HCID 86711711, compound → 1-[1-(8-acetyl-9-methyl-9H-purin-6-yl)piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one

HRID 528032Notes

Reaction equation

HRID 528032 reaction equation
CON(C)[C:4]([C:6]1[N:7]([CH3:31])[C:8]2[C:13]([N:14]=1)=[C:12]([N:15]1[CH2:20][CH2:19][CH:18]([N:21]3[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[NH:23][C:22]3=[O:30])[CH2:17][CH2:16]1)[N:11]=[CH:10][N:9]=2)=[O:5].[CH3:33][Mg]Cl>C1COCC1>[C:4]([C:6]1[N:7]([CH3:31])[C:8]2[C:13]([N:14]=1)=[C:12]([N:15]1[CH2:20][CH2:19][CH:18]([N:21]3[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[NH:23][C:22]3=[O:30])[CH2:17][CH2:16]1)[N:11]=[CH:10][N:9]=2)(=[O:5])[CH3:33]

Participants

4

Reactant 2

HCID 86711711HCID 86711711, compoundHCID 178418332HCID 178418332, compound

Product 1

HCID 569485771-[1-(8-acetyl-9-methyl-9H-purin-6-yl)piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-oneYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

N-Methoxy-N,9-dimethyl-6-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]-9H-purine-8-carboxamide (30 mg, 0.07 mmol) was dissolved into THF (2 mL) under nitrogen and cooled to −78° C. Methylmagnesium chloride (3 M in THF; 0.046 mL, 0.14 mmol) was added to the reaction mixture. The reaction was stirred at −78° C. for 30 minutes and slowly warmed to room temperature. After 1 hour, the crude reaction mixture was concentrated, diluted with ethyl acetate, washed with water and saturated potassium carbonate. The organic layer was collected, was concentrated, was dissolved into methanol and was purified by preparative HPLC to afford 1-[1-(8-acetyl-9-methyl-9H-purin-6-yl)piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one (9.3 mg, 0.023 mmol, 34% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.85 (s, 1H), 8.35 (s, 1H), 7.20-7.14 (m, 1H), 6.96-6.88 (m, 3H), 6.27-4.92 (m, 2H), 4.66-4.45 (m, 1H), 3.93 (s, 3H), 3.42-3.20 (m, 2H), 2.63 (s, 3H), 2.42-2.26 (m, 2H), 1.87 (br d, 2H). MS (EI) for C20H21N7O2: 392 (MH+).

Workup

  1. temperatureslowly warmed to room temperature
  2. waitAfter 1 hour
  3. customthe crude reaction mixture
  4. concentrationwas concentrated
  5. additiondiluted with ethyl acetate
  6. washwashed with water and saturated potassium carbonate
  7. customThe organic layer was collected
  8. concentrationwas concentrated
  9. dissolutionwas dissolved into methanol
  10. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-3f80ba1930324dc0ac286fce5c3bc23c
Source dataset
uspto-grants-2016_05
Patent number
US09346807B2

Reaction notes

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