Imidazol-1-YL-oxo-acetic acid tert-butyl ester → 2-Amino-7-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester

HRID 2188003Notes

Reaction equation

HRID 2188003 reaction equation
[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH:14]([CH2:17][N:18]3[C:26](=[O:27])[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][C:24]=4OCC4C=CC=CC=4)[C:19]3=[O:36])[N:13]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:12][C:11]=2[S:10][C:9]=1[NH2:44])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:45]([O:49][C:50]([C:52]1[C:60]2[CH2:59][CH2:58][N:57]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH:56]([CH2:68][N:69]3[C:77](=[O:78])[C:76]4[C:71](=[CH:72][CH:73]=[CH:74][C:75]=4OCC4C=CC=CC=4)[C:70]3=[O:87])[C:55]=2[S:54][C:53]=1[NH2:88])=[O:51])([CH3:48])([CH3:47])[CH3:46].C(OC(=O)C(N1C=CN=C1)=O)(C)(C)C>ClCCl>[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH:14]([CH2:17][N:18]3[C:26](=[O:27])[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:19]3=[O:36])[N:13]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:12][C:11]=2[S:10][C:9]=1[NH2:44])=[O:7])([CH3:3])([CH3:4])[CH3:2].[C:45]([O:49][C:50]([C:52]1[C:60]2[CH2:59][CH2:58][N:57]([C:61]([O:63][C:64]([CH3:66])([CH3:67])[CH3:65])=[O:62])[CH:56]([CH2:68][N:69]3[C:70](=[O:87])[C:71]4[C:76](=[CH:75][CH:74]=[CH:73][CH:72]=4)[C:77]3=[O:78])[C:55]=2[S:54][C:53]=1[NH2:88])=[O:51])([CH3:46])([CH3:47])[CH3:48]

Participants

6

Reactant 3

HCID 11217804Imidazol-1-YL-oxo-acetic acid tert-butyl esterHCID 695856252-Amino-7-(4-benzyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl esterHCID 695860022-Amino-5-(4-benzyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester

Product 2

HCID 695856542-Amino-7-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl esterHCID 695857032-Amino-5-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the above mixture of 2-amino-5-(4-benzyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester and 2-amino-7-(4-benzyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester (0.15 g, 0.24 mmol) in distilled dichloromethane (4 ml) under nitrogen was added imidazol-1-yl-oxo-acetic acid tert-butyl ester (0.14 g, 0.72 mmol) and the reaction mixture was stirred at ambient temperature for 1.5 hour. The volatiles were evaporated in vacuo and the crude residue was purified by silica gel chromatography using dichloromethane as eluent. Pure fractions were collected and the solvent evaporated in vacuo affording 50 mg of 2-(tert-butoxyoxalyl-amino)-5-(4-benzyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester (A) and 50 mg of 2-(tert-butoxyoxalyl-amino)-7-(4-benzyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-tert-butyl ester (B). Another 50 mg remained as a mixture of the two isomers (A) and (B).

Workup

  1. customThe volatiles were evaporated in vacuo
  2. customthe crude residue was purified by silica gel chromatography
  3. customPure fractions were collected
  4. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-2dd88ac91ed147da8143034f4623cf8a
Source dataset
uspto-grants-2002_06
Patent number
US06410556B1

Reaction notes

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