Morpholine → HCID 178433776, compound

HRID 510397Notes

Reaction equation

HRID 510397 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>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:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[CH:7]=[C:6]([OH:24])[N:5]2[N:9]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 14798Sodium HydroxideHCID 86724881HCID 86724881, compound

Product 1

HCID 178433776HCID 178433776, compoundYield 30.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 5,7-dichloro-2-methyl-3-(1-naphthalenylmethyl)pyrazolo[1,5-a]pyrimidine (0.06 g, 0.175 mmol), prepared using a similar route as was used in Example 1 step c, in Tetrahydrofuran (THF) (5 mL), was added sodium hydroxide (0.877 mL, 1.753 mmol). The reaction was stirred at rt for 18 and 50° C. for 7 h. The reaction mixture was acidified and extracted with EtOAc (80 mL×2). The organic phases were combined, dried and concentrated. To the crude mixture in ethanol (1 mL) was added morpholine (0.076 mL, 0.877 mmol). The reaction mixture was subjected to MW irradiation at 150° C. for 3 h. The reaction mixture was concentrated. The residue was purified by reverse-phase HPLC (25˜55% CH3CN (0.1% TFA)/Water (0.1% TFA)) to give the product (0.02 g, 9%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.05 (br. s., 3H) 3.30 (m, 4H) 3.67 (m, 4H) 4.37 (br. s., 2H) 5.03 (br. s., 1H) 7.01 (br. s., 1H) 7.40 (t, J=7.71 Hz, 1H) 7.56 (m, 2H) 7.79 (d, J=8.34 Hz, 1H) 7.95 (d, J=7.33 Hz, 1H) 8.27 (m, 1H); LC/MS: MS (ES+) m/e 375.1 [M+H]+.

Workup

  1. extractionextracted with EtOAc (80 mL×2)
  2. customdried
  3. concentrationconcentrated
  4. customThe reaction mixture was subjected to MW irradiation at 150° C. for 3 h
  5. concentrationThe reaction mixture was concentrated
  6. customThe residue was purified by reverse-phase HPLC (25˜55% CH3CN (0.1% TFA)/Water (0.1% TFA))

Sources & evidence

ORD record
ord-ecdd92495cf24addaeb1437f6b41100d
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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