Acetic Acid → 1-{1-[8-(4,5-Dimethyl-4H-1,2,4-triazol-3-yl)-9-methyl-9H-purin-6-yl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 528049Notes

Reaction equation

[CH3:1][N:2]1[C:10]([C:11]([NH:13][NH2:14])=O)=[N:9][C:8]2[C:3]1=[N:4][CH:5]=[N:6][C:7]=2[N:15]1[CH2:20][CH2:19][CH:18]([N:21]2[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[NH:23][C:22]2=[O:30])[CH2:17][CH2:16]1.C(O[CH2:40][CH3:41])(OCC)(OCC)C.[CH3:42][NH2:43].C(O)(=O)C>CO.C(O)=O.C(#N)C.O.O1CCOCC1>[CH3:42][N:43]1[C:40]([CH3:41])=[N:14][N:13]=[C:11]1[C:10]1[N:2]([CH3:1])[C:3]2[C:8]([N:9]=1)=[C:7]([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:6]=[CH:5][N:4]=2

Participants

Conditions

Temperature: 130 °C

Procedure

Into an Ace pressure tube were placed 9-methyl-6-(4-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)-9H-purine-8-carbohydrazide (115 mg, 0.28 mmol, 1.0 equiv), triethyl orthoacetate (80 μL, 0.43 mmol, 1.5 equiv), methylamine (775 μL, 2M in THF, 1.55 mmol, 5.5 equiv), and acetic acid (0.5 mL), and dioxane (1.5 mL). The tube was sealed and heated at 130° C. for 12 hours. The tube was cooled to room temperature and diluted with methanol (1 mL). The title compound was isolated by preparative reverse-phase HPLC (acetonitrile/water with 1% formic acid, 25-45% gradient). Purified fractions were combined, frozen, and lyophilized to yield 28 mg material. 1H-NMR (400 MHz, DMSO-d6): δ 10.81 (s, 1H), 8.31 (s, 1H), 7.12 (m, 1H), 6.87 (m, 3H), 5.5 (br s, 2H), 4.52 (m, 1H), 3.98 (d, 3H), 3.82 (s, 3H), 2.40 (s, 3H), 2.32 (dd, 2H), 1.82 (d, 2H); MS (EI) for C22H24N10O, found 445.3 (MH+).

Workup

customThe tube was sealed
temperatureThe tube was cooled to room temperature

Sources & evidence

ORD record: ord-88b9de65ebc24d4abaf8ffcb20879cd7
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346807B2

Reaction notes

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