ChemicalBook CAS DataBase List lifitegrast impurity C

lifitegrast impurity C synthesis

6synthesis methods

Product Name:lifitegrast impurity C
CAS Number:851785-70-1
Molecular formula:C20H20Cl2N2O5S
Molecular Weight:471.35

851784-82-2 Synthesis

2-(tert-butoxycarbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid

851784-82-2
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$11.00/250mg

851785-21-2 Synthesis

methyl (S)-2-amino-3-(3-(methylsulfonyl)phenyl)propanoate hydrochloride

851785-21-2
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$18.00/100mg

851785-70-1
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Yield:851785-70-1 91.8%

Reaction Conditions:

Stage #1: 2-(tert-butoxycarbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid;methyl (2s)-2-amino-3-(3-(methylsulfonyl)phenyl)propionate hydrochloridewith N-ethyl-N,N-diisopropylamine;N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate in N,N-dimethyl-formamide at 0 - 20;
Stage #2: with hydrogenchloride in water;

Steps:

15 Example 15: Synthesis of (S)-2-(5,7-dichloro-l,2,3i4-tetrahydroisoquinoline-6- carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid

2-(ieri-butoxycarbonyl)-5,7-dichloro- l,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (20 g), HATU (27.5 g) was charged in DMF (60 ml) and diisopropyl ethylamine (22,2 g) was added. Reaction mass was cooled to 0-5°C and added methyl (S)-2-amino-3-(3- (m.ethylsuIfonyl)phenyl)propanoate hydrochloride (17.6g) lot wise at 0-5°C. Temperature of reaction mass was raised to room temperature. Stirred and reaction monitored by TLC. After completion of reaction, Water (100 ml) and MDC (100 ml) was added. Stirred and separated the layers. Organic layer washed with brine and 10% sodium carbonate solution. Organic layer distilled and charged 1 N HC1 (100 ml) to the residue. After complete hydrolysis pH of reaction mass was adjusted to 5.0-5.5 using sodium hydroxide solution. Reaction mass was filtered and solid so obtained was dried to get (S)-2-(5 ,7-dichloro- 1 ,2,3 ,4- tetrahydroisoquinoline-6-carb^ acid (25 g, (0185) 91.8% yield).

References:

WO2019/73325,2019,A1 Location in patent:Page/Page column 19