Carbon Tetrachloride → 1-{1-[9-Methyl-8-(5-methyl-1,3,4-oxadiazol-2-yl)-9H-purin-6-yl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 528051Notes

Reaction equation

HRID 528051 reaction equation
[C:1]([NH:4][NH:5][C:6]([C:8]1[N:9]([CH3:33])[C:10]2[C:15]([N:16]=1)=[C:14]([N:17]1[CH2:22][CH2:21][CH:20]([N:23]3[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[NH:25][C:24]3=[O:32])[CH2:19][CH2:18]1)[N:13]=[CH:12][N:11]=2)=[O:7])(=O)[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(C(C)C)CC)(C)C.C(Cl)(Cl)(Cl)Cl>C(#N)C>[CH3:33][N:9]1[C:8]([C:6]2[O:7][C:1]([CH3:2])=[N:4][N:5]=2)=[N:16][C:15]2[C:10]1=[N:11][CH:12]=[N:13][C:14]=2[N:17]1[CH2:18][CH2:19][CH:20]([N:23]2[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=3[NH:25][C:24]2=[O:32])[CH2:21][CH2:22]1

Participants

6

Reactant 4

HCID 5943Carbon TetrachlorideHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 68298139HCID 68298139, compound

Product 1

HCID 668023071-{1-[9-Methyl-8-(5-methyl-1,3,4-oxadiazol-2-yl)-9H-purin-6-yl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

N′-acetyl-9-methyl-6-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]-9H-purine-8-carbohydrazide (85 mg, 0.19 mmol, 1 equiv) and triphenylphosphine (90 mg, 0.34 mmol, 1.8 equiv) were weighed out into a 2 dram vial and suspended in acetonitrile (1 mL). Diisopropylethylamine (165 mL, 0.95 mmol, 5 equiv) and carbontetrachloride (36 μL, 0.38 mmol, 2 equiv) were added and the reaction stirred at room temperature overnight during which time a precipitate formed. Analysis by LCMS indicated about a 40% conversion to the desired product. Neither heating to 80° C. for several hours, nor the addition of additional carbontetrachloride, DIPEA, or TPP furthered the cyclization. The precipitate was collected, dissolved in DMF (3.5 mL) and purified by preparative reverse-phase HPLC (acetonitrile/water with 1% formic acid). Fraction containing pure 1-{1-[9-methyl-8-(5-methyl-1,3,4-oxadiazol-2-yl)-9H-purin-6-yl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one were combined. The desired material precipitated upon concentration of the fractions, was collected by filtration, washed with water, and dried under vacuum, which resulted in the isolation of 16 mg of material. 1H NMR (400 MHz, DMSO-d6) δ 10.80 (s, 1H), 8.33 (s, 1H), 7.16-7.10 (m, 1H), 6.93-6.82 (m, 3H), 4.53 (t, 1H), 4.03 (s, 3H), 2.59 (s, 3H), 2.30 (d, 2H), 1.83 (d, 2H). MS (EI) for C21H21N9O2: 432 (MH+).

Workup

  1. customformed

Sources & evidence

ORD record
ord-72ced400708e4d01bef1cd162dd206c8
Source dataset
uspto-grants-2016_05
Patent number
US09346807B2

Reaction notes

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