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

HRID 2367566Notes

Reaction equation

HRID 2367566 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)[CH:18]=2)[CH:10]=1)[CH3:2].[NH2:26][NH2:27]>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)=[CH:19][CH:18]=2)[CH:10]=1)[CH3:2]

Participants

4

Reactant 2

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

Product 1

HCID 585047056-[6-[(3R)-3-Ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-1H-indazol-3-amineYield 28.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-[6-[(3R)-3-Ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-2-fluorobenzonitrile (0.464 g, 1.359 mmol) was taken up in CH3CN (5 mL) followed by the addition of hydrazine (0.171 mL, 5.44 mmol) and Hunig's (1.899 mL, 10.87 mmol) in a 20 mL microwave vial. The reaction was irradiated at 150° C. for 1 hour. The reaction mixture was then concentrated and the resulting residue was purified using reverse phase HPLC (5-30% 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 (×1). 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=354 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.89 (t, 3H), 1.60-1.82 (m, 2H), 2.83 (d, J=4.0 Hz, 3H), 3.10 (d, J=2.3 Hz, 1H), 3.43 (d, J=2.5 Hz, 1H), 3.52 (dd, J=11.5, 2.9 Hz, 1H), 3.84 (d, J=11.4 Hz, 1H), 3.89 (dd, J=11.2, 3.2 Hz, 1H), 4.03 (q, J=7.1 Hz, 1H), 4.14-4.26 (m, 1H), 4.29-4.38 (m, 1H), 5.38 (s, 2H), 6.55 (bs, 2H), 7.59 (d, J=8.6 Hz, 1H), 7.71 (d, J=8.6 Hz, 1H), 7.97 (bs, 1H), 11.50 (bs, 1H).

Workup

  1. customThe reaction was irradiated at 150° C. for 1 hour
  2. concentrationThe reaction mixture was then concentrated
  3. customthe resulting residue was purified
  4. additiondiluted with EtOAc
  5. washThe organics were washed with saturated NaHCO3 solution (2×) that
  6. extractionwas back extracted with EtOAc (×1)
  7. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-0c510cfbc76c4f91865b712675b32608
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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