tert-butyl 2-(bis(tert-butoxycarbonyl)amino)-5-(trimethylstannyl)-1H-benzo[d]imidazole-1-carboxylate → HCID 178508158, compound

HRID 388114Notes

Reaction equation

HRID 388114 reaction equation
Cl.Cl.[NH2:3][C:4]1[NH:8][C:7]2[CH:9]=[CH:10][C:11]([C:13]3[N:18]=[C:17]4[N:19]([CH2:23][CH:24]5[CH2:29][CH2:28][O:27][CH2:26][CH2:25]5)[C:20](=[O:22])[NH:21][C:16]4=[N:15][CH:14]=3)=[CH:12][C:6]=2[N:5]=1.C(OC(N(C(OC(C)(C)C)=O)C1N(C(OC(C)(C)C)=O)C2C=CC([Sn](C)(C)C)=CC=2N=1)=O)(C)(C)C.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>[NH2:3][C:4]1[NH:8][C:7]2[CH:9]=[CH:10][C:11]([C:13]3[N:18]=[C:17]4[N:19]([CH2:23][CH:24]5[CH2:25][CH2:26][O:27][CH2:28][CH2:29]5)[C:20](=[O:22])[NH:21][C:16]4=[N:15][CH:14]=3)=[CH:12][C:6]=2[N:5]=1

Participants

6

Reactant 3

HCID 66699913tert-butyl 2-(bis(tert-butoxycarbonyl)amino)-5-(trimethylstannyl)-1H-benzo[d]imidazole-1-carboxylateHCID 866263956-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-oneHCID 178478668HCID 178478668, compound

Product 1

HCID 178508158HCID 178508158, compoundYield 12.7%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

6-(2-Amino-1H-benzo[d]imidazol-5-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one di hydrochloride. A solution of tert-butyl 2-(bis(tert-butoxycarbonyl)amino)-5-(trimethylstannyl)-1H-benzo[d]imidazole-1-carboxylate (120 mg, 0.20 mmol), 6-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 101.B) (63 mg, 0.2 mmol), and dichlorobis(triphenylphosphine)palladium(II) (14 mg, 0.02 mmol) in DMF (5 mL) was reacted for 1.5 h at 90° C. The product was purified by reverse-phase semi-preparatory HPLC (20-100% 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 (10.2 mg, 12.7% yield). 1H NMR (400 MHz, DMSO-d6) δ 12.54 (d, J=11.2, 2H), 12.09 (s, 1H), 8.53 (s, 1H), 8.49 (s, 1H), 7.97 (s, 1H), 7.90 (d, J=8.4, 1H), 7.44 (d, J=8.4, 1H), 3.84 (d, J=10.8, 2H), 3.79 (d, J=10.8, 2H), 3.26 (t, J=10.8, 2H), 2.13 (m, 1H), 1.58 (m, 2H), 1.35-1.23 (m, 3H); MS (ESI) m/z 366.1 [M+1]+.

Workup

  1. customThe product was purified by reverse-phase semi-preparatory HPLC (20-100% 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-3ac80f5aa71f494e944deac702d62bdf
Source dataset
uspto-grants-2013_02
Patent number
US08372976B2

Reaction notes

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