Dichloromethane → Methyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-yl)-2-fluorobenzoate

HRID 595990Notes

Reaction equation

[NH2:1][C:2]1[C:3]([C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[C:11]([F:19])[CH:10]=2)=[N:4][C:5](Br)=[CH:6][N:7]=1.CC1(C)C(C)(C)OB([C:28]2[CH2:37][CH2:36][C:31]3([O:35][CH2:34][CH2:33][O:32]3)[CH2:30][CH:29]=2)O1.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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].O>[NH2:1][C:2]1[C:3]([C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[C:11]([F:19])[CH:10]=2)=[N:4][C:5]([C:28]2[CH2:37][CH2:36][C:31]3([O:35][CH2:34][CH2:33][O:32]3)[CH2:30][CH:29]=2)=[CH:6][N:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of methyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate (10 g, 30.7 mmol) in DME (77 mL) was added 4,4,5,5-tetramethyl-2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1,3,2-dioxaborolane (9.79 g, 36.8 mmol), PdCl2(dppf).CH2Cl2 adduct (1.252 g, 1.533 mmol), H2O (25.6 mL) and then last sodium carbonate (9.75 g, 92 mmol). The reaction was heat at 100° C. in oil bath for 2 h. Cooled down. The reaction mixture was extracted by EtOAc 3 times, the organic was washed with water and brine, dried and concentrated. The crude material was recrystallized in DCM and heptane (1:1) to give product methyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-yl)-2-fluorobenzoate in 75% yield. LCMS (m/z): 382.2 (MH+), 0.82 min.

Workup

temperatureCooled down
extractionThe reaction mixture was extracted by EtOAc 3 times
washthe organic was washed with water and brine
customdried
concentrationconcentrated
customThe crude material was recrystallized in DCM

Sources & evidence

ORD record: ord-6b3206fe38aa4597ba2cf56b3c788984
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242996B2

Reaction notes

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