Boron tribromide → Pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [2-bromo-4-(5-chloro-2-hydroxy-phenyl)-thiazol-5-yl]-amide

HRID 529751Notes

Reaction equation

[Br:1][C:2]1[S:3][C:4]([NH:16][C:17]([C:19]2[CH:20]=[N:21][N:22]3[CH:27]=[CH:26][CH:25]=[N:24][C:23]=23)=[O:18])=[C:5]([C:7]2[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:8]=2[O:14]C)[N:6]=1.B(Br)(Br)Br.C(=O)([O-])O.[Na+]>C(Cl)Cl>[Br:1][C:2]1[S:3][C:4]([NH:16][C:17]([C:19]2[CH:20]=[N:21][N:22]3[CH:27]=[CH:26][CH:25]=[N:24][C:23]=23)=[O:18])=[C:5]([C:7]2[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:8]=2[OH:14])[N:6]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [2-bromo-4-(5-chloro-2-methoxy-phenyl)-thiazol-5-yl]-amide (4.3 g, 9.3 mmol) in DCM (90 mL) at −78° C. under an atmosphere of N2 was added boron tribromide (1M in DCM, 45 mL, 45 mmol) dropwise. The mixture was stirred at −78° C. for 1 hour and then allowed slowly to room temperature and stirred for a further 16 hours. The mixture was poured cautiously onto an aqueous solution of sodium hydrogen carbonate, stirred for 15 mins, filtered and the solid collected and dried to afford pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [2-bromo-4-(5-chloro-2-hydroxy-phenyl)-thiazol-5-yl]-amide as a beige solid (6 g, >100%). LCMS (Method 3) [M+H]+=450.1, RT=3.71 min. 1H NMR (400 MHz, DMSO-d6) δ: 15.96 (s, 1H), 9.18 (dd, 1H, J=1.6, 6.9 Hz), 8.70 (dd, 1H, J=1.8, 4.0 Hz), 8.59 (s, 1H), 7.80 (d, 1H, J=2.8 Hz), 7.15 (dd, 1H, J=4.0, 7.1 Hz), 7.05 (dd, 1H, J=2.8, 8.6 Hz), 6.77 (d, 1H, J=8.6 Hz).

Workup

customallowed slowly to room temperature
stirringstirred for a further 16 hours
stirringstirred for 15 mins
filtrationfiltered
customthe solid collected
customdried

Sources & evidence

ORD record: ord-1b9736fdd2884efc96fcd3bc5f37f856
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346815B2

Reaction notes

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