2-(1-(6-hydrazinyl-2-methylpyrimidin-4-yl)azetidin-3-yl)-1-methyl-1H-benzo[d]imidazole → 2-(1-(6-(5-ethyl-3-methyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)azetidin-3-yl)-1-methyl-1H-benzo[d]imidazole

HRID 2202821Notes

Reaction equation

HRID 2202821 reaction equation
[NH:1]([C:3]1[N:8]=[C:7]([CH3:9])[N:6]=[C:5]([N:10]2[CH2:13][CH:12]([C:14]3[N:18]([CH3:19])[C:17]4[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=4[N:15]=3)[CH2:11]2)[CH:4]=1)[NH2:2]>C(O)(=O)C>[CH2:4]([C:5]1[N:1]([C:3]2[N:8]=[C:7]([CH3:9])[N:6]=[C:5]([N:10]3[CH2:11][CH:12]([C:14]4[N:18]([CH3:19])[C:17]5[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=5[N:15]=4)[CH2:13]3)[CH:4]=2)[N:2]=[C:7]([CH3:9])[N:6]=1)[CH3:3]

Participants

3

Reactant 1

HCID 894937102-(1-(6-hydrazinyl-2-methylpyrimidin-4-yl)azetidin-3-yl)-1-methyl-1H-benzo[d]imidazole

Product 1

HCID 715488502-(1-(6-(5-ethyl-3-methyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)azetidin-3-yl)-1-methyl-1H-benzo[d]imidazole

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of Intermediate 11 (50 mg, 0.16 mmol) and A (46 mg, 0.32 mmol) in acetic acid (1.6 mL) was heated at 100° C. for 30 min. The solvent was removed in vacuo and the residue was purified by reverse phase chromatography (MeCN/H2O/0.1% TFA). The fractions containing the product were partitioned between EtOAc and saturated NaHCO3. The organic layer was washed with 50% saturated brine solution, dried over Na2SO4 and concentrated to provide Example 35 as an off-white solid. 1H NMR: (500 MHz, DMSO-d6) δ 7.60 (d, J=8 Hz, 1H), 7.53 (d, J=8 Hz, 1H), 7.21 (m, 2H), 6.52 (s, 1H), 4.58 (m, 2H), 4.45 (m, 3H), 3.74 (s, 3H), 3.22 (q, J=7.5 Hz, 2H), 2.44 (s, 3H), 2.30 (s, 3H) 1.25 (t, J=7.5 Hz, 3H). MS: m/z=389.5 (M+H).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by reverse phase chromatography (MeCN/H2O/0.1% TFA)
  3. additionThe fractions containing the product
  4. customwere partitioned between EtOAc and saturated NaHCO3
  5. washThe organic layer was washed with 50% saturated brine solution
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-89f37380bbb04c739b42dda5b7addc74
Source dataset
uspto-grants-2016_06
Patent number
US09365562B2

Reaction notes

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