1,4-Dioxane → HCID 67064514, compound

HRID 1409249Notes

Reaction equation

HRID 1409249 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.[CH3:25][N:26]([CH3:36])[C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1.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>[CH3:25][N:26]([CH3:36])[C:27]1[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][CH:28]=1

Participants

7

Reactant 3

HCID 312751,4-DioxaneHCID 27625273-(Dimethylamino)benzeneboronic acidHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064514HCID 67064514, compoundYield 26%

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), 3-(dimethylamino)phenylboronic acid (49.8 mg, 0.302 mmol), and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (17 mg, 23 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 (35-40% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (25.4 mg, 26%). 1H NMR (DMSO-d6) δ: 11.09 (s, 1H), 7.90-7.98 (m, 2H), 7.86 (s, 1H), 7.48-7.60 (m, 2H), 7.31-7.38 (m, 1H), 7.28-7.32 (m, 1H), 7.19 (d, J=8.1 Hz, 1H), 6.92 (dd, J=8.1, 2.3 Hz, 1H), 6.30 (s, 1H), 2.91 (s, 6H), 2.33 (s, 3H), 1.39 (s, 6H); ESI-MS: m/z 430.3 (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 (35-40% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-305990773b0a42d9a70c1c2127ab300f
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

Loading…