Tributyltin Chloride → 7-(1,1-Dimethoxyethyl)-3-[2-(pyridin-4-yl)pyrimidin-4-yl]imidazo[1,2-alpha]pyrimidine

HRID 1796093Notes

Reaction equation

HRID 1796093 reaction equation
Br[C:2]1[N:6]2[CH:7]=[CH:8][C:9]([C:11]([O:15][CH3:16])([O:13][CH3:14])[CH3:12])=[N:10][C:5]2=[N:4][CH:3]=1.C([Mg]Cl)(C)C.C([Sn](Cl)(CCCC)CCCC)CCC.Cl[C:37]1[CH:42]=[CH:41][N:40]=[C:39]([C:43]2[CH:48]=[CH:47][N:46]=[CH:45][CH:44]=2)[N:38]=1>C1COCC1.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>[CH3:14][O:13][C:11]([C:9]1[CH:8]=[CH:7][N:6]2[C:2]([C:41]3[CH:42]=[CH:37][N:38]=[C:39]([C:43]4[CH:48]=[CH:47][N:46]=[CH:45][CH:44]=4)[N:40]=3)=[CH:3][N:4]=[C:5]2[N:10]=1)([O:15][CH3:16])[CH3:12]

Participants

7

Reactant 4

HCID 15096Tributyltin ChlorideHCID 127647084-Chloro-2-(pyridin-4-yl)pyrimidineHCID 180012923-Bromo-7-(1,1-dimethoxyethyl)imidazo[1,2-a]pyrimidineHCID 178418918HCID 178418918, compound

Product 1

HCID 102921157-(1,1-Dimethoxyethyl)-3-[2-(pyridin-4-yl)pyrimidin-4-yl]imidazo[1,2-alpha]pyrimidineYield 28%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-45 °C

Procedure

To a solution of 3-bromo-7-(1,1-dimethoxyethyl)imidazo[1,2-α]pyrimidine (1.0 g, 3.5 mmol) at −45° C. was added isopropylmagnesium chloride (2.6 ml of a 2M solution in THF, 5.2 mmol) dropwise. After stirring at −45° C. for 1.5 h tri-n-butylstannyl chloride (1.52 ml, 5.6 mmol) was added dropwise. The solution was stirred at −45° C. for 15 min then the cooling bath was removed and the solution stirred at room temperature for 1.5 h. After this time half of the solution was taken and degassed with N2 for 15 min. 4-Chloro-2-(pyridin-4-yl)pyrimidine (prepared according to J. Med. Chem., 1982, 25(7), 837-842) (487 mg, 2.55 mmol) and tetrakis(triphenylphosphine)palladium(0) (294 mg, 0.26 mmol) were then added and the mixture heated at reflux for 18 h. After this time the solvent was evaporated and the residue partitioned between dichloromethane (2×40 ml) and water (40 ml). The combined organic layers were washed with brine (40 ml), dried (MgSO4) and evaporated. The residue was chromatographed on silica gel, eluting with 1:1 isohexane:ethyl acetate followed by dichloromethane:MeOH (97:3), to afford 7-(1,1-dimethoxyethyl)-3-[2-(pyridin-4-yl)pyrimidin-4-yl]imidazo[1,2-α]pyrimidine (171 mg, 28%) as an off-white solid: δH (360 MHz, CDCl3) 1.76 (3H, s), 3.33 (6H, s), 7.66-7.69 (2H, m), 8.28 (2H, dd, J 4.6 and 1.5), 8.60 (1H, s), 8.80-8.90 (3H, m), 10.30 (1H, d, J 7.3); m/z (ES+) 363 (M++H).

Workup

  1. additionwas added dropwise
  2. customthe cooling bath was removed
  3. stirringthe solution stirred at room temperature for 1.5 h
  4. customdegassed with N2 for 15 min
  5. temperaturethe mixture heated
  6. temperatureat reflux for 18 h
  7. customAfter this time the solvent was evaporated
  8. customthe residue partitioned between dichloromethane (2×40 ml) and water (40 ml)
  9. washThe combined organic layers were washed with brine (40 ml)
  10. dry with materialdried (MgSO4)
  11. customevaporated
  12. customThe residue was chromatographed on silica gel
  13. washeluting with 1:1 isohexane

Sources & evidence

ORD record
ord-2d8997824deb49d188c5db10f4f251f0
Source dataset
uspto-grants-2006_04
Patent number
US07030128B2

Reaction notes

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