Pyridine → HCID 69585188, compound

HRID 1243153Notes

Reaction equation

HRID 1243153 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[CH2:6][OH:7].ClC(Cl)(O[C:12](=[O:18])OC(Cl)(Cl)Cl)Cl.N1C2C(=CC=CC=2)C=CC=1.ClC([O-])=O.[CH2:34]([N:36]([CH2:57][CH3:58])[C:37]1[CH:42]=[CH:41][C:40]([NH:43][C:44]([C:46]2([NH2:56])[CH2:55][CH2:54][C:53]3[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=3)[CH2:47]2)=[O:45])=[CH:39][CH:38]=1)[CH3:35].N1C=CC=CC=1>C1(C)C=CC=CC=1.C(Cl)Cl.Cl.O1CCCC1>[O:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[CH2:6][O:7][C:12](=[O:18])[NH:56][C:46]1([C:44]([NH:43][C:40]2[CH:39]=[CH:38][C:37]([N:36]([CH2:57][CH3:58])[CH2:34][CH3:35])=[CH:42][CH:41]=2)=[O:45])[CH2:55][CH2:54][C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH2:47]1

Participants

10

Reactant 6

HCID 1049PyridineHCID 7047QuinolineHCID 7360Tetrahydrofurfuryl alcoholHCID 94429TriphosgeneHCID 21226386CarbonochloridateHCID 865961192-Amino-1,2,3,4-tetrahydro-naphthalene-2-carboxylic acid (4-diethylamino-phenyl)-amide

Product 1

HCID 69585188HCID 69585188, compound

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent2×HCID 21877217Toluene methylene chlorideSolvent

Procedure

To a cold solution (0° C.) of tetrahydro-2-furanmethanol (0.013 mL, 0.13 mmol) in toluene:methylene chloride (1:1, 0.03 mL) was added triphosgene (30 mg, 0.1 mmol) and quinoline (0.018 mL, 0.15 mmole) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction was cooled at 0° C., diluted with 3 N HCl and extracted with ethyl acetate twice. The combined organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The cold (−40° C.) solution of crude chloroformate (0.075 mmol) in anhydrous tetrahydrofuran (0.5 mL) was added to amine from Example 8A (17 mg, 0.05 mmol) and pyridine (0.009 mL, 0.105 mmole) in anhydrous tetrahydrofuran (0.1 mL) at −40° C. The reaction mixture was allowed to warm at room temperature, stirred overnight and concentrated under reduced pressure. The residue was purified by reverse-phase HPLC to provide the titled compound.

Workup

  1. temperatureThe reaction was cooled at 0° C.
  2. extractionextracted with ethyl acetate twice
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. temperatureto warm at room temperature
  8. stirringstirred overnight
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-148ae965f00a45f5b3c5252228175245
Source dataset
uspto-grants-2006_10
Patent number
US07115767B2

Reaction notes

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