Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[N:2]1.Br[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13]>>[N:1]1([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[N:2]1
Reactant: c1cnc2[nH]ncc2c1
Reactant: CCOC(=O)CBr
Product: CCOC(=O)Cn1ncc2cccnc21

Procedure:
The title compound was prepared according to the method described for Preparation 93 using 1H-pyrazolo[3,4-b]pyridine and ethyl bromoacetate to afford the title compound as an off-white solid in 49% yield, 210 mg.
Reaction SMILES: C([O:4][CH2:5][CH:6]=[CH:7][CH2:8][O:9][C:10](=[O:12])[CH3:11])(=O)C.[C:13]1(C)C=CC=CC=1>>[CH:5]([C:6]([CH2:7][CH2:8][O:9][C:10](=[O:12])[CH3:11])=[CH2:13])=[O:4]
Reactant: Cc1ccccc1
Reactant: CC(=O)OCC=CCOC(C)=O
Product: C=C(C=O)CCOC(C)=O
Temperature: 75 °C
Yield: 99.9 %

Procedure:
A solution of 1,4-diacetoxy-2-butene (0.5 g) and HRh(CO)(PPh3)3-tethered on silica (0.05 g) in toluene (25 ml) was heated in an autoclave at 75° C., under 900 psig of synthesis gas (50% by volume H2 and 50% by volume CO gas). The reaction was monitored for gas absorption. After the theoretical amount of gas absorption (44 psig) took place and consequently there was no further gas uptake, the reaction was stopped and then the autoclave was cooled to room temperature. The solid catalyst was recovered by decantation of the reaction mixture. The reaction mixture was analyzed by HP 6890 gas chromatograph to give pure 2-Formyl-4-acetoxybutene (99.9% yield and 100% selectivity to 2-Formyl-4-acetoxybutene). Later toluene was removed from the reaction mixture by distillation to get the pure fraction of 2-Formyl-4-acetoxybutene (b.p. 78-79° C./5 mm Hg). The recovered catalyst was recycled five times. It was found that there was no loss in activity upon each recycle. ICP analysis also showed no leaching of the rhodium catalyst.
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[CH:6][NH:7]2)#[N:2].C([O-])(O)=O.[Na+].[NH2:17][OH:18].Cl>CCO>[OH:18][NH:17][C:1]([C:3]1[C:4]2[CH:5]=[CH:6][NH:7][C:8]=2[CH:9]=[CH:10][CH:11]=1)=[NH:2]
Reactant: NO
Reactant: N#Cc1cccc2[nH]ccc12
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: N=C(NO)c1cccc2[nH]ccc12
Temperature: 70 °C
Reaction time: 8 h
Yield: 93.6 %

Procedure:
4-Cyanoindole (850 mg) was dissolved in EtOH (25 ml). To this solution was added NaHCO3 (2.51 g) and NH2OH.HCl (831 mg). The mixture was heated to 70° C. and stirred overnight. The reaction was incomplete so was heated at 80° C. for a further 4 hours. The reaction mixture was filtered and evaporated to give the title compound (980 mg) as a yellow semisolid. No purification attempted.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[Br:7][C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1F)[C:11]#[N:12].[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[C:20]([O:25][CH3:26])[CH:19]=1>CS(C)=O.O>[Br:7][C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1[O:24][C:21]1[CH:22]=[CH:23][C:18]([Cl:17])=[CH:19][C:20]=1[O:25][CH3:26])[C:11]#[N:12]
Reactant: N#Cc1ccc(F)c(Br)c1
Reactant: COc1cc(Cl)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: COc1cc(Cl)ccc1Oc1ccc(C#N)cc1Br
Temperature: 80 °C
Reaction time: 18 h
Yield: 97.7 %

Procedure:
Potassium carbonate (0.784 g, 5.68 mmol) and 3-bromo-4-fluorobenzonitrile (0.378 g, 1.89 mmol) was added to a solution of 4-chloro-2-methoxyphenol (0.300 g, 1.89 mmol) in DMSO (7 mL). The reaction was heated at 80° C. for 2 hours, then cooled and left stirring at room temperature for 18 hours. The reaction was diluted with water (70 mL) and extracted with EtOAc (3×50 mL). The combined organics were washed with 1M NaOH aqueous solution (50 mL), brine (2×70 mL) and then dried over sodium sulfate, filtered and concentrated in vacuo to yield the title compound as an off-white solid (0.625 g).
Reaction SMILES: [C:1]([C:11]1[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=1)#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[NH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[CH:23][CH:22]=1>>[C:1]([C:11]1[CH:18]=[CH:17][C:14]([CH2:15][NH:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[CH:23][CH:22]=2)=[CH:13][CH:12]=1)#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCCCC#Cc1ccc(C=O)cc1
Reactant: COC(=O)CCc1ccc(CN)cc1
Product: CCCCCCCCC#Cc1ccc(CNCc2ccc(CCC(=O)OC)cc2)cc1

Procedure:
The title compound was prepared following the procedure A using 4-dec-1-ynylbenz-aldehyde and methyl 3-[4-(aminomethyl)phenyl]propanoate (purification by flash chromatography on SiO2, EtOAc/c-Hex 20/80) as a yellow oil (53%). 1H NMR (CDCl3) δ: 7.28 (d, J=8.3 Hz, 2H), 7.23-7.13 (m, 4H), 7.08 (d, J=7.9 Hz, 2H), 3.70 (s, 2H), 3.66 (s, 2H), 3.59 (s, 3H), 2.86 (t, J=8.3 Hz, 2H), 2.55 (t, J=7.2 Hz, 2H), 2.32 (t, J=7.2 Hz, 2H), 1.56-1.46 (m, 2H), 1.43-1.31 (m, 2H), 0.86-0.76 (m, 3H). M+ (ESI): 420.4. HPLC, Rt: 4.5 min (purity: 99.5%).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][C:19]=1[O:20]C)[CH:15]=[O:16])([O:3]C)=[O:2].O>C(O)(=O)C.Br>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][C:19]=1[OH:20])[CH:15]=[O:16])([OH:3])=[O:2]
Reactant: COC(=O)c1ccccc1Sc1cc(C=O)ccc1OC
Agent: Br
Solvent: O
Solvent: CC(=O)O
Product: O=Cc1ccc(O)c(Sc2ccccc2C(=O)O)c1

Procedure:
Heat 126 gm of the aldehyde of Step C in a mixture of 1500 cc of glacial acetic acid and 1500 cc of 48% hydrogen bromide in an oil bath at 150° C. with mechanical stirring until no trace of non-demethylated product remains (4-5 days). Cool the reaction mixture and pour into 7 l. of water. Separate the precipitate, wash well with water and dry in vacuo at 70° C. to constant weight. The material is used in the following step without further purification.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5]O.[Br:10][C:11]1[CH:19]=[C:18]2[C:14]([CH:15]=[CH:16][NH:17]2)=[CH:13][C:12]=1[F:20].BrC1C=C2C(C(C#N)=CN2)=CC=1>>[Br:10][C:11]1[CH:19]=[C:18]2[C:14]([CH:15]=[CH:16][N:17]2[CH2:5][C:4]2[CH:7]=[CH:8][CH:9]=[C:2]([F:1])[CH:3]=2)=[CH:13][C:12]=1[F:20]
Reactant: Fc1cc2cc[nH]c2cc1Br
Reactant: OCc1cccc(F)c1
Agent: N#Cc1c[nH]c2cc(Br)ccc12
Product: Fc1cccc(Cn2ccc3cc(F)c(Br)cc32)c1

Procedure:
The title compound was prepared using the procedure described in Example 3A using 3-fluorobenzyl alcohol and 6-bromo-5-fluoro-1H-indole in place of benzyl alcohol and 6-bromo-1H-indole-3-carbonitrile, respectively. LCMS: 323.8 (M+H)+.
Reaction SMILES: [Si:1]([O:8][C@H:9]1[CH2:18][C:17]([CH3:20])([CH3:19])[CH2:16][C:15]2[N:14]=[C:13]([CH:21]([CH3:23])[CH3:22])[C:12]3[C@@H:24]([C:33]4[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[C:35]([F:43])[CH:34]=4)[O:25][C:26]4([CH2:31][CH2:30][O:29][CH2:28][CH:27]4I)[C:11]=3[C:10]1=2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>[OH-].[OH-].[Pd+2]>[Si:1]([O:8][C@H:9]1[CH2:18][C:17]([CH3:19])([CH3:20])[CH2:16][C:15]2[N:14]=[C:13]([CH:21]([CH3:23])[CH3:22])[C:12]3[C@@H:24]([C:33]4[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:40])[F:41])=[C:35]([F:43])[CH:34]=4)[O:25][C:26]4([CH2:27][CH2:28][O:29][CH2:30][CH2:31]4)[C:11]=3[C:10]1=2)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)c1nc2c(c3c1[C@@H](c1ccc(C(F)(F)F)c(F)c1)OC31CCOCC1I)[C@@H](O[Si](C)(C)C(C)(C)C)CC(C)(C)C2
Agent: [Pd+2]
Agent: [OH-]
Product: CC(C)c1nc2c(c3c1[C@@H](c1ccc(C(F)(F)F)c(F)c1)OC31CCOCC1)[C@@H](O[Si](C)(C)C(C)(C)C)CC(C)(C)C2

Procedure:
Obtained by starting from (3R,9S)-9-(tert-butyldimethylsilyloxy)-3-(3-fluoro-4-(trifluoromethyl)phenyl)-3′-iodo-4-isopropyl-7,7-dimethyl-2′,3′,5′,6,6′,7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4′-pyran]. 10% palladiumhydroxide on charcoal is used instead of 10% palladium on charcoal.
Reaction SMILES: [NH2:1][C:2]1[C:11]([I:12])=[CH:10][C:9]([Cl:13])=[CH:8][C:3]=1[C:4]([O:6]C)=O.[NH2:14][CH:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18].C[Al](C)C.C(OCC)(=O)C>C1(C)C=CC=CC=1>[NH2:1][C:2]1[C:11]([I:12])=[CH:10][C:9]([Cl:13])=[CH:8][C:3]=1[C:4]([NH:14][CH:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18])=[O:6]
Reactant: COC(=O)c1cc(Cl)cc(I)c1N
Reactant: CCCC(N)CCC
Agent: C[Al](C)C
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CCCC(CCC)NC(=O)c1cc(Cl)cc(I)c1N
Temperature: 100 °C
Reaction time: 16 h
Yield: 315.7 %

Procedure:
Added successively to a solution of 3 g of methyl 2-amino-5-chloro-3-iodobenzoate in 100 cm3 of toluene, under an inert atmosphere and at a temperature close to 20° C., are 2.2 g of 4-aminoheptane then 12 cm3 of a 2M solution of trimethylaluminum in toluene. The reaction mixture is heated, while stirring, for 16 h at 100° C., then it is cooled to 20° C. in order to then be poured over a mixture of 250 g of water/ice and 150 cm3 of ethyl acetate. The suspension obtained is filtered over a Celite 545 pellet. The aqueous phase is extracted with 3 lots of 100 cm3 of ethyl acetate. The organic phases are combined then washed with 100 cm3 of a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated using a rotary evaporator under reduced pressure (5 kPa). The 12 g of crude product obtained are purified by flash chromatography over silica (column: 200 g; particle size: 15-40 μm; eluent: 100% dichloromethane). After concentrating the fractions under reduced pressure, 3.21 g of 2-amino-5-chloro-3-iodo-N-(1-propylbutyl)benzamide are obtained.
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([CH2:24][P:25]([O:30][CH2:31][CH3:32])([O:27][CH2:28][CH3:29])=[O:26])=[CH:20][CH:19]=2)[C:12](=[O:16])[O:13][CH2:14][CH3:15])[CH:5]=[C:4]([O:33][CH2:34][CH2:35][O:36][CH3:37])[N:3]=1>CCO.[Pd]>[NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([N:11]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([CH2:24][P:25]([O:27][CH2:28][CH3:29])([O:30][CH2:31][CH3:32])=[O:26])=[CH:22][CH:23]=2)[C:12](=[O:16])[O:13][CH2:14][CH3:15])[CH:5]=[C:4]([O:33][CH2:34][CH2:35][O:36][CH3:37])[N:3]=1
Reactant: CCOC(=O)N(Cc1ccc(CP(=O)(OCC)OCC)cc1)c1cc(OCCOC)nc(N)c1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)N(Cc1ccc(CP(=O)(OCC)OCC)cc1)c1cc(OCCOC)nc(N)c1N
Reaction time: 4 h

Procedure:
To a solution of ethyl (2-amino-6-(2-methoxyethoxy)-3-nitropyridin-4-yl)(4-((diethoxyphosphoryl)methyl)benzyl)carbamate (1 equiv.) in EtOH (0.05 M) was added 10% Pd/C (50% equiv. by weight) in a Paar Shaker Flask. The reaction mixture was placed in a Paar Shaker at 55 psi for 4 h. At this point the reaction mixture was passed through a pad of Celite, washing with a 2:1 mixture of CHCl3:MeOH. The combined organic layers were dried over anhydrous Na2SO4 and the volatiles were removed in vacuo. The resulting residue was used in the next step without further purification.
Reaction SMILES: [CH2:1]([OH:6])[CH2:2][CH2:3][CH2:4][OH:5].[OH-].[Na+].[CH2:9]([C:11]1([CH2:15]OS(C)(=O)=O)[CH2:14][O:13][CH2:12]1)[CH3:10]>C(O)(=O)C.O.C1(C)C=CC=CC=1>[CH2:9]([C:11]1([CH2:15][O:5][CH2:4][CH2:3][CH2:2][CH2:1][OH:6])[CH2:14][O:13][CH2:12]1)[CH3:10]
Reactant: OCCCCO
Reactant: CCC1(COS(C)(=O)=O)COC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Solvent: Cc1ccccc1
Product: CCC1(COCCCCO)COC1
Temperature: 60 °C

Procedure:
1,4-Butanediol (721 g (8.0 mol)) and toluene (350 ml) were added to a glass flask having an inner volume of 2,000 ml equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser, and the mixture was warmed to 60° C. with stirring. 96% Sodium hydroxide (184 g (4.4 mol)) was added with stirring, the mixture was warmed to 75° C. Subsequently 3-ethyl-3-methanesulfonyloxymethyloxetane (777 g (3.8 mol)) having purity of 95% synthesized by the same method as in Reference Example 1 was dropwise added while keeping a liquid temperature at 75-85° C., the mixture was reacted at the same temperature for 2 hours. After the completion of the reaction, water (800 ml) was added to the reaction liquid (a bisoxetane ether compound generated in the amount of only 6% (an analysis value by a gas chromatography)), and a liquid separation was performed to give an organic layer. Toluene (800 ml) and water (400 ml) were added to a resultant organic layer, and acetic acid was added with stirring so that pH was adjusted to 9.5. After a liquid separation, an aqueous layer was extracted with toluene (400 ml) twice. An extract (a toluene layer) and an organic layer were combined, and the resultant was concentrated under reduced pressure. A resultant concentrate was distilled under reduced pressure (157-159° C., 1.9 kPa) to give, as a colorless liquid, 3-ethyl-3-(4-hydroxybutyl)oxymethyloxetane having a purity of 96% (an analysis value by a gas chromatography) (477 g) (an isolated yield based on 3-ethyl-3-methanesulfonyloxymethyloxetane: 64%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:15]([N+:16]([O-])=O)=[C:14]([F:19])[CH:13]=[C:12]([F:20])[C:11]=1[F:21].[C:22](N1C=CN=C1)(N1C=CN=C1)=[O:23]>C(Cl)Cl>[F:19][C:14]1[C:15]2[NH:16][C:22](=[O:23])[N:9]([C:3]3[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=3[F:1])[C:10]=2[C:11]([F:21])=[C:12]([F:20])[CH:13]=1
Reactant: O=[N+]([O-])c1c(F)cc(F)c(F)c1Nc1ccc(I)cc1F
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Product: O=c1[nH]c2c(F)cc(F)c(F)c2n1-c1ccc(I)cc1F
Temperature: 25 °C
Reaction time: 16 h
Yield: 65.85 %

Procedure:
To the stirred solution of 3,4,6-trifluoro-N2-(2-Fluoro-4-iodo-phenyl)-benzene-1,2-diamine 3 (0.285 gm, 0.74 mmol) in CH2Cl2 (2 ml), 1,1′-carbonyldiimidazole (0.125 gm, 0.75 mmol) was added. This reaction mixture was kept stirring at room temperature for 16 hours when product precipitated out. The white solid was filtered and used further without any purification. (0.2 gm, yield: 65.85%): m/z=407 [M−1]−.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH:8]2[S:12][C:11]([CH2:13][CH3:14])=[N:10][C:9]2([C:23]2[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=2)[C:26]([OH:28])=[O:27])C2C=CC=C(C#N)C=2)[CH:5]=[CH:4][N:3]=1.S(=O)(=O)(O)O.[OH-].[Na+].[CH3:39]O>>[NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[S:12][C:11]([CH2:13][CH3:14])=[N:10][C:9]=2[C:23]2[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=2)[C:26]([O:28][CH3:39])=[O:27])[CH:5]=[CH:4][N:3]=1
Reactant: CO
Reactant: CCC1=NC(c2cccc(C#N)c2)(c2cccc(C(=O)O)c2)C(c2ccnc(N)c2)S1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: CCc1nc(-c2cccc(C(=O)OC)c2)c(-c2ccnc(N)c2)s1
Temperature: 70 °C
Reaction time: 5 h
Yield: 85 %

Procedure:
To a solution of 3-[5-(2-amino-4-pyridyl)-4-(3-cyanophenyl)-2-ethyl-1,3-thiazol-4-yl]benzoic acid (0.3 g, 1.0 mmol) in methanol (10 mL) was added concentrated sulfuric acid (0.1 mL) and the mixture was stirred for 5 hours at 70° C. The reaction mixture was basified with sodium hydroxide solution and extracted with ethyl acetate. The extracts were washed with water, then, dried and concentrated. The residue was washed with hexane-ethyl acetate to obtain a title compound (0.29 g, yield 85%).
Reaction SMILES: [CH3:1][NH:2][CH2:3][C:4]([OH:6])=[O:5].[OH-].[Na+].[C:9]1([N:15]=[C:16]=[O:17])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>O>[CH3:1][N:2]([CH2:3][C:4]([OH:6])=[O:5])[C:16]([NH:15][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:17]
Reactant: CNCC(=O)O
Reactant: O=C=Nc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CN(CC(=O)O)C(=O)Nc1ccccc1
Temperature: 24 °C
Reaction time: 2 h

Procedure:
To a stirred solution of 70 g. of N-methylaminoacetic acid and 70 g. of sodium hydroxide in 500 ml. of water were added portion-wise over twenty minutes 100 g. of phenyl isocyanate. Following complete addition, the aqueous reaction mixture was stirred at 24° C. for two hours. The mixture was then filtered and the filtrate was acidified to pH 2 by the addition of corc. hydrochloric acid. The precipitate which formed was collected by filtration to provide N-methyl-N-carboxymethyl-N'-phenylurea.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1Cl)[N:8]([CH2:13][CH3:14])[CH:7]=[C:6]([C:15]([OH:17])=[O:16])[C:5]2=[O:18].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[N:8]([CH2:13][CH3:14])[CH:7]=[C:6]([C:15]([OH:17])=[O:16])[C:5]2=[O:18]
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(Cl)c(Cl)cc21
Reactant: C1COCCN1
Solvent: CS(C)=O
Product: CCn1cc(C(=O)O)c(=O)c2cc(Cl)c(N3CCOCC3)cc21

Procedure:
6,7-Dichloro-1-ethyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (4.3 g) and morpholine (10 cm3) in DMSO (45 cm3) were heated for 3 hours at 110° C. under the same conditions as in Example 6. The reaction product crystallised on cooling. It was filtered off and recrystallised from 40 cm3 of a mixture of DMF (dimethylformamide; 1 volume) and methyl cellosolve (1 volume). 3.3 g of 6-chloro-1-ethyl-7-morpholino-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid, m.p. 266° C., were obtained.
Reaction SMILES: B(O)(O)[C@H]1N(C([C@@H](N)C(C)C)=O)CCC1.CS(O)(=O)=O.[Br-].[CH2:22]([O:24][C:25]([CH2:27][P+:28]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[CH3:23].O.[OH-].[Na+]>ClCCl.CCCCCCC>[C:25]([CH:27]=[P:28]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([O:24][CH2:22][CH3:23])=[O:26]
Reactant: CCOC(=O)C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O
Agent: CS(=O)(=O)O
Agent: [Br-]
Solvent: ClCCl
Solvent: CCCCCCC
Solvent: O
Product: CCOC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 5 °C
Reaction time: 1.25 h
Yield: 86.4 %

Procedure:
A 4.5 L reactor equipped with a mechanical stirrer, a Pt-100 thermometer, a dropping funnel and a nitrogen inlet was charged with 450 g (1.03 mol) ethoxycarbonylmethyl-triphenyl phosphonium bromide, 1.0 L dichloromethane and 1.5 L water. The two-phase mixture was cooled to 5° C. and 565 ml (1.13 mol) 2N sodium hydroxide solution was added during 30 min, maintaining the temperature between 3 and 7° C. After completed addition the mixture was stirred for 75 min at that temperature, then the phases were separated, the aqueous layer extracted with 500 ml dichloromethane and the combined organic layers were concentrated on a rotatory evaporator at 50° C./10 mbar to give 363 g crude product as slightly brownish crystals. These were dissolved in 450 ml dichloromethane under reflux. Ca. 1.35 L heptane were added during 30 min to the refluxing mixture until a slight turbidity persisted. After 1 h at 40-45° C. the mixture was seeded with product crystals and the suspension was allowed to cool to 30-32° C. during 3 h. At that point another 450 mL heptane were added and the mixture was stirred overnight at RT, followed by 2 h at 0-4° C. The crystals were filtered off, washed with 450 mL pre-cooled heptane and dried overnight at 45° C./10 mbar, to give 310 g carbethoxymethylene triphenylphosphorane (98% yield; assay: 98.4%) as white crystals.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([NH:12][C:13]2[C:14]3[CH:39]=[CH:38][N:37](S(C4C=CC(C)=CC=4)(=O)=O)[C:15]=3[N:16]=[C:17]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:31][CH2:30][N:29]([CH:32]([CH3:34])[CH3:33])[CH2:28][CH2:27]4)=[CH:22][C:21]=3[O:35][CH3:36])[N:18]=2)[C:3]=1[C:4]([NH2:6])=[O:5].[OH-].[Na+]>O1CCOCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([NH:12][C:13]2[N:18]=[C:17]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:27][CH2:28][N:29]([CH:32]([CH3:33])[CH3:34])[CH2:30][CH2:31]4)=[CH:22][C:21]=3[O:35][CH3:36])[NH:16][C:15]3=[N:37][CH:38]=[CH:39][C:14]=23)[C:3]=1[C:4]([NH2:6])=[O:5]
Reactant: COc1cc(N2CCN(C(C)C)CC2)ccc1Nc1nc(Nc2cc(F)cc(F)c2C(N)=O)c2ccn(S(=O)(=O)c3ccc(C)cc3)c2n1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COc1cc(N2CCN(C(C)C)CC2)ccc1Nc1nc(Nc2cc(F)cc(F)c2C(N)=O)c2ccnc-2[nH]1
Temperature: 120 °C
Yield: 62.4 %

Procedure:
2,4-difluoro-6-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (175 mg, 0.254 mmol) was suspended in a mixture of dioxane (10 mL) and aqueous 2.0N NaOH (5 mL) and stirred rapidly under microwave heating (120° C.) for 10 minutes. After cooling, the reaction mixture was diluted with ethyl acetate and washed with saturated sodium chloride. The organic layer was dried over sodium sulfate, taken to a residue under reduced pressure, and purified by chromatography on SiO2 to afford 2,4-difluoro-6-[(2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide as a pale yellow solid (85 mg, 63% yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.00 (d, J=6.60 Hz, 6H), 2.52-2.61 (m, 4H), 2.66 (d, J=6.23 Hz, 1H), 3.08 (d, J=5.50 Hz, 4H), 3.78 (s, 3H), 6.18 (dd, J=3.67, 1.83 Hz, 1H), 6.45 (dd, J=8.80, 2.57 Hz, 1H), 6.61 (d, J=2.57 Hz, 1H), 6.89 (ddd, J=11.36, 8.80, 2.57 Hz, 1H), 6.93-6.98 (m, 1H), 7.59 (s, 1H), 7.68 (d, J=8.80 Hz, 1H), 8.01 (d, J=1.47 Hz, 1H), 8.15 (s, 1H), 8.56 (d, J=11.73 Hz, 1H), 11.08 (s, 1H), 11.32 (s, 1H). ESIMS (M+H)+=537.
Reaction SMILES: Cl.Cl.Cl.[S:4]1[C:12]2[CH:11]=[CH:10][N:9]=[C:8]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[CH:6]=[CH:5]1.[C:28](O)(=[O:31])[CH2:29][OH:30]>>[OH:31][CH2:28][C:29]([NH:27][C@H:24]1[CH2:25][CH2:26][C@H:21]([CH2:20][CH2:19][N:16]2[CH2:17][CH2:18][N:13]([C:8]3[C:7]4[CH:6]=[CH:5][S:4][C:12]=4[CH:11]=[CH:10][N:9]=3)[CH2:14][CH2:15]2)[CH2:22][CH2:23]1)=[O:30]
Reactant: N[C@H]1CC[C@H](CCN2CCN(c3nccc4sccc34)CC2)CC1
Reactant: O=C(O)CO
Agent: Cl
Product: O=C(CO)N[C@H]1CC[C@H](CCN2CCN(c3nccc4sccc34)CC2)CC1

Procedure:
The title compound was prepared in analogy to example 4 starting from trans-4-[2-(4-thieno[3,2-c]pyridin-4-yl-piperazin-1-yl)-ethyl]-cyclohexylamine trihydrochloride (intermediate B) (150 mg, 0.33 mmol) and glycolic acid (26 mg, 0.34 mmol). Purification by flash chromatography on silica gel (CH2Cl2/MeOH 95:5). White solid (67 mg, 50%), MS (ISP) m/z=403.3 [(M+H)+].
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[C:14]([C:15]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[C:16]4[C:21]=2[CH:20]=[CH:19][CH:18]=[CH:17]4)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[CH:4][CH:3]=1.C([Li])CCC.[B:33]([O:38]C)(OC)[O:34]C.Cl>O1CCCC1>[C:5]1([C:8]2[C:9]3[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:15]([C:22]3[CH:23]=[CH:24][C:25]([B:33]([OH:38])[OH:34])=[CH:26][CH:27]=3)=[C:16]3[C:21]=2[CH:20]=[CH:19][CH:18]=[CH:17]3)[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1
Reactant: Brc1ccc(-c2c3ccccc3c(-c3ccccc3)c3ccccc23)cc1
Reactant: COB(OC)OC
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OB(O)c1ccc(-c2c3ccccc3c(-c3ccccc3)c3ccccc23)cc1
Temperature: -78 °C
Reaction time: 2 h
Yield: 83.6 %

Procedure:
20.0 g (48.9 mmol) of 9-(4-bromophenyl)-10-phenylanthracene was put into a 500 mL three-necked flask. Then, the atmosphere in the flask was substituted with nitrogen. After 300 mL of tetrahydrofuran (abbreviation: THF) was added to this flask, the flask was put into a constant low temperature bath and the reaction solution was cooled to −78° C. 34.2 mL (53.8 mmol) of n-butyllithium (1.57 mol/L hexane solution) was dropped into this solution and the solution was stirred at −78° C. for 2 hours. Thereafter, 12.6 mL (112 mmol) of trimethyl borate was added to the solution. Then, the flask was taken out from the constant low temperature bath, and the reaction solution was stirred for 24 hours to be returned to room temperature. After the reaction was completed, 200 mL of 1.0 mol/L hydrochloric acid was added to the reaction solution and the reaction solution was stirred at room temperature for 1 hour. An organic layer of the mixture was washed with water and the aqueous layer was extracted with ethyl acetate. The extracted solution was mixed with the organic layer, and the mixture was washed with a saturated aqueous sodium chloride solution, and then dried over magnesium sulfate. After the drying, this mixture was subjected to suction filtration, and the filtrate was condensed to obtain a residue. The obtained residue was recrystallized by a mixed solvent of chloroform and hexane; 15.3 g of objective 4-(10-phenyl-9-anthryl)phenylboronic acid was obtained as a white powdered solid in a yield of 84%. A synthetic scheme of 4-(10-phenyl-9-anthryl)phenylboronic acid is illustrated below (synthetic scheme b-5).