Dichloromethane → 8-ethyl-4-methyl-2-(methylthio)-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 886780Notes

Reaction equation

HRID 886780 reaction equation
Br[C:2]1[C:14](=[O:15])[N:13]([CH2:16][CH3:17])[C:5]2[N:6]=[C:7]([S:11][CH3:12])[N:8]=[C:9]([CH3:10])[C:4]=2[CH:3]=1.[NH:18]1[C:22](B(O)O)=[CH:21][CH:20]=[N:19]1.C(Cl)Cl.C(N(CC)CC)C>COCCOC.O>[CH2:16]([N:13]1[C:5]2[N:6]=[C:7]([S:11][CH3:12])[N:8]=[C:9]([CH3:10])[C:4]=2[CH:3]=[C:2]([C:20]2[NH:19][N:18]=[CH:22][CH:21]=2)[C:14]1=[O:15])[CH3:17]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 112519791H-Pyrazole-5-boronic acidHCID 576069666-bromo-8-ethyl-4-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one

Product 1

HCID 576069658-ethyl-4-methyl-2-(methylthio)-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-oneYield 77.4%

Reagents, catalysts & solvents 1

HCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

To a solution of 6-bromo-8-ethyl-4-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one (0.765 g, 2.43 mmol) in DME-H2O (10:1 11 mL) was added 1H-pyrazol-5-ylboronic acid (Frontier, 0.408 g, 3.65 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with CH2Cl2 (Pd(dpppf), 0.198 g, 0.243 mmol) and triethylamine (0.736 g, 7.29 mmol) at room temperature. Then the reaction mixture was heated to reflux and reacted for 4 h. After cooling down to room temperature, the reaction mixture was partitioned with water and ethyl acetate. After separation, the organic layer was dried with Na2SO4, and the product 8-ethyl-4-methyl-2-(methylthio)-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one (0.567 g, 77% yield) was obtained by silica gel column chromatography. 1H NMR (400 MHz, CDCl3): δ 13.3 (bs, 1H), 8.54 (s, 1H), 7.82-7.07 (m, 2H), 4.45 (q, J=7.2 Hz, 2H), 2.71 (s, 3H), 2.60 (s, 3H), 1.26 (t, J=7.2 Hz, 3H).

Workup

  1. temperatureThen the reaction mixture was heated
  2. temperatureto reflux
  3. customreacted for 4 h
  4. customthe reaction mixture was partitioned with water and ethyl acetate
  5. customAfter separation
  6. dry with materialthe organic layer was dried with Na2SO4

Sources & evidence

ORD record
ord-bacaa3f86e1f4455a6c0aaa8c650990e
Source dataset
uspto-grants-2012_08
Patent number
US08247408B2

Reaction notes

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