Potassium Phosphate, Tribasic → 6-(4-Hydroxyphenyl)-1-(2-morpholinoethyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-one

HRID 1014709Notes

Reaction equation

HRID 1014709 reaction equation
Cl.[OH:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]3[N:15]([CH2:19][CH2:20][N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[C:16](=[O:18])[NH:17][C:12]3=[N:11][CH:10]=2)=[CH:5][CH:4]=1.BrC1N=C2N(CCN3CCOCC3)C(=O)NC2=NC=1.CNC(C1C=CC(B(O)O)=CC=1)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:14]=[C:13]3[N:15]([CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[C:16](=[O:18])[NH:17][C:12]3=[N:11][CH:10]=2)=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27735264-(Methylcarbamoyl)benzeneboronic acidHCID 866263996-Bromo-1-(2-morpholinoethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-oneHCID 1358710156-(4-Hydroxyphenyl)-1-(2-morpholinoethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride

Product 1

HCID 1358710166-(4-Hydroxyphenyl)-1-(2-morpholinoethyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-oneYield 16%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

6-(4-Hydroxyphenyl)-1-(2-morpholinoethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride. 6-Bromo-1-(2-morpholinoethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (300 mg, 0.95 mmol), [4-(N-methylaminocarbonyl)phenyl]boronic acid (205 mg, 1.15 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane (80 mg, 0.09 mmol) and potassium phosphate (805 mg, 3.8 mmol) in DMF (30 mL) and water (8 mL) were reacted according to General Procedure 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 diethylether (few drops) and sonicated. This procedure was repeated twice more to provide 6-(4-hydroxyphenyl)-1-(2-morpholinoethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (67 mg, 16%) as a colorless solid hydrochloride salt. 1H NMR (400 MHz, CD3OD-d6) 8.38 (s, 1H), 8.84 (d, J=8.4, 2H), 7.44 (s, 1H), 7.39 (d, J=8.4, 2H), 4.45 (t, J=5.6, 2H); 4.07 (d, J=12.4, 2H), 3.82 (d, J=12.4, 2H), 3.69-3.64 (m, 4H); MS (ESI) m/z 342.15 [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 diethylether (few drops)
  4. customsonicated

Sources & evidence

ORD record
ord-5df02a0c2e4746f9a6d2323fd7d7d99e
Source dataset
uspto-grants-2011_07
Patent number
US07981893B2

Reaction notes

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