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Acetic Acid → tert-Butyl-(2R)-4-((6-(5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl)-2-(hydroxymethyl)piperazine-1-carboxylate

HRID 906417
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인쇄 미리보기

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HRID 906417 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22](Br)[CH:23]=3)[C:18](=[O:26])[N:17](S(C3C=CC=CC=3)(=O)=O)[CH:16]=2)[CH2:10][C@@H:9]1[CH2:36][OH:37])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:38]1([NH:41][C:42](=[O:60])[C:43]2[CH:48]=[C:47](B3OC(C)(C)C(C)(C)O3)[C:46]([CH3:58])=[C:45]([F:59])[CH:44]=2)[CH2:40][CH2:39]1.C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C>CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([C:47]4[CH:48]=[C:43]([C:42](=[O:60])[NH:41][CH:38]5[CH2:39][CH2:40]5)[CH:44]=[C:45]([F:59])[C:46]=4[CH3:58])[CH:23]=3)[C:18](=[O:26])[NH:17][CH:16]=2)[CH2:10][C@@H:9]1[CH2:36][OH:37])=[O:7])([CH3:3])([CH3:4])[CH3:2]
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참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 67389810tert-butyl-(2R)-4-((6-bromo-1-oxo-2-(phenylsulfonyl)-1,2-dihydroisoquinolin-4-yl)methyl)-2-(hydroxymethyl)piperazine-1-carboxylate

생성물 1

HCID 67389794
tert-Butyl-(2R)-4-((6-(5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl)-2-(hydroxymethyl)piperazine-1-carboxylate
수율 27.4%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

A solution of tert-butyl-(2R)-4-((6-bromo-1-oxo-2-(phenylsulfonyl)-1,2-dihydroisoquinolin-4-yl)methyl)-2-(hydroxymethyl)piperazine-1-carboxylate (Example 11e, 2.3 g) in DMF (20 mL) was treated with N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (1.24 g), Pd-118 (0.08 g) and potassium carbonate (0.86 g) under nitrogen. The resulting mixture was heated at 80° C. for 10 h. The reaction mixture was diluted with water (300 mL), acidified with acetic acid (to pH 5) and extracted with ethyl acetate (300 mL). The organic was dried (MgSO4), filtered and evaporated to afford crude product. Purification (SiO2 chromatography, elution with 1% AcOH in ethyl acetate) afforded the subtitle compound (0.60 g) as a solid.

후처리

  1. extractionextracted with ethyl acetate (300 mL)
  2. dry with materialThe organic was dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customPurification (SiO2 chromatography, elution with 1% AcOH in ethyl acetate)

출처 및 근거

ORD 기록
ord-d23c5e27b39244ef99044997d6ca0c56
출처 데이터셋
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08012980B2

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