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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 528049
Notes
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Reaction equation

HRID 528049 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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 6329MethylamineHCID 66221Triethyl orthoacetateHCID 66799788HCID 66799788, compound

Product 1

HCID 668022991-{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

Reagents, catalysts & solvents 4

HCID 284
Formic Acid
Solvent
HCID 887MethanolSolvent
HCID 312751,4-DioxaneSolvent
HCID 18373917Acetonitrile--water (1/1)Solvent

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

  1. customThe tube was sealed
  2. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes