Hydrazine → HCID 178434214, compound

HRID 2367480Notes

Reaction equation

HRID 2367480 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:15]=[C:14]([NH2:16])[N:13]=[C:12]([N:17]3[C@H:22]([CH3:23])[CH2:21][CH2:20][C@H:19]([C:24]([NH:26][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[O:25])[CH2:18]3)[CH:11]=2)=[CH:6][C:5]=1F)(=O)[CH3:2].Cl.CON.C([O-])([O-])=O.[K+].[K+].CCN(C(C)C)C(C)C.[NH2:54][NH2:55]>COCCOC.CCO>[NH2:16][C:14]1[N:13]=[C:12]([N:17]2[C@H:22]([CH3:23])[CH2:21][CH2:20][C@H:19]([C:24]([NH:26][CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)=[O:25])[CH2:18]2)[CH:11]=[C:10]([C:7]2[CH:6]=[C:5]3[C:4]([C:1]([CH3:2])=[N:54][NH:55]3)=[CH:9][CH:8]=2)[N:15]=1

Participants

8

Reactant 5

HCID 9321HydrazineHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 58504436(3S,6R)-1-[6-(4-Acetyl-3-fluorophenyl)-2-amino-4-pyrimidinyl]-6-methyl-N-(phenylmethyl)-3-piperidinecarboxamide

Product 1

HCID 178434214HCID 178434214, compoundYield 10.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

Into a sealed tube, (3S,6R)-1-[6-(4-acetyl-3-fluorophenyl)-2-amino-4-pyrimidinyl]-6-methyl-N-(phenylmethyl)-3-piperidinecarboxamide (90 mg, 0.195 mmol), O-methylhydroxylamine hydrochloride (16.3 mg, 0.20 mmol), and K2CO3 (32.3 mg, 0.234 mmol) were stirred together in DME (3 mL) for 4 hours at 57° C. The reaction mixture was filtered, and the filtrate containing the oxime intermediate was concentrated in vacuo to 2 mL. Then EtOH (3 mL), Hunig's base (0.05 mL, 0.27 mmol), and hydrazine anhydrous (0.013 mL, 0.410 mmol) were added, and the resulting yellow mixture was heated overnight at 120° C. in an oil bath. The solution turned black. LCMS showed mainly product. The black solid was filtered and the yellow filtrate was evaporated. The resulting yellow residue was dissolved in CH3OH, and purified by HPLC (CH3CN/H2O w/0.1% HCO2H) to afford a formic acid salt of the title compound (9 mg) as a light yellow solid. LC-MS (ES) m/z=456 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 1.32 (m, 4H), 1.75-1.91 (m, 3H), 1.97-2.12 (m, 1H), 2.41-2.53 (m, 1H), 2.60 (s, 3H), 3.11-3.27 (m, 1H), 4.33-4.50 (m, 2H), 4.56-4.74 (m, 1H), 6.59 (s, 1H), 7.23-7.41 (m, 5H), 7.54-7.63 (m, 1H), 7.96 (m, 1H), 7.94 (s, 1H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. additionthe filtrate containing the oxime intermediate
  3. concentrationwas concentrated in vacuo to 2 mL
  4. filtrationThe black solid was filtered
  5. customthe yellow filtrate was evaporated
  6. dissolutionThe resulting yellow residue was dissolved in CH3OH
  7. custompurified by HPLC (CH3CN/H2O w/0.1% HCO2H)

Sources & evidence

ORD record
ord-62ac067d1f7748aa89b22baa3f87345f
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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