Cesium carbonate → (S)-tert-butyl (1-((9-cyclopropyl-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

HRID 1398299ノート

反応式

HRID 1398299 の反応式
Br[C:2]1[C:17]([O:18][CH2:19][C@@H:20]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:21][CH:22]([CH3:24])[CH3:23])=[CH:16][C:5]2[N:6]([CH3:15])[C:7](=[O:14])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][CH:9]=3.[CH:33]1(B(O)O)[CH2:35][CH2:34]1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:33]1([C:2]2[C:17]([O:18][CH2:19][C@@H:20]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:29])[CH3:30])[CH2:21][CH:22]([CH3:23])[CH3:24])=[CH:16][C:5]3[N:6]([CH3:15])[C:7](=[O:14])[C:8]4[C:13]([C:4]=3[CH:3]=2)=[CH:12][CH:11]=[N:10][CH:9]=4)[CH2:35][CH2:34]1

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 2760897Cyclopropylboronic acidHCID 86710307(S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

生成物 1

HCID 86710310(S)-tert-butyl (1-((9-cyclopropyl-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate収率 51%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
90 °C

実験手順

A mixture of (S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (150 mg, 0.297 mmol) (as prepared in Ex. 3, Part A), cyclopropylboronic acid (28.1 mg, 0.327 mmol), tetrakis(triphenylphosphine)palladium (17.2 mg, 0.015 mmol) and Cs2CO3 (291 mg, 0.892 mmol) in toluene (5 mL) and water (0.43 mL) mixture was purged with nitrogen for 5 min then heated at 90° C. overnight (16 h). After cooling, toluene was removed under reduced pressure and the product was extracted with ethyl acetate (20 mL). The organic phase was washed with brine (2×20 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography (EtOAc-hexane) to afford (S)-tert-butyl (1-((9-cyclopropyl-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (70 mg, 0.150 mmol, 51% yield) as an off-white gummy solid. LC/MS (ESI) m/z 466.4 [(M+H)+, calcd for C27H36N3O4 466.3]; LC/MS retention time (method E): tR=1.19 min.

後処理

  1. customas prepared in Ex
  2. temperatureAfter cooling
  3. customtoluene was removed under reduced pressure
  4. extractionthe product was extracted with ethyl acetate (20 mL)
  5. washThe organic phase was washed with brine (2×20 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica-gel column chromatography (EtOAc-hexane)

出典と根拠

ORDレコード
ord-7f07cffe28a04cfe9c08e44680cb5f4d
出典データセット
uspto-grants-2014_12
特許番号
US08901305B2

反応ノート

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