Methylamine → Ethyl 4-[(4-methoxyphenyl)amino]-6-(methylcarbamoyl)quinoline-3-carboxylate

HRID 1850817Notes

Reaction equation

HRID 1850817 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:5]2[NH:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1.[B-](F)(F)(F)F.CC([PH+](C(C)(C)C)C(C)(C)C)(C)C.CN.C1CCN2[C:49](=[N:50][CH2:51]CC2)CC1.C1C[O:60]CC1>CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd]>[CH3:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([NH:17][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:51](=[O:60])[NH:50][CH3:49])[CH:3]=3)[N:8]=[CH:7][C:6]=2[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:19][CH:20]=1

Participants

7

Reactant 5

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 23735926Ethyl 6-bromo-4-((4-methoxyphenyl)amino)quinoline-3-carboxylate

Product 1

HCID 25020059Ethyl 4-[(4-methoxyphenyl)amino]-6-(methylcarbamoyl)quinoline-3-carboxylateYield 71%

Reagents, catalysts & solvents 1

HCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)Catalyst

Procedure

Ethyl 6-bromo-4-[(4-methoxyphenyl)amino]quinoline-3-carboxylate (0.25 g, 0.623 mmol) was added to THF followed by Herrmann's palladacycle (trans-di(μ-acetato)-bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II), 0.031 mmol), [(t-Bu)3PH]BF4 (tri tertiarybutyl phosphonium tetrafluoroborate, 0.125 mmol), Mo(CO)6 (molybdenum hexacarbonyl, 1.246 mmol), methylamine (1.5 equiv., 2N in THF) and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene, 1.869 mmol). The reaction mixture was irradiated at 130° C. for 5 minutes in a microwave reactor. The reaction mixture was concentrated and then purified on column (silica gel, dichloromethane/methanol 98:2) to give 0.25 g (71%) of ethyl 4-[(4-methoxyphenyl)amino]-6-(methylcarbamoyl)quinoline-3-carboxylate. 1H NMR (300 MHz, CDCl3) δ 10.96 (s, 1H, —NH—) 9.24 (s, 1H, aromatic), 8.14-7.98 (m, 2H, aromatic), 7.73 (s, 1H, aromatic), 7.16 (d, 2H, J=9 Hz, aromatic), 6.98 (d, 2H, J=9 Hz, aromatic), 4.46 (q, 2H, J=7 Hz, —CH2—), 3.87 (s, 3H, —OCH3), 1.48 (t, 3H, J=7Hz, —CH3); LC-MS (m/z) 380.0 (M+1).

Workup

  1. customThe reaction mixture was irradiated at 130° C. for 5 minutes in a microwave reactor
  2. concentrationThe reaction mixture was concentrated
  3. custompurified on column (silica gel, dichloromethane/methanol 98:2)

Sources & evidence

ORD record
ord-291ad4baf0c54ca3b6196b12d3e945e2
Source dataset
uspto-grants-2015_02
Patent number
US08957092B2

Reaction notes

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