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 44837Notes

Reaction equation

HRID 44837 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 (0.10 g, 0.271 mmol, see Example 355) 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-9c86c0118b304ff3b13d06f543024371
Source dataset
uspto-grants-2013_09
Patent number
US08541418B2

Reaction notes

Loading…