Diisopropylethylamine → 2-Amino-6-(4-methoxy-benzyl)-5-(7-methoxy-1-oxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester

HRID 1242092Notes

Reaction equation

HRID 1242092 reaction equation
C(O[C:4](=[O:15])[C:5]1[C:10]([CH2:11]Br)=[CH:9][CH:8]=[CH:7][C:6]=1[O:13][CH3:14])C.[CH:16]([N:19](C(C)C)CC)(C)C.[C:25]([O:29][C:30]([C:32]1[C:40]2[CH:39](C)[CH:38](N)[N:37]([CH2:43][C:44]3[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][CH:45]=3)[CH2:36][C:35]=2[S:34][C:33]=1[NH2:52])=[O:31])([CH3:28])([CH3:27])[CH3:26]>C(#N)C>[C:25]([O:29][C:30]([C:32]1[C:40]2[CH2:39][CH:38]([CH2:16][N:19]3[CH2:11][C:10]4[C:5](=[C:6]([O:13][CH3:14])[CH:7]=[CH:8][CH:9]=4)[C:4]3=[O:15])[N:37]([CH2:43][C:44]3[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][CH:45]=3)[CH2:36][C:35]=2[S:34][C:33]=1[NH2:52])=[O:31])([CH3:27])([CH3:26])[CH3:28]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 10038926Ethyl 2-bromomethyl-6-methoxybenzoateHCID 69586093HCID 69586093, compound

Product 1

HCID 695857602-Amino-6-(4-methoxy-benzyl)-5-(7-methoxy-1-oxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

6-Bromomethyl-2-methoxy-benzoic acid ethyl ester (71.1 mg, 0.260 mmol) dissolved in acetonitrile (5 ml) and diisopropylethylamine (453 μl, 2.60 mmol) was stirred at room temperature. To this mixture 2-amino-5-amino-methyl-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester (200 mg, 0.52 mmol) dissolved in acetonitrile (5 ml) was added syringe pump (0.2 ml/min.). Once addition was complete, the reaction mixture was allowed to stir for 2 hours. The reaction mixture was concentrated in vacuo, and the residue diluted with ethylacetate (50 ml). The organic layer was washed with saturated sodium bicarbonate (2×25 ml) and brine (2×25 ml). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue (308 mg) was subjected to column chromatography using a gradient of hexane/ethyl acetate (95:5) to (50:50) and then dichloromethane/ethyl acetate (95:5) as eluents, which afforded 106 mg (75%) of 2-amino-6-(4-methoxy-benzyl)-5-(7-methoxy-1-oxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester as an oil.

Workup

  1. additionwas added syringe pump (0.2 ml/min.)
  2. additionOnce addition
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. additionthe residue diluted with ethylacetate (50 ml)
  5. washThe organic layer was washed with saturated sodium bicarbonate (2×25 ml) and brine (2×25 ml)
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-02204e09ea734703b7a6adf1a3bb8bc7
Source dataset
uspto-grants-2006_10
Patent number
US07115624B1

Reaction notes

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