Potassium Carbonate → 5-Bromo-2-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]pyrimidine

HRID 1505669Notes

Reaction equation

[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9](B3OC(C)(C)C(C)(C)O3)[CH:8]=2)[CH:4]=[N:3]1.[Br:22][C:23]1[CH:24]=[N:25][C:26](I)=[N:27][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[Br:22][C:23]1[CH:24]=[N:25][C:26]([C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([C:5]3[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=3)[CH:8]=2)=[N:27][CH:28]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 1-Methyl-4-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-pyrazole (intermediate 1, 5.0 g, 17.5 mmol) in 1,4-dioxane (80 mL) was added 5-Bromo-2-iodo-pyrimidine (6.0 g, 21.0 mmol) and potassium carbonate (7.3 g, 5.25 mmol) in a sealed tube. The reaction mixture was purged with nitrogen for 30 min. Then Tetrakis(triphenyl phospine)Palladium(0) (2.02 g, 0.17 mmol) was added and the reaction mixture was heated at 100° C. O/N. It was filtered through a celite pad and the filtrate was concentrated under reduced pressure. Purification by flash chromatography on silica (EtOAc/hexane) afforded the title compound as a yellow solid (2.5 g, 45%). 1H NMR (400 MHz, DMSO-d6): δ 9.09 (s, 1H), 8.49 (t, J=1.64 Hz, 1H), 8.25 (s, 1H), 8.18 (dd, J=1.2, 4.74 Hz, 1H), 7.90 (d, J=1.2 Hz, 1H), 7.75-7.73 (m, 1H), 7.52 (t, J=4.0 Hz, 1H), 3.88 (s, 3H). HPLC (Condition A): Rt 4.19 min (purity 98.9%). MS (ESI+): 317.0.

Workup

customThe reaction mixture was purged with nitrogen for 30 min
filtrationIt was filtered through a celite pad
concentrationthe filtrate was concentrated under reduced pressure
customPurification by flash chromatography on silica (EtOAc/hexane)

Sources & evidence

ORD record: ord-caf6867b03a241a287ece75bd46d66a5
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216991B2

Reaction notes

Loading…