4-Fluorophenol → HCID 57960805, compound

HRID 449040Notes

Reaction equation

HRID 449040 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([CH:18]3[CH2:21][CH2:20][CH2:19]3)[N:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[C:12]=23)=[CH:4][CH:3]=1.[F:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl.CN(C)CC(O)=O>[Cu]I.CN(C=O)C.O1CCOCC1>[CH:18]1([C:10]2[N:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[C:12]3=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([O:29][C:26]4[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=4)=[CH:3][CH:4]=3)[N:9]=2)[CH2:21][CH2:20][CH2:19]1

Participants

8

Reactant 4

HCID 97324-FluorophenolHCID 10796Cesium carbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 66915518HCID 66915518, compound

Product 1

HCID 57960805HCID 57960805, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 1-(4-bromo-phenyl)-3-cyclobutyl-imidazo[1,5-a]pyrazin-8-ylamine (30.0 mg, 0.0874 mmol), 4-fluorophenol (29.4 mg, 0.262 mmol), copper(I) iodide (5 mg, 0.03 mmol), Cs2CO3 (114 mg, 0.350 mmol), N,N-dimethylglycine hydrochloride (10 mg, 0.08 mmol) and 5:1 dioxane:DMF (1 mL) was microwaved at 120° C. for 4 h (CEM; PowerMAX). The mixture was filtered through a syringe filter pad to remove any solid particles, then concentrated in vacuo. DMF (1 mL) was added to bring the mixture to a homogeneous solution, and Gilson HPLC was used to purify. The fractions containing the product were passed through a benzene-sulfonic acid SPE cartridge, washed with MeOH (10 mL), and flushed out using 2M NH3 in MeOH. The material was concentrated in vacuo to afford the title compound as a yellow solid. 1H NMR (400 MHz, CDCl3): δ=1.99-2.09 (m, 1H), 2.11-2.24 (m, 1H), 2.45-2.55 (m, 2H), 2.58-2.69 (m, 2H), 3.77-3.87 (m, 1H), 5.12 (br. s., 2H), 7.01-7.13 (m, 8H), 7.61-7.65 (m, 2H). MS (ES+): m/z 374.98 (100) [MH+]. HPLC: tR=2.55 min (ZQ3, polar—5 min).

Workup

  1. filtrationThe mixture was filtered through a syringe
  2. filtrationfilter pad
  3. customto remove any solid particles
  4. concentrationconcentrated in vacuo
  5. additionDMF (1 mL) was added
  6. customto purify
  7. additionThe fractions containing the product
  8. washwashed with MeOH (10 mL)
  9. customflushed out
  10. concentrationThe material was concentrated in vacuo

Sources & evidence

ORD record
ord-a6e4626fc795464fb0230fdd387299d3
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

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