Triethylamine → 7-(1-[(N-acetyl)aminomethyl]-3-azabicyclo[3.1.0]-hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, ethyl ester

HRID 373700

Reaction equation

HRID 373700 reaction equation
[C:1]([NH:4][CH2:5][C:6]12[CH2:11][CH:10]1[CH2:9][NH:8][CH2:7]2)(=[O:3])[CH3:2].[CH2:12](N(CC)CC)[CH3:13].Cl[C:20]1[N:29]=[C:28]2[C:23]([C:24](=[O:41])[C:25]([C:38]([OH:40])=[O:39])=[CH:26][N:27]2[C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:37])=[CH:22][C:21]=1[F:42].N1C2C(=CC=CN=2)C=CC=1>C(#N)C>[C:1]([NH:4][CH2:5][C:6]12[CH2:11][CH:10]1[CH2:9][N:8]([C:20]1[N:29]=[C:28]3[C:23]([C:24](=[O:41])[C:25]([C:38]([O:40][CH2:12][CH3:13])=[O:39])=[CH:26][N:27]3[C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=3[F:37])=[CH:22][C:21]=1[F:42])[CH2:7]2)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1360691,8-NaphthyridineHCID 105460847-Chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acidHCID 157134281-[(N-acetyl)aminomethyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 157134527-(1-[(N-acetyl)aminomethyl]-3-azabicyclo[3.1.0]-hex-3-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, ethyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 1-[(N-acetyl)aminomethyl]-3-azabicyclo[3.1.0]hexane (115.5 mg, 0.75 mmol) and triethylamine (312 μl, 2.25 mmol) in acetonitrile (20 ml) was treated with the ethyl ester of 7-chloro-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (283 mg, 0.74 mmol) and heated to 80° for 20 hours. Additional 1-(N-acetyl)-aminomethyl-3-azabicyclo[3.1.0]hexane (97 mg) was added portionwise over 2.5 hours until thin layer chromatography indicated the absence of starting naphthyridine. The reaction mixture was concentrated in vacuo, and the residue chromatographed on silica gel (eluant: 189:10:1 chloroform:methanol:concentrated ammonium hydroxide). The title product was obtained as a colorless oil (280.3 mg, 0.56 mmol, 76% yield).

Workup

  1. temperatureheated to 80° for 20 hours
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue chromatographed on silica gel (eluant: 189:10:1 chloroform:methanol:concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-a0316a98f81d40b4918b1a91f0e1fb74
Source dataset
uspto-grants-1992_11
Patent number
US05164402

Linked notes

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