Potassium Phosphate, Tribasic → 6-(4-(4,5-Dimethyl-1H-imidazol-2-YL)phenyl)-1-((tetrahydro-2H-pyran-4-YL)methyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-one

HRID 388118Notes

Reaction equation

HRID 388118 reaction equation
CC1N=C(C2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)NC=1C.[CH3:23][C:24]1[N:25]=[C:26]([C:30]2[CH:35]=[CH:34][C:33]([C:36]3[N:41]=[C:40]4[N:42]([CH2:46][CH:47]5[CH2:52][CH2:51][O:50][CH2:49][CH2:48]5)[C:43](=[O:45])[NH:44][C:39]4=[N:38][CH:37]=3)=[CH:32][CH:31]=2)[NH:27][C:28]=1[CH3:29].BrC1N=C2N(CC3CCOCC3)C(=O)NC2=NC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[CH3:29][C:28]1[N:27]=[C:26]([C:30]2[CH:35]=[CH:34][C:33]([C:36]3[N:41]=[C:40]4[N:42]([CH2:46][CH:47]5[CH2:52][CH2:51][O:50][CH2:49][CH2:48]5)[C:43](=[O:45])[NH:44][C:39]4=[N:38][CH:37]=3)=[CH:32][CH:31]=2)[NH:25][C:24]=1[CH3:23]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 666999106-(4-(4,5-Dimethyl-1H-imidazol-2-yl)phenyl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one 4,5-Dimethyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazoleHCID 866263956-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one

Product 1

HCID 249858776-(4-(4,5-Dimethyl-1H-imidazol-2-YL)phenyl)-1-((tetrahydro-2H-pyran-4-YL)methyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-oneYield 19%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 6228DimethylformamideSolvent

Procedure

6-(4-(4,5-Dimethyl-1H-imidazol-2-yl)phenyl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one 4,5-Dimethyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazole (0.16 g, 0.53 mmol), 6-bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 101.B) (0.168 g, 0.53 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.044 g, 0.053 mmol) and potassium phosphate (0.45 g, 2.14 mmol) were reacted in DMF (2 mL) according to General Procedure B2, except reaction was heated for 2 h. Purification by silica gel chromatography (10% methanol in ethyl acetate) gave the title compound as an off-white solid (40.0 mg, 19% yield). 1H NMR (400 MHz, DMSO-d6) δ 12.1(s, 1H), 8.52(s, 1H), 8.06(d, J=8.6, 2H), 7.93 (d, J=8.20, 2H), 4.0-3.69(m, 4H), 3.26 (t, J=11.1, 2H), 2.2 (s, 3H), 2.15 (m, 1H), 2.05 (s,3H), 1.7 (m, 2H), 1.13 (m,2H); MS (ESI) m/z 405.4[M+1]+; mp 250-254° C. (dec.)

Workup

  1. customaccording to General Procedure B2, except reaction
  2. temperaturewas heated for 2 h
  3. customPurification by silica gel chromatography (10% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-1ab6a1d7e8504cedbfe7a5ab2cb7e58d
Source dataset
uspto-grants-2013_02
Patent number
US08372976B2

Reaction notes

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