Trifluoroacetic acid → 7-(1-Ethyl-1H-pyrazol-4-yl)-5-({[(3S)-3-fluoro-3-piperidinyl]methyl}oxy)-1,6-naphthyridine

HRID 473328ノート

反応式

HRID 473328 の反応式
[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[C:10]([O:18][CH2:19][C@:20]3([F:33])[CH2:25][CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21]3)[N:9]=2)[CH:5]=[N:4]1)[CH3:2].FC(F)(F)C(O)=O>C(Cl)Cl.CO>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[C:10]([O:18][CH2:19][C@:20]3([F:33])[CH2:25][CH2:24][CH2:23][NH:22][CH2:21]3)[N:9]=2)[CH:5]=[N:4]1)[CH3:2]

参加物

5

反応物 2

HCID 6422Trifluoroacetic acid2 回HCID 682098821,1-Dimethylethyl (3S)-3-({[7-(1-ethyl-1H-pyrazol-4-yl)-1,6-naphthyridin-5-yl]oxy}methyl)-3-fluoro-1-piperidinecarboxylate

生成物 1

HCID 545755127-(1-Ethyl-1H-pyrazol-4-yl)-5-({[(3S)-3-fluoro-3-piperidinyl]methyl}oxy)-1,6-naphthyridine収率 72.2%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 1,1-dimethylethyl (3S)-3-({[7-(1-ethyl-1H-pyrazol-4-yl)-1,6-naphthyridin-5-yl]oxy}methyl)-3-fluoro-1-piperidinecarboxylate (1.1 g, 2.415 mmol) in DCM (3 ml) was added trifluoroacetic acid (3 ml, 38.9 mmol) and this was stirred at room temp for 3 h. The reaction had gone to completion and so was concentrated in vacuo to yield the crude product. The TFA salt was dissolved in methanol and loaded onto an SCX cartridge (20 g). The impurities were eluted with methanol, and the product was eluted with 2M ammonia in methanol. The filtrate was concentrated in vacuo to yield a cream gummy solid (620 mg). This was purified by large-scale MDAP (Method C). The appropriate vials were combined and concentrated in vacuo to give the product as the TFA salt. To form the free base, this was dissolved in methanol and purified through an SCX cartridge (20 g) eluting with methanol. The product was eluted with 2M ammonia in methanol. The filtrate was concentrated in vacuo to yield the title compound as a clear glass (500 mg).

後処理

  1. concentrationso was concentrated in vacuo
  2. customto yield the crude product
  3. washThe impurities were eluted with methanol
  4. washthe product was eluted with 2M ammonia in methanol
  5. concentrationThe filtrate was concentrated in vacuo

出典と根拠

ORDレコード
ord-6ca3f26967aa43688a9d29f5621201b5
出典データセット
uspto-grants-2014_01
特許番号
US08633319B2

反応ノート

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