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Morpholine → 3-Butyl-8-chloro-1-[4-(5-oxo-4-phenyl-4,5-dihydro-1H-tetrazol-1-yl)butyl]-3,7-dihydro-1H-purine-2,6-dione

HRID 1097708
ノート
印刷プレビュー

反応式

HRID 1097708 の反応式
CS(O[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:18](=[O:19])[C:17]2[N:16](CC=C)[C:15]([Cl:23])=[N:14][C:13]=2[N:12]([CH2:24][CH2:25][CH2:26][CH3:27])[C:11]1=[O:28])(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+].[C:35]1([N:41]2[C:45](=[O:46])[N:44]=[N:43][NH:42]2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.N1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO.CN(C=O)C>[CH2:24]([N:12]1[C:13]2[N:14]=[C:15]([Cl:23])[NH:16][C:17]=2[C:18](=[O:19])[N:10]([CH2:9][CH2:8][CH2:7][CH2:6][N:44]2[C:45](=[O:46])[N:41]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[N:42]=[N:43]2)[C:11]1=[O:28])[CH2:25][CH2:26][CH3:27]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 594051074-[3-butyl-8-chloro-2,6-dioxo-7-(2-propen-1-yl)-2,3,6,7-tetrahydro-1H-purin-1-yl]butyl methanesulfonateHCID 178518970HCID 178518970、化合物

生成物 1

HCID 593958593-Butyl-8-chloro-1-[4-(5-oxo-4-phenyl-4,5-dihydro-1H-tetrazol-1-yl)butyl]-3,7-dihydro-1H-purine-2,6-dione収率 51%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

A mixture of 4-[3-butyl-8-chloro-2,6-dioxo-7-(2-propen-1-yl)-2,3,6,7-tetrahydro-1H-purin-1-yl]butyl methanesulfonate (50 mg, 0.12 mmol), Cs2CO3 (45 mg, 0.14 mmol) and DMF (3 ml) was treated with 1-phenyl-1,2-dihydro-5H-tetrazol-5-one (23 mg, 0.14 mmol) and stirred for 60 h at 50° C. After cooling, the mixture was degassed by applying a vacuum and then nitrogen was introduced. Pd(PPh3)4 (20 mg, 0.017 mmol) was added and the mixture degassed once more. Morpholine (150 μl, 1.7 mmol) was added and the mixture was stirred under nitrogen for 18 h, then partitioned between 2M HCl (aq) and EtOAc. The organic layer was separated and the aqueous layer extracted again with EtOAc. The combined extracts were concentrated, giving a yellow residue. MeOH was added and then passed down an aminopropyl column with the product eluting with 2% AcOH/MeOH. Further purification by MDAP gave the title compound as an off-white solid (27 mg, 51%). NB. ca. 10% O-alkylated material present.

後処理

  1. temperatureAfter cooling
  2. customthe mixture was degassed
  3. additionnitrogen was introduced
  4. customthe mixture degassed once more
  5. stirringthe mixture was stirred under nitrogen for 18 h
  6. custompartitioned between 2M HCl (aq) and EtOAc
  7. customThe organic layer was separated
  8. extractionthe aqueous layer extracted again with EtOAc
  9. concentrationThe combined extracts were concentrated
  10. customgiving a yellow residue
  11. washeluting with 2% AcOH/MeOH
  12. customFurther purification by MDAP

出典と根拠

ORDレコード
ord-a7b7cc396f744785b8737aa13354e97e
出典データセット
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08143264B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート