2-(3-(Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetic acid → 2-[3-[5-Amino-6-(6-fluoro-1,3-benzoxazol-2-yl)pyrazin-2-yl]phenyl]acetic acid

HRID 908457Notes

Reaction equation

CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([CH2:15][C:16]([OH:18])=[O:17])[CH:12]=[CH:13][CH:14]=2)O1.Br[C:21]1[N:22]=[C:23]([C:28]2[O:29][C:30]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:31]=3[N:32]=2)[C:24]([NH2:27])=[N:25][CH:26]=1>C1(C)C=CC=CC=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>[NH2:27][C:24]1[N:25]=[CH:26][C:21]([C:9]2[CH:10]=[C:11]([CH2:15][C:16]([OH:18])=[O:17])[CH:12]=[CH:13][CH:14]=2)=[N:22][C:23]=1[C:28]1[O:29][C:30]2[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:31]=2[N:32]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetic acid (85 mg), 5-bromo-3-(6-fluoro-1,3-benzoxazol-2-yl)pyrazin-2-amine (100 mg) in toluene-dioxane (1 ml-1.5 ml) and 2M aqueous sodium carbonate (5 ml) was degassed. Pd(dppf)Cl2 (24 mg) was added. The resulting mixture was heated to 85° C. for 6 hours. 1-Butanol (5 ml) was added to the mixture and the mixture was washed with brine (3×5 ml). The resulting organic layer was concentrated and purified by chromatography on silica gel eluting with a gradient of methanol in ethyl acetate to give the title compound (15 mg) as a solid. NMR Spectrum: (DMSOd6, 400 MHz) 7.25 (m, 2H), 7.30 (m, 1H), 7.40 (m, 1H), 7.90 (m, 6H), 8.80 (s, 1H); Mass spectrum: M+H+ 365.

Workup

customwas degassed
additionPd(dppf)Cl2 (24 mg) was added
addition1-Butanol (5 ml) was added to the mixture
washthe mixture was washed with brine (3×5 ml)
concentrationThe resulting organic layer was concentrated
custompurified by chromatography on silica gel eluting with a gradient of methanol in ethyl acetate

Sources & evidence

ORD record: ord-f7cc78f7ff2f4111be41191c7ac6094c
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08017611B2

Reaction notes

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