Triethylamine → HCID 11534441, compound

HRID 1664919Notes

Reaction equation

HRID 1664919 reaction equation
C(N(CC)CC)C.[F:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[C:10]=1[C@H:16]1[CH2:22][N:21]2[C:23]([C:26]3([C:29]([F:32])([F:31])[F:30])[CH2:28][CH2:27]3)=[CH:24][N:25]=[C:20]2[C@H:19]([NH2:33])[CH2:18][CH2:17]1.Cl[C:35](OC1C=CC([N+]([O-])=O)=CC=1)=[O:36].[CH3:47][C:48]1[CH:49]=[C:50]([CH:55]2[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]2)[C:51](=[O:54])[NH:52][N:53]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.C(Cl)(Cl)Cl>[F:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[C:10]=1[C@H:16]1[CH2:22][N:21]2[C:23]([C:26]3([C:29]([F:30])([F:31])[F:32])[CH2:28][CH2:27]3)=[CH:24][N:25]=[C:20]2[C@H:19]([NH:33][C:35]([N:58]2[CH2:59][CH2:60][CH:55]([C:50]3[C:51](=[O:54])[NH:52][N:53]=[C:48]([CH3:47])[CH:49]=3)[CH2:56][CH2:57]2)=[O:36])[CH2:18][CH2:17]1

Participants

8

Reactant 5

HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 821294-Nitrophenyl chloroformateHCID 59722662HCID 59722662, compoundHCID 67440361HCID 67440361, compound

Product 1

HCID 11534441HCID 11534441, compoundYield 25.4%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Triethylamine (55 μL, 0.39 mmol) was added to a solution of the hydrochloride salt of (6S,9R)-6-(2,6-difluorophenyl)-3-[1-(trifluoromethyl)cyclopropyl]-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-amine (40 mg, 0.10 mmol) and 4-nitrophenyl chloroformate (22 mg, 0.11 mmol) in tetrahydrofuran (5 mL) at 0° C. After 30 min, 6-methyl-4-piperidin-4-ylpyridazin-3(2H)-one (38 mg, 0.20 mmol), triethylamine (55 μL, 0.39 mmol) and chloroform (5 mL) were added and the mixture was heated to 50° C. After 30 min, the reaction mixture was allowed to cool to ambient temperature. Saturated aqueous sodium carbonate was added and the mixture was extracted with dichloromethane. The organic extracts were washed with saturated aqueous sodium bicarbonate (3×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol) gave the title compound (15 mg). MS 591.2536 (M+1).

Workup

  1. waitAfter 30 min
  2. temperatureto cool to ambient temperature
  3. extractionthe mixture was extracted with dichloromethane
  4. washThe organic extracts were washed with saturated aqueous sodium bicarbonate (3×), saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol)

Sources & evidence

ORD record
ord-df5bbec9101d48b99190b83053ab9abe
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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