Dichloromethane → tert-butyl 4-(3-amino-6-(3,6-dihydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoate

HRID 595960Notes

Reaction equation

[NH2:1][C:2]1[C:3]([C:9]2[CH:21]=[CH:20][C:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[C:11]([F:22])[CH:10]=2)=[N:4][C:5](Br)=[CH:6][N:7]=1.C(Cl)Cl.[C:26]1(B2OC(C)(C)C(C)(C)O2)[CH2:31][CH2:30][CH2:29][CH2:28]C=1.C(OCC)(=[O:43])C>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]>[NH2:1][C:2]1[C:3]([C:9]2[CH:21]=[CH:20][C:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[C:11]([F:22])[CH:10]=2)=[N:4][C:5]([C:30]2[CH2:31][CH2:26][O:43][CH2:28][CH:29]=2)=[CH:6][N:7]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of tert-butyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate (21 g, 57.0 mmol) in DME (127 mL) was added PdCl2(dppf).CH2Cl2 adduct (2.329 g, 2.85 mmol), 2-(cyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (13.18 g, 62.7 mmol), and 2 M Na2CO3aqueous solution (63.4 mL). The reaction was heated at 110° C. for 16 h. To the reaction mixture was added 200 mL of ethyl acetate, washed with water (2×100 mL), brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography eluting with 0-100% of EtOAc/DCM to provide tert-butyl 4-(3-amino-6-(3,6-dihydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoate (18 g, 48.5 mmol, 85%). LCMS (m/z): 372.3 (MH+), 0.95 min.

Workup

washwashed with water (2×100 mL), brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash chromatography
washeluting with 0-100% of EtOAc/DCM

Sources & evidence

ORD record: ord-73336f647bac4e2b8ed8284c66731fb4
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242996B2

Reaction notes

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