1,4-Dioxane → HCID 67064496, compound

HRID 1409150Notes

Reaction equation

HRID 1409150 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.O1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1>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:27]1[C:28]2[CH:29]=[CH:12][C:13]([C:2]3[N:7]4[N:8]=[CH:9][CH:10]=[C:6]4[N:5]=[C:4]([NH:11][C:12](=[O:23])[C:13]4[CH:18]=[CH:17][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=4)[CH:3]=3)=[CH:14][C:15]=2[CH2:25][CH2:26]1

Participants

5

Reactant 2

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

Product 1

HCID 67064496HCID 67064496, compoundYield 27%

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), 3-dihydrobenzofuran-5-ylboronic acid (50 mg, 305 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (9 mg, 12 mmol) 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, 45-70% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (16.8 mg, 27%). Melting point (174.2.0-184.3° C.). 1HNMR (400 MHz, DMSO-d6) δ ppm 1.46 (s, 6H) 3.32 (t, J=8.59 Hz, 2H) 4.67 (t, J=8.72 Hz, 2H) 6.56 (d, J=2.27 Hz, 1H) 7.01 (d, J=8.59 Hz, 1H) 7.62 (d, J=8.34 Hz, 2H) 7.95 (dd, J=8.46, 1.64 Hz, 1H) 8.00-8.08 (m, 4H) 8.19 (d, J=2.02 Hz, 1H) 11.20 (s, 1H). ESI-MS: m/z 415.3 (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, 45-70% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-36676250dcc74565bae8760c5eecbb6f
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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