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

反応式

HRID 60157 の反応式
[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]

参加物

5

反応物 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)-dione2 回

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-0e41429d939a45ddb02b8777bcd9c56b
出典データセット
uspto-grants-2016_09
特許番号
US09440973B2

関連ノート

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