Hydrazine → 6-[6-[(3R)-3-Ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-4-fluoro-1H-indazol-3-amine

HRID 2367568Notes

Reaction equation

HRID 2367568 reaction equation
[CH2:1]([C@@H:3]1[CH2:8][O:7][CH2:6][CH2:5][N:4]1[C:9]1[N:14]=[C:13]([NH:15][CH3:16])[N:12]=[C:11]([C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[C:19]([F:25])[CH:18]=2)[CH:10]=1)[CH3:2].[NH2:26][NH2:27].CCN(C(C)C)C(C)C>CC#N>[CH2:1]([C@@H:3]1[CH2:8][O:7][CH2:6][CH2:5][N:4]1[C:9]1[N:14]=[C:13]([NH:15][CH3:16])[N:12]=[C:11]([C:17]2[CH:24]=[C:23]3[C:20]([C:21]([NH2:22])=[N:26][NH:27]3)=[C:19]([F:25])[CH:18]=2)[CH:10]=1)[CH3:2]

Participants

5

Reactant 3

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 585047634-[6-[(3R)-3-Ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-2-fluorobenzonitrile

Product 1

HCID 462149586-[6-[(3R)-3-Ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-4-fluoro-1H-indazol-3-amineYield 29.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-[6-[(3R)-3-Ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-2-fluorobenzonitrile (0.453 g, 1.261 mmol) was taken up in CH3CN (5 mL) followed by the addition of hydrazine (0.158 mL, 5.04 mmol) and Hunig's base (1.76 mL, 10.1 mmol) in a 20 mL microwave vial. The reaction was irradiated at 150° C. for 1 hour. The reaction mixture was concentrated and purified by reverse phase HPLC (8-28% CH3CN/H2O, 0.1% TFA). Fractions were combined and diluted with EtOAc. The organics were washed with saturated NaHCO3 solution (2×) that was back extracted with EtOAc. The organics were combined and dried over Na2SO4. The product was taken up in 2 mL H2O and lyophilized to afford the title compound (137 mg) as a white fluffy powder. LC-MS (ES) m/z=372 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.88 (t, 3H), 1.60-1.81 (m, 2H), 2.82 (d, J=4.0 Hz, 3H), 3.05-3.16 (m, 1H), 3.43 (d, J=2.53 Hz, 1H), 3.51 (dd, J=11.5, 2.9 Hz, 1H), 3.83 (d, J=11.4 Hz, 1H), 3.89 (dd, J=11.1, 3.0 Hz, 1H), 4.03 (d, J=7.1 Hz, 1H), 4.16-4.28 (m, 1H), 4.30-4.43 (m, 1H), 5.26 (s, 2H), 6.58 (bs, 2H), 7.36 (d, J=12.4 Hz, 1H), 7.84 (bs, 1H), 11.89 (s, 1H).

Workup

  1. customThe reaction was irradiated at 150° C. for 1 hour
  2. concentrationThe reaction mixture was concentrated
  3. custompurified by reverse phase HPLC (8-28% CH3CN/H2O, 0.1% TFA)
  4. additiondiluted with EtOAc
  5. washThe organics were washed with saturated NaHCO3 solution (2×) that
  6. extractionwas back extracted with EtOAc
  7. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-a0198861cd7b46aca63ef78d898757ea
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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