18-Crown-6 → HCID 178435251, compound

HRID 1594901Notes

Reaction equation

HRID 1594901 reaction equation
C(OC([N:8]1[C:12]2[CH:13](C3C=CC(C#N)=C(F)C=3)[N:14]([C:17](OC(C)(C)C)=O)[CH2:15][CH2:16][C:11]=2[N:10]=[CH:9]1)=O)(C)(C)C.[CH2:33]([C:35]1([C:44]2[CH:49]=[CH:48][CH:47]=[C:46]([OH:50])[CH:45]=2)[CH2:41][CH2:40][CH2:39][CH2:38][N:37]([CH3:42])[C:36]1=[O:43])[CH3:34].[F-].[K+].C1O[CH2:69][CH2:68]OCCOCCOCCOCCOC1>CC#N>[CH2:33]([C:35]1([C:44]2[CH:45]=[C:46]([CH:47]=[CH:48][CH:49]=2)[O:50][C:69]2[CH:68]=[C:17]([N:14]3[C:13]4[NH:10][CH:9]=[N:8][C:12]=4[CH2:11][CH2:16][CH2:15]3)[CH:15]=[CH:16][C:11]=2[C:12]#[N:8])[CH2:41][CH2:40][CH2:39][CH2:38][N:37]([CH3:42])[C:36]1=[O:43])[CH3:34]

Participants

6

Reactant 4

HCID 2855718-Crown-6HCID 522689Potassium FluorideHCID 27945733-Ethylhexahydro-3-(3-hydroxyphenyl)-1-methyl-2H-azepin-2-oneHCID 540442074-(4-Cyano-3-fluoro-phenyl)-6,7-dihydro-4h-imidazo [4,5-c]pyridine-3,5-dicarboxylic acid di-tert-butyl ester

Product 1

HCID 178435251HCID 178435251, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-(4-Cyano-3-fluoro-phenyl)-6,7-dihydro-4H-imidazo[4,5-c]pyridine-3,5-dicarboxylic acid di-tert-butyl ester (as described above in Step B) (0.120 g, 0.270 mmol), 3-ethyl-3-(3-hydroxy-phenyl)-1-methyl-azepan-2-one (0.067 g, 0.270 mmol), KF.Al2O3 (0.080 g) and 18-Crown-6 (0.007 g) were refluxed in CH3CN (5 mL) under Ar for 24 h. The solution was filtered and concentrated in vacuo. The residue was dissolved in CH2Cl2 (10 mL) and TFA (5 mL) and stirred at RT for ½ h. The solution was concentrated in vacuo, purified using reverse phase chromatography (95/5 to 5/95 H2O/CH3CN w/0.1% TFA, flow=65 mL/min), lyophilized, and then further separated into two diastereomers using a Chiralpak AS column.

Workup

  1. filtrationThe solution was filtered
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in CH2Cl2 (10 mL)
  4. concentrationThe solution was concentrated in vacuo
  5. custompurified
  6. customfurther separated into two diastereomers

Sources & evidence

ORD record
ord-64933a4464a84314a4561094285028fd
Source dataset
uspto-grants-2001_09
Patent number
US06284755B1

Reaction notes

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