Hydrochloric Acid → HCID 71532471, compound

HRID 510440Notes

Reaction equation

HRID 510440 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]2[N:9]=[C:10]([CH3:23])[C:11]([CH2:12][C:13]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH:16]=[CH:15][CH:14]=3)=[C:4]2[N:3]=1.[OH-].[Na+].[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.Cl.O=P(Cl)(Cl)Cl.C(N(CC)C1C=CC=CC=1)C>O1CCCC1.O.C(O)C>[Cl:8][C:6]1[N:5]2[N:9]=[C:10]([CH3:23])[C:11]([CH2:12][C:13]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH:16]=[CH:15][CH:14]=3)=[C:4]2[N:3]=[C:2]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[CH:7]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 7061N,N-DiethylanilineHCID 8083MorpholineHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 86724881HCID 86724881, compound

Product 1

HCID 71532471HCID 71532471, compoundYield 59.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To the solution of 5,7-dichloro-2-methyl-3-(1-naphthalenylmethyl)pyrazolo[1,5-a]pyrimidine (1.5 g, 4.38 mmol) in Tetrahydrofuran (THF) (40 mL) was added sodium hydroxide (21.92 mL, 43.8 mmol). The reaction was stirred at rt for 18 h and heated at 50° C. for 7 h. The reaction was concentrated and acidified. The reaction mixture was extracted with EtOAc (80 mL×2). The organic phases were combined, dried and concentrated. The mixture was transferred to a 20 mL MW vial. Morpholine (1.909 mL, 21.92 mmol) and Ethanol (2 mL) was added in. The mixture was subjected to MW irradiation at 150° C. for 3 h. Water (10 mL) was added to the reaction mixture which was acidified with 6 N HCl. The reaction was extracted with EtOAc (100 mL×3). The organic phases were combined, dried and concentrated. To the resulted solid was added POCl3 (6.13 mL, 65.7 mmol) and N,N-diethylaniline (1.308 g, 8.77 mmol). The reaction was heated at 90° C. for 5 h. The reaction was cooled down. Crushed ice was added in. The aqueous mixture was extracted with EtOAc (100 mL×3). The organic phases were combined, dried and concentrated. The crude was purified on silica column (EtOAc/Hexane: 20˜40%) to give the product (1.02 g, 59%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.20 (s, 3H) 3.54-3.74 (m, 8H) 4.33 (s, 2H) 7.00 (s, 1H) 7.32 (d, J=6.57 Hz, 1H) 7.37-7.44 (m, 1H) 7.45-7.55 (m, 2H) 7.76 (d, J=8.08 Hz, 1H) 7.90 (m, 1H) 8.44 (m, 1H); LC/MS: MS (ES+) m/e 393.1 [M+H]+.

Workup

  1. temperatureheated at 50° C. for 7 h
  2. concentrationThe reaction was concentrated
  3. extractionThe reaction mixture was extracted with EtOAc (80 mL×2)
  4. customdried
  5. concentrationconcentrated
  6. customThe mixture was subjected to MW irradiation at 150° C. for 3 h
  7. extractionThe reaction was extracted with EtOAc (100 mL×3)
  8. customdried
  9. concentrationconcentrated
  10. temperatureThe reaction was heated at 90° C. for 5 h
  11. temperatureThe reaction was cooled down
  12. additionCrushed ice was added in
  13. extractionThe aqueous mixture was extracted with EtOAc (100 mL×3)
  14. customdried
  15. concentrationconcentrated
  16. customThe crude was purified on silica column (EtOAc/Hexane: 20˜40%)

Sources & evidence

ORD record
ord-ee4c322cf7364f8e80279127bc41b356
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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