Hydrazine → HCID 58504557, compound

HRID 2367476Notes

Reaction equation

HRID 2367476 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([NH:16][C:17]3[N:21]([CH3:22])[N:20]=[CH:19][CH:18]=3)=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:23]2[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[C:25](F)[CH:24]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:41][NH2:42]>CCO>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([NH:16][C:17]3[N:21]([CH3:22])[N:20]=[CH:19][CH:18]=3)=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:23]2[CH:24]=[C:25]3[C:26]([C:29]([NH2:30])=[N:41][NH:42]3)=[CH:27][CH:28]=2)[N:3]=1

Participants

5

Reactant 3

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504776HCID 58504776, compound

Product 1

HCID 58504557HCID 58504557, compoundYield 44.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
110 °C

Procedure

Into a microwave tube, (3S)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-(1-methyl-1H-pyrazol-5-yl)-3-piperidinecarboxamide (180 mg, 0.428 mmol), 3 mL of EtOH, Hunig's base (0.30 mL, 1.71 mmol), and hydrazine anhydrous (0.081 mL, 2.57 mmol) were added, and the yellow mixture was heated overnight at 110° C. in an oil bath. The solution turned black. LCMS showed mainly product. The black solids were filtered and the yellow filtrate was evaporated. The resulting yellow residue was treated with EtOAc (3 mL) at 50° C. with stirring, and the clear layer of EtOAc solution was poured out. The solid layer was then treated with water (3 mL) at 50° C. with stirring, and the suspension was filtered. The light yellow colored solid was washed by water, and dried to give the title compound (82 mg) as a light yellow solid. LC-MS (ES) m/z=433 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.39-1.57 (m, 1H), 1.62-1.84 (m, 2H), 2.04 (m, 1H), 2.55-2.71 (m, 1H), 2.81-2.94 (m, 1H), 2.97-3.11 (m, 1H), 3.67 (s, 3H), 4.39-4.73 (m, 2H), 5.38 (s, 2H), 6.11 (s, 2H), 6.21 (s, 1H), 6.69 (s, 1H), 7.33 (s, 1H), 7.56-7.77 (m, 2H), 7.97 (s, 1H), 10.00 (s, 1H), 11.50 (s, 1H).

Workup

  1. filtrationThe black solids were filtered
  2. customthe yellow filtrate was evaporated
  3. additionThe resulting yellow residue was treated with EtOAc (3 mL) at 50° C.
  4. additionthe clear layer of EtOAc solution was poured out
  5. additionThe solid layer was then treated with water (3 mL) at 50° C.
  6. stirringwith stirring
  7. filtrationthe suspension was filtered
  8. washThe light yellow colored solid was washed by water
  9. customdried

Sources & evidence

ORD record
ord-fed4a1a85b1741e7a53cf0434799747a
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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