Sodium Carbonate → Methyl 4-(3-amino-6-(oxetan-3-yl)pyrazin-2-yl)-2-fluorobenzoate

HRID 596109Notes

Reaction equation

[NH2:1][C:2]1[C:3]([C:17]2[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[C:19]([F:27])[CH:18]=2)=[N:4][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:6][N:7]=1.C(=O)([O-])[O-].[Na+].[Na+].I[CH:35]1[CH2:38][O:37][CH2:36]1>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].C(Cl)Cl>[NH2:1][C:2]1[C:3]([C:17]2[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[C:19]([F:27])[CH:18]=2)=[N:4][C:5]([CH:35]2[CH2:38][O:37][CH2:36]2)=[CH:6][N:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To methyl 4-(3-amino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-yl)-2-fluorobenzoate (150 mg, 0.402 mmol) in DME (6 mL) and sodium carbonate (1.5 mL, 3.0 mmol) was added 3-iodooxetane (370 mg, 2.01 mmol) and PdCl2(dppf)-CH2Cl2 (32.8 mg, 0.042 mmol). The reaction mixture was heated in microwave at 100° C. for 15 min. The reaction mixture was partitioned between ethylacetate and water. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and evaporated. The crude product was purified by prep HPLC to isolate the product (13.5 mg, 11.0%). LCMS (m/z): 304.2 (MH+), 0.61 min.

Workup

customThe reaction mixture was partitioned between ethylacetate and water
customThe organic layer was separated
washwashed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
customevaporated
customThe crude product was purified by prep HPLC

Sources & evidence

ORD record: ord-dc1b7c08f9c54032b2d480e4df587911
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242996B2

Reaction notes

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