1,4-Dioxane → 4-(2-hydroxypropan-2-yl)-N-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-yl)benzamide

HRID 1256330Notes

Reaction equation

Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[C:25]1(B(O)O)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.O1CCOCC1>CO>[OH:23][C:20]([C:17]1[CH:18]=[CH:19][C:14]([C:13]([NH:12][C:4]2[CH:3]=[C:2]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:7]3[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]3[N:5]=2)=[O:24])=[CH:15][CH:16]=1)([CH3:22])[CH3:21]

Participants

Conditions

Temperature: 110 °C

Procedure

A suspension of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2F, 49 mg, 0.142 mmol), phenylboronic acid (23 mg, 0.189 mmol), and [1,1′-bis[1,1′-Bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (9.3 mg, 13 mmol) in 2:1 1,4-dioxane/saturated aqueous NaHCO3 (0.76 mL of 1,4-dioxane and 0.38 mL of saturated aqueous NaHCO3) was prepared in a 10 mL microwave reaction vessel and the sealed reaction vessel warmed to 110° C. for 10 minutes in a CEM microwave reactor. The reaction mixture was cooled to rt, diluted with methanol, filtered, and purified via preparative HPLC (65-75% MeCN/H2O+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (13.9 mg, 25%). Decomposition observed at 199.8° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46 (s, 6 H), 2.40 (s, 3 H), 5.20 (br. s., 1 H), 6.40 (s, 1 H), 7.58-7.66 (m, 5 H), 7.97 (s, 1 H), 8.02 (d, J=8.59 Hz, 2 H), 8.06 (dd, J=6.57, 3.03 Hz, 2 H), 11.20 (s, 1 H); ESI-MS: m/z 387.2 (M+H)+.

Workup

customthe sealed reaction vessel
temperatureThe reaction mixture was cooled to rt
filtrationfiltered
custompurified via preparative HPLC (65-75% MeCN/H2O+0.01% TFA)

Sources & evidence

ORD record: ord-17db305823be411ea1e6c902f6c6811e
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461163B2

Reaction notes

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