Trifluoroacetic acid → 2-Amino-N-((2R)-3-(benzyloxy)-1-(2-(2-(dimethylamino)-2-oxoethyl)-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide

HRID 1036676Notes

Reaction equation

HRID 1036676 reaction equation
[CH2:1]([O:8][CH2:9][C@@H:10]([NH:36][C:37](=[O:49])[C:38]([NH:41]C(=O)OC(C)(C)C)([CH3:40])[CH3:39])[C:11]([N:13]1[CH2:35][CH2:34][CH2:33][C:15]2([C:19](=[O:20])[N:18]([CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[CH2:17][CH:16]2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:14]1)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[NH2:41][C:38]([CH3:40])([CH3:39])[C:37]([NH:36][C@H:10]([CH2:9][O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:11]([N:13]1[CH2:35][CH2:34][CH2:33][C:15]2([C:19](=[O:20])[N:18]([CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[CH2:17][CH:16]2[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:14]1)=[O:12])=[O:49]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71060339tert-butyl 1-((2R)-3-(benzyloxy)-1-(2-(2-(dimethylamino)-2-oxoethyl)-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamate

Product 1

HCID 710604792-Amino-N-((2R)-3-(benzyloxy)-1-(2-(2-(dimethylamino)-2-oxoethyl)-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A diasteromeric mixture of tert-butyl 1-((2R)-3-(benzyloxy)-1-(2-(2-(dimethylamino)-2-oxoethyl)-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamate (386 mg; 0.569 mmol) was solubilised in dichloromethane (3 ml) at room temperature. Trifluoroacetic acid (439 ul; 5.69 mmol) was added and mixture stirred at RT for 72 hours. The solvent was removed in vacuo and the crude product was dissolved in methanol and loaded onto a pre-wetted 10 g SCX-2 cartridge. Methanol (50 ml) was passed through the cartridge and the product was eluted with 2M NH3 in methanol. Concentration of the ammonia fraction afforded the title compound as a diastereomeric mixture. Diastereomers were separated by chiral SFC, collecting the second peak.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe crude product was dissolved in methanol
  3. washthe product was eluted with 2M NH3 in methanol

Sources & evidence

ORD record
ord-683c033a4a6c4ecd8617cd890b0085bf
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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