Potassium Carbonate → 1-(4-(8-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1H-[1,2,3]triazolo[4,5-c][1,5]naphthyridin-1-yl)piperidin-1-yl)-2-methylpropan-1-one

HRID 711374Notes

Reaction equation

HRID 711374 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]=[N:13][N:14]([CH:15]4[CH2:20][CH2:19][N:18]([C:21](=[O:25])[CH:22]([CH3:24])[CH3:23])[CH2:17][CH2:16]4)[C:5]=3[C:4]=2[N:3]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]([C:41]([F:44])([F:43])[F:42])[C:37]([NH2:40])=[N:38][CH:39]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:40][C:37]1[N:38]=[CH:39][C:34]([C:2]2[CH:11]=[CH:10][C:9]3[N:8]=[CH:7][C:6]4[N:12]=[N:13][N:14]([CH:15]5[CH2:20][CH2:19][N:18]([C:21](=[O:25])[CH:22]([CH3:24])[CH3:23])[CH2:17][CH2:16]5)[C:5]=4[C:4]=3[N:3]=2)=[CH:35][C:36]=1[C:41]([F:44])([F:42])[F:43]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 468641035-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amineHCID 866906991-(4-(8-chloro-1H-[1,2,3]triazolo[4,5-c][1,5]naphthyridin-1-yl)piperidin-1-yl)-2-methylpropan-1-one

Product 1

HCID 668035711-(4-(8-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1H-[1,2,3]triazolo[4,5-c][1,5]naphthyridin-1-yl)piperidin-1-yl)-2-methylpropan-1-oneYield 55.9%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A mixture of 1-(4-(8-chloro-1H-[1,2,3]triazolo[4,5-c][1,5]naphthyridin-1-yl)piperidin-1-yl)-2-methylpropan-1-one (60 mg, 0.17 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amine (53 mg, 0.18 mmol), K2CO3 (70 mg, 0.51 mmol) and Pd(dppf)Cl2 (6 mg) in dioxane/H2O (3:1, 4 mL) was stirred and microwaved at 160° C. for 0.5 h. The solvent was removed, and the residue was purified by ISCO (MeOH/H2O=20%-80%) to afford 1-(4-(8-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1H-[1,2,3]triazolo[4,5-c][1,5]naphthyridin-1-yl)piperidin-1-yl)-2-methylpropan-1-one as white solid (46 mg). 1HNMR (400 MHz, dmso) δ 9.61 (s, 1H), 9.21 (d, J=2.1 Hz, 1H), 8.66 (dd, J=12.5, 5.5 Hz, 2H), 8.55 (d, J=8.9 Hz, 1H), 7.10 (s, 2H), 6.17-6.01 (m, 1H), 4.78-4.59 (m, 1H), 4.35-4.26 (m, 1H), 3.40-3.37 (m, 2H), 3.05-2.97 (m, 1H), 2.93-2.82 (m, 1H), 2.64-2.52 (m, 1H), 2.39-2.21 (m, 1H), 2.16-1.96 (m, 1H), 1.07 (s, 6H). MS (m/z): 485 (M+H)+.

Workup

  1. custommicrowaved at 160° C. for 0.5 h
  2. customThe solvent was removed
  3. customthe residue was purified by ISCO (MeOH/H2O=20%-80%)

Sources & evidence

ORD record
ord-9f6ba85167ea4e9ebb4b6f0c9c112346
Source dataset
uspto-grants-2015_11
Patent number
US09181264B2

Reaction notes

Loading…