Piperidine → 5-(2-Oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoic acid (4-amino-2-hydroxyphenyl)-amide

HRID 1354851Notes

Reaction equation

HRID 1354851 reaction equation
C1C2C(COC(=O)[NH:17][C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25](=[O:39])[CH2:26][CH2:27][CH2:28][CH2:29][CH:30]4[CH:37]5[CH:33]([NH:34][C:35](=[O:38])[NH:36]5)[CH2:32][S:31]4)=[C:20]([OH:40])[CH:19]=3)C3C(=CC=CC=3)C=2C=CC=1.N1CCCCC1>C1COCC1.CN(C=O)C.CCOC(C)=O.O.[Cl-].[Na+].O>[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25](=[O:39])[CH2:26][CH2:27][CH2:28][CH2:29][CH:30]2[CH:37]3[CH:33]([NH:34][C:35](=[O:38])[NH:36]3)[CH2:32][S:31]2)=[C:20]([OH:40])[CH:19]=1

Participants

8

Reactant 2

HCID 8082PiperidineHCID 72447733{3-Hydroxy-4-[5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoylamino]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl ester

Product 1

HCID 724476805-(2-Oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoic acid (4-amino-2-hydroxyphenyl)-amideYield 81.6%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

{3-Hydroxy-4-[5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoylamino]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl ester (390) (0.152 g, 0.266 mmol) was dissolved in a mixture of THF (10 mL) and DMF (4 mL). Piperidine (0.53 mL, 5.3 mmol) was added. The mixture was shaken at room temperature for 3 h. LC-MS indicated complete de-protection at this point. The mixture was diluted with EtOAc (100 mL), water (2×50 mL) and brine (2×50 mL) via extraction, dried over MgSO4 and concentrated under reduced pressure to give an oil. Purification by flash chromatography on silica gel using a gradient of hexane and EtOAc (eluting with 15–100% EtOAc/hexane in 30 minutes) gave the desired product (391) as a beige oil (0.076 g, 0.217 mmol, 81.6% yield). LC-MS (ESI): (exact mass: 350.14) m/e=351.3 [M+1]+ (100%), 701.3 [2M+1]+ (15%).

Workup

  1. dry with materialdried over MgSO4
  2. concentrationconcentrated under reduced pressure
  3. customto give an oil
  4. customPurification by flash chromatography on silica gel using a gradient of hexane and EtOAc (eluting with 15–100% EtOAc/hexane in 30 minutes)

Sources & evidence

ORD record
ord-3148b6792df54e798ed20d20cd8713c4
Source dataset
uspto-grants-2007_05
Patent number
US07223759B2

Reaction notes

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