Hydrochloric Acid → HCID 42634764, compound

HRID 409432Notes

Reaction equation

HRID 409432 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]([O:11][C:12]([N:14]2[CH2:18][C@@H:17]([N:19]([CH2:32][C:33]3[CH:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[C:35]([C:43]([F:46])([F:45])[F:44])[CH:34]=3)[C:20]3[N:25]=[CH:24][C:23]([C:26]4[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=4)=[CH:22][N:21]=3)[CH2:16][C@H:15]2[CH2:47][CH3:48])=[O:13])[CH:8]=[CH:9][CH:10]=1)=[O:4].Cl.O1CCOCC1>O.CCOCC>[C:3]([C:5]1[CH:6]=[C:7]([O:11][C:12]([N:14]2[CH2:18][C@@H:17]([N:19]([CH2:32][C:33]3[CH:34]=[C:35]([C:43]([F:44])([F:45])[F:46])[CH:36]=[C:37]([C:39]([F:41])([F:42])[F:40])[CH:38]=3)[C:20]3[N:25]=[CH:24][C:23]([C:26]4[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=4)=[CH:22][N:21]=3)[CH2:16][C@H:15]2[CH2:47][CH3:48])=[O:13])[CH:8]=[CH:9][CH:10]=1)([OH:4])=[O:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 42634587HCID 42634587, compound

Product 1

HCID 42634764HCID 42634764, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid 3-methoxycarbonylphenyl ester (0.037 mmol; 25 mg), aqueous 6M HCl (0.5 mL) and 1,4-dioxane (0.1 mL) is stirred at 100° C. for 19 hours. The mixture is cooled to ambient temperature, then diluted with water and Et2O. The product is extracted three times with Et2O. The combined organic layer is washed with brine, dried over Na2SO4, filtered, concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (eluent: dichloromethane/methanol) to give (2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid 3-carboxy-phenyl ester (8.0 mg, 33%); ESI-MS m/z: 663 [M+1]+, Retention time 2.14 min (condition A).

Workup

  1. temperatureThe mixture is cooled to ambient temperature
  2. extractionThe product is extracted three times with Et2O
  3. washThe combined organic layer is washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue is purified by silica gel column chromatography (eluent: dichloromethane/methanol)

Sources & evidence

ORD record
ord-0d1074a8d0b245e980026796096c77cb
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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