3-Methylbutanal → 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

HRID 60157

반응식

HRID 60157 반응식
[Si:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[C:19]([CH:24]([C:26]3C=CC(Cl)=[CH:28][CH:27]=3)[OH:25])=[C:20]([Cl:23])[N:21]=[CH:22][C:15]=2[N:14]([CH3:33])[C:13]1=[O:34])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li+].[CH3:36]C([N-]C(C)C)C.CC(C)CC=O>C1COCC1>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[C:19]([CH:24]([OH:25])[CH2:26][CH:27]([CH3:36])[CH3:28])=[C:20]([Cl:23])[N:21]=[CH:22][C:15]=2[N:14]([CH3:33])[C:13]1=[O:34])([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:2])[CH3:3]

참가 물질

5

반응물 3

HCID 115523-MethylbutanalHCID 2724682Lithium diisopropylamideHCID 1317370763-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-((4-chlorophenyl) (hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione2회

생성물 1

HCID 1317370773-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione수율 32.9%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

To a solution of 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (See Compound 49, step 3, 1.149 g, 3 mmol) in THF (30 mL) at −78° C. was added LDA (2M in THF, 7.5 mL, 15 mmol) dropwise. The reaction was stirred at −78° C. for 30 min then 3-methylbutanal (516 mg, 6 mmol) in THF (5 mL) was added dropwise. The reaction was stirred at −78° C. for 20 min, quenched with aq. NH4Cl (5 mL) then diluted with EA (15 mL) and water (5 mL). The organic layer was washed with brine (20 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (464 mg, 30% yield) as a white solid. LCMS: MH+ 470 and TR=2.198 min.

후처리

  1. stirringThe reaction was stirred at −78° C. for 20 min
  2. customquenched with aq. NH4Cl (5 mL)
  3. additionthen diluted with EA (15 mL) and water (5 mL)
  4. washThe organic layer was washed with brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to a residue which
  7. customwas purified by chromatography
  8. washeluted with PE/EA (2:1)

출처 및 근거

ORD 기록
ord-0e41429d939a45ddb02b8777bcd9c56b
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440973B2

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