m-Toluidine → Ethyl 2-chloro-4-((1,3-dioxoisoindolin-2-yl)methyl)-6-(m-tolylamino)pyrimidine-5-carboxylate

HRID 515960Notes

Reaction equation

HRID 515960 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:4]([CH2:14][N:15]2[C:23](=[O:24])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]2=[O:25])[N:3]=1.[NH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH3:33])[CH:28]=1.C(N(CC)C(C)C)(C)C.C([O-])(O)=O.[Na+]>CC#N>[Cl:1][C:2]1[N:3]=[C:4]([CH2:14][N:15]2[C:23](=[O:24])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]2=[O:25])[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:6]([NH:26][C:27]2[CH:28]=[C:29]([CH3:33])[CH:30]=[CH:31][CH:32]=2)[N:7]=1

Participants

6

Reactant 4

HCID 7934m-ToluidineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 58317519Ethyl 2,4-dichloro-6-((1,3-dioxoisoindolin-2-yl)methyl)pyrimidine-5-carboxylate

Product 1

HCID 58317687Ethyl 2-chloro-4-((1,3-dioxoisoindolin-2-yl)methyl)-6-(m-tolylamino)pyrimidine-5-carboxylateYield 69.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of ethyl 2,4-dichloro-6-((1,3-dioxoisoindolin-2-yl)methyl)pyrimidine-5-carboxylate (45.3 mg, 0.119 mmol) in MeCN (1 mL) was added m-toluidine (0.020 mL, 0.187 mmol) and N,N-diisopropylethylamine (0.037 mL, 0.212 mmol). The mixture was stirred at RT for 12 h. Saturated aq NaHCO3 was added to the mixture, which was subsequently extracted with EtOAc. The organic layers were washed again with saturated aq NaHCO3, water, and brine, were dried over anhydrous Na2SO4, and then filtered through SiO2. The filtrate was concentrated under reduced pressure and the residue was washed with IPE to give the title compound as a pale brown solid (37.1 mg, 69%). 1H NMR (400 MHz, CDCl3) δ ppm 1.50 (t, J=7.2 Hz, 3H), 2.36 (s, 3H), 4.52 (q, J=7.2 Hz, 2H), 5.20 (s, 2H), 6.97-6.98 (m, 1H), 7.23-7.27 (m, 1H), 7.33 (br s, 1H), 7.45-7.47 (m, 1H), 7.73-7.78 (m, 2H), 7.89-7.94 (m, 2H), 10.67 (br s, 1H).

Workup

  1. extractionwas subsequently extracted with EtOAc
  2. washThe organic layers were washed again with saturated aq NaHCO3, water, and brine
  3. dry with materialwere dried over anhydrous Na2SO4
  4. filtrationfiltered through SiO2
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. washthe residue was washed with IPE

Sources & evidence

ORD record
ord-bb069eb9bdcb48c3b581a9a7ac2f9f7f
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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