Diisopropylethylamine → N-[2,6-dimethyl-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine methyl ester

HRID 1726775Notes

Reaction equation

HRID 1726775 reaction equation
[CH3:1][C:2]1[CH:10]=[C:9]([C:11]([NH:13][C@@H:14]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)[CH3:15])=[O:12])[CH:8]=[C:7]([CH3:26])[C:3]=1[C:4](O)=[O:5].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.[CH3:55][O:56][C:57](=[O:69])[C@H:58]([CH2:60][NH:61][C:62]([C:64]1[S:65][CH:66]=[CH:67][CH:68]=1)=[O:63])[NH2:59].C(N(C(C)C)CC)(C)C>ClCCl.C(OCC)(=O)C>[CH3:55][O:56][C:57](=[O:69])[C@H:58]([CH2:60][NH:61][C:62]([C:64]1[S:65][CH:66]=[CH:67][CH:68]=1)=[O:63])[NH:59][C:4](=[O:5])[C:3]1[C:2]([CH3:1])=[CH:10][C:9]([C:11]([NH:13][C@@H:14]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)[CH3:15])=[O:12])=[CH:8][C:7]=1[CH3:26]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 537457262,6-dimethyl-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoic acidHCID 688207093-(thiophene-2-carbonyl)amino-L-alanine methyl ester hydrochloride

Product 1

HCID 60115113N-[2,6-dimethyl-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine methyl esterYield 54.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2,6-dimethyl-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoic acid (Example 31; 100 mg, 0.29 mmol) in dichloromethane (1 mL) at 25° C. was added benzotriazol-1-yloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent, 140 mg, 0.32 mmol), 3-(thiophene-2-carbonyl)amino-L-alanine methyl ester HCl salt (Example 301; 114 mg, 0.43 mmol), followed by diisopropylethylamine (250 μL, 1.4 mmol) slowly dropwise. After stirring for 2 h, the reaction was diluted with ethyl acetate (50 mL) and washed with 1N HCl (10 mL), saturated aqueous sodium bicarbonate (10 mL) and brine (15 mL). The organic layer was dried (MgSO4), filtered, evaporated and flash chromatographed (silica, 50% ethyl acetate in petroleum ether) to give N-[2,6-dimethyl-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine methyl ester (88 mg, 54%) as an off-white solid.

Workup

  1. washwashed with 1N HCl (10 mL), saturated aqueous sodium bicarbonate (10 mL) and brine (15 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customflash chromatographed (silica, 50% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-60f9742ba886477494880f7ef6de669e
Source dataset
uspto-grants-2009_02
Patent number
US07491741B2

Reaction notes

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