Tetramethyltin → 6-Amino-2-cyclopropyl-5-methylpyrimidine-4-carboxylic acid ethyl ester

HRID 245282Notes

Reaction equation

HRID 245282 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:11](Br)=[C:10]([NH2:13])[N:9]=[C:8]([CH:14]2[CH2:16][CH2:15]2)[N:7]=1)=[O:5])[CH3:2].[CH3:17][Sn](C)(C)C>ClCCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[C:11]([CH3:17])=[C:10]([NH2:13])[N:9]=[C:8]([CH:14]2[CH2:16][CH2:15]2)[N:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 11661TetramethyltinHCID 11414935HCID 11414935, compound

Product 1

HCID 594320826-Amino-2-cyclopropyl-5-methylpyrimidine-4-carboxylic acid ethyl esterYield 50%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
150 °C

Procedure

6-Amino-5-bromo-2-cyclopropylpyrimidine-4-carboxylic acid ethyl ester (300 mg, 1.05 mmol; see WO 2005/063721 A1 for preparation), tetramethyltin (937 mg, 5.24 mmol), and bis(triphenylphosphine)palladium(II) dichloride (74 mg, 0.105 mmol) were combined in 5 mL of 1,2-dichloroethane and heated in a CEM microwave reactor at 150° C. for 20 min. The resulting reaction mixture was filtered and concentrated. The product was purified by flash chromatography on silica gel (ethyl acetate/hexane gradient) followed by a purification by reverse phase chromatography to yield the title compound (116 mg, 50% yield): mp 130-132° C.: 1H NMR (DMSO-d6) δ 6.85 (br s, 2H), 4.27 (q, 2H), 1.94 (s, 3H), 1.87 (m, 1H), 1.28 (t, 3H), 0.84 (d, 4H).

Workup

  1. customThe resulting reaction mixture
  2. filtrationwas filtered
  3. concentrationconcentrated
  4. customThe product was purified by flash chromatography on silica gel (ethyl acetate/hexane gradient)
  5. customfollowed by a purification by reverse phase chromatography

Sources & evidence

ORD record
ord-a8c8920dde974ee89c12c8f94352fccf
Source dataset
uspto-grants-2014_02
Patent number
US08658791B2

Reaction notes

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