Diisopropylethylamine → 2-(((R)-3-acetylthiazolidin-4-carbonyl)amino)-3-((3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carbonyl)amino)propionic acid methyl ester

HRID 896273Notes

Reaction equation

HRID 896273 reaction equation
[CH3:1][O:2][C:3](=[O:28])[CH:4]([NH2:27])[CH2:5][NH:6][C:7]([N:9]1[CH2:26][CH2:25][C:12]2([N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:15][N:14]([CH3:23])[C:13]2=[O:24])[CH2:11][CH2:10]1)=[O:8].[C:29]([N:32]1[C@H:36]([C:37](O)=[O:38])[CH2:35][S:34][CH2:33]1)(=[O:31])[CH3:30].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>ClCCl>[CH3:1][O:2][C:3](=[O:28])[CH:4]([NH:27][C:37]([C@@H:36]1[CH2:35][S:34][CH2:33][N:32]1[C:29](=[O:31])[CH3:30])=[O:38])[CH2:5][NH:6][C:7]([N:9]1[CH2:10][CH2:11][C:12]2([N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:15][N:14]([CH3:23])[C:13]2=[O:24])[CH2:25][CH2:26]1)=[O:8]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 197107(4R)-3-Acetyl-4-thiazolidinecarboxylic acidHCID 695629412-Amino-3-((3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carbonyl)amino)propionic acid methyl ester

Product 1

HCID 695638682-(((R)-3-acetylthiazolidin-4-carbonyl)amino)-3-((3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carbonyl)amino)propionic acid methyl esterYield 73.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 301 mg (0.77 mmol) of 2-amino-3-((3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carbonyl)amino)propionic acid methyl ester in 7.5 ml of dichloromethane, 135 mg (0.77 mmol) of (R)-3-acetylthiazolidin-4-carboxylic acid, 342 mg (0.77 mmol) of BOP reagent and 0.15 ml (0.86 mmol) of N,N-diisopropylethylamine were added, and the resulting mixture was stirred overnight at room temperature. To the reaction mixture, 10 ml of semi-saturated saline was added, and the resulting mixture was extracted with ethyl acetate. Organic phases were combined, washed with 0.5M hydrochloric acid, with saturated aqueous sodium hydrogen carbonate solution and with saturated saline, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (chloroform:methanol=100:1-10:1) to obtain 309 mg of 2-(((R)-3-acetylthiazolidin-4-carbonyl)amino)-3-((3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carbonyl)amino)propionic acid methyl ester (yield: 73%).

Workup

  1. additionTo the reaction mixture, 10 ml of semi-saturated saline was added
  2. extractionthe resulting mixture was extracted with ethyl acetate
  3. washwashed with 0.5M hydrochloric acid, with saturated aqueous sodium hydrogen carbonate solution and with saturated saline
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (chloroform:methanol=100:1-10:1)

Sources & evidence

ORD record
ord-9a629e58b5af4ee2a816cb30d8db9af7
Source dataset
uspto-grants-2005_07
Patent number
US06919349B2

Reaction notes

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