HCID 86732071, compound → HCID 71548049, compound

HRID 1498812Notes

Reaction equation

HRID 1498812 reaction equation
[NH:1]([C:3]1[N:8]=[C:7]([CH3:9])[N:6]=[C:5]([C@@H:10]2[CH2:12][C@H:11]2[C:13]2[N:17]([CH3:18])[C:16]3[CH:19]=[CH:20][CH:21]=[CH:22][C:15]=3[N:14]=2)[CH:4]=1)[NH2:2].CN(C)[C:25](=[N:27][C:28](=O)[CH2:29][O:30][CH3:31])[CH3:26]>C(O)(=O)C>[CH3:31][O:30][CH2:29][C:28]1[N:1]([C:3]2[N:8]=[C:7]([CH3:9])[N:6]=[C:5]([C@@H:10]3[CH2:12][C@H:11]3[C:13]3[N:17]([CH3:18])[C:16]4[CH:19]=[CH:20][CH:21]=[CH:22][C:15]=4[N:14]=3)[CH:4]=2)[N:2]=[C:25]([CH3:26])[N:27]=1

Participants

4

Reactant 2

HCID 86732071HCID 86732071, compoundHCID 86732073HCID 86732073, compound

Product 1

HCID 71548049HCID 71548049, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

A solution of 2-((1R,2R)-2-(6-hydrazinyl-2-methylpyrimidin-4-yl)cyclopropyl)-1-methyl-1H-benzo[d]imidazole (4-7, 25.0 mg, 0.0850 mmol, 1.0 eq) in acetic acid (3 mL) was added to a round bottom flask containing N-(1-(dimethylamino)ethylidene)-2-methoxyacetamide (200 mg, 1.26 mmol, 14.9 eq; prepared according to procedure 2-1). The acetic acid solution was heated at 100° C. for 30 minutes, allowed to cool to room temperature and concentrated to dryness. The residue was partitioned between saturated aqueous sodium bicarbonate solution (100 mL) and ethyl acetate (100 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated to dryness. The resulting residue was purified by reverse phase liquid chromatography (H2OCH3CN gradient w/ 0.1% NH4OH present) to afford 2-((1R,2R)-2-(6-(5-(methoxymethyl)-3-methyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)-1-methyl-1H-benzo[d]imidazole (4-8) as a white solid. 1H NMR (500 MHz, CDCl3) δ 7.69 (m, 2H), 7.24 (m, 3H), 5.11 (s, 2H), 3.81 (s, 3H), 3.57 (s, 3H), 2.83 (m, 2H), 2.69 (s, 3H), 2.56 (s, 3H), 2.04 (m, 1H), 1.98 (m, 1H). HRMS m/z (M+H) 390.2039 found, 390.2037 required.

Workup

  1. concentrationconcentrated to dryness
  2. customThe residue was partitioned between saturated aqueous sodium bicarbonate solution (100 mL) and ethyl acetate (100 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe resulting residue was purified by reverse phase liquid chromatography (H2OCH3CN gradient w/ 0.1% NH4OH present)

Sources & evidence

ORD record
ord-7aa6d9a836294ac683cf8e8c683e8977
Source dataset
uspto-grants-2015_12
Patent number
US09200001B2

Reaction notes

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