Potassium Phosphate, Tribasic → HCID 136373231, compound

HRID 388147Notes

Reaction equation

HRID 388147 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][CH:20]4[CH2:25][CH2:24][CH2:23][CH2:22][N:21]4[CH3:26])[C:16](=[O:18])[NH:17][C:12]3=[N:11][CH:10]=2)=[CH:5][CH:4]=1.BrC1N=C2N(CC3CCCCN3C)C(=O)NC2=NC=1.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][CH:20]4[CH2:25][CH2:24][CH2:23][CH2:22][N:21]4[CH3:26])[C:16](=[O:18])[NH:17][C:12]3=[N:11][CH:10]=2)=[CH:7][CH:8]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 86626417HCID 86626417, compoundHCID 136373230HCID 136373230, compound

Product 1

HCID 136373231HCID 136373231, compoundYield 17.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

6-(4-Hydroxyphenyl)-1-((1-methylpiperidin-2-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride. 6-Bromo-1-((1-methylpiperidin-2-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (0.25 g, 0.766 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane (0.063 g, 0.077 mmol) were combined in DMF (30.0 mL). Potassium phosphate (0.65 g, 3.07 mmol) in water (8.0 mL) was added and the reaction stirred at 100° C. for 2 h. The cooled reaction solution was filtered through Celite and the filter cake was washed with ethyl acetate. Filtrate and ethyl acetate wash were combined and solvent removed under reduced pressure. The resulting material was purified using reverse-phase semi-preparatory HPLC (10-80% 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 the desired product (0.045 g, 0.133 mmol, 17.30% yield) as the hydrochloride salt. 1H NMR (400 MHz, DMSO-d6) δ 12.13 (s, 1H), 9.76 (s, 1H), 8.52 (s, 1H), 8.42 (s, 1H), 7.87 (d, J=8.4, 2H), 6.87 (d, J=8.4, 2H), 4.23 (dd, J=8.4 and 5.6, 2H), 4.15-4.12 (m, 1H), 2.07 (m, 1H), 1.84 (m, 1H), 1.76-1.73 (m, 2H), 1.64-1.57 (m, 2H), 1.28 (m, 3H), 0.89-0.85 (m, 2H); MS (ESI) m/z 340.1[M+1]+.

Workup

  1. customThe cooled reaction solution
  2. filtrationwas filtered through Celite
  3. washthe filter cake was washed with ethyl acetate
  4. washFiltrate and ethyl acetate wash
  5. customsolvent removed under reduced pressure
  6. customThe resulting material was purified
  7. customreverse-phase semi-preparatory HPLC (10-80% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  8. concentrationThe desired fractions were concentrated
  9. additiontreated with 4N hydrochloric acid in diethyl ether (few drops)
  10. customsonicated

Sources & evidence

ORD record
ord-187ba1c0234243638c7b127965a33f71
Source dataset
uspto-grants-2013_02
Patent number
US08372976B2

Reaction notes

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