Hydrazine hydrate (1:1) → HCID 10223351, compound

HRID 2221287Notes

Reaction equation

HRID 2221287 reaction equation
O.NN.[C:4]([C:8]1[CH:35]=[CH:34][C:11]([CH2:12][N:13]2[C:21]3[C:16](=[CH:17][C:18]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=4)=[CH:19][CH:20]=3)[C:15]([C:29](=O)[C:30]([OH:32])=[O:31])=[CH:14]2)=[CH:10][CH:9]=1)([CH3:7])([CH3:6])[CH3:5].C[O-].[Na+]>COCCO>[C:4]([C:8]1[CH:35]=[CH:34][C:11]([CH2:12][N:13]2[C:21]3[C:16](=[CH:17][C:18]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=4)=[CH:19][CH:20]=3)[C:15]([CH2:29][C:30]([OH:32])=[O:31])=[CH:14]2)=[CH:10][CH:9]=1)([CH3:7])([CH3:5])[CH3:6]

Participants

5

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 10224267AleplasininHCID 10942334Sodium Methoxide

Product 1

HCID 10223351HCID 10223351, compoundYield 46.7%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
60 °C

Procedure

Hydrazine monohydrate (0.56 mL, 11.75 mmol) was added to a stirring solution of 2-[1-[4-(tert-Butyl)benzyl]-5-(3-methylphenyl)-1H-indol-3-yl]-2-oxoacetic acid (WAY-201417, 1.0 g, 2.35 mmol) in 2-methoxyethanol (10 mL). After the mixture was heated to 60° C. Sodium methoxide (1.34 g, 23.5 mmol) was added portionwise to the mixture. The reaction mixture was then slowly heated to 150° C., and concentrated. The mixture was kept stirring at 150° C. for 1 hour. The reaction mixture was cooled and poured onto ice water (100 mL). The aquoues mixture was extracted with methylene chloride and acidified with concentrated hydrocloric acid at 0° C. The organic extracts were washed with water and brine. Evaporation of the solvent and purification by flash column chromatography (5% methanol in methylene chloride) afforded an orange solid (0.452 g), m.p. 91-92° C. Mass spectrum [+ESI, (M+H)+] m/z 412. 1H NMR (400 MHz, DMSO-d6) δ 12.00 (br s, 1H), 7.75 (s, 1H), 7.51 (d, 1H, J=8.55 Hz), 7.45 (s, 1H), 7.42-7.37 (m, 3H), 7.32-7.29 (m, 3H), 7.15 (d, 2H, J=8.25 Hz), 7.19 (d, 1H, J=7.48 Hz), 5.34 (s, 2H), 3.70 (s, 2H), 2.37 (s, 3H), and 1.22 ppm (s, 9H). Elemental Analysis for C28H27NO3 0.1 H2O Calculated: C, 81.36; H, 7.12; N, 3.39. Found: C, 81.15; H, 6.76; N, 3.52.

Workup

  1. temperatureThe reaction mixture was then slowly heated to 150° C.
  2. concentrationconcentrated
  3. temperatureThe reaction mixture was cooled
  4. additionpoured onto ice water (100 mL)
  5. extractionThe aquoues mixture was extracted with methylene chloride
  6. customacidified with concentrated hydrocloric acid at 0° C
  7. washThe organic extracts were washed with water and brine
  8. customEvaporation of the solvent and purification by flash column chromatography (5% methanol in methylene chloride)

Sources & evidence

ORD record
ord-d0724a6fea8c4d8ca6bbb0742f4fd264
Source dataset
uspto-grants-2008_05
Patent number
US07368471B2

Reaction notes

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