Diisopropylethylamine → HCID 59463243, compound

HRID 1712959Notes

Reaction equation

HRID 1712959 reaction equation
Cl.[CH2:2]([O:9][C:10]1[CH:16]=[CH:15][C:13](N)=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CC[N:19]([CH:23](C)C)C(C)C.ClC(Cl)([O:29]C(=O)OC(Cl)(Cl)Cl)Cl.[N:38]1[CH:43]=[CH:42][CH:41]=[C:40]([C:44]2[CH2:48][CH:47]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=3[OH:55])[NH:46][N:45]=2)[CH:39]=1>ClCCCl.CN(C=O)C>[CH2:2]([O:9][C:10]1[CH:16]=[CH:15][CH:13]=[CH:12][C:11]=1[NH:19][C:23]([N:46]1[CH:47]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[OH:55])[CH2:48][C:44]([C:40]2[CH:39]=[N:38][CH:43]=[CH:42][CH:41]=2)=[N:45]1)=[O:29])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 27238314-Benzyloxyaniline hydrochlorideHCID 226963962-(3-pyridin-3-yl-4,5-dihydro-1H-pyrazol-5-yl)phenol

Product 1

HCID 59463243HCID 59463243, compoundYield 84.9%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent3×HCID 6228DimethylformamideSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-benzyloxyaniline hydrochloride (34.5 mg, 0.146 mmol) in DCE (1 mL) was added a solution of DIPEA (0.0525 mL, 0.302 mmol) in DCE (0.5 mL) at rt. Upon cooling to −78° C., triphosgene (14.4 mg, 0.0487 mmol) in DCE (1.0 mL) was added and the reaction mixture was allowed to warm to rt and stir for 1 h. The reaction mixture was then heated at 60° C. for and 2 h. The solution was allowed to cool to rt and then cooled to −78° C. whereupon a solution of 2-(3-pyridin-3-yl-4,5-dihydro-1H-pyrazol-5-yl)phenol (35.0 mg, 0.146 mmol) in DMF (0.5 mL) was added. The reaction mixture was shaken at rt for 15 hours. The reaction was quenched with the addition of water (2 mL) and extracted with DCM. The organic solutions were combined, dried over anhydrous MgSO4, filtered, and concentrated. The residue was purified by RP-HPLC to give N-[2-(benzyloxy)phenyl]-5-(2-hydroxyphenyl)-3-pyridin-3-yl-4,5-dihydro-1H-pyrazole-1-carboxamide (19.20 mg, 28.2%). LCMS: (FA) ES+ 465.6, ES-463.2.

Workup

  1. temperatureto warm to rt
  2. temperatureThe reaction mixture was then heated at 60° C. for and 2 h
  3. temperatureto cool to rt
  4. additionwas added
  5. stirringThe reaction mixture was shaken at rt for 15 hours
  6. customThe reaction was quenched with the addition of water (2 mL)
  7. extractionextracted with DCM
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by RP-HPLC

Sources & evidence

ORD record
ord-e5794293dc7746d8a782718d9b96ef2c
Source dataset
uspto-grants-2010_09
Patent number
US07795249B2

Reaction notes

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