(4-Chlorophenyl)acetic acid → HCID 86656358, compound

HRID 1942488Notes

Reaction equation

HRID 1942488 reaction equation
[CH:1]1([NH:4][CH2:5][CH2:6][C@H:7]2[CH2:12][CH2:11][C@@H:10]([N:13]([C:17]([C:19]3[C:20]([C:40]([F:43])([F:42])[F:41])=[CH:21][C:22]4[O:27][C:26]([CH3:29])([CH3:28])[C:25](=[O:30])[N:24]([CH2:31][CH2:32][NH:33][C:34](=[O:38])[CH:35]([F:37])[F:36])[C:23]=4[CH:39]=3)=[O:18])[CH:14]([CH3:16])[CH3:15])[CH2:9][N:8]2[C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:3][CH2:2]1.[Cl:51][C:52]1[CH:57]=[CH:56][C:55]([CH2:58][C:59](O)=[O:60])=[CH:54][CH:53]=1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O.O.C(N(CC)CC)C>[Cl:51][C:52]1[CH:57]=[CH:56][C:55]([CH2:58][C:59]([N:4]([CH:1]2[CH2:3][CH2:2]2)[CH2:5][CH2:6][C@H:7]2[CH2:12][CH2:11][C@@H:10]([N:13]([C:17]([C:19]3[C:20]([C:40]([F:41])([F:42])[F:43])=[CH:21][C:22]4[O:27][C:26]([CH3:28])([CH3:29])[C:25](=[O:30])[N:24]([CH2:31][CH2:32][NH:33][C:34](=[O:38])[CH:35]([F:37])[F:36])[C:23]=4[CH:39]=3)=[O:18])[CH:14]([CH3:16])[CH3:15])[CH2:9][N:8]2[C:44]([O:46][C:47]([CH3:48])([CH3:50])[CH3:49])=[O:45])=[O:60])=[CH:54][CH:53]=1

Participants

8

Reactant 4

HCID 15880(4-Chlorophenyl)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67331414HCID 67331414, compound

Product 1

HCID 86656358HCID 86656358, compoundYield 86.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of tert-butyl (2R,5R)-2-[2-(cyclopropylamino)ethyl]-5-[{[4-{2-[(difluoroacetyl)-amino]ethyl}-2,2-dimethyl-3-oxo-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]carbonyl}-(isopropyl)amino]piperidine-1-carboxylate (86 mg) in N,N-dimethylformamide (1 ml) were added 4-chlorophenylacetic acid (22 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (34 mg), 1-hydroxybenzotriazole monohydrate (24 mg) and triethylamine (50 μl), and the mixture was stirred at room temperature overnight. To the reaction solution was added water, and the mixture was extracted with ethyl acetate (50 ml). The organic layer was washed with water and a saturated aqueous sodium chloride solution. Then, the mixture was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (the developing solvent: hexane/acetone=2/1) to give the title compound (90 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (50 ml)
  2. washThe organic layer was washed with water
  3. dry with materialThen, the mixture was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (the developing solvent

Sources & evidence

ORD record
ord-b98f011bad2a43dcb72c7f284d9a13c1
Source dataset
uspto-grants-2013_03
Patent number
US08389511B2

Reaction notes

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