Hydrazine hydrate (1:1) → Gsk-2334470

HRID 2367299Notes

Reaction equation

HRID 2367299 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([NH:15][CH3:16])[N:12]=[C:11]([N:17]3[C@H:22]([CH3:23])[CH2:21][CH2:20][C@H:19]([C:24]([NH:26][CH:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)=[O:25])[CH2:18]3)[CH:10]=2)=[CH:5][C:4]=1F)#[N:2].O.[NH2:35][NH2:36]>CCO>[NH2:2][C:1]1[C:3]2[C:4](=[CH:5][C:6]([C:9]3[N:14]=[C:13]([NH:15][CH3:16])[N:12]=[C:11]([N:17]4[C@H:22]([CH3:23])[CH2:21][CH2:20][C@H:19]([C:24]([NH:26][CH:27]5[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]5)=[O:25])[CH2:18]4)[CH:10]=3)=[CH:7][CH:8]=2)[NH:36][N:35]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 58504379(3S,6R)-1-[6-(4-Cyano-3-fluorophenyl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide

Product 1

HCID 46215815Gsk-2334470Yield 152.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To (3S,6R)-1-[6-(4-cyano-3-fluorophenyl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide (260 mg, 0.58 mmol) in EtOH (10 mL) as a suspension at room temperature in a microwave vial was added hydrazine monohydrate (807 uL, 16.7 mmol, 30 equiv) in one portion. The mixture was capped and heated at 100° C. for 48 hours. A duplicate run was performed. The crude reactions from both runs were combined, and concentrated in vacuo. The residue was taken up in 10 mL of water. The resulting suspension was sonicated briefly, and filtered. The solids collected were dried under vacuum at room temperature over P2O5 for 18 hours, and then at 65° C. under vacuum for another 18 hours to afford the title compound (410 mg) as a cream-colored solid. LC-MS (ES) m/z=463 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 1.16-1.32 (m, 3H), 1.29 (d, J=6.8 Hz, 3H), 1.34-1.45 (m, 2H), 1.65-1.68 (m, 1H), 1.76-1.81 (m, 5H), 1.85-1.92 (m, 2H), 1.97-2.05 (m, 1H), 2.35-2.42 (m, 1H), 2.97 (s, 3H), 3.11-3.15 (m, 1H), 3.64-3.70 (m, 1H), 4.45-4.65 (bs, 1H), 4.72-4.92 (bs, 1H), 6.45 (s, 1H), 7.52 (dd, J=8.5, 1.14 Hz, 1H), 7.75 (d, J=8.3 Hz, 1H), 7.85 (s, 1H).

Workup

  1. customThe mixture was capped
  2. concentrationconcentrated in vacuo
  3. customThe resulting suspension was sonicated briefly
  4. filtrationfiltered
  5. customThe solids collected
  6. dry with materialwere dried under vacuum at room temperature over P2O5 for 18 hours

Sources & evidence

ORD record
ord-2abae0daf75140a9aec96bd9a5507e6b
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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