(2R,5R)-5-Azidomethyl-4-[2-(6-chloro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester → (2R,5S)-5-(Acetylamino-methyl)-4-[2-(6-chloro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475281Notes

Reaction equation

HRID 1475281 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][N:15]=[N+]=[N-])[N:11]([CH2:18][C:19]([N:21]2[C:29]3[C:24](=[CH:25][CH:26]=[C:27]([Cl:30])[CH:28]=3)[C:23]([CH3:32])([CH3:31])[CH2:22]2)=[O:20])[CH2:10][C@H:9]1[CH3:33])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:34]([OH:37])(=S)[CH3:35]>>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][NH:15][C:34](=[O:37])[CH3:35])[N:11]([CH2:18][C:19]([N:21]2[C:29]3[C:24](=[CH:25][CH:26]=[C:27]([Cl:30])[CH:28]=3)[C:23]([CH3:32])([CH3:31])[CH2:22]2)=[O:20])[CH2:10][C@H:9]1[CH3:33])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 2

HCID 86723926(2R,5R)-5-Azidomethyl-4-[2-(6-chloro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl esterHCID 178418634HCID 178418634, compound

Product 1

HCID 86723927(2R,5S)-5-(Acetylamino-methyl)-4-[2-(6-chloro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl esterYield 56%

Procedure

(2R,5R)-5-Azidomethyl-4-[2-(6-chloro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (81 mg, 0.17 mmol) was dissolved in thioacetic acid (459 μL) and left to stir for 18.5 h, then concentrated. The crude oil was purified by column chromatography on silica gel (gradient elution, 0-100%, EtOAc/petrol) to give the title compound (47 mg, 56%) as a colourless solid. 1H NMR (Me-d3-OD): 8.15 (1H, d), 7.21 (1H, d), 7.09 (1H, dd), 4.24-4.14 (1H, m), 4.06-3.96 (2H, m), 3.84 (1H, d), 3.71 (1H, d), 3.56 (1H, d), 3.48-3.40 (1H, m), 3.25-3.13 (1H, m), 3.04-2.96 (1H, m), 2.92 (1H, dd), 2.65 (1H, dd), 1.97 (3H, s), 1.49 (9H, s), 1.38 (6H, s), 1.32-1.19 (3H, m).

Workup

  1. waitleft
  2. concentrationconcentrated
  3. customThe crude oil was purified by column chromatography on silica gel (gradient elution, 0-100%, EtOAc/petrol)

Sources & evidence

ORD record
ord-9ed81ff8533f47ff86eaf5d3dd4f8e8a
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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