Hydrazine hydrate (1:1) → HCID 178440924, compound

HRID 1640207Notes

Reaction equation

HRID 1640207 reaction equation
[C:1]([C:4]1[CH:9]=[C:8]([O:10][C:11]2[CH:20]=[C:19]3[C:14]([CH2:15][CH2:16][CH:17]([C:21]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH:25]=4)=[O:22])[CH2:18]3)=[CH:13][CH:12]=2)[CH:7]=[CH:6][N:5]=1)(=O)[CH3:2].O.[NH2:35]N.COC(OC)[N:40]([CH3:42])C>O>[C:30]([C:26]1[CH:25]=[C:24]([NH:23][C:21]([CH:17]2[CH2:16][CH2:15][C:14]3[C:19](=[CH:20][C:11]([O:10][C:8]4[CH:7]=[CH:6][N:5]=[C:4]([C:1]5[CH:2]=[CH:42][NH:40][N:35]=5)[CH:9]=4)=[CH:12][CH:13]=3)[CH2:18]2)=[O:22])[CH:29]=[CH:28][CH:27]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

5

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 78373Dimethylformamide dimethyl acetalHCID 58902307HCID 58902307, compound

Product 1

HCID 178440924HCID 178440924, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
115 °C

Procedure

A solution of 7-[(2-acetylpyridin-4-yl)oxy]-N-(3-tert-butylphenyl)-1,2,3,4-tetrahydronaphthalene-2-carboxamide (0.516 g, 1.16 mmol) in 1,1-dimethoxy-N,N-dimethylmethanamine (20 mL) was allowed to stir at 115° C. for 12 h. The reaction mixture was concentrated. The residue was dissolved in ethanol (20 mL) and hydrazine hydrate (0.600 mL, 12.3 mmol) was added. The reaction mixture was allowed to stir at 90° C. for 1 h and then diluted with water. The solution was extracted with EtOAc and the combined organic solutions were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give N-(3-tert-butylphenyl)-7-{[2-(1H-pyrazol-3-yl)-pyridin-4-yl]oxy}-1,2,3,4-tetrahydronaphthalene-2-carboxamide 1-231 (0.184 g, 0.394 mmol, 34%) as a white solid. 1H NMR (400 MHz, d6-DMSO, HCl salt) δ: 10.02 (s, 1H), 8.63-8.51 (m, 1H), 8.05-7.96 (m, 1H), 7.85-7.77 (m, 1H), 7.68-7.62 (m, 1H), 7.54-7.46 (m, 1H), 7.37-7.03 (m, 7H), 3.06-2.73 (m, 5H), 2.18-2.05 (m, 1H), 1.88-1.74 (m, 1H), and 1.25 (s, 9H). LCMS: (FA) ES+467.8, ES−465.5.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionThe residue was dissolved in ethanol (20 mL)
  3. stirringto stir at 90° C. for 1 h
  4. extractionThe solution was extracted with EtOAc
  5. washthe combined organic solutions were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-6d40234819cd4c04a086f6fb279c1797
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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