1,4-Dioxane → HCID 67064392, compound

HRID 1409152Notes

Reaction equation

HRID 1409152 reaction equation
Cl[C:2]1[N:7]2[N:8]=[CH:9][CH:10]=[C:6]2[N:5]=[C:4]([NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=2)[CH:3]=1.[CH:24](/B(O)O)=[CH:25]\[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.O1CCOCC1>CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:22][C:19]([C:16]1[CH:17]=[CH:18][C:13]([C:12]([NH:11][C:4]2[CH:3]=[C:2](/[CH:24]=[CH:25]/[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=2)=[O:23])=[CH:14][CH:15]=1)([CH3:21])[CH3:20]

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 5702628Styrylboronic acidHCID 86652272N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064392HCID 67064392, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 50 mg, 151 mmol), (E)-styrylboronic acid (45 mg, 302 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (9 mg, 12 μmol) in 2:1 1,4-dioxane/saturated aqueous NaHCO3 (670 microliters of 1,4-dioxane and 330 microliters of saturated aqueous NaHCO3) was prepared in a 2 mL microwave reaction vessel and the sealed reaction vessel warmed to 110° C. for 20 minutes. The reaction mixture was cooled to rt, diluted with methanol, filtered, and purified via preparative HPLC, 50-80% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (5.8 mg, 10%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46 (s, 6H) 3.85 (s, 3H) 6.59 (d, J=2.27 Hz, 1H) 7.22 (dd, J=8.08, 1.77 Hz, 1H) 7.55 (t, J=7.83 Hz, 1H) 7.59-7.70 (m, 4H) 7.98-8.09 (m, 3H) 8.20 (d, J=2.02 Hz, 1H) 11.27 (s, 1H). ESI-MS: m/z 399.3 (M+H)+.

Workup

  1. customwas prepared in a 2 mL microwave reaction vessel
  2. customthe sealed reaction vessel
  3. temperatureThe reaction mixture was cooled to rt
  4. filtrationfiltered
  5. custompurified via preparative HPLC, 50-80% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-3afc14b8e1a341408eab917a8b5f46a5
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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