Hydrazine → HCID 58504384, compound

HRID 2367638Notes

Reaction equation

HRID 2367638 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=C(F)[C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][C@H:19]2[CH2:24][CH3:25])[N:3]=1.[CH3:26][O-:27].[Na+].[NH2:29][NH2:30].[CH3:31]CN(C(C)C)C(C)C>O.CCOC(C)=O.CN(C)C=O>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]3[C:11]([C:12]([NH2:13])=[N:29][NH:30]3)=[C:26]([O:27][CH3:31])[CH:15]=2)[CH:5]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][C@H:19]2[CH2:24][CH3:25])[N:3]=1

Participants

8

Reactant 4

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 10942334Sodium MethoxideHCID 66990829HCID 66990829, compound

Product 1

HCID 58504384HCID 58504384, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 20 mL vial was added 4-{2-amino-6-[(3R)-3-ethyl-4-morpholinyl]-4-pyrimidinyl}-2,6-difluorobenzonitrile (850 mg, 2.461 mmol), N,N-dimethylformamide (DMF) (5 mL) and sodium methoxide 1M (2.461 mL, 2.461 mmol). The reaction was stirred for 30 min at room temperature. The reaction was then poured into EtOAc (10 mL) followed by H2O (15 mL). The aqueous was extracted with EtOAc (×1) and then dried over Na2SO4 and concentrated to a yellow solid that was taken up in acetonitrile (5 mL) and added to a 20 mL microwave vial followed by hydrazine (0.309 mL, 9.85 mmol) and DIEA (3.44 mL, 19.69 mmol). The reaction was irradiated at 150° C. for 3 h. The reaction mixture was then concentrated for purification via flash chromatography (120 g, 50-100%, DCM:MeOH:NH4OH). Fractions were combined and concentrated to afford 6-{2-amino-6-[(3R)-3-ethyl-4-morpholinyl]-4-pyrimidinyl}-4-(methyloxy)-1H-indazol-3-amine (421.5 mg, 1.084 mmol, 44% yield) as a tan solid. LC-MS (ES) m/z=370 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 0.87 (t, J=7.45 Hz, 3H), 1.58-1.82 (m, 2H), 3.04-3.14 (m, 1H), 3.37-3.46 (m, 1H), 3.48-3.55 (m, 1H), 3.83 (d, J=11.62 Hz, 1H), 3.83 (d, J=11.6 Hz, 1H) 3.85-3.91 (m, 1H), 3.94 (s, 3H), 4.08-4.24 (m, 1H), 4.25-4.39 (m, 1H), 5.02 (s, 2H), 6.07 (s, 2H), 6.50 (s, 1H), 6.91 (s, 1H), 7.48 (s, 1H), 11.54 (s, 1H).

Workup

  1. extractionThe aqueous was extracted with EtOAc (×1)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated to a yellow solid that
  4. additionadded to a 20 mL microwave vial
  5. customThe reaction was irradiated at 150° C. for 3 h
  6. concentrationThe reaction mixture was then concentrated for purification via flash chromatography (120 g, 50-100%, DCM:MeOH:NH4OH)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-395b22cd3e054fbbaa7a5218b2d2b54b
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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