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 2176695Notes

Reaction equation

HRID 2176695 reaction equation
[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

Participants

5

Reactant 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

Product 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-amineYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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 C25H21F3N8.

Workup

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

Sources & evidence

ORD record
ord-2f8877024b8249a89621a07c1669c724
Source dataset
uspto-grants-2015_06
Patent number
US09066954B2

Reaction notes

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