Ethanol → (S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-9-vinyl-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate

HRID 1398401Notes

Reaction equation

HRID 1398401 reaction equation
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.B1(C=C)OB([CH:39]=[CH2:40])OB(C=C)O1.C1C=CN=CC=1.C([O-])([O-])=O.[Na+].[Na+].C(O)C>C1(C)C=CC=CC=1.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>[C:28]([O:27][C:26](=[O:32])[NH:25][C@@H:20]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH2:19][O:18][C:17]1[C:2]([CH:39]=[CH2:40])=[CH:3][C:4]2[C:13]3[C:8](=[CH:9][N:10]=[CH:11][CH:12]=3)[C:7](=[O:14])[N:6]([CH3:15])[C:5]=2[CH:16]=1)([CH3:31])([CH3:30])[CH3:29]

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27348062,4,6-Trivinylboroxin-Pyridine ComplexHCID 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

Product 1

HCID 86710388(S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-9-vinyl-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamateYield 34%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

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 (0.250 g, 0.496 mmol) (prepared as described in Example 3, Part B) 2,4,6-trivinylcyclotriboroxane pyridine complex (0.239 g, 0.991 mmol), Na2CO3 (0.158 g, 1.487 mmol) and Pd(PPh3)4 (0.029 g, 0.025 mmol) in toluene (1 mL) water (0.1 mL), and ethanol (0.3 mL) was purged with nitrogen gas and heated at 90° C. for 16 h. After cooling, the reaction mixture was transferred to separatory funnel containing water (10 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (60% ethyl acetate: petroleum ether) to afford a (S)-tert-butyl(4-methyl-1-((6-methyl-5-oxo-9-vinyl-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate (0.150 g, 0.166 mmol, 34% yield) as a yellow solid. LC/MS (ESI) m/e 452.4, [(M+H)+, calcd for C26H34N3O4, 452.2]; LC/MS retention time (method D): tR=0.95 min.

Workup

  1. customwas purged with nitrogen gas
  2. temperatureAfter cooling
  3. customthe reaction mixture was transferred to separatory funnel
  4. additioncontaining water (10 mL)
  5. extractionextracted with ethyl acetate (3×10 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulphate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel (60% ethyl acetate: petroleum ether)

Sources & evidence

ORD record
ord-726dd43ac2b647ecbe4ee02e65faa0db
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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