Triethylamine → HCID 59722567, compound

HRID 1664882Notes

Reaction equation

HRID 1664882 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].[Cl-].[Cl-].[F:47][C:48]1[CH:49]=[C:50]2[N:56]([CH:57]3[CH2:62][CH2:61][NH2+:60][CH2:59][CH2:58]3)[C:55](=[O:63])[NH:54][C:51]2=[NH+:52][CH:53]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1>[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:60]2[CH2:59][CH2:58][CH:57]([N:56]3[C:50]4[C:51](=[N:52][CH:53]=[C:48]([F:47])[CH:49]=4)[NH:54][C:55]3=[O:63])[CH2:62][CH2:61]2)=[O:34])[CH2:18][CH2:17]1

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 821294-Nitrophenyl chloroformateHCID 67438873(6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-amineHCID 67440359HCID 67440359, compound

Product 1

HCID 59722567HCID 59722567, compoundYield 45.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (19 μL, 0.135 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 (18.8 mg, 0.045 mmol) and 4-nitrophenyl chloroformate (9.0 mg, 0.045 mmol) in tetrahydrofuran (2 mL) at 0° C. After 1 h, 6-fluoro-2-oxo-1-piperidinium-4-yl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-4-ium dichloride (14 mg, 0.045 mmol) and triethylamine (19 μL, 0.135 mmol) were added and the mixture allowed to warm to ambient temperature. After 1 h, 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 sodium sulfate, filtered and concentrated. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (12.5 mg). MS 608.2229 (M+1).

Workup

  1. waitAfter 1 h
  2. extractionthe mixture was extracted with dichloromethane
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-d40c74bac081497599640f52ebf1efd4
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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