Morpholine → N-(3-(4-fluorophenyl)-1-(2-morpholinoethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide

HRID 1525443Notes

Reaction equation

HRID 1525443 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:11]([NH:21][C:22](=[O:24])[CH3:23])[N:10]([CH2:25][CH2:26]O)[N:9]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[NH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:11]([NH:21][C:22](=[O:24])[CH3:23])[N:10]([CH2:25][CH2:26][N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)[N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 70983184N-(3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide

Product 1

HCID 70983554N-(3-(4-fluorophenyl)-1-(2-morpholinoethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamideYield 44.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of N-(3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide (269 mg, 0.74 mmol) in CH2Cl2 (9 mL) and triethylamine (155 μl, 1.11 mmol) was added methanesulphonyl chloride (65 μl, 0.81 mmol and the reaction stirred at room temperature for 16 h. The reaction mixture was poured onto ice/water and the organic layer was dried over MgSO4, filtered and evaporated. The crude product was dissolved in THF (10 ml) and morpholine (320 μl, 3.7 mmol) was added. The reaction was heated to 55° C. for 24 h before evaporating the solvent in vacuo. The crude was partitioned between CH2Cl2 and dilute aqueous NaHCO3 and the organic layer was dried over MgSO4, filtered and evaporated. Purification using chromatography (silica gel, gradient 0 to 10% methanol/CH2Cl2) gave N-(3-(4-fluorophenyl)-1-(2-morpholinoethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide as a white solid (141 mg) which was used as such in the subsequent step.

Workup

  1. additionThe reaction mixture was poured onto ice/water
  2. dry with materialthe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. dissolutionThe crude product was dissolved in THF (10 ml)
  6. temperatureThe reaction was heated to 55° C. for 24 h
  7. custombefore evaporating the solvent in vacuo
  8. customThe crude was partitioned between CH2Cl2 and dilute aqueous NaHCO3
  9. dry with materialthe organic layer was dried over MgSO4
  10. filtrationfiltered
  11. customevaporated
  12. customPurification

Sources & evidence

ORD record
ord-815f5c1207d74cb39e4a1eefba078071
Source dataset
uspto-grants-2015_07
Patent number
US09079909B2

Reaction notes

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