Triethylamine → HCID 11606545, compound

HRID 1664918Notes

Reaction equation

HRID 1664918 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]([CH2:26][C:27]([F:30])([F:29])[F:28])=[CH:24][N:25]=[C:20]2[C@H:19]([NH2:31])[CH2:18][CH2:17]1.Cl[C:33](OC1C=CC([N+]([O-])=O)=CC=1)=[O:34].[CH3:45][C:46]1[CH:47]=[C:48]([CH:53]2[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]2)[C:49](=[O:52])[NH:50][N:51]=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]([CH2:26][C:27]([F:28])([F:29])[F:30])=[CH:24][N:25]=[C:20]2[C@H:19]([NH:31][C:33]([N:56]2[CH2:57][CH2:58][CH:53]([C:48]3[C:49](=[O:52])[NH:50][N:51]=[C:46]([CH3:45])[CH:47]=3)[CH2:54][CH2:55]2)=[O:34])[CH2:18][CH2:17]1

Participants

8

Reactant 5

HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 821294-Nitrophenyl chloroformateHCID 59722662HCID 59722662, compoundHCID 67439283HCID 67439283, compound

Product 1

HCID 11606545HCID 11606545, compoundYield 66.4%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Triethylamine (22 μL, 0.16 mmol) was added to a solution of the hydrochloride salt of (6S,9R)-6-(2,6-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-amine (15 mg, 0.04 mmol) and 4-nitrophenyl chloroformate (19 mg, 0.043 mmol) in tetrahydrofuran (5 mL) at 0° C. After 30 min, 6-methyl-4-piperidin-4-ylpyridazin-3(2H)-one (15 mg, 0.08 mmol), triethylamine (22 μL, 0.16 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 layer was 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 565.2346 (M+1).

Workup

  1. waitAfter 30 min
  2. temperatureto cool to ambient temperature
  3. extractionthe mixture was extracted with dichloromethane
  4. washThe organic layer was 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-94bc1faec62f480984f461e97cabdc22
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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