4-(Morpholin-4-yl)benzene-1,2-diamine → 4-(2-(5-Nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-1H-benzo[d]imidazol-6-yl)morpholine

HRID 1047559Notes

Reaction equation

HRID 1047559 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][O:14]1)[N:8]=[C:7]2[CH:19]=O)([O-:3])=[O:2].[O:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:28]=[C:29]([NH2:34])[C:30]([NH2:33])=[CH:31][CH:32]=2)[CH2:23][CH2:22]1.S(=O)(O)[O-].[Na+]>C1COCC1.Cl.C(OCC)(=O)C>[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][O:14]1)[N:8]=[C:7]2[C:19]1[NH:33][C:30]2[CH:31]=[CH:32][C:27]([N:24]3[CH2:23][CH2:22][O:21][CH2:26][CH2:25]3)=[CH:28][C:29]=2[N:34]=1)([O-:3])=[O:2]

Participants

7

Reactant 3

HCID 141123324-(Morpholin-4-yl)benzene-1,2-diamineHCID 23665763Sodium BisulfiteHCID 86673211HCID 86673211, compound

Product 1

HCID 1363522614-(2-(5-Nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-1H-benzo[d]imidazol-6-yl)morpholineYield 50%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde (214 mg, 0.777 mmol) and 4-morpholinobenzene-1,2-diamine (150 mg, 0.777 mmol) were dissolved in dry THF (10 mL), and 2N HCl (1 drop) was added. The solution was heated at a gentle reflux for 30 min and then 1N sodium bisulfite (1 mL) was added. After overnight at reflux, the solution was cooled to room temperature, and diluted with ethyl acetate (40 mL). The mixture was washed with water and brine, dried over Na2SO4, and concentrated. Purification by flash chromatography (20% ethyl acetate/hexane) afforded the title compound as a pale yellow solid in a 50% yield. 1H NMR: (400 MHz, DMSO-d6): δ 9.49 (d, 1H, J=2.0 Hz), 8.41 (dd, 1H, J=2.0 and 9.2 Hz), 8.00 (d, 1H, J=9.2 Hz), 7.71 (m, 1H), 7.12 (m, 2H), 6.05 (dd, 1H, J=2.4 and 9.2 Hz), 4.75 (dd, 1H, J=2.4 and 6.8 Hz), 4.05 (m, 1H), 3.89 (m, 4H), 3.63 (m, 1H), 3.54-3.47 (m, 1H), 3.22 (m, 4H), 2.21 (m, 2H), 1.87 (m, 1H), 1.73 (m, 1H).

Workup

  1. temperatureThe solution was heated at
  2. temperaturea gentle reflux for 30 min
  3. temperatureAfter overnight at reflux
  4. washThe mixture was washed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customPurification by flash chromatography (20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-8cbfcf2b3d6246d8b4c0d34ea4a3bf47
Source dataset
uspto-grants-2013_10
Patent number
US08569511B2

Reaction notes

Loading…