1,4-Dioxane → HCID 67064199, compound

HRID 1409271Notes

Reaction equation

HRID 1409271 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.[CH:25]1([CH2:28][O:29][C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][N:31]=2)[CH2:27][CH2:26]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>[CH:25]1([CH2:28][O:29][C:30]2[N:31]=[CH:32][C:33]([C:2]3[N:7]4[N:8]=[C:9]([CH3:11])[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])([CH3:22])[CH3:21])=[CH:16][CH:15]=4)[CH:3]=3)=[CH:34][CH:35]=2)[CH2:26][CH2:27]1

Participants

7

Reactant 3

HCID 312751,4-DioxaneHCID 242087972-(Cyclopropylmethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064199HCID 67064199, compoundYield 41%

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, 100 mg, 0.290 mmol), 2-(cyclopropylmethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (104 mg, 0.377 mmol), and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (21 mg, 29 μmol) in 2:1 1,4-dioxane/saturated aqueous NaHCO3 (0.966 mL of 1,4-dioxane and 0.483 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 (75-75% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (53.7 mg, 41%). 1H NMR (DMSO-d6) δ: 11.19 (s, 1H), 8.90 (d, J=2.5 Hz, 1H), 8.40 (dd, J=8.8, 2.5 Hz, 1H), 8.01 (d, J=8.6 Hz, 2H), 7.98 (s, 1H), 7.61 (d, J=8.6 Hz, 2H), 7.07 (d, J=8.8 Hz, 1H), 6.38 (s, 1H), 5.19 (br. s., 1H), 4.22 (d, J=7.1 Hz, 2H), 2.40 (s, 3H), 1.45 (s, 6H), 1.25-1.36 (m, 1H), 0.52-0.62 (m, 2H), 0.30-0.42 (m, 2H); ESI-MS: m/z 458.3 (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 (75-75% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-8fe2e09cac224a19b6c687e87eb8222c
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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