Sodium hydride → 1-[(S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidin-1-yl]-propan-1-one

HRID 242337Notes

Reaction equation

HRID 242337 reaction equation
[OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7](=[O:10])[CH2:8][CH3:9])[CH2:3]1.[H-].[Na+].[CH2:13]([N:20]1[CH2:30][CH2:29][C:23]2[N:24]=[CH:25][N:26]=[C:27](Cl)[C:22]=2[CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1>[CH2:13]([N:20]1[CH2:30][CH2:29][C:23]2[N:24]=[CH:25][N:26]=[C:27]([O:1][C@H:2]3[CH2:6][CH2:5][N:4]([C:7](=[O:10])[CH2:8][CH3:9])[CH2:3]3)[C:22]=2[CH2:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 253240466-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido(4,3-d)pyrimidineHCID 574952991-[(3S)-3-hydroxypyrrolidin-1-yl]propan-1-one2×

Product 1

HCID 574953491-[(S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidin-1-yl]-propan-1-oneYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-((S)-3-hydroxy-pyrrolidin-1-yl)-propan-1-one (intermediate 2) (358 mg, 2.503 mmol) in 5 mL of THF was added NaH (108 mg, 2.70 mmol) under Ar. The mixture was stirred at rt for 15 min, then 6-benzyl-4-chloro-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (500 mg, 1.925 mmol) and 5 mL of THF were added and stirred at rt for 5 h. The reaction was quenched with H2O and extracted with ethylacetate, the org. layer was washed with brine, dried over MgSO4, filtered and evaporated to dryness. The residue was purified by flash-chromatography using Isco Companion system (12 g of SiO2) CH2Cl2/MeOH (95/5). The collected fractions were combined, evaporated and dried over high vacuum to give 1-[(S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidin-1-yl]-propan-1-one. (m=560 mg, yield 78%) MS: [M+H]+=367.6, Rt(7)=0.64 min.

Workup

  1. stirringstirred at rt for 5 h
  2. customThe reaction was quenched with H2O
  3. extractionextracted with ethylacetate
  4. washlayer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue was purified by flash-chromatography
  9. customevaporated
  10. customdried over high vacuum

Sources & evidence

ORD record
ord-e47fbbb724dd4387948d19b9a6495a7a
Source dataset
uspto-grants-2014_02
Patent number
US08653092B2

Reaction notes

Loading…