Hydrazine → 6-{2-Amino-6-[2-(4-phenyl-1H-imidazol-2-yl)-4-morpholinyl]-4-pyrimidinyl}-1H-indazol-3-amine

HRID 2367355Notes

Reaction equation

HRID 2367355 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH:19]([C:23]3[NH:24][CH:25]=[C:26]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[N:27]=3)[CH2:18]2)[N:3]=1.[NH2:34][NH2:35]>C(O)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[C:14]3[C:11]([C:12]([NH2:13])=[N:34][NH:35]3)=[CH:10][CH:9]=2)[CH:5]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH:19]([C:23]3[NH:24][CH:25]=[C:26]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:27]=3)[CH2:18]2)[N:3]=1

Participants

4

Reactant 2

HCID 9321HydrazineHCID 178509578HCID 178509578, compound

Product 1

HCID 1785082736-{2-Amino-6-[2-(4-phenyl-1H-imidazol-2-yl)-4-morpholinyl]-4-pyrimidinyl}-1H-indazol-3-amineYield 69.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 4-{2-amino-6-[2-(4-phenyl-1H-imidazol-2-yl)-4-morpholinyl]-4-pyrimidinyl}-2-fluorobenzonitrile (310 mg, 0.702 mmol) and hydrazine (2.5 mL, 79 mmol) in ethanol (4 mL) was heated under microwave conditions with stirring for 1 hour. The mixture was concentrated to afford the crude title compound (400 mg) as a yellow solid. This material was combined with another batch of crude title compound (100 mg). The combined material was washed with CH2Cl2 (2×8 mL) and dried in vacuo. The resulting residue was purified by Prep-HPLC using CH3CN in water (0.5% ammonium hydrogen carbonate in water) from 25% to 30% to afford the title compound (220 mg) as a yellow solid. LC-MS (ES) m/z=454 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 3.08-3.14 (m, 1H), 3.18-3.24 (m, 1H), 3.72 (m, 1H), 4.04-4.07 (m, 1H), 4.30-4.34 (m, 1H), 4.59-4.64 (m, 1H), 4.73-4.75 (m, 1H), 5.39 (s, 2H), 6.21 (s, 2H), 6.71 (s, 1H), 7.16-7.20 (m, 1H), 7.31-7.36 (m, 2H), 7.61-7.63 (m, 2H), 7.71 (d, J=8.4 Hz, 1H), 7.78 (d, J=7.2 Hz, 2H), 7.99 (s, 1H), 11.53 (s, 1H), 12.33-12.62 (m, 1H).

Workup

  1. temperaturewas heated under microwave conditions
  2. concentrationThe mixture was concentrated
  3. customto afford the crude title compound (400 mg) as a yellow solid
  4. washThe combined material was washed with CH2Cl2 (2×8 mL)
  5. customdried in vacuo
  6. customThe resulting residue was purified by Prep-HPLC

Sources & evidence

ORD record
ord-f2a67e625bbb48ea9331fc278845cdef
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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