1,2-Dimethoxyethane → methyl 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoate

HRID 595948Notes

Reaction equation

[F:1][C:2]1[CH:11]=[C:10](B2OC(C)(C)C(C)(C)O2)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].Br[C:22]1[C:23]([NH2:34])=[N:24][CH:25]=[C:26]([CH:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[N:27]=1.COCCOC.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].CCOC(C)=O>[NH2:34][C:23]1[C:22]([C:10]2[CH:9]=[CH:8][C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([F:1])[CH:11]=2)=[N:27][C:26]([CH:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[CH:25][N:24]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of methyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (259 mg, 1.308 mmol), 3-bromo-5-(tetrahydro-2H-pyran-4-yl)pyrazin-2-amine (225 mg, 0.872 mmol), and PdCl2(dppf) (64 mg, 0.087 mmol) was added DME (6.5 mL) and 2 M Na2CO3 solution (3.2 mL). The reaction mixture was heated at the microwave synthesizer (120° C., 10 min). The reaction mixture was worked up with EtOAc. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered off, and concentrated in vacuo. The crude product was purified by flash chromatography (gradient EtOAc in heptane) to yield the desired product (192 mg, 67%). LCMS (m/z): 332.2 (MH+), 0.63 min.

Workup

washThe organic layer was washed with water and brine
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered off
concentrationconcentrated in vacuo
customThe crude product was purified by flash chromatography (gradient EtOAc in heptane)

Sources & evidence

ORD record: ord-29476fdb85774640a1dcd70fb79e76d4
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242996B2

Reaction notes

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