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Acetic Acid → N-Cyclopropyl-3-fluoro-5-[2-(3-hydroxy-2,2-dimethylpropyl)-4-{[(3R)-3-(hydroxymethyl)piperazin-1-yl]sulfonyl}-1-oxo-1,2-dihydroisoquinolin-6-yl]-4-methylbenzamide

HRID 906453
ノート
印刷プレビュー

反応式

HRID 906453 の反応式
[OH-].[Na+].[CH:3]1([NH:6][C:7](=[O:46])[C:8]2[CH:13]=[C:12]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[C:20](=[O:24])[N:19]([CH2:25][C:26]([CH3:30])([CH3:29])[CH2:27][OH:28])[CH:18]=[C:17]4[S:31]([N:34]3[CH2:39][CH2:38][N:37]4C(=O)[O:41][CH2:42][C@H:36]4[CH2:35]3)(=[O:33])=[O:32])[C:11]([CH3:44])=[C:10]([F:45])[CH:9]=2)[CH2:5][CH2:4]1.C(O)(=O)C>CO>[CH:3]1([NH:6][C:7](=[O:46])[C:8]2[CH:13]=[C:12]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[C:20](=[O:24])[N:19]([CH2:25][C:26]([CH3:30])([CH3:29])[CH2:27][OH:28])[CH:18]=[C:17]4[S:31]([N:34]3[CH2:39][CH2:38][NH:37][C@@H:36]([CH2:42][OH:41])[CH2:35]3)(=[O:33])=[O:32])[C:11]([CH3:44])=[C:10]([F:45])[CH:9]=2)[CH2:4][CH2:5]1
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

5

反応物 3

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 67389817N-Cyclopropyl-3-fluoro-5-[2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-4-{[(8aR)-3-oxotetrahydro[1,3]oxazolo[3,4-a]pyrazin-7(1H)-yl]sulfonyl}-1,2-dihydroisoquinolin-6-yl]-4-methylbenzamide

生成物 1

HCID 59285296N-Cyclopropyl-3-fluoro-5-[2-(3-hydroxy-2,2-dimethylpropyl)-4-{[(3R)-3-(hydroxymethyl)piperazin-1-yl]sulfonyl}-1-oxo-1,2-dihydroisoquinolin-6-yl]-4-methylbenzamide収率 21.2%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
90 °C

実験手順

2 N aqueous NaOH solution (2 mL) was added to a solution of N-cyclopropyl-3-fluoro-5-[2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-4-{[(8aR)-3-oxotetrahydro[1,3]oxazolo[3,4-a]pyrazin-7(1H)-yl]sulfonyl}-1,2-dihydroisoquinolin-6-yl]-4-methylbenzamide (Example 49d, 0.291 g) in methanol (2 mL) and the mixture stirred at 90° C. for 45 min. The reaction was neutralised with acetic acid and the volatiles removed under reduced pressure before partitioning between water and DCM. The organic layer was separated and the aqueous extracted further (2×) and the combined organics dried (MgSO4), filtered and evaporated. The residue was purified by SCX (eluting with methanol to remove impurities, then flushing with methanolic ammonia to elute product). Further purification by preparative HPLC (Xbridge column using a 95-5% gradient of 0.3% aqueous ammonia in acetonitrile), solvent evaporation under reduced pressure and trituration with diethyl ether gave the title compound (0.059 g).

後処理

  1. customthe volatiles removed under reduced pressure
  2. custombefore partitioning between water and DCM
  3. customThe organic layer was separated
  4. extractionthe aqueous extracted further (2×)
  5. dry with materialthe combined organics dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by SCX (
  9. washeluting with methanol
  10. customto remove impurities
  11. customflushing with methanolic ammonia
  12. washto elute product)
  13. customFurther purification by preparative HPLC (Xbridge column
  14. customsolvent evaporation under reduced pressure and trituration with diethyl ether

出典と根拠

ORDレコード
ord-8cf9c51c8566425ea33e755605f60a03
出典データセット
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08012980B2

反応ノート

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