HCID 87332960, compound → HCID 58851478, compound

HRID 1696491Notes

Reaction equation

HRID 1696491 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=2[Cl:21])=[O:12])[N:7]([C:22]2[CH:31]=[C:30]([CH:32]=[O:33])[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:23]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:34][Mg]Cl>C1COCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=2[Cl:21])=[O:12])[N:7]([C:22]2[CH:31]=[C:30]([CH:32]([OH:33])[CH3:34])[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:23]=2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 87332960HCID 87332960, compoundHCID 178418332HCID 178418332, compound3×

Product 1

HCID 58851478HCID 58851478, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To this aldehyde (150 mg, 0.312 mmol) in THF (5 mL) at 0° C. was added dropwise MeMgCl (0.37 mL, 82 mg, 1.09 mmol). The mixture was stirred at 0° C. for 1 h and then warmed to RT and stirred for 7 h. The mixture was treated with an additional batch of MeMgCl (0.2 mL, 0.6 mmol), stirred overnight at RT, treated with additional MeMgCl (0.3 mL, 0.9 mmol) and then quenched with H2O (25 mL) and diluted with EtOAc (25 mL) and 5% citric acid (10 mL). The organic phase was separated, washed with brine dried (Na2SO4), filtered, concentrated and purified to yield 1-(3-t-butyl-1-(4-(1-hydroxyethyl)naphthalen-2-yl)-1H-pyrazol-5-yl)-3-(2,3-dichlorophenyl)urea (65 mg, 42% yield). 1H-NMR (300 MHz, DMSO-d6): δ 1.31 (s, 9H), 1.49 (d, J=6.2 Hz, 3H), 5.47-5.48 (m, 1H), 5.53-5.54 (m, 1H), 6.45 (s, 1H), 7.28-7.31 (m, 2H), 7.57-7.60 (m, 2H), 7.83 (s, 1H), 7.94 (s, 1H), 8.02-8.18 (m, 3H), 8.78 (s, 1H), 9.31 (s, 1H); MS (ESI) m/z: 499.0 (M+H+).

Workup

  1. temperaturewarmed to RT
  2. stirringstirred for 7 h
  3. stirringstirred overnight at RT
  4. customquenched with H2O (25 mL)
  5. additiondiluted with EtOAc (25 mL) and 5% citric acid (10 mL)
  6. customThe organic phase was separated
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. custompurified

Sources & evidence

ORD record
ord-3e40f5474e334960b62bfac7018891a1
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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