Ammonia → 4-(4-Cyano-2-methoxyphenyl)-5-ethoxy-2,7-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide

HRID 2090221Notes

Reaction equation

HRID 2090221 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[C:13](=[CH:14][C:15]([CH3:22])=[N:16][C:17]=3[O:19][CH2:20][CH3:21])[NH:12][C:11]([CH3:23])=[C:10]2[C:24]([OH:26])=O)=[C:5]([O:27][CH3:28])[CH:4]=1)#[N:2].C(OCC)(=O)C.C(N1C=CN=C1)([N:37]1C=CN=C1)=O.N>ClCCl.CO.C1CCCCC1.C(OCC)(=O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[C:13](=[CH:14][C:15]([CH3:22])=[N:16][C:17]=3[O:19][CH2:20][CH3:21])[NH:12][C:11]([CH3:23])=[C:10]2[C:24]([NH2:37])=[O:26])=[C:5]([O:27][CH3:28])[CH:4]=1)#[N:2]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 8857Ethyl AcetateHCID 682631,1'-CarbonyldiimidazoleHCID 593496604-(4-Cyano-2-methoxyphenyl)-5-ethoxy-2,7-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid

Product 1

HCID 249930444-(4-Cyano-2-methoxyphenyl)-5-ethoxy-2,7-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 21226129Dichloromethane methanolSolventHCID 21867204Cyclohexane ethylacetateSolvent

Procedure

640 mg (1.69 mmol) of the compound from Example 27A are introduced into 30 ml of ethyl acetate and, after addition of 342 mg (2.11 mmol) of 1,1′-carbonyldiimidazole, stirred at room temperature overnight. A TLC check (silica gel; mobile phase: cyclohexane/ethyl acetate 1:1 or dichloromethane/methanol 9:1) shows complete conversion. The volatile components are removed in a rotary evaporator, and the residue is taken up in 20 ml of DMF. Then 2.36 ml of ammonia (28% by weight solution in water, 16.87 mmol) are added, and the reaction mixture is heated at 50° C. for 8 h. The solvent is distilled out under reduced pressure, and the residue is purified by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5). 368 mg (58% of theory) of the title compound are obtained.

Workup

  1. customThe volatile components are removed in a rotary evaporator
  2. temperaturethe reaction mixture is heated at 50° C. for 8 h
  3. distillationThe solvent is distilled out under reduced pressure
  4. customthe residue is purified by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5)

Sources & evidence

ORD record
ord-2f223560705542cdbdd808fffb95c0dd
Source dataset
uspto-grants-2013_05
Patent number
US08436180B2

Reaction notes

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