Hydrochloric Acid → HCID 67482695, compound

HRID 1817759Notes

Reaction equation

HRID 1817759 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH2:13][C:12](=[O:14])[N:11]([CH:15]([C:17]3[CH:27]=[CH:26][C:20]([C:21](OCC)=[O:22])=[CH:19][CH:18]=3)[CH3:16])[N:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[OH-].[Na+].Cl.[Na+].[Cl-].CCN(C(C)C)C(C)C.Cl.[C:43]([O:47][C:48](=[O:52])[CH2:49][CH2:50][NH2:51])([CH3:46])([CH3:45])[CH3:44].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CO.O1CCOCC1.CN(C=O)C.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH2:13][C:12](=[O:14])[N:11]([CH:15]([C:17]3[CH:18]=[CH:19][C:20]([C:21]([NH:51][CH2:50][CH2:49][C:48]([O:47][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:52])=[O:22])=[CH:26][CH:27]=3)[CH3:16])[N:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

12

Reactant 7

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2724699PyBOP2×HCID 16218890Tert-butyl 3-aminopropanoate hydrochlorideHCID 67482987HCID 67482987, compound

Product 1

HCID 67482695HCID 67482695, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolventHCID 21966525Dioxane MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Ethyl 4-{1-[3-(3,5-dichlorophenyl)-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]ethyl}benzoate (2.23 g, 5.50 mmol) was dissolved in MeOH-dioxane (1:1, 50 ml). A solution of NaOH (0.7 g/15 ml ) was added. The mixture was heated to 60° C. for 1 hr. This was acidified with 2N HCl (10 ml), and the solvent was removed and residue vacuum dried to give a pale yellow solid (mixture of product acid and NaCl). This solid was suspended in DMF (15 ml), followed with DIEA (4.8 ml), beta-alanine t-butyl ester hydrochloride (3 g ). A solution of PyBOP (3.43 g) in DMF (5 ml) was then added. After stirring at room temperature for 3 hr, more PyBOP (1 g) was added and the reaction mixture was stirred overnight. After addition of water (5 ml), the mixture was heated to 60° C. for 30 min. Ethyl acetate (150 ml) was added, and the organic layer was washed with 0.5 N HCl 2×, 5% K2CO3 2×, brine 2×. Evaporation of solvent gave an oily residue, which after flash column chromatography (SiO2, 0-30% ethyl acetate in DCM) afforded tert-butyl N-(4-{1-[3-(3,5-dichlorophenyl)-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]ethyl}benzoyl)-β-alaninate as a white solid. NMR (500 MHz, DMSO-d6) δ: 1.37 (s, 9H); 1.78 (d, J=7.1 Hz, 3H); 2.45 (t, J=7.0 Hz, 2H); 3.42 (q, J=7.0 Hz, 2H); 5.99 (s, 1H); 7.30 (d, J=8.3 Hz, 2H); 7.47 (t, J=1.0 Hz, 1H). 7.73 (d, J=8.3 Hz, 2H); 7.76 (d, J=1.9 Hz, 2H); 8.43 (t, J=5.6 Hz, 1H); 11.34 (s, 1H). MS C25H27Cl2N3O4 Cald: 503.14; Obsd (M+Na): 526.05.

Workup

  1. customthe solvent was removed
  2. customresidue vacuum dried
  3. customto give
  4. stirringthe reaction mixture was stirred overnight
  5. temperaturethe mixture was heated to 60° C. for 30 min
  6. washthe organic layer was washed with 0.5 N HCl 2×, 5% K2CO3 2×, brine 2×
  7. customEvaporation of solvent
  8. customgave an oily residue, which after flash column chromatography (SiO2, 0-30% ethyl acetate in DCM)

Sources & evidence

ORD record
ord-8354903211d4414ca428d2ae99100a40
Source dataset
uspto-grants-2009_10
Patent number
US07598285B2

Reaction notes

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