Trifluoroacetic acid → N-Cyclopropyl-3-fluoro-5-(2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-4-(piperazin-1-ylmethyl)-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide

HRID 906403노트

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HRID 906403 반응식
[CH:1]1([NH:4][C:5](=[O:33])[C:6]2[CH:11]=[C:10]([C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[C:18](=[O:22])[N:17]([CH2:23][C:24]([CH3:28])([CH3:27])[CH2:25][OH:26])[CH:16]=[C:15]4[CH:29]=O)[C:9]([CH3:31])=[C:8]([F:32])[CH:7]=2)[CH2:3][CH2:2]1.C([N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1)(OC(C)(C)C)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(C(F)(F)F)=O>ClCCCl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH:1]1([NH:4][C:5](=[O:33])[C:6]2[CH:11]=[C:10]([C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[C:18](=[O:22])[N:17]([CH2:23][C:24]([CH3:27])([CH3:28])[CH2:25][OH:26])[CH:16]=[C:15]4[CH2:29][N:41]3[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]3)[C:9]([CH3:31])=[C:8]([F:32])[CH:7]=2)[CH2:2][CH2:3]1

참가 물질

7

반응물 4

HCID 6422Trifluoroacetic acidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 86640963N-Cyclopropyl-3-fluoro-5-(4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide

생성물 1

HCID 59285288N-Cyclopropyl-3-fluoro-5-(2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-4-(piperazin-1-ylmethyl)-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide수율 37.5%

시약·촉매·용매 2

HCID 11026Titanium isopropoxide촉매HCID 111,2-Dichloroethane용매

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온도
20 °C

실험 절차

A solution of N-cyclopropyl-3-fluoro-5-(4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide (Example 1f, 0.15 g) in DCE (5 mL) was treated with 1-Boc-piperazine (0.19 g) and titanium(IV) isopropoxide (0.30 mL) under nitrogen. The resulting mixture was stirred at 20° C. for 16 h before adding sodium triacetoxyborohydride (0.28 g). The mixture was stirred at room temperature for 2 h before adding TFA (5 mL). The mixture stirred at room temperature for 2 h and evaporated to dryness. The mixture was quenched with 10% aq ammonia (5 mL) and extracted with ethyl acetate. The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified by preparative HPLC (Phenomenex Gemini column using a 95-5% gradient of aqueous 0.2% ammonia in acetonitrile as eluent) to afford the title compound (0.065 g) as a white solid.

후처리

  1. stirringThe mixture was stirred at room temperature for 2 h
  2. stirringThe mixture stirred at room temperature for 2 h
  3. customevaporated to dryness
  4. customThe mixture was quenched with 10% aq ammonia (5 mL)
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic was dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto afford crude product
  10. customThe crude product was purified by preparative HPLC (Phenomenex Gemini column

출처 및 근거

ORD 기록
ord-3272be2fdeb94b31b5db9312d06595ec
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08012980B2

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