Hydrazine hydrate (1:1) → HCID 58504744, compound

HRID 2367320Notes

Reaction equation

HRID 2367320 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH:9]2[C:14]([NH2:16])=[O:15])[CH:5]=[C:4]([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[C:19](F)[CH:18]=2)[N:3]=1.O.[NH2:27][NH2:28]>C(O)C.O>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH:9]2[C:14]([NH2:16])=[O:15])[CH:5]=[C:4]([C:17]2[CH:18]=[C:19]3[C:20]([C:23]([NH2:24])=[N:27][NH:28]3)=[CH:21][CH:22]=2)[N:3]=1

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 58504784HCID 58504784, compound

Product 1

HCID 58504744HCID 58504744, compoundYield 10.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-3-morpholinecarboxamide (360 mg, 1.05 mmol) and hydrazine monohydrate (2.58 mL, 52.6 mmol) in ethanol (10 mL) was stirred at 90° C. in a sealed tube for 16 hours. The mixture was cooled and diluted with water. Attempts to extract the product from the water using 90/10 CH2Cl2/IPA were unsuccessful, so the aqueous phase was combined with the residue from the concentrated CH2Cl2/IPA extractions and the mixture was concentrated in vacuo. The residue was purified by silica gel chromatography (68 g SiO2, CHCl3 to 80/20/2 CHCl3/CH3OH/NH4OH gradient with a 10 minute hold at 90/10/1 CHCl3/CH3OH/NH4OH) to give the title compound (40 mg) as an off-white solid. LC-MS (ES) m/z=355 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 3.29-3.41 (m, 1H), 3.41-3.50 (m, 1H), 3.61 (dd, J=11.6, 3.5 Hz, 1H), 3.85-3.93 (m, 1H), 3.99-4.18 (bs, 1H), 4.35 (d, J=11.6 Hz, 1H), 4.82-5.08 (bs, 1H), 5.39 (s, 2H), 6.12 (s, 2H), 6.55 (s, 1H), 7.19 (s, 1H), 7.35 (s, 1H), 7.57 (d, J=8.3 Hz, 1H), 7.72 (d, J=8.6 Hz, 1H), 7.95 (s, 1H), 11.54 (s, 1H).

Workup

  1. temperatureThe mixture was cooled
  2. extractionto extract the product from the water using 90/10 CH2Cl2/IPA
  3. extractionwas combined with the residue from the concentrated CH2Cl2/IPA extractions
  4. concentrationthe mixture was concentrated in vacuo
  5. customThe residue was purified by silica gel chromatography (68 g SiO2, CHCl3 to 80/20/2 CHCl3/CH3OH/NH4OH gradient with a 10 minute hold at 90/10/1 CHCl3/CH3OH/NH4OH)

Sources & evidence

ORD record
ord-bd079bea29f34dbc84813005476b58ba
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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