Boron tribromide → 4-(5-(2-amino-5-bromopyridin-3-yl)-1H-tetrazol-1-yl)-2,3-difluorophenol

HRID 1896079Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][C:17]([O:20]C)=[C:16]([F:22])[C:15]=3[F:23])[N:12]=[N:11][N:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.B(Br)(Br)Br>C(Cl)Cl>[NH2:8][C:5]1[C:4]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[C:16]([F:22])[C:15]=3[F:23])[N:12]=[N:11][N:10]=2)=[CH:3][C:2]([Br:1])=[CH:7][N:6]=1

Participants

Conditions

Temperature: 0 °C

Procedure

As shown in step 4-i of Scheme 4,5-bromo-3-(1-(2,3-difluoro-4-methoxyphenyl)-1H-tetrazol-5-yl)pyridin-2-amine (Compound 1005, 20.0 g, 7.663 mmol) in 150 mL of DCM was cooled 0° C. Boron tribromide (20.0 mL of a 1M solution in DCM, 20 mmol) was added dropwise. After the addition was complete, the reaction mixture was warmed to room temperature and stirred for 48 hours. The reaction was carefully quenched with crushed ice and extracted with EtOAc (3×200 mL). The combined organics were washed with water, washed with brine, and dried over sodium sulfate. After filtration, the volatiles were removed under reduced pressure to yield a brown solid, which was triturated with pentane to yield 4-(5-(2-amino-5-bromopyridin-3-yl)-1H-tetrazol-1-yl)-2,3-difluorophenol (Compound 1016) as a pale brown solid.

Workup

additionAfter the addition
temperaturethe reaction mixture was warmed to room temperature
customThe reaction was carefully quenched with crushed ice
extractionextracted with EtOAc (3×200 mL)
washThe combined organics were washed with water
washwashed with brine
dry with materialdried over sodium sulfate
filtrationAfter filtration
customthe volatiles were removed under reduced pressure
customto yield a brown solid, which
customwas triturated with pentane

Sources & evidence

ORD record: ord-50bbfa8d10a645398a82502c093b4289
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08518938B2

Reaction notes

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