2-Morpholinoethylamine → HCID 59632577, compound

HRID 2369098Notes

Reaction equation

HRID 2369098 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21]([OH:24])([CH3:23])[CH3:22])[CH:9]=2)=[C:4]([CH3:25])[CH:3]=1.[O:26]1[CH2:31][CH2:30][N:29]([CH2:32][CH2:33][NH2:34])[CH2:28][CH2:27]1.CC(C)([O-])C.[Na+].C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C>C([O-])(O)=O.[Na+].CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:20][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]([Cl:19])[C:13]=1[N:12]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:34][CH2:33][CH2:32][N:29]3[CH2:30][CH2:31][O:26][CH2:27][CH2:28]3)=[CH:3][C:4]=2[CH3:25])=[CH:9][C:10]([C:21]([OH:24])([CH3:23])[CH3:22])=[N:11]1

Participants

8

Reactant 4

HCID 4082852-MorpholinoethylamineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 59632125HCID 59632125, compound

Product 1

HCID 59632577HCID 59632577, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 2-(5-(4-bromo-2-methylphenyl)-1-(2,6-dichlorophenyl)-1H-pyrazol-3-yl)propan-2-ol ((160 mg, 0.36 mmol), 2-morpholinoethanamine (75 mL, 0.57 mmol), sodium tert-butoxide (54 mg, 0.57 mmol), biphenyl-2-yldi-tert-butylphosphine (13.1 mg, 44 μmol), and Pd2(dba)3 (19.8 mg, 22 μmol) was placed in a microwave reaction vial and heated at 160° C. for 15 minutes. After cooling, the reaction was diluted with saturated aqueous NaHCO3, and EtOAc. The layers were separated and the aqueous was extracted with EtOAc (3×). Combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure to afford a dark oil. This material was purified by reverse phase preparative HPLC eluting with a gradient of MeCN/H2O with 0.05% TFA. The product peak from the HPLC was basified by addition of saturated aqueous NaHCO3, and concentrated under reduced pressure to remove most of the solvents. The basic aqueous was extracted with CH2Cl2 (3×). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure to afford 2-(1-(2,6-dichlorophenyl)-5-(2-methyl-4-(2-morpholinoethylamino)phenyl)-1H-pyrazol-3-yl)propan-2-ol (67 mg, 38% yield) as a white foam. 1H NMR (400 MHz CDCl3): δ 7.34-7.29 (2H, m), 7.20 (1H, m), 6.84 (1H, d), 6.46 (1H, d), 6.32 (1H, s), 6.23 (1H, m), 4.32 (1H, s), 3.74-3.66 (4H, m), 3.15-3.07 (2H, m), 2.66 (1H, s), 2.63-2.55 (2H, t), 2.48-2.40 (4H, m), 2.33 (3H, s), 1.67 (6H, s). MS(ES): 489 [M+H]+.

Workup

  1. customwas placed in a microwave reaction vial
  2. temperatureAfter cooling
  3. customThe layers were separated
  4. extractionthe aqueous was extracted with EtOAc (3×)
  5. washCombined organic extracts were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto afford a dark oil
  10. customThis material was purified by reverse phase preparative HPLC
  11. washeluting with a gradient of MeCN/H2O with 0.05% TFA
  12. additionThe product peak from the HPLC was basified by addition of saturated aqueous NaHCO3
  13. concentrationconcentrated under reduced pressure
  14. customto remove most of the solvents
  15. extractionThe basic aqueous was extracted with CH2Cl2 (3×)
  16. dry with materialThe combined organic extracts were dried over Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9c65080d6f8c43779023672c5d001df3
Source dataset
uspto-grants-2014_04
Patent number
US08703805B2

Reaction notes

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