Patent JP-5315047-B2 (JP)
IPC: C07D239/42
Filed: 2006-05-17
Granted: 2013-10-16
Abstract: Preparation of an indole compound (I) comprises either reacting a boroindole compound (IV) with an aminopyrimidine compound (V) or with pyrimidine compound (VI) to obtain an indole compound (VII); or subsequently reacting (VII) with an amine compound (H-N(R2)(R3)); or reacting an alkenyl compound (IX) with (V) to obtain aminophenyl compound (X); and isolating (I) in free or its salts. Preparation of an indole compound of formula (I) comprises either reacting a boroindole of formula (IV) with an aminopyrimidine of formula (V) or with pyrimidine compound of formula (VI) to obtain an indole compound of formula (VII); or subsequently reacting (VII) with an amine compound of formula (H-N(R2)(R3)); or reacting an alkenyl compound of formula (IX) with (V) to obtain aminophenyl compound of formula (X); and isolating (I) in free form or its salts. R1 : H, 1-12C-alkyl, 6-14C-aryl, 3-8C-cycloalkyl or 4-15-membered het ring; R2, R3 : H, 1-12C-alkyl, 6-14C-aryl (where aryl is optionally substituted by 1-6C-alkyl, 3-8C-cycloalkyl 4-15-membered het ring); P : H or for hydrogen atom or for a N-protecting group; either R4, R5 : OH, O-1-12C-alkyl, O-6-14C-aryl, O-3-8C-cycloalkyl, 1-12C-alkyl or O-het (where het is 4-15 membered het ring); or R4R5B : a ring with 4-7C, where carbon atoms are carbon atoms in the ring and the ring instead of the respective carbon atoms two oxygen atoms or contained two oxygen atoms and a nitrogen atom; and X, Y 1>hal, O-SO 2-R2 or O-C(O)-R2. Independent claims are included for: (1) indole compounds of formula (II); (2) a indole compound (IV); (3) the preparation of (IV), comprising reacting an indole compound of formula (XI) with a base; subsequently reacting with boronic acidester of formula B(R4)-R5 and optionally removing the N-protecting group; (4) an amino benzene compound of formula (X); and (5) an amino benzene compound of formula (XVI). R1 : H, 1-12C-alkyl, 6-14C-aryl, 3-8C-cycloalkyl or 4-15-membered het ring, preferably H or C 2H 5; R2 : H; R3 : 1-4C-alkyl; P : H, C(O)-O-R6, SO 3-R6, O-SO 2-R6, Si-R6 or benzyl, preferably H, O-tosylate or benzyl; R6 : H, 1-12C-alkyl, 6-14C-aryl (where aryl is optionally substituted by one, two or three 1-6C-alkyl), 3-8C-cycloalkyl or 4-15-membered het ring; D : N(R2)-R3, halo, O-SO 2-R2 or O-C(O)-R2, preferably Cl or N(R2)(R3); R2, R3 : H, 1-12C-alkyl, 6-14C-aryl (where the aryl is optionally substituted by one, two or three 1-6C-alkyl), 3-6C-cycloalkyl or 4-15-membered het ring, preferably H or 1-4C-alkyl; and either R4, R5 : OH, O-1-12C-alkyl, O-6-14C-aryl, O-3-8C-cycloalkyl, 1-12C-alkyl or O-het (where het is a 4-15-membered het ring); or R4R5B : 4-7C ring, where the carbon atoms are optionally substituted by two O or N atoms, preferably borolane, boronane, borepane, borocane, [1,3,2]dioxaborolane, [1,3,2]dioxaborinane, [1,3,2]dioxaborepane, [1,3,2]dioxaborocane or [1,3,6,2]dioxazaborocane. Where when P is H and D is N(R2)(R3), then R1 is not H; when P is C(O)-O-1-12C-alkyl and R1 is 1-12C-alkyl, then R4 and R5 is not OH. In formula (II): R1 : H, 1-12C-alkyl, 6-14C-aryl, 3-8C-cycloalkyl or 4-15-membered het ring, preferably H or C 2H 5; and P : H, C(O)-O-R6, SO 3-R6, O-SO 2-R6, Si-R6 or benzyl, preferably H, O-tosylate or benzyl. In formula (IV): R1 : H, 1-12C-alkyl, 6-14C-aryl, 3-8C-cycloalkyl or 4-15-membered het ring, preferably acridinyl, azepinyl, azetidinyl, aziridinyl, benzimidazalinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4H-carbazolyl, carbolinyl, quinazolyl, quinolinyl, 4H-quinolinyl, qunoxalinyl, quinuclidinyl, chromyl, chromenyl, deca-hydroquinolinyl, dibenzofuranyl, dibenzothiophenyl, dihydrofuran[2,3-b]-tetrahydrofur anyl, dihydrofuranyl, di-oxolyl, dioxanyl, 2H, 6H-1,5,2-dithiazinyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolyl, benzimidazolyl, isothiazolidinyl, 2-isothiazolinyl, isothiazolyl, isoxazolyl, isoxazolidinyl, 2-isoxazolinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxa-diazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinyl, oxothiolanyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, piperidinyl, purynyl, pyranyl, pyrazinyl, pyroazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pryidooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridothiophenyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinoliyl, tetrahydropyridinyl, 6H-1,2,5-thiadazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiomorpholinyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl or xanthenyl; and P : H. 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