1,4-Dioxane → N-(7-(6-ethoxypyridin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

HRID 1409269Notes

Reaction equation

HRID 1409269 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.[CH2:25]([O:27][C:28]1[N:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)[CH3:26].O1CCOCC1>CO.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[CH2:25]([O:27][C:28]1[N:33]=[CH:32][C:31]([C:2]2[N:7]3[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]3[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=3)[CH:3]=2)=[CH:30][CH:29]=1)[CH3:26]

Participants

7

Reactant 3

HCID 312751,4-DioxaneHCID 120122372-Ethoxypyridine-5-boronic AcidHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 66878339N-(7-(6-ethoxypyridin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamideYield 40.1%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 887MethanolSolvent

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, 100 mg, 0.290 mmol), 6-ethoxypyridin-3-ylboronic acid (63 mg, 0.377 mmol), and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (21 mg, 29 μmol) in 2:1 1,4-dioxane/saturated aqueous NaHCO3 (0.966 mL of 1,4-dioxane and 0.483 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 (50-60% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (50.2 mg, 40%). Melting point (183.5-185.5° C.). 1H NMR (DMSO-d6) δ: 11.13 (s, 1H), 8.85 (dd, J=2.5, 0.5 Hz, 1H), 8.34 (dd, J=8.6, 2.5 Hz, 1H), 7.95 (d, J=8.8 Hz, 2H), 7.92 (s, 1H), 7.55 (d, J=8.6 Hz, 2H), 6.98 (dd, J=8.8, 0.8 Hz, 1H), 6.32 (s, 1H), 5.11 (br. s., 1H), 4.37 (q, J=6.9 Hz, 2H), 2.34 (s, 3H), 1.39 (s, 6H), 1.31 (t, 3H); ESI-MS: m/z 432.2 (M+H)+. Melting point (183.5-185.5° C.).

Workup

  1. customwas prepared in a 10 mL microwave reaction vessel
  2. customthe sealed reaction vessel
  3. temperatureThe reaction mixture was cooled to rt
  4. filtrationfiltered
  5. custompurified via preparative HPLC (50-60% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-462680c150d841a8b309a2d146dadede
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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