Dichloromethane → Ethyl 4-(pyrazolo[1,5-a]pyrimidin-3-yl)benzoate

HRID 588375Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][C:9](B(O)O)=[CH:8][CH:7]=1)=[O:5])[CH3:2].Br[C:16]1[CH:17]=[N:18][N:19]2[CH:24]=[CH:23][CH:22]=[N:21][C:20]=12.C(Cl)Cl.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O>[N:18]1[N:19]2[CH:24]=[CH:23][CH:22]=[N:21][C:20]2=[C:16]([C:9]2[CH:10]=[CH:11][C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:7][CH:8]=2)[CH:17]=1

Participants

Conditions

Temperature: 85 °C

Procedure

Water (160 mL) was added dropwise at room temperature to a mixture of 4-ethoxycarbonylphenylboronic acid (50 g, 0.26 mol), 3-bromopyrazolo[1,5-a]pyrimidine (56.25 g, 0.28 mol), Pd(ddpf)Cl2.CH2Cl2 (4.25 g, 5.21 mmol), and Cs2CO3 (169.42 g, 0.52 mol) in 1,4-dioxane (1 L). The reaction mixture was then heated 85° C. for 4 h. The reaction mixture was cooled, poured into water and extracted with EtOAc (2×300 mL). The combined organic layers were dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel chromatography eluting with a gradient of petroleum ether: EtOAc (100:10 to 3:1) to deliver the title compound (64 g, 93%) as a yellow solid.

Workup

temperatureThe reaction mixture was cooled
extractionextracted with EtOAc (2×300 mL)
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationthe filtrate was concentrated under reduced pressure
customThe crude product was purified by silica gel chromatography
washeluting with a gradient of petroleum ether: EtOAc (100:10 to 3:1)

Sources & evidence

ORD record: ord-151e3f75b2c54638be3ddc4985ba5cf2
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227956B2

Reaction notes

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