Triethylamine → HCID 11606124, compound

HRID 1664915Notes

Reaction equation

HRID 1664915 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].[N:45]1[C:49]2([CH2:54][CH2:53][NH:52][CH2:51][CH2:50]2)[C:48](=[O:55])[NH:47][CH:46]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.C(Cl)(Cl)Cl>[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([N:45]=[CH:46][NH:47][C:48]3=[O:55])[CH2:54][CH2:53]2)=[O:34])[CH2:18][CH2:17]1

Participants

8

Reactant 5

HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 821294-Nitrophenyl chloroformateHCID 22975579HCID 22975579, 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 11606124HCID 11606124, compoundYield 68.8%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (42 μL, 0.30 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 (25 mg, 0.061 mmol) and 4-nitrophenyl chloroformate (14 mg, 0.070 mmol) in tetrahydrofuran (5 mL) at 0° C. After 40 min, the hydrochloride salt of 1,3,8-triazaspiro[4.5]dec-1-en-4-one (21 mg, 0.091 mmol), triethylamine (34 μL, 0.24 mmol) and chloroform (5 mL) were added and the mixture allowed to warm to ambient temperature. After 18 h, saturated aqueous sodium carbonate was added and the mixture was extracted with dichloromethane. The organic extracts were washed with saturated aqueous sodium bicarbonate (3×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→85% dichloromethane/methanol) gave the title compound (22 mg). MS 525.2000 (M+1).

Workup

  1. waitAfter 18 h
  2. extractionthe mixture was extracted with dichloromethane
  3. washThe organic extracts were 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→85% dichloromethane/methanol)

Sources & evidence

ORD record
ord-25e33e33faad449a820ea98f45dedac8
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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