Hydrazine hydrate (1:1) → HCID 178508270, compound

HRID 2367412Notes

Reaction equation

HRID 2367412 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[CH:19]([C:23]3[NH:27][C:26]4[CH:28]=[CH:29][C:30]([F:32])=[CH:31][C:25]=4[N:24]=3)[CH2:18]2)[N:3]=1.[OH2:33].[NH2:34][NH2:35]>C(O)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]3[C:11]([C:12]([NH2:13])=[N:34][NH:35]3)=[CH:14][CH:15]=2)[CH:5]=[C:4]([N:17]2[CH2:22][CH2:21][O:33][CH:19]([C:23]3[NH:27][C:26]4[CH:28]=[CH:29][C:30]([F:32])=[CH:31][C:25]=4[N:24]=3)[CH2:18]2)[N:3]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 178509575HCID 178509575, compound

Product 1

HCID 178508270HCID 178508270, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 4-{2-amino-6-[2-(5-fluoro-1H-benzimidazol-2-yl)-4-morpholinyl]-4-pyrimidinyl}-2-fluorobenzonitrile (120 mg, 0.277 mmol) in ethanol (3.0 mL) at room temperature was added hydrazine hydrate (139 mg, 2.77 mmol). The reaction vessel was sealed and heated in Biotage Initiator using initial high to 120° C. for 1 hour. After cooling the reaction, the solvent was evaporated in vacuo to give the crude product which was triturated with EtOAc (1×5 mL). The resulting solid was filtered through a medium fritted glass funnel, and collected to afford the title compound (37 mg). LC-MS (ES) m/z=446 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 3.10-3.17 (m, 2H), 3.81 (t, J=9.6 Hz, 1H), 4.12 (d, J=10.4 Hz, 1H), 4.34 (d, J=12.0 Hz, 1H), 4.82-4.84 (m, 2H), 5.39 (s, 2H), 6.23 (s, 2H), 6.71 (s, 1H), 7.02-7.09 (m, 1H), 7.25 (d, J=8.8 Hz, 0.5H), 7.41-7.49 (m, 1H), 7.61 (d, J=9.6 Hz, 1.5H), 7.71 (d, J=8.0 Hz, 1H), 7.98 (s, 1H), 11.53 (s, 1H), 12.7 (bs, 1H).

Workup

  1. customThe reaction vessel was sealed
  2. temperatureheated in Biotage Initiator
  3. customhigh to 120° C.
  4. customfor 1 hour
  5. temperatureAfter cooling
  6. customthe reaction
  7. customthe solvent was evaporated in vacuo
  8. customto give the crude product which
  9. customwas triturated with EtOAc (1×5 mL)
  10. filtrationThe resulting solid was filtered through a medium fritted glass funnel
  11. customcollected

Sources & evidence

ORD record
ord-36cc50f82bb2455c89f712f72a7af69b
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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