US 10,889,574 B2
Method for producing diphenylmethane derivative
Hee-kyoon Yoon, Cheongju-si (KR); Se-Hwan Park, Yongin-si (KR); Ji-sung Yoon, Yongi-si (KR); Soongyu Choi, Yongin-si (KR); Hee Jeong Seo, Yongin-si (KR); Eun-Jung Park, Yongin-si (KR); Younggyu Kong, Yongin-si (KR); Kwang-Seop Song, Yongin-si (KR); Min Ju Kim, Yongin-si (KR); and So Ok Park, Yongin-si (KR)
Assigned to DAEWOONG PHARMACEUTICAL CO., LTD., Hwaseong-si (KR); and GREEN CROSS CORPORATION, Yongin (KR)
Filed by DAEWOONG PHARMACEUTICAL CO., LTD., Gyeonggi-do (KR); and GREEN CROSS CORPORATION, Gyeonggi-do (KR)
Filed on Aug. 30, 2019, as Appl. No. 16/557,180.
Application 16/557,180 is a division of application No. 16/310,005, previously published as PCT/KR2017/006271, filed on Jun. 15, 2017.
Claims priority of application No. 10-2016-0075910 (KR), filed on Jun. 17, 2016.
Prior Publication US 2019/0382390 A1, Dec. 19, 2019
Int. Cl. C07D 409/04 (2006.01); C07D 407/04 (2006.01); C07D 307/78 (2006.01); B01D 9/00 (2006.01); C07B 51/00 (2006.01)
CPC C07D 409/04 (2013.01) [B01D 9/005 (2013.01); C07D 307/78 (2013.01); C07D 407/04 (2013.01); C07B 51/00 (2013.01); C07B 2200/13 (2013.01); Y02P 20/55 (2015.11)] 15 Claims
 
1. A method for producing a compound of the following Formula 1a, the method comprising the steps of:
(1) reacting a compound of the following Formula 2 with a compound of the following Formula 3 and subjecting the resultant to a cyclization reaction, to obtain a compound of the following Formula 4;
(2) subjecting the compound of Formula 4 to aldehydation or amidation, followed by reacting the resultant with a compound of the following Formula 5 and performing reduction, to obtain a compound of the following Formula 6; and
(3) reacting the compound of Formula 6 with a compound of the following Formula 7, and performing deprotection and reduction,

OG Complex Work Unit Drawing
in the formulae,
A is oxygen (O);
n is 1 or 2;
PG is a protecting group;
X′ is halogen or C1-7 alkyl;
X, Y, and Hal are each independently halogen;
B is (B-1)

OG Complex Work Unit Drawing
in which Ra, Rb, Rc, and Rd are each independently hydrogen, halogen, hydroxy, mercapto, cyano, nitro, amino, carboxy, oxo, C1-7 alkyl, C1-7 alkylthio, C2-7 alkenyl, C2-7 alkynyl, C1-7 alkoxy, C1-7 alkoxy-C1-7 alkyl, C2-7 alkenyl-C1-7 alkyloxy, C2-7 alkynyl-C1-7 alkyloxy, C3-10 cycloalkyl, C3-7 cycloalkylthio, C5-10 cycloalkenyl, C3-10 cycloalkyloxy, C3-10 cycloalkyloxy-C1-7 alkoxy, phenyl-C1-7 alkyl, C1-7 alkylthio-phenyl, phenyl-C1-7 alkoxy, mono- or di-C1-7 alkylamino, mono- or di-C1-7 alkylamino-C1-7 alkyl, C1-7 alkanoyl, C1-7 alkanoylamino, C1-7 alkylcarbonyl, C1-7 alkoxycarbonyl, carbarmoyl, mono- or di-C1-7 alkyl carbamoyl, C1-7 alkylsulfonylamino, phenylsulfonylamino, C1-7 alkylsulfinyl, C6-14 arylsulfanyl, C6-14 arylsulfonyl, C6-14 aryl, 5- to 13-membered heteroaryl, 5- to 10-membered heterocycloalkyl, 5- to 10-membered heterocycloalkyl-C1-7 alkyl, or 5- to 10-membered heterocycloalkyl-C1-7 alkoxy;
ring C is C3-10 cycloalkyl, C5-10 cycloalkenyl, C6-14 aryl, 5- to 13-membered heteroaryl, or 5- to 10-membered heterocycloalkyl;
the alkyl, alkenyl, alkynyl, and alkoxy are each independently unsubstituted, or have one or more substituents selected from the group consisting of halogen, hydroxy, cyano, nitro, amino, mercapto, C1-7 alkyl, and C2-7 alkynyl;
the cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocycloalkyl are each independently unsubstituted, or have one or more substituents selected from the group consisting of halogen, hydroxy, cyano, nitro, amino, mercapto, C1-4 alkyl, and C1-4 alkoxy; and
the heteroaryl and heterocycloalkyl each independently contain one or more heteroatoms selected from the group consisting of N, S, and O.