Water → Ethyl 4-chloro-2-(methylthio)-5-oxo-8-phenyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-6-carboxylate

HRID 1798898Notes

Reaction equation

HRID 1798898 reaction equation
[Cl:1][C:2]1[C:7]([C:8](OCC)=[O:9])=[C:6]([N:13]([CH2:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:5]=[C:4]([S:27][CH3:28])[N:3]=1.[Li+].CC([N-]C(C)C)C.O>O1CCCC1>[Cl:1][C:2]1[C:7]2[C:8](=[O:9])[CH:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:20][N:13]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:6]=2[N:5]=[C:4]([S:27][CH3:28])[N:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 2724682Lithium diisopropylamideHCID 59506511HCID 59506511, compound

Product 1

HCID 59506342Ethyl 4-chloro-2-(methylthio)-5-oxo-8-phenyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-6-carboxylateYield 102.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cooled solution of ethyl 4-chloro-6-((3-ethoxy-3-oxopropyl)(phenyl)amino)-2-(methylthio)pyrimidine-5-carboxylate (23.0 g, 54.25 mmol) in tetrahydrofuran (400 mL), LDA [generated at 0° C. using diisopropylamine (25.37 mL, 179.4 mmol) and n-BuLi (74.2 mL, 173.9 mmol) in tetrahydrofuran (300 mL)] was added dropwise. The reaction mixture was further stirred for additional 1 h and water (500 mL) was added to the reaction mixture. The organic layer was separated and the aqueous layer was extracted using EtOAc (200 mL×2). The combined organic layer was washed with water (500 mL) and brine (500 mL); dried over anhydrous sodium sulphate and concentrated under reduced pressure to give crude product. Crude product from two batches of the same size were combined and purified by silica gel column chromatography (polarity) to provide ethyl 4-chloro-2-(methylthio)-5-oxo-8-phenyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-6-carboxylate (21 g, 51.2% yield). 1H NMR (400 MHz, CDCl3): δ 7.48-7.43 (m, 2H), 7.37-7.28 (m, 3H), 4.37 (dd, J=7.2, 13.6 Hz, 1H), 4.27 (q, J=7.2 Hz, 2H), 4.11 (dd, J=4.8, 13.6 Hz, 1H), 3.75 (dd, J=4.8, 7.2 Hz, 1H), 2.17 (s, 3H), 1.29 (t, J=7.2 Hz, 3H). LCMS [M+H]: 378

Workup

  1. additionwas added dropwise
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted
  4. washThe combined organic layer was washed with water (500 mL) and brine (500 mL)
  5. dry with materialdried over anhydrous sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customto give crude product
  8. custompurified by silica gel column chromatography (polarity)

Sources & evidence

ORD record
ord-5abf271ba4244136bbb394ae485b953c
Source dataset
uspto-grants-2013_01
Patent number
US08343983B2

Reaction notes

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