Sodium Carbonate → Methyl 5-amino-2-phenethylbenzo[f][1,7]naphthyridine-8-carboxylate

HRID 340309Notes

Reaction equation

HRID 340309 reaction equation
C(O[C:6]([NH:8][C:9]1[CH:14]=[C:13]([C:15]([O:17][CH3:18])=[O:16])[CH:12]=[CH:11][C:10]=1B(O)O)=O)(C)(C)C.ClC1N=C(CCC2C=CC=CC=2)C=CC=1C#[N:26].Cl[C:40]1[C:41](C#N)=[N:42][CH:43]=[C:44](/[CH:46]=[CH:47]/[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH:45]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.CCOC(C)=O.O>[NH2:26][C:6]1[C:41]2[N:42]=[CH:43][C:44]([CH2:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[CH:45][C:40]=2[C:10]2[CH:11]=[CH:12][C:13]([C:15]([O:17][CH3:18])=[O:16])=[CH:14][C:9]=2[N:8]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 668752372-(Tert-butoxycarbonylamino)-4-(methoxycarbonyl)phenylboronic acidHCID 66875239(E)-3-chloro-5-styrylpicolinonitrileHCID 856827592-Chloro-6-phenethylnicotinonitrile

Product 1

HCID 66874950Methyl 5-amino-2-phenethylbenzo[f][1,7]naphthyridine-8-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-(tert-butoxycarbonylamino)-4-(methoxycarbonyl)phenylboronic acid (from Example 85/Step 1) (1.0 eq.) and 2-chloro-6-phenethylnicotinonitrile (prepared from (E)-3-chloro-5-styrylpicolinonitrile (from Example 32/Step 1) following the procedure described in Example 114/Step 3) (1.0 eq.), tetrakis(triphenyl-phosphine)palladium (5 mol %), and 2N aqueous sodium carbonate solution (2.0 eq.) in toluene/ethanol (2:1, 0.03 M) was stirred at 100° C. overnight. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc and water. The two phases were separated, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-60% EtOAc/Hexanes to give methyl 5-amino-2-phenethylbenzo[f][1,7]naphthyridine-8-carboxylate as a white solid.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customThe two phases were separated
  3. extractionthe aqueous layer was extracted twice with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated en vacuo
  7. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-3cfd743e048a42439645bbd1ebe06595
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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