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Diethyl Ether → 9-Cyclopentyl-2-((5-((3R)-3-hydroxy-1-pyrrolidinyl)-2-pyridinyl)amino)-8-methyl-8,9-dihydro-7H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-7-one

HRID 79169
ノート
印刷プレビュー

反応式

HRID 79169 の反応式
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([N:22]5[CH2:26][CH2:25][C@@H:24]([O:27][Si](C(C)(C)C)(C)C)[CH2:23]5)=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:35]=[CH:36][C:37](=[O:40])[N:38]([CH3:39])[C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(O)=O.[Na+].C(OCC)C>C1COCC1.CO>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([N:22]5[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]5)=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:35]=[CH:36][C:37](=[O:40])[N:38]([CH3:39])[C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 3283Diethyl EtherHCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 582996139-Cyclopentyl-2-((5-((3R)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-2-pyridinyl)amino)-8-methyl-8,9-dihydro-7H-pyrido[3',2':4,5]pyrrolo[2,3-d]-pyrimidin-7-one

生成物 1

HCID 58299984
9-Cyclopentyl-2-((5-((3R)-3-hydroxy-1-pyrrolidinyl)-2-pyridinyl)amino)-8-methyl-8,9-dihydro-7H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-7-one
収率 50%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Compound 276 (53.0 mg, 94.7 μmol) was dissolved in THF (2 mL).). Tetrabutylammonium fluoride, 1.0M in THF (0.500 mL, 500 μmol) was added and the reaction was stirred at room temperature for 4.5 hours. The solvent was evaporated to give an orange oil. Preparative reverse phase HPLC (gradient elution 0.1% TFA in water/10-70% acetonitrile) afforded a yellow solid. This residue was added to aqueous NaHCO3 (saturated, 10 mL) and extracted with dichloromethane+10% methanol (3×30 mL). The combined organics were dried (MgSO4) and evaporated to give a yellow solid. This product was taken up in methanol (2 mL) and 1 mL methanol (saturated at room temperature with HCl) was added. 20 mL diethyl ether was added to precipitate the product, which was washed with ether and dried in vacuo to give compound 275 as yellow solid (21 mg, 50%). 1H NMR (500 MHz, DMSO-d6) δ 9.21 (s, 2 H) 8.56 (d, J=8.56 Hz, 2 H) 7.63 (d, J=2.69 Hz, 4 H) 7.44-7.57 (m, 2 H) 6.87 (d, J=8.56 Hz, 2 H) 5.43 (quin, J=8.62 Hz, 1 H) 4.47 (br. s., 1 H) 4.00 (s, 3 H) 3.09-3.21 (m, 1H) 2.00-2.22 (m, 5 H) 1.90-2.04 (m, 1 H) 1.66-1.85 (m, 2 H) ppm.

後処理

  1. customThe solvent was evaporated
  2. customto give an orange oil
  3. washPreparative reverse phase HPLC (gradient elution 0.1% TFA in water/10-70% acetonitrile)
  4. customafforded a yellow solid
  5. extractionextracted with dichloromethane+10% methanol (3×30 mL)
  6. dry with materialThe combined organics were dried (MgSO4)
  7. customevaporated
  8. customto give a yellow solid
  9. customto precipitate the product, which
  10. washwas washed with ether
  11. customdried in vacuo

出典と根拠

ORDレコード
ord-d3216716a00a45069d717770bbc2dae0
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08841312B2

反応ノート

読み込み中…

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