Triethylamine → HCID 11555773, compound

HRID 1664912Notes

Reaction equation

HRID 1664912 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].[NH:45]1[CH2:50][CH2:49][CH:48]([C:51]2[C:52](=[O:57])[NH:53][CH:54]=[CH:55][CH:56]=2)[CH2:47][CH2:46]1.C(=O)([O-])[O-].[Na+].[Na+]>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:45]2[CH2:50][CH2:49][CH:48]([C:51]3[C:52](=[O:57])[NH:53][CH:54]=[CH:55][CH:56]=3)[CH2:47][CH2:46]2)=[O:34])[CH2:18][CH2:17]1

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 821294-Nitrophenyl chloroformateHCID 59722661HCID 59722661, 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 11555773HCID 11555773, compoundYield 16.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Triethylamine (40 μL, 0.285 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, 0.095 mmol) and 4-nitrophenyl chloroformate (19 mg, 0.095 mmol) in dichloromethane (2 mL) at 0° C. After 15 min, a solution of the hydrochloride salt of 3-piperidin-4-ylpyridin-2(1H)-one (23 mg, 0.105 mmol) in dichloromethane (1 mL) and triethylamine (26 μL, 0.19 mmol) were added and the mixture was allowed to warm to ambient temperature. After 3 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 (8.5 mg). MS 650.2244 (M+1).

Workup

  1. waitAfter 3 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-4eb7808fa75440e3b2301cc884c45465
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

Loading…