Iodine → 2-(methylsulfanyl)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one

HRID 2184177Notes

Reaction equation

HRID 2184177 reaction equation
[CH2:1]([NH:3][C:4]1[C:9]([CH:10]=O)=[CH:8][N:7]=[C:6]([S:12][CH3:13])[N:5]=1)[CH3:2].C(O[C:17](=[O:29])[CH2:18][C:19]1[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[C:21]([O:27][CH3:28])[CH:20]=1)C.N12CCCN=C1CCCCC2.II>C(OCC)(=O)C.CCCCCCC>[CH3:13][S:12][C:6]1[N:7]=[CH:8][C:9]2[CH:10]=[C:18]([C:19]3[CH:20]=[C:21]([O:27][CH3:28])[CH:22]=[C:23]([O:25][CH3:26])[CH:24]=3)[C:17](=[O:29])[N:3]([CH2:1][CH3:2])[C:4]=2[N:5]=1

Participants

7

Reactant 4

HCID 807IodineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 107504444-(Ethylamino)-2-(methylthio)pyrimidine-5-carbaldehyde2×HCID 11831071Ethyl 2-(3,5-dimethoxyphenyl)acetate

Product 1

HCID 111991132-(methylsulfanyl)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-oneYield 57%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Conditions

Temperature
80 °C

Procedure

A 5-L round bottomed flask was charged with 516 g (2.62 mol) of 4-ethylamino-2-methylsulfanyl-pyrimidine-5-carboxaldehyde, 587 g (2.62 mol) of (3,5-dimethoxyphenyl)-acetic acid ethyl ester and 391 mL (2.62 mol) of 1,8-diazabicyclo[5.4.0]undec-7-ene. The mixture was heated at 80° C. for 1 hour. Thin layer chromatography (TLC) (silica, 6:4/heptane:ethyl acetate, developed in an iodine chamber) showed all the 4-ethylamino-2-methylsulfanyl-pyrimidine-5-carbaldehyde was consumed. Ethyl alcohol (absolute, 2.75 L) was added to the reaction vessel, which was allowed to cool to room temperature. The solid was collected by filtration, washed once with ethyl alcohol, and dried in a vacuum oven at 45° C. for 12 hours to provide 530 g (57% yield) of 2-(methylsulfanyl)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one. Proton NMR (s,1H), 6.83 (d, 2H), 6.51 (s, 1H), 4.36 (q, 2H), 3.75 (s, 1H), 2.58 (s, 3H), (t, 3H). The combined mother liquor and washes were allowed to stand at room temperature for 7 days. At this time a second crop was collected, washed once with ethyl alcohol, and dried in a vacuum oven at 45° C. for 12 hours to provide 79 g (8.5% yield) of 2-(methylsulfanyl)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidine-7-one. Proton NMR (DMSO) is consistent with the structure.

Workup

  1. customwas consumed
  2. additionEthyl alcohol (absolute, 2.75 L) was added to the reaction vessel, which
  3. temperatureto cool to room temperature
  4. filtrationThe solid was collected by filtration
  5. washwashed once with ethyl alcohol
  6. customdried in a vacuum oven at 45° C. for 12 hours

Sources & evidence

ORD record
ord-1e7f2f8f19254c35bcbbf205e4066564
Source dataset
uspto-grants-2005_05
Patent number
US06900316B2

Reaction notes

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