Diisopropylethylamine → 2-Amino-5-(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 1242095Notes

Reaction equation

HRID 1242095 reaction equation
[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH:14]([CH2:17][NH2:18])[N:13]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[CH2:12][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][CH:14]([CH2:17][N:18]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])[N:13]([CH2:19][C:20]3[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=3)[CH2:12][C:11]=2[S:10][C:9]=1[NH2:28])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 695855102-Amino-5-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 695855092-Amino-5-(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 66.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of 2-amino-5-aminomethyl-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester (3.00 g, 7.45 mmol) and diisopropyl ethylamine (1.93 ml, 11.2 mmol) in acetonitrile at room temperature was added a solution of 6-bromomethyl-2-(tert-butyl-dimethyl-silanyloxy)-benzoic acid ethyl ester (2.78 g, 7.45 mmol) in acetonitril over 48 hours. The solution was stirred for 12 hours after the addition was complete. The volatiles were evaporated in vacuo and the residue was taken into 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 a mixture of 20% ethyl acetate/Hexane, which afforded 3.2 g (66. %) of 2-amino-5-(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. additionafter the addition
  2. customThe volatiles were evaporated in vacuo
  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 a mixture of 20% ethyl acetate/Hexane, which

Sources & evidence

ORD record
ord-40cb71d57390483ab8e284881f9290b5
Source dataset
uspto-grants-2006_10
Patent number
US07115624B1

Reaction notes

Loading…