Methanol → 2,4-Bis(methyloxy)-5-(4-methyl-1,3-thiazol-2-yl)pyrimidine

HRID 1925038Notes

Reaction equation

HRID 1925038 reaction equation
I[C:2]1[S:3][CH:4]=[C:5]([CH3:7])[N:6]=1.C(=O)(O)[O-].[Na+].[CH3:13][O:14][C:15]1[N:20]=[C:19]([O:21][CH3:22])[C:18](B(O)O)=[CH:17][N:16]=1.CO>COCCOC.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:13][O:14][C:15]1[N:20]=[C:19]([O:21][CH3:22])[C:18]([C:2]2[S:3][CH:4]=[C:5]([CH3:7])[N:6]=2)=[CH:17][N:16]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 2736209(2,4-Dimethoxypyrimidin-5-yl)boronic acidHCID 231545942-Iodo-4-methyl-1,3-thiazole

Product 1

HCID 594483702,4-Bis(methyloxy)-5-(4-methyl-1,3-thiazol-2-yl)pyrimidineYield 106.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

2-iodo-4-methyl-1,3-thiazole (prepared according to procedure described in JACS 123 (6), 1017-1022, (2001), 250 mg, 1.111 mmol) was dissolved in 1,2-Dimethoxyethane (DME) (4.629 ml). Pd(Ph3P)4 (64.2 mg, 0.056 mmol) was added and the mixture was stirred at room temperature for 10 minutes. 1M aqueous sol. Sodium bicarbonate (4.443 ml, 4.44 mmol) and [2,4-bis(methyloxy)-5-pyrimidinyl]boronic acid (409 mg, 2.222 mmol) were added and the resulting mixture was stirred at 85° C. for 2 hours. The mixture was allowed to cool to rt and it was diluted with DCM (5 mL). The aqueous was separated and extracted with DCM (2×5 mL). The organics were combined and dried (Na2SO4 then rotaevaporator) to give a yellow solid that was purified by silica chromatography (Biotage SP1, 25+M), eluting with DCM:MeOH from 100:0 to 9:1 to afford the title compound as a pale yellow solid (280 mg, 78% yield).

Workup

  1. stirringthe resulting mixture was stirred at 85° C. for 2 hours
  2. temperatureto cool to rt
  3. customThe aqueous was separated
  4. extractionextracted with DCM (2×5 mL)
  5. dry with materialdried (Na2SO4
  6. customto give a yellow solid
  7. customthat was purified by silica chromatography (Biotage SP1, 25+M)
  8. washeluting with DCM

Sources & evidence

ORD record
ord-f8552351a1444f3b960d00fe19895fad
Source dataset
uspto-grants-2012_05
Patent number
US08178549B2

Reaction notes

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