Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[Na+].[CH:3]1([CH:8]([C:25]2[CH:30]=[CH:29][C:28]([CH2:31][N:32]3[C:37](=[O:38])[CH2:36][O:35][C:34]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[N:33]3)=[CH:27][CH:26]=2)[C:9]([NH:11][C:12]2[CH:13]=[C:14]([CH2:18][CH2:19][C:20]([O:22]CC)=[O:21])[CH:15]=[CH:16][CH:17]=2)=[O:10])[CH2:7][CH2:6][CH2:5][CH2:4]1.Cl>O1CCOCC1.O>[CH:3]1([CH:8]([C:25]2[CH:30]=[CH:29][C:28]([CH2:31][N:32]3[C:37](=[O:38])[CH2:36][O:35][C:34]([C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)=[N:33]3)=[CH:27][CH:26]=2)[C:9]([NH:11][C:12]2[CH:13]=[C:14]([CH2:18][CH2:19][C:20]([OH:22])=[O:21])[CH:15]=[CH:16][CH:17]=2)=[O:10])[CH2:4][CH2:5][CH2:6][CH2:7]1
Reactant: CCOC(=O)CCc1cccc(NC(=O)C(c2ccc(CN3N=C(c4ccccc4)OCC3=O)cc2)C2CCCC2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)CCc1cccc(NC(=O)C(c2ccc(CN3N=C(c4ccccc4)OCC3=O)cc2)C2CCCC2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
11.05 ml of 1 N aqueous sodium hydroxide solution were added to a solution of 4.18 g (7.363 mmol) of ethyl 3-{3-[(cyclopentyl{4-[(5-oxo-2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazin-4-yl)methyl]phenyl}acetyl)amino]phenyl}propanoate (Example 180A) in 195 ml of dioxane/water (4:1 v/v). The mixture was stirred at room temperature overnight and then acidified to pH 1 with 1 N hydrochloric acid and extracted repeatedly with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated on a rotary evaporator. The crude product was dissolved in ethyl acetate and filtered through silica gel. Activated carbon was added to the filtrate, and the mixture was heated at reflux and filtered through Tonsil. Concentration under reduced pressure gave 3.20 g (81% of theory) of the title compound.
Reaction SMILES: C([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[CH2:13][N:14]1[CH:22]=[C:21]2[C:16]([N:17]=[C:18]([C:36]3[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=3)[C:19]([C:30]3[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=3)=[C:20]2[C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[N:15]1)C1C=CC=CC=1.C(O)=O>CCO.[Pd]>[F:29][C:26]1[CH:27]=[CH:28][C:23]([C:20]2[C:21]3[C:16](=[N:15][N:14]([CH2:13][CH:9]4[CH2:10][CH2:11][CH2:12][NH:8]4)[CH:22]=3)[N:17]=[C:18]([C:36]3[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=3)[C:19]=2[C:30]2[CH:31]=[CH:32][N:33]=[CH:34][CH:35]=2)=[CH:24][CH:25]=1
Reactant: Fc1ccc(-c2nc3nn(CC4CCCN4Cc4ccccc4)cc3c(-c3ccc(F)cc3)c2-c2ccncc2)cc1
Agent: [Pd]
Solvent: O=CO
Solvent: CCO
Product: Fc1ccc(-c2nc3nn(CC4CCCN4)cc3c(-c3ccc(F)cc3)c2-c2ccncc2)cc1
Yield: 85.6 %

Procedure:
To a solution of 2-(1-benzylpyrrolidin-2-ylmethyl)-4,6-bis(4-fluorophenyl)-5-(4-pyridyl)pyrazolo[3,4-b]pyridine (83 mg, 0.1 mmol, obtained in example 259) in EtOH (6.9 mL), 10% Pd/C (8 mg) and formic acid (0.34 mL) were added and heated a reflux for 2 h. It was allowed to cool and filtered through celite, washed with EtOH and concentrated. The crude product obtained was purified by chromatography on silica gel using hexane-EtOAc-MeOH—NH3 of increasing polarity as eluent, to afford 40 mg of the title compound (yield: 57%)
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20]CC3C=CC=CC=3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CCO.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CC=C(c2ccc(NCc3ccccc3)cc2)CC1
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(N)cc2)CC1
Reaction time: 1 h
Yield: 87.9 %

Procedure:
A solution of 4-(4-benzylamino-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.27 g) in EtOH (10 mL) containing Pd/C 10% (50 mg) was hydrogenated at room temperature. After 1 hour, the catalyst was removed by filtration and the filtrate was evaporated under reduced pressure to give the title compound (0.18 g) as a pale pink oil.
Reaction SMILES: [CH3:1][CH:2]1[C:7]([CH3:19])([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[N:15]=[N:16][NH:17][CH:18]=3)[CH:9]=2)[CH2:6][CH2:5][NH:4][CH2:3]1.Br[CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:1][CH:2]1[C:7]([CH3:19])([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[N:15]=[N:16][NH:17][CH:18]=3)[CH:9]=2)[CH2:6][CH2:5][N:4]([CH2:21][CH2:22][O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:3]1
Reactant: CC1CNCCC1(C)c1cccc(-c2c[nH]nn2)c1
Reactant: BrCCOc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1CN(CCOc2ccccc2)CCC1(C)c1cccc(-c2c[nH]nn2)c1
Reaction time: 8 h
Yield: 13.3 %

Procedure:
To a solution of 3,4-dimethyl-4-(3-(1H-1,2,3-triazol-4-yl)phenyl)piperidine (Preparation 44, 50 mg, 0.20 mmol) in N,N-dimethylformamide (6 mL) was added commercially available 2-(bromoethoxy)benzene (43 mg, 0.22 mmol) and sodium hydrogencarbonate (48 mg, 0.56 mmol). The resultant mixture was heated to 80° C. and stirred overnight. The reaction mixture was cooled, poured onto saturated aqueous sodium hydrogencarbonate solution (100 mL) and extracted with ethyl acetate (3×20 mL). The combined extracts were dried over MgSO4, filtered and concentrated in vacuo to give an off-white gum. The crude product was partially purified by chromatography on a 5 g silica Waters Sep-Pak3 eluting with dichloromethane and then 5% methanol in dichloromethane. The pure fractions were collected to give the title compound as a clear oil as a clear gum (10 mg, 13.6%).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=O.CSC.B>C1COCC1>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][NH:5][CH2:6]2
Reactant: O=C1NCc2c(Br)cccc21
Agent: B
Solvent: CSC
Solvent: C1CCOC1
Product: Brc1cccc2c1CNC2
Temperature: 0 °C

Procedure:
To a solution of 4-bromoisoindolin-1-one (4 mmol) in THF (8 mL) was added borane-dimethyl sulfide complex (2M in THF, 14 mL) at 0° C. The reaction mixture was allowed to stir at reflux overnight and was then cooled to 0° C. The reaction mixture was quenched by the slow addition of MeOH (2 mL) and then 3N HCl. The reaction mixture was allowed to stir at reflux for 3 hr and then concentrated. Water was added to the residue and the pH of the solution was adjusted to >9 with 4N NaOH. The solution was extracted with diethyl ether. The organic solutions from this basic extraction were combined, dried over Na2SO4, filtered and concentrated to give 4-bromoisoindoline, which was dissolved in THF (5 mL). To this solution was added potassium carbonate (4 mmol) in water (0.5 mL), and BOC2O (2 mmol). The reaction mixture was allowed to stir at rt overnight. The reaction mixture was diluted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give tert-butyl 4-bromo-1,3-dihydro-2H-isoindole-2-carboxylate (0.8 mmol, 20%).
Reaction SMILES: [CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[N:9]([CH2:20][CH2:21][OH:22])[C:8]=2[C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][C:24]=2O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH:1]1([C:7]2[C:15]3[CH:14]=[CH:13][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][C:10]=3[N:9]3[C:8]=2[C:23]2[CH:24]=[CH:25][C:26]([OH:29])=[CH:27][C:28]=2[O:22][CH2:21][CH2:20]3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c(-c3ccc(O)cc3O)n(CCO)c2c1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CCOc1cc(O)ccc1-3
Reaction time: 4 h
Yield: 58.9 %

Procedure:
To a solution of methyl 3-cyclohexyl-2-(2,4-dihydroxyphenyl)-1-(2-hydroxyethyl)-1H-indole-6-carboxylate (10.3 g, 28.2 mmol) in tetrahydrofuran (500 ml) were added triphenylphosphine (7.3 g, 27.7 mmol) and diethyl azodicarboxylate (4.4 ml, 27.7 mmol) under ice-cooling, and the mixture was stirred for 4 hr. The reaction mixture was concentrated and the obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=3:2) to give methyl 12-cyclohexyl-3-hydroxy-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxylate (6.5 g, yield 66%).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH:5]([CH3:11])[NH:6]2.Cl.CN(C)CCCN=C=NCC.[F:24][C:25]1[C:30](=[O:31])[NH:29][C:28]([CH2:32][C:33]([O-])=[O:34])=[N:27][C:26]=1[N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.[Na+].O>CN(C)C=O.N1C=CC=CC=1>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH:5]([CH3:11])[N:6]2[C:33](=[O:34])[CH2:32][C:28]1[NH:29][C:30](=[O:31])[C:25]([F:24])=[C:26]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)[N:27]=1
Reactant: CC1Cc2c(Br)cccc2N1
Reactant: O=C([O-])Cc1nc(N2CCOCC2)c(F)c(=O)[nH]1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: c1ccncc1
Solvent: O
Product: CC1Cc2c(Br)cccc2N1C(=O)Cc1nc(N2CCOCC2)c(F)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 72 h
Yield: 51.1 %

Procedure:
150 mg of 4-bromo-2-methyl-2,3-dihydro-1H-indole [reference example 4a] and 197 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are added to a solution of 217 mg of sodium (5-fluoro-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate (obtained in step 2a of example 6a) in 7 ml of N,N-dimethylformamide and 7 ml of pyridine. The reaction mixture is stirred at ambient temperature for 72 hours, then 50 ml of water are added and the mixture is extracted with ethyl acetate. The organic phase is washed successively with a 0.1N hydrochloric acid solution, water and a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue is triturated from dichloromethane, filtered and washed with diethyl ether so as to give 163 mg of 2-{2-[4-bromo-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-5-fluoro-6-(morpholin-4-yl)pyrimidin-4(3H)-one.
Reaction SMILES: C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C([S:43][C:44]([CH3:81])([CH2:74][N:75]1[CH2:80][CH2:79][S:78][CH2:77][CH2:76]1)[CH2:45][NH:46][C:47]([C:49]1[NH:50][C:51]2[C:56]([CH:57]=1)=[CH:55][C:54]([O:58][CH2:59][CH2:60][O:61][CH3:62])=[CH:53][C:52]=2[N:63]([CH3:73])[S:64]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=1)(=[O:66])=[O:65])=O)C1C=CC=CC=1.C1(SC)C=CC=CC=1.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:62][O:61][CH2:60][CH2:59][O:58][C:54]1[CH:55]=[C:56]2[C:51](=[C:52]([N:63]([CH3:73])[S:64]([C:67]3[CH:72]=[CH:71][CH:70]=[CH:69][N:68]=3)(=[O:66])=[O:65])[CH:53]=1)[NH:50][C:49]([C:47]1[S:43][C:44]([CH3:81])([CH2:74][N:75]3[CH2:76][CH2:77][S:78][CH2:79][CH2:80]3)[CH2:45][N:46]=1)=[CH:57]2
Reactant: COCCOc1cc(N(C)S(=O)(=O)c2ccccn2)c2[nH]c(C(=O)NCC(C)(CN3CCSCC3)SCc3ccccc3)cc2c1
Agent: O=C([O-])O
Agent: O=P(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: CSc1ccccc1
Product: COCCOc1cc(N(C)S(=O)(=O)c2ccccn2)c2[nH]c(C3=NCC(C)(CN4CCSCC4)S3)cc2c1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 15.1 %

Procedure:
To a mixture of triphenylphosphine oxide (178 mg) and dichloromethane (8 mL) was added trifluoromethanesulfonic anhydride (0.11 mL) at 0° C., the mixture was stirred at 0° C. for 15 min, and dichloromethane (4 mL) was added. A mixture of N-[2-(benzylthio)-2-methyl-3-thiomorpholinopropyl]-5-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide (220 mg), thioanisole (0.075 mL) and dichloromethane (3 mL) was added to the reaction solution at −78° C., and the mixture was stirred at −78° C. for 10 min. Aqueous sodium bicarbonate was added, and the mixture was extracted with dichloromethane. The extract was washed with saturated brine, dried over sodium sulfate, and filtrated, and the filtrate was concentrated. The residue was subjected to silica gel column chromatography, and eluted with ethyl acetate. The obtained amorphous solid was purified by preparative HPLC to give the title compound (28 mg, yield 15%) as a colorless amorphous solid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:30])[NH:22][C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][N:24]=3)=[CH:17][C:16]=2[N+:31]([O-])=O)=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[Cl-].[NH4+]>C(O)C.O.C(OCC)(=O)C.[Fe]>[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:30])[NH:22][C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][N:24]=3)=[CH:17][C:16]=2[NH2:31])=[CH:10][CH:9]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1ccc(Oc2ccc(C(=O)Nc3ccc(Cl)cn3)cc2[N+](=O)[O-])cc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CCO
Product: CC(C)(C)OC(=O)Nc1ccc(Oc2ccc(C(=O)Nc3ccc(Cl)cn3)cc2N)cc1
Temperature: 80 °C
Yield: 94.5 %

Procedure:
A suspension of the product of Example 199B (282 mg, 0.5816 mmol), iron powder (200 mg, 3.577 mmol), and ammonium chloride (204 mg, 3.809 mmol) in ethanol (8 mL) and water (4 mL) was heated at 80° C. for 45 minutes. After cooling to room temperature, the mixture was diluted with ethyl acetate (100 mL) and washed with water (2×50 mL) and brine (50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated under vacuum to provide the title compound as a beige solid (250 mg, 94%).
Reaction SMILES: [CH3:1][N:2]([CH3:17])[S:3]([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[CH:10][CH:9]=1)(=[O:5])=[O:4]>CO.[Pd]>[CH3:17][N:2]([CH3:1])[S:3]([CH2:6][CH2:7][C:8]1[CH:9]=[CH:10][C:11]([NH2:14])=[CH:12][CH:13]=1)(=[O:4])=[O:5]
Reactant: CN(C)S(=O)(=O)CCc1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Solvent: CO
Product: CN(C)S(=O)(=O)CCc1ccc(N)cc1
Yield: 91.4 %

Procedure:
A suspension of 912 mg (3.53 mmol) of 2-(4-nitro-phenyl)-ethanesulfonic acid dimethylamide (as prepared in the previous step) in MeOH (30 mL) was hydrogenated with 10% Pd/C (Degussa type E101-NE/W, Aldrich, 50% by weight water) at 20 psi H2 at RT for 2 days. The mixture was filtered through Celite, the filter cake was washed with MeOH, and the solvents were evaporated in vacuo. Silica gel chromatography of the residue on a 25-g Varian MegaBond Elut SPE column with 50% EtOAc-hexane afforded 737 mg (91%) of the title compound as a white solid: 1H-NMR (CD3CN; 400 MHz): δ 7.01 (d, 2H, J=8.4 Hz), 6.61 (d, 2H, J=8.4 Hz), 4.06 (br s, 2H), 3.19-3.13 (m, 2H), 2.95-2.88 (m, 2H), 2.84 (s, 6H).
Reaction SMILES: [C:1]([CH2:3][C@@H:4]([NH:9][C:10]([C:12]1[CH:31]=[CH:30][C:15]2[N:16]([CH:25]([CH2:28][CH3:29])[CH2:26][CH3:27])[C:17]([CH2:19][C:20]3[S:21][CH:22]=[CH:23][CH:24]=3)=[N:18][C:14]=2[CH:13]=1)=[O:11])[CH2:5][CH:6]([CH3:8])[CH3:7])#[N:2].[F:32][C:33]([F:39])([F:38])[C:34]([NH:36][NH2:37])=O.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[CH3:8][CH:6]([CH3:7])[CH2:5][C@H:4]([NH:9][C:10]([C:12]1[CH:31]=[CH:30][C:15]2[N:16]([CH:25]([CH2:28][CH3:29])[CH2:26][CH3:27])[C:17]([CH2:19][C:20]3[S:21][CH:22]=[CH:23][CH:24]=3)=[N:18][C:14]=2[CH:13]=1)=[O:11])[CH2:3][C:1]1[N:2]=[C:34]([C:33]([F:39])([F:38])[F:32])[NH:36][N:37]=1
Reactant: CCC(CC)n1c(Cc2cccs2)nc2cc(C(=O)N[C@H](CC#N)CC(C)C)ccc21
Reactant: NNC(=O)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CCC(CC)n1c(Cc2cccs2)nc2cc(C(=O)N[C@H](Cc3n[nH]c(C(F)(F)F)n3)CC(C)C)ccc21
Temperature: 200 °C
Yield: 9.6 %

Procedure:
A mixture of 50 mg 1-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid ((S)-1-cyanomethyl-3-methyl-butyl)-amide, 45 mg of trifluoroacetic acid hydrazide and 4 mg of potassium carbonate in 0.6 ml of ethanol was heated to 200° C. in a microwave reactor for 24 h. The solvent was removed and the residue was purified by HPLC to obtain 6 mg (10%) of 1-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid [(S)-3-methyl-1-(5-trifluoromethyl-1H-[1,2,4]triazol-3-ylmethyl)-butyl]-amide.
Reaction SMILES: [F:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([F:18])=[C:4](F)[C:3]=1F.[CH:21]([C:24]1[CH:30]=[CH:29][CH:28]=[C:27]([CH:31]([CH3:33])[CH3:32])[C:25]=1[NH2:26])([CH3:23])[CH3:22]>>[CH:31]([C:27]1[CH:28]=[CH:29][CH:30]=[C:24]([CH:21]([CH3:23])[CH3:22])[C:25]=1[NH:26][C:3]1[C:4]([NH:26][C:25]2[C:27]([CH:31]([CH3:32])[CH3:33])=[CH:28][CH:29]=[CH:30][C:24]=2[CH:21]([CH3:23])[CH3:22])=[C:5]([F:18])[C:6]2[C:7](=[O:17])[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:14](=[O:16])[C:15]=2[C:2]=1[F:1])([CH3:33])[CH3:32]
Reactant: O=C1c2ccccc2C(=O)c2c(F)c(F)c(F)c(F)c21
Reactant: CC(C)c1cccc(C(C)C)c1N
Product: CC(C)c1cccc(C(C)C)c1Nc1c(F)c2c(c(F)c1Nc1c(C(C)C)cccc1C(C)C)C(=O)c1ccccc1C2=O
Reaction time: 6 h
Yield: 69.7 %

Procedure:
2 g of 1,2,3,4-Tetrafluoroanthraquinone and 25 g of 2,6-diisopropylaniline were charged in a 50 cc, four necked flask and the reaction was carried out at 180° C. for about 6 hours. After completion of reaction, 2,6-diisopropylaniline was distilled out from the reaction solution and a column purification using a column with a silica gel was effected to give rise to 2.96 g of 2,3-bis(2,6-diisopropylanilino)-1,4-difluoroanthraquinone (Dye 24') (yield 69.7 mol %). The physical properties of Dye 24' and analytical values defining the compound are tabulated in Table 24.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH:4]1[O:8][C:7](=[O:9])[N:6]([C:10]2[CH:15]=[CH:14][C:13]([C@H:16]3[CH2:21][CH2:20][C@H:19]([O:22][CH2:23][S:24][CH3:25])[CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5]1.I([O-])(=O)(=O)=[O:27].[Na+]>CO.O>[CH3:25][S:24]([CH2:23][O:22][C@H:19]1[CH2:20][CH2:21][C@H:16]([C:13]2[CH:12]=[CH:11][C:10]([N:6]3[CH2:5][CH:4]([CH2:3][O:2][CH3:1])[O:8][C:7]3=[O:9])=[CH:15][CH:14]=2)[CH2:17][CH2:18]1)=[O:27]
Reactant: COCC1CN(c2ccc([C@H]3CC[C@H](OCSC)CC3)cc2)C(=O)O1
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COCC1CN(c2ccc([C@H]3CC[C@H](OCS(C)=O)CC3)cc2)C(=O)O1
Reaction time: 24 h

Procedure:
1.71 g (4.68 mmol) of (RS)-5-methoxymethyl-3-[4-(trans-4-methylsulfanylmethoxy-cyclohexyl)-phenyl]-oxazolidin-2-one were dissolved in 100 ml of methanol, cooled to 0° and treated dropwise while stirring during 40 minutes with a solution of 1.0 g (4.68 mmol) of sodium metaperiodate dissolved in 40 ml of water. The reaction mixture was held at about 4° for 24 hours. Thereafter, it was diluted with water and the product was extracted with methylene chloride. The organic phase was washed with water, dried over sodium sulfate and filtered. The filtrate was filtered through 50 g of silica gel 60 and washed separately with methanol. After evaporation of the methanol eluate the diastereomer mixture, (RS)-3-[4-(trans-4-methanesulfinylmethoxy-cyclohexyl)-phenyl]-5-methoxymethyl-oxazolidin-2-one, was crystallized from benzene. M.p.: 98°-100°.
Reaction SMILES: Cl[C:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)/[C:4](=[N:13]/[S:14]([C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)(=[O:16])=[O:15])/[CH:3]=1.[CH3:22][NH:23][CH3:24]>C1COCC1>[CH3:22][N:23]([CH3:24])[C:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[N:13][S:14]([C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)(=[O:16])=[O:15])[CH:3]=1
Reactant: O=C1C(Cl)=C/C(=N\S(=O)(=O)c2cccs2)c2ccccc21
Reactant: CNC
Solvent: C1CCOC1
Product: CN(C)C1=CC(=NS(=O)(=O)c2cccs2)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 100 %

Procedure:
33.5 mg (E)-N-(3-chloro-4-oxonaphthalen-1(4H)-ylidene)thiophene-2-sulfonamide was dissolved in 2 ml THF, to which was added 0.4 ml dimethylamine in THF solution (2 M). The wine-red solution was stirred at r.t. for 10 min and concentrated. The residue was suspended in 50 ml ethyl acetate and washed with water and brine. Dried over Na2SO4, the organic phase was filtered and the filtrate was concentrated to dryness affording the title compound 36 mg (100%) as a wine-red solid, m.p.: 183-185° C.
Reaction SMILES: Cl[CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.C([O-])([O-])=O.[Cs+].[Cs+].[OH:16][C:17]1[CH:26]=[C:25]2[C:20]([C:21]([O:27][C:28]3[CH:41]=[CH:40][C:31]4[C:32]([C:36]([NH:38][CH3:39])=[O:37])=[C:33]([CH3:35])[O:34][C:30]=4[CH:29]=3)=[CH:22][CH:23]=[N:24]2)=[CH:19][CH:18]=1>CC#N>[CH3:39][NH:38][C:36]([C:32]1[C:31]2[CH:40]=[CH:41][C:28]([O:27][C:21]3[C:20]4[C:25](=[CH:26][C:17]([O:16][CH2:2][CH2:3][N:4]5[CH2:9][CH2:8][O:7][CH2:6][CH2:5]5)=[CH:18][CH:19]=4)[N:24]=[CH:23][CH:22]=3)=[CH:29][C:30]=2[O:34][C:33]=1[CH3:35])=[O:37]
Reactant: CNC(=O)c1c(C)oc2cc(Oc3ccnc4cc(O)ccc34)ccc12
Reactant: ClCCN1CCOCC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: CNC(=O)c1c(C)oc2cc(Oc3ccnc4cc(OCCN5CCOCC5)ccc34)ccc12
Yield: 67.8 %

Procedure:
A solution of 4-(2-chloroethyl)morpholine (2.1 g, 11.5 mmol) and Cs2CO3 (7.5 g, 23 mmol) in CH3CN (100 mL) was stirred for 45 minutes at room temperature. To the solution was added 6-[(7-hydroxyquinolin-4-yl)oxy]-N,2-dimethyl-1-benzofuran-3-carboxamide (2 g, 5.75 mmol). The mixture was heated to reflux for 3 hrs. Inorganic salt was removed by filtration and the solution was concentrated. The residue was purified by a silica gel column chromatography (using 1 to 10% MeOH/CH2Cl2) to give 1.8 g of free base N,2-dimethyl-6-[7-(2-morpholinoethoxy)quinolin-4-yloxy]benzofuran-3-carboxamide as a solid. The compound was then dissolved in hot isopropanol and stirred at room temperature overnight. 1.13 g of N,2-dimethyl-6-[7-(2-morpholinoethoxy)quinolin-4-yloxy]benzofuran-3-carboxamide as polymorph Form 2 was collected by filtration. Note, Form 2 is anhydrous and must be prepared under water-free conditions in order to prevent hydrate formation (such as Form 4 as described in Example 6).
Reaction SMILES: [OH-].[Li+].OO.C[O:6][C:7](=[O:29])[C:8]([CH3:28])([C:10]1[CH:15]=[CH:14][C:13]([C:16]#[C:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][CH3:27])=[CH:20][CH:19]=2)=[CH:12][CH:11]=1)[CH3:9].S([O-])(O)(=O)=O.[K+]>O.C1COCC1>[CH3:28][C:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16]#[C:17][C:18]2[CH:19]=[CH:20][C:21]([O:24][CH2:25][CH2:26][CH3:27])=[CH:22][CH:23]=2)=[CH:12][CH:11]=1)([CH3:9])[C:7]([OH:29])=[O:6]
Reactant: CCCOc1ccc(C#Cc2ccc(C(C)(C)C(=O)OC)cc2)cc1
Agent: O=S(=O)([O-])O
Agent: OO
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: CCCOc1ccc(C#Cc2ccc(C(C)(C)C(=O)O)cc2)cc1
Temperature: 25 °C
Reaction time: 120 h

Procedure:
A mixture of 26 mg (1.1 mmol) lithiumhydroxide and 99 μL (1.1 mmol) hydrogen peroxide in 0.7 mL water is added to 0.25 g (0.74 mmol) 2-methyl-2-[4-(4-propoxy-phenylethynyl)-phenyl]-propionic acid methyl ester (XI.4) in 7 mL THF. The reaction mixture is stirred at rt for 5 d. After that time, 0.5 N potassium hydrogensulfate solution is added. The precipitate is filtered off, washed with water and dried at 45° C. to yield the desired product.