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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
ノート
印刷プレビュー

反応式

HRID 906417 の反応式
[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]
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

7

反応物 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

生成物 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
収率 27.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-d23c5e27b39244ef99044997d6ca0c56
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

読み込み中…

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