Hydrazine → HCID 58504683, compound

HRID 2367637Notes

Reaction equation

HRID 2367637 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[C:14](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.[O-:26][CH2:27][CH3:28].[Na+].[NH2:30][NH2:31].CCN(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:15]=[C:14]3[C:11]([C:12]([NH2:13])=[N:30][NH:31]3)=[C:10]([O:26][CH2:27][CH3:28])[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

Participants

8

Reactant 4

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 2723922Sodium ethoxideHCID 66990829HCID 66990829, compound

Product 1

HCID 58504683HCID 58504683, compoundYield 54.5%

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 ethoxide 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 sealed and heated in a microwave reactor at 150° C. for 3 h. The reaction mixture was concentrated to a yellow oil and purified 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-(ethyloxy)-1H-indazol-3-amine (514 mg) as a tan solid. LC-MS (ES) m/z=384 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 0.87 (t, J=7.45 Hz, 3H), 1.45 (t, J=6.95 Hz, 3H), 1.58-1.80 (m, 2H), 3.01-3.14 (m, 1H), 3.37-3.47 (m, 1H), 3.46-3.56 (m, 1H), 3.83 (d, J=11.4 Hz, 2H), 3.85-3.91 (m, 1H), 4.21 (q, J=6.99 Hz, 3H), 4.25-4.39 (m, 1H), 5.00 (s, 2H), 6.07 (s, 2H), 6.49 (s, 1H), 6.90 (s, 1H), 7.47 (s, 1H), 11.53 (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 sealed
  6. temperatureheated in a microwave reactor at 150° C. for 3 h
  7. concentrationThe reaction mixture was concentrated to a yellow oil
  8. custompurified via flash chromatography (120 g, 50-100%, DCM:MeOH:NH4OH)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c201c2ec6be7482e8f5c05e7168b1267
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

Loading…