Trifluoroacetic acid → N-((6-(3,5-difluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-7-(4-fluoropiperidin-4-yl)-1,5-naphthyridin-4-amine

HRID 40398ノート

反応式

HRID 40398 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[CH:11][C:12]3[N:13]([C:15]([CH2:18][NH:19][C:20]4[CH:21]=[CH:22][N:23]=[C:24]5[C:29]=4[N:28]=[CH:27][C:26]([C:30]4(O)[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]4)=[CH:25]5)=[N:16][N:17]=3)[N:14]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.CCN(S(F)(F)[F:50])CC.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:8][C:6]1[CH:5]=[C:4]([C:9]2[CH:10]=[CH:11][C:12]3[N:13]([C:15]([CH2:18][NH:19][C:20]4[C:29]5[C:24](=[CH:25][C:26]([C:30]6([F:50])[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]6)=[CH:27][N:28]=5)[N:23]=[CH:22][CH:21]=4)=[N:16][N:17]=3)[N:14]=2)[CH:3]=[C:2]([F:1])[CH:7]=1

参加物

5

反応物 3

HCID 6422Trifluoroacetic acidHCID 123472(Diethylamino)sulfur trifluorideHCID 57691230Tert-butyl 4-(8-((6-(3,5-difluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylamino)-1,5-naphthyridin-3-yl)-4-hydroxypiperidine-1-carboxylate

生成物 1

HCID 44180709N-((6-(3,5-difluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-7-(4-fluoropiperidin-4-yl)-1,5-naphthyridin-4-amine収率 60%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A solution of tert-butyl 4-(8-((6-(3,5-difluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylamino)-1,5-naphthyridin-3-yl)-4-hydroxypiperidine-1-carboxylate (30 mg, 51 μmol) in 0.5 mL of DCM was cooled to −78 C. Then added DAST (13 μl, 102 μmol) and let stir to room temperature over 30 min. TFA was then added to the reaction mixture and stirred for 30 min. The solvent was then removed by rotary evaporation and the residue was redissolved in MeOH and free based through a cation exchange column. Purification via MPLC (DCM/MeOH+1% NH4OH) yielded the title compound (15 mg, 60% yield). M/Z=491.2 [M+H], calc 490.18 for C25H21F3Ns.

後処理

  1. customThe solvent was then removed by rotary evaporation
  2. dissolutionthe residue was redissolved in MeOH
  3. customPurification via MPLC (DCM/MeOH+1% NH4OH)

出典と根拠

ORDレコード
ord-087561a6b4224ee696333ff5d8e43fbd
出典データセット
uspto-grants-2013_09
特許番号
US08524900B2

反応ノート

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