Browse Prior Art Database

IMPURITIES OF (R)-2-(3-(DIISOPROPYLAMINO)-1-PHENYLPROPYL)-4-(HYDROXYMETHYL) PHENOL AND ITS SALT

IP.com Disclosure Number: IPCOM000235756D
Publication Date: 2014-Mar-25
Document File: 3 page(s) / 72K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 52% of the total text.

Page 01 of 3

IMPURITIES OF (R)-2-(3-(DIISOPROPYLAMINO)-1-PHENYLPROPYL)-4- (HYDROXYMETHYL) PHENOL AND ITS SALT

    ((R)-(3-(3-(Diisopropyl-amino)-1-Phenylpropyl)-4-hydroxyphenyl) phenol, referred as to 'compound A', has the following formula:

    For the purpose of clarity and as an aid in the understanding of the impurities involved in the synthesis of Compound A and its salt, as disclosed herein, the following terms and abbreviations are defined below:

Impurity 1 (R)-(3-(3-(Diisopropyl-amino)-1-Phenylpropyl)-4-methoxyphenyl)methanol

Impurity II (R)-3-(2-hydroxy-5-(hydroxymethyl) phenyl)-N,N-diisopropyl-3-phenyl propan-1-amine oxide

Impurity III 2-((S)-3-(diisopropylamino)-1-phenylpropyl)-4-((2-((R)-3-(diisopropylamino)-1- phenylpropyl)-4-(hydroxymethyl) phenoxy)methyl)phenol

1


Page 02 of 3

[M+H] 665.4

Impurity IV (2-((S)-3-(diisopropylamino)-1-phenylpropyl)-4-(2-((R)-3-(diisopropylamino)-1- phenylpropyl)-4-(hydroxymethyl) phenoxy) phenyl)methanol

[M+H] 665.4

Impurity 1: (R)-(3-(3-(Diisopropyl-amino)-1-Phenylpropyl)-4-methoxyphenyl)methanol

    Impurity 1 may be prepared comprising oxidation of N,N-diisopropyl-3-(2-methoxy-5- methylphenyl)-3-phenylpropan-1-amine with FeSO4.7H2O-Na2S2O8 in acetonitrile-water (17vol. each) solvent mixture followed by reduction in sodium borohydride to obtain impurity I with HPLC purity >97%.

H1 NMR: 0.84(12H) dd, 2.01(2H) m, 2.25(2H) m, 2.89(1H) m, 3.70(3H) S, 4.32 (1H) t,
4.38(2H) d, 6.85 (1H) d, 7.08(1H) dd, 7.13(1H) m, 7.24(5H) m. C13 NMR: 36.40, 40.96,
43.65, 48.43, 55.98, 63.24, 111.07, 125.94, 126.23, 126.31,128.34, 128.59, 133.03, 134.43, 145.21, 153.94.

2


Page 03 of 3

The N,N-diisopropyl-3-(2-methoxy-5-methylphenyl)-3-phenylpropan-1-amine used to prepare impurity I can be obtained commercially or it can be...