1,4-Dioxane → N-(7-(benzo[d][1,3]dioxol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

HRID 1256333

Reaction equation

HRID 1256333 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9](C)[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.[O:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[C:33](B(O)O)[C:28]=2[O:27][CH2:26]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]>[O:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[C:33]([C:2]3[N:7]4[N:8]=[CH:9][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])([CH3:21])[CH3:22])=[CH:16][CH:15]=4)[CH:3]=3)[C:28]=2[O:27][CH2:26]1

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 41926592,3-Methylenedioxyphenyl boronic acidHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064590N-(7-(benzo[d][1,3]dioxol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamideYield 4.5%

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-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 50 mg, 0.151 mmol), benzo[d][1,3]dioxol-4-ylboronic acid (50 mg, 0.302 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (9 mg, 12 μmol) in 2:1 1,4-dioxane/saturated aqueous NaHCO3 (330 microliters of 1,4-dioxane and 670 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, 5-95% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (2.8 mg, 4%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46 (s, 6 H) 5.20 (s, 1 H) 6.18 (s, 2 H) 6.57 (d, J=2.27 Hz, 1 H) 7.17 (d, J=8.34 Hz, 1 H) 7.56-7.69 (m, 3 H) 7.72 (d, J=1.77 Hz, 1 H) 7.98-8.10 (m, 3 H) 8.19 (d, J=2.27 Hz, 1 H) 11.23 (s, 1 H). ESI-MS: m/z 417.0 (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, 5-95% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-f5cc2718e4ad40c5b2d22a420d2f2ca5
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Linked notes

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