4-(Tri-n-butylstannyl)thiazole → (R)-8-cyclopentyl-7-ethyl-5-methyl-2-(4-(thiazol-4-yl)-1H-imidazol-1-yl)-7,8-dihydropteridin-6(5H)-one

HRID 2093690Notes

Reaction equation

HRID 2093690 reaction equation
Br[C:2]1[N:3]=[CH:4][N:5]([C:7]2[N:16]=[CH:15][C:14]3[N:13]([CH3:17])[C:12](=[O:18])[C@@H:11]([CH2:19][CH3:20])[N:10]([CH:21]4[CH2:25][CH2:24][CH2:23][CH2:22]4)[C:9]=3[N:8]=2)[CH:6]=1.C([Sn](CCCC)(CCCC)[C:31]1[N:32]=[CH:33][S:34][CH:35]=1)CCC>CN(C=O)C.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>[CH:21]1([N:10]2[C:9]3[N:8]=[C:7]([N:5]4[CH:6]=[C:2]([C:31]5[N:32]=[CH:33][S:34][CH:35]=5)[N:3]=[CH:4]4)[N:16]=[CH:15][C:14]=3[N:13]([CH3:17])[C:12](=[O:18])[C@H:11]2[CH2:19][CH3:20])[CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

5

Reactant 2

HCID 27632584-(Tri-n-butylstannyl)thiazoleHCID 58405474(R)-2-(4-bromo-1H-imidazol-1-yl)-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one

Product 1

HCID 58405905(R)-8-cyclopentyl-7-ethyl-5-methyl-2-(4-(thiazol-4-yl)-1H-imidazol-1-yl)-7,8-dihydropteridin-6(5H)-oneYield 18.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

(R)-2-(4-bromo-1H-imidazol-1-yl)-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one (Example 43, 0.11 g, 0.271 mmol), 4-(tributylstannyl)thiazole (2-54, 0.10 g, 0.271 mmol) and Pd(PPh3)4 (31 mg, 0.0271) were dissolved in DMF in a screw cap vial and a stream of nitrogen was bubbled through the mixture for 2 minutes. The vial was sealed and the resulting solution was stirred at 100° C. for 19 h. The reaction mixture was diluted with brine, extracted with EtOAc, dried with Na2SO4 then purified by flash chromatography with a silica gel column by eluting with a mixture of Hexane:EtOAc and then further purified by preparative HPLC to give the title compound (20.7 mg). LCMS: 410.1 m/z (M+H)+; ret. Time: 3.94 (Analytical Method A).

Workup

  1. customcap vial
  2. customa stream of nitrogen was bubbled through the mixture for 2 minutes
  3. customThe vial was sealed
  4. additionThe reaction mixture was diluted with brine
  5. extractionextracted with EtOAc
  6. dry with materialdried with Na2SO4
  7. customthen purified by flash chromatography with a silica gel column
  8. washby eluting with a mixture of Hexane
  9. customEtOAc and then further purified by preparative HPLC

Sources & evidence

ORD record
ord-a2b28048771443428a82c92597218cf9
Source dataset
uspto-grants-2013_05
Patent number
US08445503B2

Reaction notes

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