Hydrochloric Acid → HCID 71275064, compound

HRID 510413Notes

Reaction equation

HRID 510413 reaction equation
Cl[C:2]1[CH:7]=[C:6](Cl)[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-:24].[Na+].[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.Cl>O1CCCC1.C(O)C>[CH3:23][C:10]1[C:11]([CH2:12][C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:16]=[CH:15][CH:14]=2)=[C:4]2[N:3]=[C:2]([N:3]3[CH2:4][CH2:11][O:24][CH2:7][CH2:2]3)[CH:7]=[C:6]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[N:5]2[N:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 14798Sodium HydroxideHCID 86724881HCID 86724881, compound

Product 1

HCID 71275064HCID 71275064, compoundYield 23.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To the solution of 5,7-dichloro-2-methyl-3-(1-naphthalenylmethyl)pyrazolo[1,5-a]pyrimidine (0.2 g, 0.584 mmol) in Tetrahydrofuran (THF) (5 mL) was added sodium hydroxide (2.045 mL, 4.09 mmol). The reaction was stirred at rt for 18 h. The reaction was acidified. The reaction was extracted with EtOAc (80 mL×2). The organic phases were combined, washed with Brine, dried and concentrated. The mixture was transferred to 5 mL MW vial. Morpholine (0.509 mL, 5.84 mmol) and Ethanol (1 mL) was added in. The reaction mixture was subjected to MW irradiation at 150° C. for 3 h. 6 N HCl was added to the reaction to acidify the solution. The reaction mixture was extracted with EtOAc (50 mL×2). The organic phases were combined, washed with Brine, dried and concentrated. The residue was purified by reversed phase HPLC (25˜55% CH3CN (0.1% TFA)/Water (0.1% TFA)) to give the product (30 mg, 11%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.17 (s, 3H) 3.52-3.64 (m, 8H) 3.66-3.73 (t, J=4.63 Hz, 4H) 3.74-3.82 (t, J=4.44 Hz, 4H) 4.30 (s, 2H) 5.78 (s, 1H) 7.31 (d, J=6.57 Hz, 1H) 7.37-7.43 (m, 1H) 7.43-7.53 (m, 2H) 7.75 (d, J=8.08 Hz, 1H) 7.84-7.94 (m, 1H) 8.46-8.56 (m, 1H); LC/MS: MS (ES+) m/e 444.2 [M+H]+.

Workup

  1. extractionThe reaction was extracted with EtOAc (80 mL×2)
  2. washwashed with Brine
  3. customdried
  4. concentrationconcentrated
  5. customThe reaction mixture was subjected to MW irradiation at 150° C. for 3 h
  6. extractionThe reaction mixture was extracted with EtOAc (50 mL×2)
  7. washwashed with Brine
  8. customdried
  9. concentrationconcentrated
  10. customThe residue was purified by reversed phase HPLC (25˜55% CH3CN (0.1% TFA)/Water (0.1% TFA))

Sources & evidence

ORD record
ord-21fcf330cd734b30ac56ca60d9e97c52
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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