Sodium Hydroxide → HCID 178441170, compound

HRID 1696549Notes

Reaction equation

HRID 1696549 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH2:10][NH:11][C:12]3=[O:17])=[CH:4][CH:3]=1.[OH-].[Na+].[C:20](Cl)(OCC(Cl)(Cl)Cl)=[O:21].[NH2:29][C:30]1[NH:34][N:33]=[C:32]([C:35]([CH3:38])([CH3:37])[CH3:36])[CH:31]=1.CCN(C(C)C)C(C)C>CCOC(C)=O.O>[C:35]([C:32]1[CH:31]=[C:30]([NH:29][C:20]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[CH:16]=[CH:15][CH:14]=[C:13]4[C:9]=3[CH2:10][NH:11][C:12]4=[O:17])=[CH:6][CH:7]=2)=[O:21])[NH:34][N:33]=1)([CH3:38])([CH3:37])[CH3:36]

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 870632,2,2-Trichloroethyl chloroformateHCID 219075114-(4-Aminophenyl)isoindolin-1-oneHCID 178441179HCID 178441179, compound

Product 1

HCID 178441170HCID 178441170, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(4-aminophenyl)isoindolin-1-one (0.327 g, 1.46 mmol, made according to literature procedures) in EtOAc (5 mL) was added NaOH (2N, 2 mL, 4 mmol) and Troc-Cl (0.618 g, 2.92 mmol) and the resulting mixture was stirred at RT for 6 h. Water (20 mL) was added and the mixture was extracted with EtOAc (3×20 mL), dried (MgSO4) and concentrated. The residue was dissolved in DMF (2 mL) to which was added 5-amino-3-t-butylpyrazole (0.831 g, 5.97 mmol, made according to literature procedures) and i-Pr2NEt (0.406 g, 2.92 mmol) and the solution was stirred at 90° C. overnight. Water (100 mL) was added and the mixture was extracted with EtOAc (3×100 mL), dried (MgSO4) and concentrated. Addition of CH2Cl2 to the residue resulted in precipitation of the product. The product was collected and dried to yield 1-(3-t-butyl-1H-pyrazol-5-yl)-3-(4-(1-oxoisoindolin-4-yl)phenyl)urea (270 mg, 48% yield) as a light brown powder. 1H-NMR (DMSO-d6): δ 9.31 (s, br, 1H), 8.95 (s, br, 1H), 8.65 (s, br, 1H), 7.65-7.63 (m, 2H), 7.58-7.52 (m, 5H), 6.00 (s, br, 1H), 4.51 (s, 2H), 1.25 (s, 9H), one NH is not visible. MS expected 390.2 found 390.2.

Workup

  1. extractionthe mixture was extracted with EtOAc (3×20 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in DMF (2 mL) to which
  5. stirringthe solution was stirred at 90° C. overnight
  6. extractionthe mixture was extracted with EtOAc (3×100 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. additionAddition of CH2Cl2 to the residue
  10. customresulted in precipitation of the product
  11. customThe product was collected
  12. customdried

Sources & evidence

ORD record
ord-4700a11210f84dc1badcc809b7389de7
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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