Phosphorus oxychloride → HCID 21939704, compound

HRID 1242869Notes

Reaction equation

HRID 1242869 reaction equation
[CH2:1]([O:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[NH:15][C:16]([CH2:18][N:19]1[C:23]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[C:32]2[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=2)=[CH:22][C:21]([C:42]([NH2:44])=O)=[N:20]1)=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1.C(OCC)(=O)C>[CH2:1]([O:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[NH:15][C:16](=[O:17])[CH2:18][N:19]1[C:23]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[C:32]2[CH:33]=[CH:34][C:35]([C:38]([F:40])([F:41])[F:39])=[CH:36][CH:37]=2)=[CH:22][C:21]([C:42]#[N:44])=[N:20]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 21062917HCID 21062917, compound

Product 1

HCID 21939704HCID 21939704, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

To an ice cold solution of 310 mg (0.33 mmol max) of 1-[(2-benzyloxy-cyclohexylcarbamoyl)-methyl]-5-(4′-trifluoromethyl-biphenyl-2-ylmethoxy)-1H-pyrazole-3-carboxylic acid amide in 3 mL of pyridine was added 0.071 mL (0.76 mmol) of phosphorus oxychloride, and the resulting mixture was stirred at 0° C. for 2.5 h. The mixture was then diluted with ethyl acetate, washed with 1 N HCl solution, dried over sodium sulfate and concentrated. Since analysis by LC-MS indicated that some starting material was still present, the reaction was repeated under the same experimental conditions, and after complete consumption of starting material, it was worked up and purified via chromatography on silica gel (Biotage) with 3:1 hexane:ethyl acetate to give 71 mg (37% yield) of N-(2-benzyloxy-cyclohexyl)-2-[3-cyano-5-(4′-trifluoromethyl-biphenyl-2-ylmethoxy)-pyrazol-1-yl]-acetamide. LC-MS—calcd for C33H31F3N4O3 [M+H]+ 589.23, found 589.2.

Workup

  1. washwashed with 1 N HCl solution
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customafter complete consumption of starting material, it
  5. custompurified via chromatography on silica gel (Biotage) with 3:1 hexane

Sources & evidence

ORD record
ord-567525b0967e4ce88fd6e151531117bd
Source dataset
uspto-grants-2006_10
Patent number
US07115749B2

Reaction notes

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