Potassium Carbonate → 1-(2-Chloro-3,6-difluorobenzyl)-8-methyl-7-[3-(morpholin-4-yl)phenyl]-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine

HRID 80560

Reaction equation

HRID 80560 reaction equation
Br[C:2]1[CH:21]=[N:20][C:5]2[NH:6][CH2:7][CH2:8][N:9]([CH2:10][C:11]3[C:16]([F:17])=[CH:15][CH:14]=[C:13]([F:18])[C:12]=3[Cl:19])[C:4]=2[C:3]=1[CH3:22].[O:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:30]=[C:31](B3OC(C)(C)C(C)(C)O3)[CH:32]=[CH:33][CH:34]=2)[CH2:25][CH2:24]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:19][C:12]1[C:13]([F:18])=[CH:14][CH:15]=[C:16]([F:17])[C:11]=1[CH2:10][N:9]1[CH2:8][CH2:7][NH:6][C:5]2[N:20]=[CH:21][C:2]([C:33]3[CH:32]=[CH:31][CH:30]=[C:29]([N:26]4[CH2:25][CH2:24][O:23][CH2:28][CH2:27]4)[CH:34]=3)=[C:3]([CH3:22])[C:4]1=2

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 41926634-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)morpholineHCID 670070637-Bromo-1-(2-chloro-3,6-difluorobenzyl)-8-methyl-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine

Product 1

HCID 670082691-(2-Chloro-3,6-difluorobenzyl)-8-methyl-7-[3-(morpholin-4-yl)phenyl]-1,2,3,4-tetrahydropyrido[2,3-b]pyrazineYield 40%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Procedure

To a solution of 7-bromo-1-(2-chloro-3,6-difluorobenzyl)-8-methyl-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine (0.048 g, 0.124 mmol) and 3-morpholinophenylboronic acid pinacol ester (0.035 g, 0.124 mmol) in DMF-H2O (9:1, 2 mL) was added PdCl2(PPh3)2 (0.0087 g, 0.0124 mmol) and K2CO3 (0.043 mg, 0.31 mmol). The resulting solution was subjected to microwave irradiation at 125° C. for 20 min. The solvent was filtered using a PTFE frit and then directly purified by prep HPLC using a gradient mixture of ACN—H2O— 0.1% TFA to yield the desired product (0.023 g 40%).

Workup

  1. customirradiation at 125° C. for 20 min
  2. filtrationThe solvent was filtered
  3. customdirectly purified by prep HPLC
  4. additiona gradient mixture of ACN—H2O— 0.1% TFA

Sources & evidence

ORD record
ord-6e4ab137b7c647629183be7e639441a0
Source dataset
uspto-grants-2014_09
Patent number
US08846664B2

Linked notes

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