6-(4-(1H-Pyrazol-1-yl)phenyl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one → 6-(4-(1H-Pyrazol-1-YL)phenyl)-1-((tetrahydro-2H-pyran-4-YL)ethyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-one

HRID 388116Notes

Reaction equation

HRID 388116 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([C:12]3[N:17]=[C:16]4[N:18]([CH2:22]C5CCOCC5)[C:19](=[O:21])[NH:20][C:15]4=[N:14][CH:13]=3)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.C[Sn](C)(C)C1C=CC(N2C=CC=N2)=CC=1.BrC1N=C2N([CH2:55][CH:56]3[CH2:61][CH2:60][O:59][CH2:58][CH2:57]3)C(=O)NC2=NC=1>CN(C=O)C>[N:1]1([C:6]2[CH:7]=[CH:8][C:9]([C:12]3[N:17]=[C:16]4[N:18]([CH2:22][CH2:55][CH:56]5[CH2:61][CH2:60][O:59][CH2:58][CH2:57]5)[C:19](=[O:21])[NH:20][C:15]4=[N:14][CH:13]=3)=[CH:10][CH:11]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 573960346-(4-(1H-Pyrazol-1-yl)phenyl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-oneHCID 666999271-(4-(Trimethylstannyl)phenyl)-1H-pyrazoleHCID 866263956-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one

Product 1

HCID 674332556-(4-(1H-Pyrazol-1-YL)phenyl)-1-((tetrahydro-2H-pyran-4-YL)ethyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-oneYield 4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-(4-(1H-Pyrazol-1-yl)phenyl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one. 1-(4-(Trimethylstannyl)phenyl)-1H-pyrazole (300 mg, 0.97 mmol), 6-bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 101.B) (304 mg, 0.97 mmol), dichlorobis(triphenylphosphine) palladium(II) (68 mg, 0.097 mmol) in DMF (15 mL) were reacted for 1.5 h at 90° C. The product was purified by reverse-phase semi-preparatory HPLC (10-60% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The desired fractions were concentrated and treated with aqueous 6N ammonium hydroxide (few drops). The volatiles were removed under reduced pressure, and the residue was taken up in water (2 mL), and the solid was filtered and rinsed with water to provide the title compound (14.5 mg, 4% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.57(s, 1H), 8.32 (d, J=8.8, 2H), 8.01 (d, J=8.8, 2H), 7.68 (s, 2H), 2.27-2.33 (m, 2H), 1.66-1.63 (m, 2H), 1.51-1.49 (m, 2H), 1.27 (m, 2H), 0.88-0.84 (m, 2H); MS (ESI) m/z 377.3 [M+1]+; mp 294-296° C.

Workup

  1. customThe product was purified by reverse-phase semi-preparatory HPLC (10-60% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  2. concentrationThe desired fractions were concentrated
  3. additiontreated with aqueous 6N ammonium hydroxide (few drops)
  4. customThe volatiles were removed under reduced pressure
  5. filtrationthe solid was filtered
  6. washrinsed with water

Sources & evidence

ORD record
ord-67753057cb4e458683cf68c9e33b7ad8
Source dataset
uspto-grants-2013_02
Patent number
US08372976B2

Reaction notes

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