6-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one → HCID 178518663, compound

HRID 1014706Notes

Reaction equation

HRID 1014706 reaction equation
C[Sn](C)(C)[C:3]1[CH:18]=[CH:17][C:6]2[NH:7][C:8](C(OC(C)(C)C)=O)=[N:9][C:5]=2[CH:4]=1.Br[C:22]1[N:27]=[C:26]2[N:28]([CH2:32][CH:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)[C:29](=[O:31])[NH:30][C:25]2=[N:24][CH:23]=1>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH:7]1[C:6]2[CH:17]=[CH:18][C:3]([C:22]3[N:27]=[C:26]4[N:28]([CH2:32][CH:33]5[CH2:38][CH2:37][O:36][CH2:35][CH2:34]5)[C:29](=[O:31])[NH:30][C:25]4=[N:24][CH:23]=3)=[CH:4][C:5]=2[N:9]=[CH:8]1

Participants

5

Reactant 2

HCID 866263956-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-oneHCID 178450790HCID 178450790, compound

Product 1

HCID 178518663HCID 178518663, compoundYield 10.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

6-(1H-Benzo[d]imidazol-5-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazol-[4,5-b]pyrazin-2(3H)-one hydrochloride. tert-Butyl 5-(trimethylstannyl)-1H-benzo[d]imidazole-2-carboxylate (640 mg, 1.7 mmol), 6-bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 101.B) (420 mg, 1.3 mmol), dichlorobis(triphenylphosphine)palladium(II) (90 mg, 0.13 mmol) in DMF (25 mL) were reacted for 1.5 h at 90° C. The product was purified by reverse-phase semi-preparatory HPLC (30-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The desired fractions were concentrated, treated with 4N hydrochloric acid in diethyl ether (few drops), and sonicated. This procedure was repeated twice more to provide 6-(1H-benzo[d]imidazol-5-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (48 mg, 10% yield) as the hydrochloride salt. 1H NMR (400 MHz, DMSO-d6) 12.07 (s, 1H), 8.55 (s, 1H), 8.52 (s, 1H), 8.33 (s, 1H), 8.06 (dd, J=8.0, 1.6, 1H), 7.80 (d, J=8.8, 1H), 3.81 (m, 2H), 3.80 (d, J=7.2, 2H), 3.27 (d, J=11.6, 2H), 2.14 (m, 1H), 1.59 (m, 2H), 1.33 (m, 2H); MS (ESI) m/z 351.2 [M+1]+.

Workup

  1. customThe product was purified by reverse-phase semi-preparatory HPLC (30-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  2. concentrationThe desired fractions were concentrated
  3. additiontreated with 4N hydrochloric acid in diethyl ether (few drops)
  4. customsonicated

Sources & evidence

ORD record
ord-ae1fcee4cbe24fbcb7af2f99a4e2f6ee
Source dataset
uspto-grants-2011_07
Patent number
US07981893B2

Reaction notes

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