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

HRID 1409153

Reaction equation

HRID 1409153 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.[S:24]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25]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]([C:26]3[CH:27]=[CH:28][S:24][CH:25]=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 581760Thiophene-3-boronic acidHCID 86652272N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 670642104-(2-hydroxypropan-2-yl)-N-(7-(thiophen-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)benzamideYield 11%

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), thiophen-3-ylboronic acid (64 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, 40-70% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (6.4 mg, 11%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46 (s, 6H) 6.61 (d, 1H) 7.63 (d, J=8.34 Hz, 2H) 7.84 (dd, J=5.18, 2.91 Hz, 1H) 7.93 (dd, J=5.18, 1.14 Hz, 1H) 8.04 (d, J=8.34 Hz, 2H) 8.23-8.40 (m, 2H) 9.12 (dd, J=3.03, 1.26 Hz, 1H) 11.24 (s, 1H). ESI-MS: m/z 379.2 (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, 40-70% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-d0df6e20d6304d68a03a64d3a156fa7c
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Linked notes

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