Benzyl 3-(2-amino-1-(6-(3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate → ethyl 4-(3-(benzyloxycarbonylamino)-2-methylphenyl)-7-(3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-1-carboxylate

HRID 2361313Notes

Reaction equation

HRID 2361313 reaction equation
[NH2:1][CH2:2][CH:3]([C:26]1[C:27]([CH3:43])=[C:28]([NH:32][C:33](=[O:42])[O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:29]=[CH:30][CH:31]=1)[C:4]1[C:12]2[C:7](=[CH:8][C:9]([N:13]3[CH2:17][CH2:16][CH:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH2:14]3)=[CH:10][CH:11]=2)[NH:6][CH:5]=1.O=[CH:45][C:46]([O:48][CH2:49][CH3:50])=[O:47].C1(C)C=CC=CC=1>O1CCOCC1>[CH2:35]([O:34][C:33]([NH:32][C:28]1[C:27]([CH3:43])=[C:26]([CH:3]2[C:4]3[C:12]4[C:7](=[CH:8][C:9]([N:13]5[CH2:17][CH2:16][CH:15]([O:18][Si:19]([C:22]([CH3:23])([CH3:24])[CH3:25])([CH3:20])[CH3:21])[CH2:14]5)=[CH:10][CH:11]=4)[NH:6][C:5]=3[CH:45]([C:46]([O:48][CH2:49][CH3:50])=[O:47])[NH:1][CH2:2]2)[CH:31]=[CH:30][CH:29]=1)=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

4

Reactant 2

HCID 67994692Benzyl 3-(2-amino-1-(6-(3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-1H-indol-3-yl)ethyl)-2-methylphenylcarbamateHCID 86599969Ethyl glyoxylate toluene

Product 1

HCID 67996827ethyl 4-(3-(benzyloxycarbonylamino)-2-methylphenyl)-7-(3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of benzyl 3-(2-amino-1-(6-(3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate (0.1010 g, 0.169 mmol) in 1,4-dioxane (4.82 mL) was added 50% ethyl 2-oxoacetate/toluene (0.067 mL, 0.337 mmol) at 10° C. The cold bath was removed, and the reaction was stirred to room temperature for 3 h. The reaction was concentrated in vacuo to give crude ethyl 4-(3-(benzyloxycarbonylamino)-2-methylphenyl)-7-(3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-1-carboxylate which was used in the subsequent step. This was added to p-xylene (41.6 mL) and 10% Pd/C (0.310 g, 0.291 mmol). The reaction was heated to 125° C. for 4.5 hr and cooled to room temperature. The solution was filtered through a pad of CELITE® and rinsed with EtOAc (150 mL). The filtrate was washed with water (40 mL), dried over MgSO4, filtered and concentrated in vacuo to give a residue which was purified by flash chromatography using an ISCO 120 g column eluting with 0-30% EtOAc/CH2Cl2. Appropriate fractions (20% elution) were combined, concentrated in vacuo to give the desired product (0.1487 g, 0.219 mmol, 15.0% yield) as a tan solid.

Workup

  1. customThe cold bath was removed
  2. concentrationThe reaction was concentrated in vacuo

Sources & evidence

ORD record
ord-1917c3da36e04d358f31592943292308
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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