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

HRID 2188017Notes

Reaction equation

HRID 2188017 reaction equation
[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH2:14][N:13]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[CH:12]([CH2:26][NH2:27])[C:11]=2[S:10][C:9]=1[NH2:28])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.C([O:40][C:41](=O)[C:42]1[C:47]([CH2:48]Br)=[CH:46][CH:45]=[CH:44][C:43]=1[O:50][Si:51]([C:54]([CH3:57])([CH3:56])[CH3:55])([CH3:53])[CH3:52])C>C(#N)C>[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH2:14][N:13]([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=3)[CH:12]([CH2:26][N:27]3[CH2:48][C:47]4[C:42](=[C:43]([O:50][Si:51]([C:54]([CH3:56])([CH3:55])[CH3:57])([CH3:52])[CH3:53])[CH:44]=[CH:45][CH:46]=4)[C:41]3=[O:40])[C:11]=2[S:10][C:9]=1[NH2:28])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 219366842-Amino-7-aminomethyl-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl esterHCID 695855186-Bromomethyl-2-(tert-butyl-dimethyl-silanyloxy)-benzoic acid ethyl ester

Product 1

HCID 695857732-Amino-7-(7-(tert-butyl-dimethyl-silanyloxy)-1-oxo-1,3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl esterYield 33%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-amino-7-aminomethyl-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester (80 mg, 0.20 mmol) and diisopropyl ethylamine (35 μl, 0.40 mmol) in acetonitrile (10 ml) at room temperature was added a solution of 6-bromomethyl-2-(tert-butyl-dimethyl-silanyloxy)-benzoic acid ethyl ester (69 mg, 0.20 mmol). The solution was stirred for 12 hours at room temperature and the solvent was evaporated in vacuo. The residue was dissolved in ethyl acetate (50 ml) and washed with water, 1 N hydrochloric acid, brine, dried (MgSO4), filtered and the solvent evaporated in vacuo. The residue was chromatographed on silica gel column eluted with 20% ethyl acetate/hexane to yield 42 mg (33%) of 2-amino-7-(7-(tert-butyl-dimethyl-silanyloxy)-1-oxo-1,3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester as an oil.

Workup

  1. customthe solvent was evaporated in vacuo
  2. dissolutionThe residue was dissolved in ethyl acetate (50 ml)
  3. washwashed with water, 1 N hydrochloric acid, brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. customThe residue was chromatographed on silica gel column
  8. washeluted with 20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-ea9fc0df9c19449bb6c93acf11f614ac
Source dataset
uspto-grants-2002_06
Patent number
US06410556B1

Reaction notes

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