Potassium Phosphate, Tribasic → 4-(8-amino-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)imidazo [1,5-a]pyrazin-1-yl)-N-(4-isopropoxypyridin-2-yl)benzamide

HRID 62481Notes

Reaction equation

HRID 62481 reaction equation
[CH:1]([O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12](=[O:28])[C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH:6]=1)([CH3:3])[CH3:2].Br[C:30]1[N:31]=[C:32]([N:40]2[CH2:45][CH2:44][N:43]3[C:46]([C:49]([F:52])([F:51])[F:50])=[N:47][N:48]=[C:42]3[CH2:41]2)[N:33]2[CH:38]=[CH:37][N:36]=[C:35]([NH2:39])[C:34]=12.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].O1CCOCC1>[NH2:39][C:35]1[C:34]2[N:33]([C:32]([N:40]3[CH2:45][CH2:44][N:43]4[C:46]([C:49]([F:52])([F:51])[F:50])=[N:47][N:48]=[C:42]4[CH2:41]3)=[N:31][C:30]=2[C:16]2[CH:15]=[CH:14][C:13]([C:12]([NH:11][C:7]3[CH:6]=[C:5]([O:4][CH:1]([CH3:2])[CH3:3])[CH:10]=[CH:9][N:8]=3)=[O:28])=[CH:18][CH:17]=2)[CH:38]=[CH:37][N:36]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 90283479N-(4-isopropoxypyridin-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 903040261-bromo-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)imidazo[1,5-a]pyrazin-8-amine

Product 1

HCID 769021804-(8-amino-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)imidazo [1,5-a]pyrazin-1-yl)-N-(4-isopropoxypyridin-2-yl)benzamideYield 18.7%

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A seal 4 ml vial containing N-(4-isopropoxypyridin-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, (31.3 mg, 0.082 mmol), 1-bromo-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)imidazo[1,5-a]pyrazin-8-amine, (30 mg, 0.074 mmol), and 2nd Generation Xphos Precatalyst (11.71 mg, 0.015 mmol) was treated with Dioxane (372 μl) via a syringe and needle. The resulting suspension was then degassed with house vacuum and back filled with N2. Potassium phosphate tribasic (112 μl, 0.223 mmol) was then added via a syringe and needle and the resulting cream suspension stirred at 60° C. for 5 h. Purification on the Mass Directed HPLC (method: 5 to 35% MeCN/Water w/0.05% TFA on a 30 mm×100 mm, 5 m Waters SunFire RP C-18 Column) afforded 8 mg of the Title compound as a yellow solid/LC-MS (M+1) 579.39.

Workup

  1. customThe resulting suspension was then degassed with house vacuum
  2. additionback filled with N2
  3. customPurification on the Mass Directed HPLC (method

Sources & evidence

ORD record
ord-781ef628bc90484798bb67fc76c77537
Source dataset
uspto-grants-2016_09
Patent number
US09446130B2

Reaction notes

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