2-(tert-butyoxyoxalyl-amino)-5-((2-(1H-indol-3-yl)-2-oxo-acetylamino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester → 2-(tert-butyoxyoxalyl-amino)-5-((2-(1H-indol-3-yl)-2-oxo-acetylamino)methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester

HRID 2188023Notes

Reaction equation

HRID 2188023 reaction equation
[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH:14]([CH2:17][NH:18][C:19](=[O:31])[C:20]([C:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[NH:24][CH:23]=3)=[O:21])[N:13](CC3C=CC(OC)=CC=3)[CH2:12][C:11]=2[S:10][C:9]=1[NH:41][C:42](=[O:50])[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[O:7])([CH3:4])([CH3:3])[CH3:2]>O1CCCC1.[Ni]>[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH:14]([CH2:17][NH:18][C:19](=[O:31])[C:20]([C:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[NH:24][CH:23]=3)=[O:21])[NH:13][CH2:12][C:11]=2[S:10][C:9]=1[NH:41][C:42](=[O:50])[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 1

HCID 1317233162-(tert-butyoxyoxalyl-amino)-5-((2-(1H-indol-3-yl)-2-oxo-acetylamino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester

Product 1

HCID 1317233172-(tert-butyoxyoxalyl-amino)-5-((2-(1H-indol-3-yl)-2-oxo-acetylamino)methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 8028TetrahydrofuranSolvent

Procedure

2-(tert-Butyoxyoxalyl-amino)-5-((2-(1H-indol-3-yl)-2-oxo-acetylamino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester (101 mg, 0.143 mmol) was dissolved in dry tetrahydrofuran (6 ml) and passed through a pipette, plugged with cotton containing Raney 2800 Nickel (0.38 g). The pipette was flushed with dry tetrahydrofuran (6 ml) and the filtrate was concentrated in vacuo. Pd on carbon (10%, 102 mg, source: Avocado) and formic acid (10% in methanol, 5 ml) were added to the flask containing 2-(tert-Butyoxyoxalyl-amino)-5-((2-(1H-indol-3-yl)-2-oxo-acetylamino) methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester. After stirring for 18 hours, the solution was filtered through a pad of celite and concentrated in vacuo. The residue was diluted in ethyl acetate, washed with saturated sodium bicarbonate (2×25 ml), brine (2×25 ml), dried (MgSO4), filtered and concentrated in vacuo. The residue was subjected to flash chromatography using a mixture of 10% methanol/dichloromethane as eluent, which afforded 2-(tert-butyoxyoxalyl-amino)-5-((2-(1H-indol-3-yl)-2-oxo-acetylamino)methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester.

Workup

  1. customThe pipette was flushed with dry tetrahydrofuran (6 ml)
  2. concentrationthe filtrate was concentrated in vacuo
  3. additionPd on carbon (10%, 102 mg, source: Avocado) and formic acid (10% in methanol, 5 ml) were added to the flask
  4. additioncontaining 2-(tert-Butyoxyoxalyl-amino)-5-((2-(1H-indol-3-yl)-2-oxo-acetylamino) methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester
  5. filtrationthe solution was filtered through a pad of celite
  6. concentrationconcentrated in vacuo
  7. additionThe residue was diluted in ethyl acetate
  8. washwashed with saturated sodium bicarbonate (2×25 ml), brine (2×25 ml)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. additiona mixture of 10% methanol/dichloromethane as eluent

Sources & evidence

ORD record
ord-2522f3f60cb849f3887c96076edcdd35
Source dataset
uspto-grants-2002_06
Patent number
US06410556B1

Reaction notes

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