Triethylamine → HCID 11657214, compound

HRID 1664880Notes

Reaction equation

HRID 1664880 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-].[O:47]=[C:48]1[N:56]([CH:57]2[CH2:62][CH2:61][NH2+:60][CH2:59][CH2:58]2)[C:55]2[C:50](=[NH+:51][CH:52]=[N:53][CH:54]=2)[NH:49]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[CH2:61][CH2:62][CH:57]([N:56]3[C:55]4[C:50](=[N:51][CH:52]=[N:53][CH:54]=4)[NH:49][C:48]3=[O:47])[CH2:58][CH2:59]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 178518671HCID 178518671, compound

Product 1

HCID 11657214HCID 11657214, compoundYield 57.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (94 μL, 0.673 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 (94 mg, 0.224 mmol) and 4-nitrophenyl chloroformate (45 mg, 0.224 mmol) in tetrahydrofuran (3 mL) at 0° C. After 1 h, 8-oxo-7-piperidinium-4-yl-8,9-dihydro-7H-purin-3-ium dichloride (66 mg, 0.224 mmol) and triethylamine (94 μL, 0.673 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 (76 mg). MS 591.2214 (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-d69a9644448c42c7b68717a6ebbf7a76
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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