Triethylamine → HCID 59722573, compound

HRID 1664908Notes

Reaction equation

HRID 1664908 reaction equation
C(N(CC)CC)C.[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][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].[C:45]1([C:51]2[CH:52]=[C:53]([CH:58]3[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]3)[C:54](=[O:57])[NH:55][N:56]=2)[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.ClCCl>[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[C@H:16]1[CH2:22][N:21]2[C:23]([CH2:26][C:27]([F:30])([F:28])[F:29])=[CH:24][N:25]=[C:20]2[C@H:19]([NH:31][C:33]([N:61]2[CH2:62][CH2:63][CH:58]([C:53]3[C:54](=[O:57])[NH:55][N:56]=[C:51]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)[CH:52]=3)[CH2:59][CH2:60]2)=[O:34])[CH2:18][CH2:17]1

Participants

8

Reactant 5

HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 821294-Nitrophenyl chloroformateHCID 59722552HCID 59722552, compoundHCID 67438873(6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-amine

Product 1

HCID 59722573HCID 59722573, compoundYield 43.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (33 μL, 0.24 mmol) was added to a solution of the hydrochloride salt of (6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-amine (33 mg, 0.08 mmol) and 4-nitrophenyl chloroformate (16 mg, 0.08 mmol) in tetrahydrofuran (1 mL) at 0° C. After 15 min, a solution of 6-phenyl-4-piperidin-4-ylpyridazin-3(2H)-one (20 mg, 0.08 mmol) in dichloromethane (1 mL) and triethylamine (22 μL, 0.16 mmol) were added and the mixture allowed to warm to ambient temperature. After 2 h, saturated aqueous sodium carbonate was added and the mixture was extracted with ethyl acetate. 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 (22 mg). MS 627.2498 (M+1).

Workup

  1. waitAfter 2 h
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol)

Sources & evidence

ORD record
ord-40b616669ec54774abfd34e4d491f442
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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