Dichloromethane → Methyl 4-(3-amino-6-(1-(4-methoxybenzyl)-6-oxo-1,4,5,6-tetrahydropyridin-3-yl)pyrazin-2-yl)-2-fluorobenzoate

HRID 596131Notes

Reaction equation

HRID 596131 reaction equation
I[C:2]1[CH2:3][CH2:4][C:5](=[O:17])[N:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[CH:7]=1.C(Cl)Cl.[NH2:21][C:22]1[C:23]([C:29]2[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[C:31]([F:39])[CH:30]=2)=[N:24][C:25](Br)=[CH:26][N:27]=1.C([O-])([O-])=O.[Na+].[Na+]>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].COCCOC>[NH2:21][C:22]1[C:23]([C:29]2[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[C:31]([F:39])[CH:30]=2)=[N:24][C:25]([C:2]2[CH2:3][CH2:4][C:5](=[O:17])[N:6]([CH2:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=3)[CH:7]=2)=[CH:26][N:27]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 1180459305-iodo-1-(4-methoxybenzyl)-3,4-dihydropyridin-2(1H)-oneHCID 118046172Methyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate

Product 1

HCID 118045295Methyl 4-(3-amino-6-(1-(4-methoxybenzyl)-6-oxo-1,4,5,6-tetrahydropyridin-3-yl)pyrazin-2-yl)-2-fluorobenzoateYield 42.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

5-iodo-1-(4-methoxybenzyl)-3,4-dihydropyridin-2(1H)-one (630 mg, 1.836 mmol), PdCl2(dppf).CH2Cl2 adduct (150 mg, 0.184 mmol), methyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate (1028 mg, 2.75 mmol) and Na2CO3 (2754 μl, 5.51 mmol) were combined in a flask and then DME (Volume: 6120 μl) was added. The mixture was degassed and purged with nitrogen and then finally heated at 90° C. for 2 h upon which complete consumption of starting material was observed. The reaction mixture was diluted with EtOAc and water and the organic layer was separated and dried (MgSO4), filtered and concentrated in vacuo and the residue purified by flash chromatography (0-60% EtOAc/DCM) to afford 361 mg of the desired product as a yellow solid. LCMS (m/z): (MH+), 463.1, 0.88 min.

Workup

  1. customThe mixture was degassed
  2. custompurged with nitrogen
  3. additionThe reaction mixture was diluted with EtOAc and water
  4. customthe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe residue purified by flash chromatography (0-60% EtOAc/DCM)

Sources & evidence

ORD record
ord-74aef9b90ff142f480baefeb02cc76b6
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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