Dichloromethane → 8-(Tert-butyldimethylsilyloxy)-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-4-amine

HRID 336138Notes

Reaction equation

HRID 336138 reaction equation
C12BC(CCC1)CCC2.Br[C:11]1[N:20]([CH2:21][CH:22]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH:23]=[CH2:24])[C:14]2[N:15]=[CH:16][N:17]=[C:18]([NH2:19])[C:13]=2[C:12]=1[C:33]1[CH:34]=[N:35][C:36]2[C:41]([CH:42]=1)=[CH:40][CH:39]=[CH:38][CH:37]=2.[OH-].[Na+].ClCCl>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[Si:26]([O:25][CH:22]1[CH2:23][CH2:24][C:11]2[N:20]([C:14]3[N:15]=[CH:16][N:17]=[C:18]([NH2:19])[C:13]=3[C:12]=2[C:33]2[CH:34]=[N:35][C:36]3[C:41]([CH:42]=2)=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH2:21]1)([C:29]([CH3:32])([CH3:30])[CH3:31])([CH3:27])[CH3:28]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 867112776-bromo-7-(2-(tert-butyldimethylsilyloxy)-3-butenyl)-5-(quinolin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Product 1

HCID 867112798-(Tert-butyldimethylsilyloxy)-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-4-amine

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 0.5 M 9-borabicyclo[3.3.1]nonane in THF (50 ml) was added to a solution of 6-bromo-7-(2-(tert-butyldimethylsilyloxy)-3-butenyl)-5-(quinolin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (2.26 g) obtained in Step 6 in THF (30 ml) under ice-cooling. The mixture was stirred at room temperature for 4 hours. After slowly adding a 3 N aqueous sodium hydroxide solution (19.5 ml) to the reaction mixture at room temperature, a [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane (676 mg) was added to the reaction mixture. The mixture was stirred under a nitrogen atmosphere at 70° C. for 4 hours. After cooling, the reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate) to obtain the title compound as a yellow, oily substance (778 mg).

Workup

  1. temperaturecooling
  2. stirringThe mixture was stirred under a nitrogen atmosphere at 70° C. for 4 hours
  3. temperatureAfter cooling
  4. extractionfollowed by extraction with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-a9bc362653ec469baf6a6c1bb9eacbf3
Source dataset
uspto-grants-2014_11
Patent number
US08889666B2

Reaction notes

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