Sodium Carbonate → Methyl 5-amino-2-(4-methoxyphenethyl)benzo[f][1,7]naphthyridine-8-carboxylate

HRID 1479597Notes

Reaction equation

HRID 1479597 reaction equation
C(OC(NC1[CH:14]=[C:13]([C:15]([O:17][CH3:18])=[O:16])[CH:12]=CC=1B(O)O)=O)(C)(C)C.Cl[C:23]1N=[C:29]([CH2:31][CH2:32][C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)[CH:28]=[CH:27][C:24]=1[C:25]#[N:26].ClC1[C:43]([C:49]#[N:50])=[N:44][CH:45]=C(Cl)C=1.C(C1C=CC(OC)=CC=1)#C.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.CCOC(C)=O.O>[NH2:50][C:49]1[C:43]2[N:44]=[CH:45][C:29]([CH2:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=3)=[CH:28][C:27]=2[C:24]2[CH:23]=[CH:14][C:13]([C:15]([O:17][CH3:18])=[O:16])=[CH:12][C:25]=2[N:26]=1

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 2510201-Ethynyl-4-methoxybenzeneHCID 27696993,5-Dichloro-2-cyanopyridineHCID 668752372-(Tert-butoxycarbonylamino)-4-(methoxycarbonyl)phenylboronic acidHCID 866523562-Chloro-6-(4-methoxyphenethyl)nicotinonitrile

Product 1

HCID 58213534Methyl 5-amino-2-(4-methoxyphenethyl)benzo[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-(4-methoxyphenethyl)nicotinonitrile (prepared from reaction of 3,5-dichloropicolinonitrile with 1-ethynyl-4-methoxybenzene following the procedure described in Example 44/Step 3 and reduction of the product 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 vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-80% EtOAc/Hexanes to give methyl 5-amino-2-(4-methoxyphenethyl)benzo[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 vaccuo
  7. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-a885f620895b44c8a89a4d4279c38263
Source dataset
uspto-grants-2016_08
Patent number
US09408907B2

Reaction notes

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