Hydrochloric Acid → 2-Chloro-9-methyl-6-((S)-3-methylmorpholin-4-yl)-9H-purine-8-carbaldehyde

HRID 1922870ノート

反応式

HRID 1922870 の反応式
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:11])=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]2[CH3:18])[N:3]=1.CN(CCN(C)C)C.[Li]CCCC.CN([CH:35]=[O:36])C.Cl>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:35]=[O:36])[N:8]2[CH3:11])=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]2[CH3:18])[N:3]=1

参加物

7

反応物 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 58222544(S)-4-(2-chloro-9-methyl-9H-purin-6-yl)-3-methylmorpholineHCID 178418339Butyllithium

生成物 1

HCID 596057572-Chloro-9-methyl-6-((S)-3-methylmorpholin-4-yl)-9H-purine-8-carbaldehyde収率 91.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-40 °C

実験手順

To a solution of 2-chloro-9-methyl-6-((S)-3-methylmorpholin-4-yl)-9H-purine (500 mg, 1.67 mmol) and TMEDA (419 μL, 2.80 mmol) in THF (10 mL) at −78° C. was added n-BuLi (1.12 mL, 2.80 mmol, 2.5M solution in hexanes). The resulting mixture was allowed to warm to −40° C. and stir for 30 min then cooled back to −78° C. before the addition of DMF (435 μL, 5.61 mmol). The reaction mixture was allowed to stir at −78° C. for 30 min then poured onto 1M HCl. The aqueous phase was extracted with EtOAc and the combined organic phases were washed with H2O and brine, then dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-50%) affording the title compound as a white solid (450 mg, 81%). LCMS (method H): RT 3.28 min [M+H]+ 296.3

後処理

  1. stirringto stir at −78° C. for 30 min
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washthe combined organic phases were washed with H2O and brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-50%)

出典と根拠

ORDレコード
ord-692b7e2eefbd4a558feb785220ba6d6e
出典データセット
uspto-grants-2012_05
特許番号
US08173650B2

反応ノート

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