl)-2-methyl-4H-pyrido[2,3-b]pyrazin-3-one (Example 113): 1H NMR (300 MHz, CDCl3) δ 8.53–8.52 (d, 1H, J=4.8 Hz), 7.35–7.32 (m, 2H), 7.19–7.13 (m, 2H), 6.85–6.36 (t, 1H, J=73.2 Hz), 2.47 (s, 3H), 2.40–2.20 (m, 1H), 2.10–2.07 (m,1H), 1.65–1.63 (d, 3H, J=6.9 Hz), 0.89–0.84 (t, 3H, J=3.7). MS(AP) m/z 394.2 [(M+H)+, 100], 435.3 [(M+H+CH3CN)+, 10].

Workup

  1. temperatureheated
  2. temperatureto reflux overnight
  3. concentrationThe reaction was concentrated in vacuo
  4. custompurified by reverse phase prep

Sources & evidence

ORD record
ord-03291fe0f3f14f03b291928189c4ff3f
Source dataset
uspto-grants-2006_06
Patent number
US07067658B2

Reaction notes

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