Nitrogen → N-[4-(2,4-difluorophenoxy)-3-(7-methyl-8-oxo-[1,2,4]triazolo[4,3-a]pyrazin-5-yl)phenyl]ethanesulfonamide

HRID 575707Notes

Reaction equation

HRID 575707 reaction equation
Br[C:2]1[N:7]2[CH:8]=[N:9][N:10]=[C:6]2[C:5](=[O:11])[N:4]([CH3:12])[CH:3]=1.[F:13][C:14]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:15]=1[O:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][S:24]([CH2:27][CH3:28])(=[O:26])=[O:25])=[CH:19][C:18]=1B1OC(C)(C)C(C)(C)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N#N>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]>[F:13][C:14]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:15]=1[O:16][C:17]1[CH:18]=[CH:19][C:20]([NH:23][S:24]([CH2:27][CH3:28])(=[O:25])=[O:26])=[CH:21][C:22]=1[C:2]1[N:7]2[CH:8]=[N:9][N:10]=[C:6]2[C:5](=[O:11])[N:4]([CH3:12])[CH:3]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 1180217235-Bromo-7-methyl-[1,2,4]triazolo[4,3-a]pyrazin-8-oneHCID 124081953N-(4-(2,4-difluorophenoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanesulfonamide

Product 1

HCID 118022239N-[4-(2,4-difluorophenoxy)-3-(7-methyl-8-oxo-[1,2,4]triazolo[4,3-a]pyrazin-5-yl)phenyl]ethanesulfonamideYield 49.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

The title compound of Example 235, step 2 (40 mg, 0.175 mmol), N-[4-(2,4-difluorophenoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethanesulfonamide (77 mg, 0.175 mmol), K3PO4 (93 mg, 0.438 mmol) and Pd(dppf)Cl2 (13 mg, 0.018 mmol) in dioxane (2 mL) and H2O (1 mL) was N2 purged and microwaved at 70° C. for 2 h. Preparative HPLCgave the title compound (38.75 mg, yield: 49.3%) as an off-white solid. 1H NMR (CDCl3, 400 MHz): δ 8.60 (s, 1H), 7.64 (d, J=2.8 Hz, 1H), 7.45 (dd, J1=8.8 Hz, J2=2.8 Hz, 1H), 7.10-7.05 (m, 1H), 6.99-6.88 (m, 3H), 6.74 (d, J=8.8 Hz, 1H), 3.67 (s, 3H), 3.18 (q, J=7.2 Hz, 2H), 1.40 (t, J=7.2 Hz, 3H). LCMS: 462.0 (M+H)+

Workup

  1. custompurged
  2. custommicrowaved at 70° C. for 2 h

Sources & evidence

ORD record
ord-e809df3f66fd403bb36af06405483509
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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