6-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one → HCID 178432081, compound

HRID 1014710Notes

Reaction equation

HRID 1014710 reaction equation
Cl.[CH3:2][C:3]1[NH:7][C:6]2[CH:8]=[CH:9][C:10]([C:12]3[N:17]=[C:16]4[N:18]([CH2:22][CH:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[C:19](=[O:21])[NH:20][C:15]4=[N:14][CH:13]=3)=[CH:11][C:5]=2[N:4]=1.CC1N(C(OC(C)(C)C)=O)C2C=C([Sn](C)(C)C)C=CC=2N=1.BrC1N=C2N(CC3CCOCC3)C(=O)NC2=NC=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>[CH3:2][C:3]1[NH:7][C:6]2[CH:8]=[CH:9][C:10]([C:12]3[N:17]=[C:16]4[N:18]([CH2:22][CH:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[C:19](=[O:21])[NH:20][C:15]4=[N:14][CH:13]=3)=[CH:11][C:5]=2[N:4]=1

Participants

6

Reactant 3

HCID 866263956-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-oneHCID 86761360HCID 86761360, compoundHCID 178432082HCID 178432082, compound

Product 1

HCID 178432081HCID 178432081, compoundYield 6.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

6-(2-Methyl-1H-benzo[d]imidazol-5-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride. tert-Butyl 2-methyl-6-(trimethylstannyl)-1H-benzo[d]imidazole-1-carboxylate (120 mg, 0.30 mmol), 6-bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 101.B) (96 mg, 0.3 mmol), dichlorobis(triphenylphosphine)palladium(II) (21 mg, 0.03 mmol) in DMF (5 mL) were reacted for 1.5 h at 90° C. The product was purified by reverse-phase semi-preparatory HPLC (10-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The desired fractions were concentrated, and treated with 4N hydrochloric acid in diethyl ether (few drops), sonicated and concentrated. This procedure was repeated twice more to provide the title compound (8 mg, 6.5% yield). 1H NMR (400 MHz, DMSO-d6) 12.12 (s, 1H), 8.62 (s, 1H), 8.31 (s, 1H), 8.15 (d, J=8.4, 1H), 7.82 (d, J=8.4, 1H), 3.85 (m, 2H), 3.81 (d, J=8.0, 2H), 3.26 (t, J=11.2, 2H), 1.90 (m, 1H), 1.61 (m, 2H), 1.35-1.23 (m, 3H), 0.89-0.86 (m, 2H); MS (ESI) m/z 365.1 [M+1]+.

Workup

  1. customThe product was purified by reverse-phase semi-preparatory HPLC (10-100% 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
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7b140bd61dcd4f28a10378751eb0930f
Source dataset
uspto-grants-2011_07
Patent number
US07981893B2

Reaction notes

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