Nitrogen → HCID 86636025, compound

HRID 449020Notes

Reaction equation

HRID 449020 reaction equation
N#N.[Cl:3][C:4]1[C:5]([CH:10]([NH:24][C:25]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)=O)[C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)=[N:6][CH:7]=[CH:8][N:9]=1.CN(C=O)C.O=P(Cl)(Cl)Cl>O.CC#N>[Cl:3][C:4]1[C:5]2[N:6]([C:25]([CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)=[N:24][C:10]=2[C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[CH:7]=[CH:8][N:9]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 86636026HCID 86636026, compound

Product 1

HCID 86636025HCID 86636025, compoundYield 101.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

In an oven-dried flask filled with N2 was added cyclohexanecarboxylic acid [(3-chloro-pyrazin-2-yl)-(4-phenoxyphenyl)-methyl]-amide (100 mg, 0.0002 mol), MeCN (6 mL) and DMF (1 mL, 0.01 mol). POCl3 was added dropwise at 0° C. The reaction mixture was allowed to warm up to rt and stirred at that temp overnight. The excess of POCl3 was removed under reduced pressure and the residue was quenched with 2 N NH3 in i-PrOH at 0° C. with vigorous stirring to adjust pH to 9. The crude reaction mixture was then charged with water and the aqueous layer was washed with DCM. The combined organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to obtain 82 mg of the title compound as a yellow oil. The compound was carried over to the next step. MS (ES+): m/z 404.09 (100)[MH+]. HPLC: tR=4.49 min (Open Lynx polar—5 min).

Workup

  1. customThe excess of POCl3 was removed under reduced pressure
  2. customthe residue was quenched with 2 N NH3 in i-PrOH at 0° C.
  3. stirringwith vigorous stirring
  4. customThe crude reaction mixture
  5. washthe aqueous layer was washed with DCM
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-38da5241999f48f6b9a76d6652fb429b
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

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