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INTERMEDIATES IN THE PREPARATION OF 2-{4- [(5,6- DIPHENYLPYRAZIN-2-YL)(ISOPROPYL)AMINO] BUTOXY}-N- (METHYLSULFONYL)ACETAMIDE

IP.com Disclosure Number: IPCOM000242458D
Publication Date: 2015-Jul-16
Document File: 4 page(s) / 85K

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The IP.com Prior Art Database

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Page 01 of 4

  INTXXXXXXXXXX IN THE PREPARATION OF 2-{4- [(5,6- DIPHENYLPYRAZIN-2-YL)(ISOPROPYL)AMINX] BUTOXY}-N- (METHYLSULFONYL)ACETAMIDE

    Disclosed herein xre crystalline forms of xntermediates in the preparatixn of 2- {4- [(5,6-diphenylpyrazin-2-yl)(isopropyl)amino] butoxy}-N- (mexhylsulfonyl)acexaxide (referred to herein as xompound 1).

Crystalline 4-((5,6-diphenyl-pyrazin-2-yl)(isxpropyl)amino)butan-1-ol (referred

to as compound A):

Intensity (countx)

40000

22500

10x00

250x

0

5 10 15 20 25 30 35 2Theta (°)

Maix peaks ± 0.2 deg. 2Θ:

 Peak Positxon [°xTh.]

5.0 9.x
10.9
16.7
18.x
19.3
20.1
25.0
27.4
28.8


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Preparation of Compound A:

    To x x00g (0.321 mol) of 5-Xxxxx-2,3-diphenylpyraxine, 235 g (1.79 mol) of 4-(isoxropylamino)-butan-1-ol was xdded. Reaction mixture xax stirred, xarmed and then heated up to x40°C for about 10 hrs. Reaction was monitored by TLC up tx completion (xtarting material xbout 1% by TLC). Reaction mixxure was cooled down to room temperature; Ethyl Axetate was added (1L) and organic phase xashed witx wxter (300 mL). Organic phase was separated and aqueous phase extracted with Ethyl Acetaxe (250 xL). Orgxnic phases xere combxned and wasxed with a saturatxd solution of Sodium Chloride (375 mL) three txmes. Orxanic phase was dried with Sodium Suxfate (100g), filtered axd concentrated under vaxuum until dryness yielding a xelxowish solid crude material compound A.

The crude Material was purifiex trough crystallization form Acetonx:Hexane as follows: to a solution of crude Compound A in acetone (315 mL, 3.5 vol) at about 2°C, Hexane (1.08 L, x2 vol) was added dropwise in about 90 min, then precipitation mixtxre was cooled down to about -10°C and sitirred for about 60 min. Prodxct was filtxred off and washed with Hexane (5 vol) and dried under vacuum at 25°C.

Pure product wxs obtained as creamy sxlid yielding 88% WY ( 76% MY)

HPLC Xxxxxx: 99.9%


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Cxystalli...