2-Methylpyrimidine-5-carbaldehyde → 1-{1-[9-Methyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 528056Notes

Reaction equation

HRID 528056 reaction equation
[NH2:1][C:2]1[C:3]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=4[NH:18][C:17]3=[O:25])[CH2:12][CH2:11]2)=[N:4][CH:5]=[N:6][C:7]=1[NH:8][CH3:9].[CH3:26][C:27]1[N:32]=[CH:31][C:30]([CH:33]=O)=[CH:29][N:28]=1>CN(C=O)C.O.O.O.O.O.O.[Fe](Cl)(Cl)Cl>[CH3:9][N:8]1[C:33]([C:30]2[CH:29]=[N:28][C:27]([CH3:26])=[N:32][CH:31]=2)=[N:1][C:2]2[C:7]1=[N:6][CH:5]=[N:4][C:3]=2[N:10]1[CH2:11][CH2:12][CH:13]([N:16]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[NH:18][C:17]2=[O:25])[CH2:14][CH2:15]1

Participants

5

Reactant 2

HCID 31609702-Methylpyrimidine-5-carbaldehydeHCID 668022691-(1-(5-amino-6-(methylamino)pyrimidin-4-yl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one

Product 1

HCID 667998991-{1-[9-Methyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-oneYield 51.7%

Reagents, catalysts & solvents 2

HCID 16211236Trichloroiron;hexahydrateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 1-(1-(5-amino-6-(methylamino)pyrimidin-4-yl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one (300 mg, 0.88 mmol) in anhydrous DMF (5 mL) were added 2-methylpyrimidine-5-carbaldehyde (108 mg, 0.88 mmol) and Iron (III) chloride hexahydrate (0.88 g, 0.24 mmol). The dark brown solution was heated to 90° C. for 14 hour in an open air vessel. The reaction mixture was cooled to room temperature and poured over ice (5 g). The resulting mixture was extracted with ethyl acetate (50 mL), the organic layer was washed with brine (10 mL), and dried over MgSO4. The solution was filtered, and concentrated under reduced pressure. The resulting solids were triturated with 15 mL of diethyl ether (15 mL) for 30 min. The precipitate was collected by vacuum filtration to give 201 mg (51% yield) of the title compound. 1H NMR (400 MHz, DMSO-d6): δ 10.86 (s, 1H), 9.16 (s, 2H), 8.33 (s, 1H), 7.18-7.11 (m, 1H), 6.98-6.87 (m, 3H), 4.55 (t, 1H), 3.86 (s, 3H), 2.71 (s, 3H), 2.34 (dd, 2H), 1.84 (d, 2H); MS (EI) for C23H23N9O: 442.3 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe resulting mixture was extracted with ethyl acetate (50 mL)
  3. washthe organic layer was washed with brine (10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationThe solution was filtered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting solids were triturated with 15 mL of diethyl ether (15 mL) for 30 min
  8. filtrationThe precipitate was collected by vacuum filtration

Sources & evidence

ORD record
ord-b1507ab0e64c4593a2ffd6b4c0459ef4
Source dataset
uspto-grants-2016_05
Patent number
US09346807B2

Reaction notes

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