Hydrochloric Acid → HCID 22262569, compound

HRID 1060974Notes

Reaction equation

HRID 1060974 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[NH:11][N:10]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=3)[C:8]=2[C:19]2[CH:24]=[CH:23][N:22]=[CH:21][N:20]=2)[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.ON1C2C=CC=CC=2N=N1.[C:44](O)(=[O:47])[CH2:45][OH:46].Cl.CN(C)CCCN=C=NCC.Cl>CO.[OH-].[Na+].C(#N)C.C(Cl)Cl>[OH:47][CH2:44][C:45]([N:11]1[C:7]([CH:4]2[CH2:5][CH2:6][NH:1][CH2:2][CH2:3]2)=[C:8]([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][N:20]=2)[C:9]([C:12]2[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=2)=[N:10]1)=[O:46]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 757Glycolic Acid2×HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9840864HCID 9840864, compound

Product 1

HCID 22262569HCID 22262569, compoundYield 77.4%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

A 1 L round bottom flask was charged with 34.2 g (102 mmol) of 5-(4-piperidyl)-4-(4-pyrimidyl)-3-(4-chlorophenyl)pyrazole, 500 mL of CH2Cl2 and 26.6 mL (153 mmol) of Hunig's base. To this suspension was added 16.5 g (122 mmol) of 1-hydroxybenzotriazole and 8.1 g (106 mmol) of glycolic acid. The additiin of glycolic acid was followed by the addition of 23.7 g (122 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The reaction was allowed to stir at ambient temperature overnight. The reaction was concentrated in vacuo to leave an oily residue. The residue was dissolved in 400 mL of methanol and 50 mL of 2.5 N NaOH. The reaction mixture was stirred at ambient temperature for 1 hour. The mixture was acidified to pH 5 with 2 N HCl and was extracted with CH2Cl2 (6×200 mL) The combined organic phases were filtered through phase paper and the filtrate was concentrated in vacuo to leave a yellow residue. The residue was treated with 75 mL of acetonitrile. A precipitate formed. The solid was filtered and washed with additional acetonitrile and Et2O to afford 31.4 g of N-(2-hydroxyacetyl)-5-(4-piperidyl)-4-(4-pyrimidyl)-3-(4-chlorophenyl)pyrazole. 1H NMR (DMSO-d6) 9.20 (s, 1H), 8.67 (d, J=4.8, 1H), 7.40 (m, 4H), 7.17 (d, J=4.0, 1H), 4.53 (m, 2H), 4.13 (s, 2H), 3.77 (m, 1H), 3.05 (t, J=12.7 Hz, 1H), 2.69 (m, 1H), 1.90 (m, 2H), 1.73 (m, 2H); MS (M+H): 398 (base peak).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customto leave an oily residue
  3. stirringThe reaction mixture was stirred at ambient temperature for 1 hour
  4. extractionwas extracted with CH2Cl2 (6×200 mL) The combined organic phases
  5. filtrationwere filtered through phase paper
  6. concentrationthe filtrate was concentrated in vacuo
  7. customto leave a yellow residue
  8. customA precipitate formed
  9. filtrationThe solid was filtered
  10. washwashed with additional acetonitrile and Et2O

Sources & evidence

ORD record
ord-29321f0362ba4576a15026f45c926a8b
Source dataset
uspto-grants-2003_02
Patent number
US06525059B1

Reaction notes

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