Triethylamine → 5-(1,1-dioxothiazinan-2-yl)-N-[[4-fluoro-2-(methylcarbamoyl)phenyl]methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide

HRID 2252804ノート

反応式

HRID 2252804 の反応式
[O:1]=[S:2]1(=[O:22])[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[N:17]=[C:16]([C:18]([OH:20])=O)[C:15]([OH:21])=[C:14]2[C:9]=1[CH:10]=[CH:11][CH:12]=[N:13]2.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(CC)CC)C.[Cl-].[F:53][C:54]1[CH:59]=[CH:58][C:57]([CH2:60][NH3+:61])=[C:56]([C:62]([NH:64][CH3:65])=[O:63])[CH:55]=1.[OH-].[Na+]>O>[O:22]=[S:2]1(=[O:1])[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[N:17]=[C:16]([C:18]([NH:61][CH2:60][C:57]2[CH:58]=[CH:59][C:54]([F:53])=[CH:55][C:56]=2[C:62]([NH:64][CH3:65])=[O:63])=[O:20])[C:15]([OH:21])=[C:14]2[C:9]=1[CH:10]=[CH:11][CH:12]=[N:13]2

参加物

8

反応物 6

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 596452235-(1,1-Dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxylic acidHCID 866001764-Fluoro-2-[(methylamino)carbonyl]benzylamine hydrochloride

生成物 1

HCID 30133965-(1,1-dioxothiazinan-2-yl)-N-[[4-fluoro-2-(methylcarbamoyl)phenyl]methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

A solution of 5-(1,1-dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxylic acid (1.00 g, 3.09 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.77 g, 4.02 mmol), and 1-hydroxy-7-azabenzotriazole (0.55 g, 4.02 mmol) in degassed dry DMP (20 mL) was aged for 30 minutes to preform the activated ester. Triethylamine (0.47 mL, 3.40 mmol) and {4-fluoro-2-[(methylamino)carbonyl]phenyl}-methanaminium chloride (0.74 g, 3.40 mmol) were added and the reaction stirred for 30 minutes. The reaction was poured into water, the pH was adjusted to 10 using 1N NaOH, and resulting solution was extracted several times with CHCl3. The combined organic extracts were dried over Na2SO4′, filtered, and concentrated to dryness in vacuo. The residue was partitioned between basic water (pH=10 using 1N NaOH) and ether. The layers were separated and the aqueous layer was extracted twice more with ether. The aqueous layer was then acidified to pH=4 using 1N HCl and extracted several times with CHCl3. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to a brown oil. Methanol was added to the flask and the flask was sonicated for 5 minutes. Solids crashed out of the solution upon sonication and were collected by vacuum filtration to afford the title compound as a whitish solid.

後処理

  1. customdry DMP (20 mL)
  2. customresulting solution
  3. extractionwas extracted several times with CHCl3
  4. dry with materialThe combined organic extracts were dried over Na2SO4′
  5. filtrationfiltered
  6. concentrationconcentrated to dryness in vacuo
  7. customThe residue was partitioned between basic water (pH=10 using 1N NaOH) and ether
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted twice more with ether
  10. extractionextracted several times with CHCl3
  11. dry with materialThe combined organic extracts were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated to a brown oil
  14. additionMethanol was added to the flask
  15. customthe flask was sonicated for 5 minutes
  16. customSolids crashed out of the solution upon sonication
  17. filtrationwere collected by vacuum filtration

出典と根拠

ORDレコード
ord-132934d695ad4cae85c6c9c0c819241e
出典データセット
uspto-grants-2008_01
特許番号
US07323460B2

反応ノート

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