Hydrochloric Acid → HCID 49847934, compound

HRID 389859Notes

Reaction equation

HRID 389859 reaction equation
[F:1][C:2]1([F:11])[CH2:7][CH2:6][CH:5]([C:8]([OH:10])=O)[CH2:4][CH2:3]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:35]([C:39]1[O:43][N:42]=[C:41]([NH:44][C:45]([C@@H:47]2[CH2:50][CH2:49][NH:48]2)=[O:46])[CH:40]=1)([CH3:38])([CH3:37])[CH3:36].Cl.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[C:35]([C:39]1[O:43][N:42]=[C:41]([NH:44][C:45]([C@@H:47]2[CH2:50][CH2:49][N:48]2[C:8]([CH:5]2[CH2:4][CH2:3][C:2]([F:1])([F:11])[CH2:7][CH2:6]2)=[O:10])=[O:46])[CH:40]=1)([CH3:38])([CH3:36])[CH3:37]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27791364,4-Difluorocyclohexanecarboxylic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 67953688HCID 67953688, compound

Product 1

HCID 49847934HCID 49847934, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4,4-difluorocyclohexanecarboxylic acid (74.5 mg; 0.454 mmol) and 1-hydroxybenzotriazole hydrate (102 mg; 0.756 mmol) in DMF (1.5 mL) is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (145 mg; 0.756 mmol). After 20 minutes of stirring, (S)-Azetidine-2-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide; hydrochloride (150 mg; 0.378 mmol) is added, followed by diisopropylethylamine (0.066 mL; 0.378 mmol) and 4-diemthylaminopyridine (3 mg; 0.025 mmol). The reaction mixture is stirred at room temperature for 1 hour. After this time, the reaction mixture is diluted with ethyl acetate and washed with water, saturated sodium bicarbonate aqueous solution and saturated ammonium chloride aqueous solution then brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography on silica gel using methanol/methylene chloride provides the title compound, m/z 370 [M+H+].

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 1 hour
  2. washwashed with water, saturated sodium bicarbonate aqueous solution and saturated ammonium chloride aqueous solution
  3. dry with materialbrine, dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-88a638ec663b4f7397bf4cf72eee3edf
Source dataset
uspto-grants-2013_02
Patent number
US08383615B2

Reaction notes

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