1,1'-Carbonyldiimidazole → HCID 86657653, compound

HRID 217473Notes

Reaction equation

HRID 217473 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:4]=1[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([CH2:17][N:18]3[CH2:22][CH2:21][CH:20]([C:23](O)=[O:24])[CH2:19]3)[CH2:13][O:14]2)=[C:9]([F:26])[CH:8]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:49][S:50]([NH2:53])(=[O:52])=[O:51].C1CCN2C(=NCCC2)CC1.[ClH:65].O1CCOCC1>CN(C=O)C.O1CCOCC1.CC(O)=O>[ClH:65].[F:36][C:2]([F:1])([F:35])[C:3]1[CH:30]=[C:29]([C:31]([F:33])([F:34])[F:32])[CH:28]=[CH:27][C:4]=1[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([CH2:17][N:18]3[CH2:22][CH2:21][CH:20]([C:23]([NH:53][S:50]([CH3:49])(=[O:52])=[O:51])=[O:24])[CH2:19]3)[CH2:13][O:14]2)=[C:9]([F:26])[CH:8]=1

Participants

9

Reactant 5

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 204431481,4-Dioxane hydrochlorideHCID 86657655HCID 86657655, compound

Product 1

HCID 86657653HCID 86657653, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 1-[(7-{[2,4-bis(trifluoromethyl)benzyl]oxy}-5-fluoro-2H-chromen-3-yl)methyl]pyrrolidine-3-carboxylic acid (98 mg) in DMF (2 mL) was added CDI (46 mg), followed by stirring at 70° C. for 12 hours. To the reaction liquid were added methanesulfonamide (27 mg) and DBU (43 mg) in this order, followed by stirring for 12 hours. To the reaction liquid was added AcOH, followed by concentration under reduced pressure, and the residue was purified by reverse phase column chromatography (H2O:MeCN=100:0 to 90:10) to obtain a yellow amorphous substance (70 mg). This yellow amorphous substance was dissolved in dioxane (1 mL), and a 4 M HCl/dioxane solution (1 mL) was added thereto, followed by stirring and then concentrating under reduced pressure. The residue was washed with hexane to obtain 1-[(7-{[2,4-bis(trifluoromethyl)benzyl]oxy}-5-fluoro-2H-chromen-3-yl)methyl]-N-(methylsulfonyl)pyrrolidine-3-carboxamide hydrochloride (60 mg) as a pale yellow solid.

Workup

  1. customTo the reaction liquid
  2. stirringby stirring for 12 hours
  3. customTo the reaction liquid
  4. concentrationfollowed by concentration under reduced pressure
  5. customthe residue was purified by reverse phase column chromatography (H2O:MeCN=100:0 to 90:10)
  6. customto obtain a yellow amorphous substance (70 mg)
  7. stirringby stirring
  8. concentrationconcentrating under reduced pressure
  9. washThe residue was washed with hexane

Sources & evidence

ORD record
ord-01ddffeaabf54a57959acce4adb50afd
Source dataset
uspto-grants-2012_06
Patent number
US08193378B2

Reaction notes

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