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Potassium Carbonate → tert-Butyl (2R)-4-({2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl}sulfonyl)-2-(hydroxymethyl)piperazine-1-carboxylate

HRID 906451
ノート
印刷プレビュー

反応式

HRID 906451 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]([CH3:25])([CH3:24])[CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH:6]=[C:5]2[S:26]([N:29]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C@@H:31]([CH2:42][OH:43])[CH2:30]1)(=[O:28])=[O:27].[CH:44]1([NH:47][C:48](=[O:66])[C:49]2[CH:54]=[C:53](B3OC(C)(C)C(C)(C)O3)[C:52]([CH3:64])=[C:51]([F:65])[CH:50]=2)[CH2:46][CH2:45]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Si:17]([O:16][CH2:15][C:14]([CH3:24])([CH3:25])[CH2:13][N:7]1[CH:6]=[C:5]([S:26]([N:29]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:36])[C@@H:31]([CH2:42][OH:43])[CH2:30]2)(=[O:28])=[O:27])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:53]3[CH:54]=[C:49]([C:48](=[O:66])[NH:47][CH:44]4[CH2:45][CH2:46]4)[CH:50]=[C:51]([F:65])[C:52]=3[CH3:64])[CH:3]=2)[C:8]1=[O:12])([C:20]([CH3:22])([CH3:21])[CH3:23])([CH3:19])[CH3:18]
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 11430Potassium CarbonateHCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 67391011tert-butyl (2R)-4-{[6-bromo-2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-4-yl]sulfonyl}-2-(hydroxymethyl)piperazine-1-carboxylate

生成物 1

HCID 86640972
tert-Butyl (2R)-4-({2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl}sulfonyl)-2-(hydroxymethyl)piperazine-1-carboxylate
収率 80%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
75 °C

実験手順

A solution of tert-butyl (2R)-4-{[6-bromo-2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-4-yl]sulfonyl}-2-(hydroxymethyl)piperazine-1-carboxylate (Example 49b, 0.58 g) in DMF (10 mL) was treated with N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.263 g), Pd-118 (0.016 g) and potassium carbonate (0.228 g). The resulting mixture was stirred at 75° C. for 6 h. The cooled reaction was concentrated under reduced pressure then purified (SiO2 chromatography, loaded in DCM, flushed with isohexane (100 mL), then DCM (200 mL), followed by a 10-100% gradient of ethyl acetate/isohexane) to afford the subtitle compound (0.537 g).

後処理

  1. customThe cooled reaction
  2. concentrationwas concentrated under reduced pressure
  3. customthen purified (SiO2 chromatography
  4. customflushed with isohexane (100 mL)

出典と根拠

ORDレコード
ord-17c2cef926e54ea0a9e828edfc9f373e
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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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