Triethylamine → HCID 59722568, compound

HRID 1664903Notes

Reaction equation

HRID 1664903 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(=[O:56])[C:49]2([CH2:54][CH2:53][NH:52][CH2:51][CH2:50]2)[CH2:48][C:47](=[O:55])[NH: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:52]2[CH2:51][CH2:50][C:49]3([C:45](=[O:56])[NH:46][C:47](=[O:55])[CH2:48]3)[CH2:54][CH2:53]2)=[O:34])[CH2:18][CH2:17]1

Participants

8

Reactant 5

HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 821294-Nitrophenyl chloroformateHCID 156710412,8-Diazaspiro[4.5]decane-1,3-dioneHCID 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 59722568HCID 59722568, compoundYield 59.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (0.28 mL, 1.97 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 (275 mg, 0.66 mmol) and 4-nitrophenyl chloroformate (139 mg, 0.69 mmol) in tetrahydrofuran (2.5 mL) at 0° C. After 15 min, a solution of the acetate salt of 2,8-diazaspiro[4.5]decane-1,3-dione (WO 2004/076455) (180 mg, 0.79 mmol) in dichloromethane (2.5 mL) and triethylamine (0.28 mL, 1.97 mmol) were added and the mixture was allowed to warm to ambient temperature. After 2 h, saturated aqueous sodium carbonate was added and the mixture was extracted with ethyl acetate (3×). 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 (213 mg). MS 540.2005 (M+1).

Workup

  1. waitAfter 2 h
  2. extractionthe mixture was extracted with ethyl acetate (3×)
  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-09b39725383d4f339c4837e1243d4196
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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