1,4-Dioxane → N-[7-(5-Benzofuranyl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl]-4-(1-hydroxy-1-methylethyl)benzamide

HRID 1409248Notes

Reaction equation

HRID 1409248 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.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[CH:35][C:36]3[O:40][CH:39]=[CH:38][C:37]=3[CH:41]=2)O1.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>[O:40]1[C:36]2[CH:35]=[CH:34][C:33]([C:2]3[N:7]4[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]4[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]4[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=4)[CH:3]=3)=[CH:41][C:37]=2[CH:38]=[CH:39]1

Participants

7

Reactant 3

HCID 312751,4-DioxaneHCID 27951905-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuranHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064417N-[7-(5-Benzofuranyl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl]-4-(1-hydroxy-1-methylethyl)benzamideYield 35%

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, 80 mg, 0.232 mmol), 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (73.6 mg, 0.302 mmol), and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (16 mg, 22 μmol) in 2:1 1,4-dioxane/saturated aqueous NaHCO3 (0.774 mL of 1,4-dioxane and 0.387 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 (60-70% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (34.4 mg, 35%). 1H NMR (DMSO-d6) δ: 11.13 (s, 1H), 8.36 (d, J=1.5 Hz, 1H), 8.10 (d, J=2.3 Hz, 1H), 7.89-8.00 (m, 4H), 7.78 (d, J=8.6 Hz, 1H), 7.55 (d, J=8.6 Hz, 2H), 7.10 (dd, 1H), 6.34 (s, 1H), 5.13 (s, 1H), 2.35 (s, 3H), 1.39 (s, 6H); ESI-MS: m/z 452.2 (M+H)+.

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 (60-70% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-97e853b141fe4d7585b5cce3edfd710a
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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