Oxalyl chloride → (2-{6-Chloro-3-[4-(2-oxo-2,3-dihydro-indol-1-yl)-piperidine-1-carbonyl]-indol-1-yl}-ethyl)-methyl-carbamic acid tert-butyl ester

HRID 1097843Notes

Reaction equation

HRID 1097843 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:24])[CH2:9][CH2:10][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([Cl:20])[CH:18]=2)[C:13]([C:21]([OH:23])=O)=[CH:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.C(Cl)(=O)C(Cl)=O.[NH:40]1[CH2:45][CH2:44][CH:43]([N:46]2[C:54]3[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=3)[CH2:48][C:47]2=[O:55])[CH2:42][CH2:41]1>CN(C)C=O>[C:1]([O:5][C:6](=[O:7])[N:8]([CH2:9][CH2:10][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([Cl:20])[CH:18]=2)[C:13]([C:21]([N:40]2[CH2:45][CH2:44][CH:43]([N:46]3[C:54]4[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=4)[CH2:48][C:47]3=[O:55])[CH2:42][CH2:41]2)=[O:23])=[CH:12]1)[CH3:24])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531Diisopropylethylamine2×HCID 27611521-Piperidin-4-yl-1,3-dihydro-2H-indol-2-oneHCID 597567001-[2-(tert-Butoxycarbonyl-methyl-amino)-ethyl]-6-chloro-1H-indole-3-carboxylic acid

Product 1

HCID 66811008(2-{6-Chloro-3-[4-(2-oxo-2,3-dihydro-indol-1-yl)-piperidine-1-carbonyl]-indol-1-yl}-ethyl)-methyl-carbamic acid tert-butyl esterYield 82.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Procedure

To a solution of 0.20 g (0.57 mmol) 1-[2-(tert-butoxycarbonyl-methyl-amino)-ethyl]-6-chloro-1H-indole-3-carboxylic acid, 0.11 ml (0.63 mmol) N,N-diisopropylethylamine and 2 drops of N,N-dimethylformamide in 4 ml dicholormethane were added 0.060 ml (0.74 mmol) oxalyl chloride at 0-5° C. After completed addition the reaction mixture was allowed to warm to room temperature and stirred for 3 h. A solution of 0.15 g (0.68 mmol) 1,3-dihydro-1-(piperidin-4-yl)-(2H)-indol-2-one and 0.11 ml (0.63 mmol) N,N-diisopropylethylamine in 2 ml dicholormethane was added. After stirring for 15 min at room temperature silica gel was added to the reaction mixture and the solvent was evaporated in vacuo. The residue was transferred to a silica gel column. Elution gave 0.26 g (82%) of the title compound as an off-white solid.

Workup

  1. additionaddition the reaction mixture
  2. stirringAfter stirring for 15 min at room temperature silica gel
  3. additionwas added to the reaction mixture
  4. customthe solvent was evaporated in vacuo
  5. washElution

Sources & evidence

ORD record
ord-8f5119c0dd8f44a9971d61101e507736
Source dataset
uspto-grants-2012_03
Patent number
US08143281B2

Reaction notes

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