Diisopropylethylamine → (S)-N-(2-Hydroxy-1-(2-methylpyrimidin-5-yl)ethyl)-4'-methyl-5-(methylsulfonyl)biphenyl-3-carboxamide

HRID 1845250Notes

Reaction equation

HRID 1845250 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([S:14]([CH3:17])(=[O:16])=[O:15])[CH:11]=[C:10]([C:18]([OH:20])=O)[CH:9]=2)=[CH:4][CH:3]=1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[Si]([O:51][CH2:52][C@H:53]([C:55]1[CH:56]=[N:57][C:58]([CH3:61])=[N:59][CH:60]=1)[NH2:54])(C(C)(C)C)(C)C.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[OH:51][CH2:52][C@@H:53]([NH:54][C:18]([C:10]1[CH:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=2)[CH:13]=[C:12]([S:14]([CH3:17])(=[O:15])=[O:16])[CH:11]=1)=[O:20])[C:55]1[CH:56]=[N:57][C:58]([CH3:61])=[N:59][CH:60]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 581879934'-Methyl-5-(methylsulfonyl)biphenyl-3-carboxylic acidHCID 67053779(S)-2-(tert-butyldimethylsilyloxy)-1-(2-methylpyrimidin-5-yl)ethanamine

Product 1

HCID 58188351(S)-N-(2-Hydroxy-1-(2-methylpyrimidin-5-yl)ethyl)-4'-methyl-5-(methylsulfonyl)biphenyl-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4′-methyl-5-(methylsulfonyl)biphenyl-3-carboxylic acid (35 mg, 0.12 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (46 mg, 0.24 mmol), 1-hydroxybenzotriazole hydrate (18 mg, 0.12 mmol), and CH2Cl2 (3 mL) were added (S)-2-(tert-butyldimethylsilyloxy)-1-(2-methylpyrimidin-5-yl)ethanamine (48 mg, 0.18 mmol) (WO 2008/130481) and N,N-diisopropylethylamine (42 μL, 0.24 mmol). The mixture was stirred at room temperature overnight and then concentrated. The residue was dissolved in MeOH (5 mL) and concentrated HCl solution (0.5 mL) was added. The mixture was stirred at room temperature for 2 h and then concentrated in vacuo. The residue was purified by preparative HPLC (100×20.2 mm, C18 column; 30-80% MeCN-water[10 mM Et2NH]) to afford a white solid.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in MeOH (5 mL)
  3. additionconcentrated HCl solution (0.5 mL) was added
  4. stirringThe mixture was stirred at room temperature for 2 h
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC (100×20.2 mm, C18 column; 30-80% MeCN-water[10 mM Et2NH])
  7. customto afford a white solid

Sources & evidence

ORD record
ord-6d59e47b884f408bb1ab89b159985460
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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