Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:10])=[O:9])=[CH:4][N:3]=1.C(Br)(=O)C(Br)=O.CCCCCCC.[CH3:24][C:25]([O-])([CH3:27])[CH3:26].[K+]>C(Cl)Cl.CN(C=O)C.C1COCC1.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([O:10][C:25]([CH3:27])([CH3:26])[CH3:24])=[O:9])=[CH:4][N:3]=1
Reactant: CC(C)(C)[O-]
Reactant: O=C(O)c1ccc(Br)nc1
Agent: O=C(Br)C(=O)Br
Agent: [K+]
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)c1ccc(Br)nc1
Temperature: 25 °C
Yield: 33.2 %

Procedure:
To a round bottom flask containing 2-bromo-5-pyridinecarboxylic acid (10.0 g, 49 mmol) in DCM (500 mL) was added oxalyl bromide (7.4 mL) and 5 drops of DMF. After some gas evolution, the reaction mixture was stirred at reflux ca 6 h, then cooled to rt and heptane 100 mL was added, followed by concentration of the mixture. The mixture was then suspended in THF 400 mL, cooled to 0° C. t-BuOK (5.8 g, 52 mmol) was then added and the r×n allowed to warm to rt and stirred for 2 h. The mixture poured into EtOAc, washed with 1 N NaOH, water, brine, dried MgSO4 filtered and concentrated. The residue was purified by silica gel chromatography Biotage 40S Heptane EtOAc 0-80% 3 L to afford the title compound 4.2 g (36%) of as a white solid. 1H NMR (400 MHz, DMSO-d6) □ ppm 8.78-8.86 (1H, m), 8.14 (1H, dd, J=8.4, 2.4 Hz), 7.81 (1H d, J=8.4 Hz), 1.56 (9H, s).
Reaction SMILES: C(N(CC)CC)C.[NH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[CH2:17][NH:18][CH2:19][CH2:20]O)[CH:10]=[CH:9]1.[CH3:22][S:23](Cl)(=[O:25])=[O:24].[H-].[Na+]>O1CCCC1.CN(C)C=O>[CH3:22][S:23]([CH:13]1[CH2:14][C:15]2[CH:17]=[N:18][CH:19]=[CH:20][N:8]3[C:16]=2[C:11]([CH:10]=[CH:9]3)=[CH:12]1)(=[O:25])=[O:24]
Reactant: OCCNCc1cccc2cc[nH]c12
Reactant: CS(=O)(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CS(=O)(=O)C1C=c2ccn3c2=C(C=NC=C3)C1
Temperature: 25 °C

Procedure:
Add triethylamine (3.19 g, 31.56 mmol) to a solution of 2-[(1H-Indol-7-ylmethyl)amino]-ethan-1-ol (2.0 g, 10.52 mmol) in tetrahydrofuran (50 ml) at 0° C. Slowly add 1.75 mL (22.09 mMol) methanesulfonyl chloride and allow the reaction to warm to room temperature. Quench the reaction with saturated aqueous sodium bicarbonate and extract into ethyl acetate. Combine the organic layers, wash sequentially with saturated aqueous ammonium chloride, water, and saturated aqueous sodium chloride, dry over magnesium sulfate, and concentrate under reduced pressure. Add sodium hydride (0.8416 g, 21.04 mmol, 60% dispersion in mineral oil) to the resulting oil in dimethylformamide (20 ml). Quench the reaction with saturated aqueous sodium bicarbonate, concentrate to about 10 ml and extract into ethyl acetate. Combine the organic layers, wash sequentially with saturated ammonium chloride, water, and saturated aqueous sodium chloride, dry over magnesium sulfate, and concentrate under reduced pressure. Purification by flash chromatography, eluting with ethyl acetate:hexane gradient gives the title compound as an off-white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.Cl.[CH2:13]([O:17][C:18](=[O:22])[C@H:19]([CH3:21])[NH2:20])[CH:14]([CH3:16])[CH3:15]>>[CH2:13]([O:17][C:18](=[O:22])[C@H:19]([CH3:21])[NH:20][C:9](=[O:11])[CH2:8][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[CH:14]([CH3:16])[CH3:15]
Reactant: O=C(O)Cc1ccc(Cl)cc1
Reactant: CC(C)COC(=O)[C@H](C)N
Agent: Cl
Product: CC(C)COC(=O)[C@H](C)NC(=O)Cc1ccc(Cl)cc1

Procedure:
Following General Procedure B and using 4-chlorophenylacetic acid (Aldrich) and L-alanine iso-butyl ester hydrochloride (from Example B above), the title compound was prepared as a solid having a melting point of 111°-113° C. The reaction was monitored by tlc on silica gel and purification was by extraction with Et2O followed by washes with aqueous K2CO3 and aqueous HCl.
Reaction SMILES: [OH-].[Na+].[CH3:3][O:4][C:5]1[CH:17]=[C:16]([C:18]([C:20]2[N:28]3[C:23]([CH:24]=[CH:25][CH:26]=[CH:27]3)=[C:22]([O:29][CH3:30])[C:21]=2[CH3:31])=[O:19])[CH:15]=[CH:14][C:6]=1[NH:7][CH2:8][C:9]([O:11]CC)=[O:10]>C(O)C>[CH3:3][O:4][C:5]1[CH:17]=[C:16]([C:18]([C:20]2[N:28]3[C:23]([CH:24]=[CH:25][CH:26]=[CH:27]3)=[C:22]([O:29][CH3:30])[C:21]=2[CH3:31])=[O:19])[CH:15]=[CH:14][C:6]=1[NH:7][CH2:8][C:9]([OH:11])=[O:10]
Reactant: CCOC(=O)CNc1ccc(C(=O)c2c(C)c(OC)c3ccccn23)cc1OC
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COc1cc(C(=O)c2c(C)c(OC)c3ccccn23)ccc1NCC(=O)O

Procedure:
3.15 ml of 1 N sodium hydroxide are added to 1 g (2.52 mmol) of ethyl 2-{2-methoxy-4-[(1-methoxy-2-methylindolizin-3-yl)carbonyl]anilino}acetate, a compound obtained in Example 195, in solution in 10 ml of ethanol, and the medium is stirred at room temperature overnight. The reaction medium is concentrated under reduced pressure. The residue is taken up in water, washed with ethyl ether and separated after settling out. The aqueous phase is neutralized with 1 N hydrochloric acid. The precipitate formed is filtered off, washed with water, dried and then taken up in ethyl ether, filtered and dried. A yellow powder is obtained.
Reaction SMILES: C1(CNCC2C=C(C3C=[C:15]4[C:19](=[C:20](C(N)=O)C=3)[NH:18][CH:17]=[C:16]4C3CCN(S(CC)(=O)=O)CC3)C=NC=2)CC1.[CH3:36][C:37]1([CH3:52])[C:41]([CH3:43])([CH3:42])[O:40][B:39]([C:44]2[CH:45]=[C:46]([CH:50]=O)[CH:47]=[N:48][CH:49]=2)[O:38]1.CC1CCCN1.[BH3-]C#N.[Na+]>>[CH3:20][CH:19]1[CH2:15][CH2:16][CH2:17][N:18]1[CH2:50][C:46]1[CH:47]=[N:48][CH:49]=[C:44]([B:39]2[O:38][C:37]([CH3:52])([CH3:36])[C:41]([CH3:43])([CH3:42])[O:40]2)[CH:45]=1
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cncc(CNCC5CC5)c4)cc23)CC1
Reactant: CC1(C)OB(c2cncc(C=O)c2)OC1(C)C
Agent: CC1CCCN1
Agent: [BH3-]C#N
Agent: [Na+]
Product: CC1CCCN1Cc1cncc(B2OC(C)(C)C(C)(C)O2)c1

Procedure:
Following the general procedure of 5-(5-{[(cyclopropylmethyl)amino]methyl}-3-pyridinyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide, 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinecarbaldehyde (30 mg, 0.129 mmol), 2-methylpyrrolidine (0.013 mL, 0.129 mmol), and NaCNBH3 (16 mg, 0.258 mmol) were reacted to give 25 mg of crude 3-[(2-methyl-1-pyrrolidinyl)methyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine. The crude 3-[(2-methyl-1-pyrrolidinyl)methyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine was then reacted with 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (30 mg, 0.0723 mmol), potassium carbonate (60 mg, 0.434 mmol), and chloro-2-(dimethylaminomethyl)-ferrocen-1-yl-(dinorbornylphosphine)palladium(II) (4.4 mg, 0.00723 mmol) to give 6 mg of the title compound (16%).
Reaction SMILES: [C:1]1(=[O:8])[O:7][C:5](=[O:6])[CH2:4][CH2:3][CH2:2]1.[CH3:9][C:10]([CH3:13])([O-:12])[CH3:11].[K+]>O1CCCC1>[C:10]([O:12][C:5](=[O:6])[CH2:4][CH2:3][CH2:2][C:1]([OH:7])=[O:8])([CH3:13])([CH3:11])[CH3:9]
Reactant: O=C1CCCC(=O)O1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)CCCC(=O)O
Temperature: 40 °C
Reaction time: 0.25 h
Yield: 53.1 %

Procedure:
Glutaric anhydride (11.41 g.) was added portion-wise to a solution of potassium tert-butoxide (14.02 g.) in tetrahydrofuran (100 ml.) at ambient temperature. After the exothermic reaction was ceased, the reaction mixture was stirred at 40° C. for 15 minutes. Tetrahydrofuran was distilled off under reduced pressure. The residue was dissolved in water. After ethyl acetate was added, the solution was adjusted to pH 9 with aqueous potassium carbonate solution under ice-cooling. The separated water layer was washed with ethyl acetate, treated with activated charcoal, overlapped with ethyl acetate, and then adjusted to pH 4.0 with 10% hydrochloric acid under ice-cooling. The ethyl acetate layer was dried over magnesium sulfate, treated with activated charcoal, filtered and concentrated under reduced pressure to give glutaric acid mono-tert-butyl ester (10 g.).
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH:9]1[CH2:14][CH:15]([CH2:18][OH:19])[CH2:16][OH:17])C1C=CC=CC=1>[Pd]>[NH:8]1[CH2:13][CH2:12][O:11][CH2:10][CH:9]1[CH2:14][CH:15]([CH2:18][OH:19])[CH2:16][OH:17]
Reactant: OCC(CO)CC1COCCN1Cc1ccccc1
Agent: [Pd]
Product: OCC(CO)CC1COCCN1
Yield: 83.9 %

Procedure:
2-((4-benzylmorpholin-3-yl)methyl)propane-1,3-diol (0.18 g, 0.68 mmol) was reacted with Pd/C (10%, 25 mg) according to the procedure as described in Example 34, Step C to give the title compound as colorless oil (0.1 g, 83%). The compound was characterized by the following spectroscopic data:
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:17])[CH:5]([C:7]1[CH:16]=[CH:15][C:10]2[N:11]=[C:12]([NH2:14])[S:13][C:9]=2[CH:8]=1)[CH3:6])[CH3:2].[CH3:18][S:19](Cl)(=[O:21])=[O:20].Cl>N1C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:17])[CH:5]([C:7]1[CH:16]=[CH:15][C:10]2[N:11]=[C:12]([NH:14][S:19]([CH3:18])(=[O:21])=[O:20])[S:13][C:9]=2[CH:8]=1)[CH3:6])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CCOC(=O)C(C)c1ccc2nc(N)sc2c1
Agent: Cl
Solvent: c1ccncc1
Product: CCOC(=O)C(C)c1ccc2nc(NS(C)(=O)=O)sc2c1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
A mixture of 4 (347 mg, 1 mmol) in pyridine (3 ml) is added to MsCl (0.13 ml, 1.21 mmol) at room temperature. The reaction mixture is stirred for 14 h at room temperature. 1N HCl (30 ml) is added to the mixture. The mixture extracted with ethyl acetate. The organic layer is dried over magnesium sulfate. The filtrate was concentrated in vacuo. The residue was purified by flash column chromatography(n-Hexane:EtOAc).
Reaction SMILES: [C:1]1([C:7]2[C:11]([CH2:12][CH2:13][C:14]([O:16]CC)=[O:15])=[CH:10][N:9]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([C:26]([NH:28][CH2:29][C:30]4[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=4)=[O:27])=[CH:22][CH:21]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].C(O)C.Cl>O1CCCC1>[C:1]1([C:7]2[C:11]([CH2:12][CH2:13][C:14]([OH:16])=[O:15])=[CH:10][N:9]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([C:26]([NH:28][CH2:29][C:30]4[CH:31]=[CH:32][C:33]([C:36]([F:38])([F:39])[F:37])=[CH:34][CH:35]=4)=[O:27])=[CH:22][CH:21]=3)[N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)CCc1cn(Cc2ccc(C(=O)NCc3ccc(C(F)(F)F)cc3)cc2)nc1-c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: O=C(O)CCc1cn(Cc2ccc(C(=O)NCc3ccc(C(F)(F)F)cc3)cc2)nc1-c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96.2 %

Procedure:
A mixture of ethyl 3-[3-phenyl-1-[4-(4-trifluoromethylbenzylaminocarbonyl)benzyl]-1H-pyrazol-4-yl]propionate (680 mg), 1 N aqueous sodium hydroxide solution (1.7 ml), ethanol (2 ml), and tetrahydrofuran (2 ml) was stirred at room temperature for two hours. The reaction mixture was acidified with dilute hydrochloric acid, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The obtained crystals were collected by filtration, and 3-[3-phenyl-1-[4-(4-trifluoromethylbenzylaminocarbonyl)benzyl]-1H-pyrazol-4-yl]propionic acid (620 mg, yield: 94%) was obtained. This was recrystallized from ethyl acetate-hexane. Melting point: 151–152° C.
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12](O)=[O:13])=[C:7]2[N:6]=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[CH:4]=1.[OH:27][CH2:28][C:29]([NH:32][S:33]([C:36]1[S:40][C:39]([NH2:41])=[N:38][CH:37]=1)(=[O:35])=[O:34])([CH3:31])[CH3:30]>>[OH:27][CH2:28][C:29]([NH:32][S:33]([C:36]1[S:40][C:39]([NH:41][C:12]([C:11]2[CH:10]=[N:9][N:8]3[C:3]([C:2]([F:26])([F:1])[F:25])=[CH:4][C:5]([C:15]4[CH:16]=[CH:17][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:19][CH:20]=4)=[N:6][C:7]=23)=[O:13])=[N:38][CH:37]=1)(=[O:35])=[O:34])([CH3:31])[CH3:30]
Reactant: CC(C)(CO)NS(=O)(=O)c1cnc(N)s1
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Product: CC(C)(CO)NS(=O)(=O)c1cnc(NC(=O)c2cnn3c(C(F)(F)F)cc(-c4ccc(C(F)(F)F)cc4)nc23)s1

Procedure:
The title compound was prepared from 7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C. 1) and 2-amino-thiazole-5-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide (example B.13) according to general procedure II. Yellow solid. MS (ISP) 607.0 [(M−H)−]; mp 292° C.
Reaction SMILES: Cl.[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16]N)=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:18][CH2:19][C:20]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:24][CH:23]=1)=O>C(O)C>[CH2:2]([O:9][C:10]1[CH:15]=[C:14]2[C:13](=[CH:12][CH:11]=1)[NH:16][C:20]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:24][CH:23]=1)=[C:19]2[CH3:18])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: NNc1ccc(OCc2ccccc2)cc1
Reactant: CCC(=O)c1ccc(OCc2ccccc2)cc1
Agent: Cl
Solvent: CCO
Product: Cc1c(-c2ccc(OCc3ccccc3)cc2)[nH]c2ccc(OCc3ccccc3)cc12
Temperature: 77.5 °C

Procedure:
4-Benzyloxy phenyl hydrazine hydrochloride (1.0 g, 4 mmol), 4-benzyloxy propiophenone (0.96 g, 4 mmol) were suspended in 15 ml of ethanol and mixture was refluxed for 12 hrs at a temperature of 75-80° C. Then the mixture was cooled to 10-15° C. within 1 hr. The white product was filtered and washed with chilled ethanol (3 ml). The title compound 5-benzyloxy-2-(4-benzyloxy phenyl)-3-methyl-1H-indole (formula-1) melting at 152-153° C. and purity by HPLC 99.5% was obtained in a yield of 1.4 g (83.6%).
Reaction SMILES: ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.[CH2:15]([O:17][C:18]([CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29](=[O:34])[CH2:28][NH:27]2)=[O:19])[CH3:16]>C1C=CC=CC=1>[CH2:15]([O:17][C:18]([CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29](=[O:34])[CH:28]=[N:27]2)=[O:19])[CH3:16]
Reactant: CCOC(=O)CCCOc1ccc2c(c1)NCC(=O)N2
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: c1ccccc1
Product: CCOC(=O)CCCOc1ccc2[nH]c(=O)cnc2c1
Yield: 81 %

Procedure:
Dichlorodicyanobenzoquinone (DDQ) 4.5 g (19.8 mM) was added to the compound 925 5 g (18 mM) dissolved in benzene 300 ml with heating, and the mixture was refluxed for 3 hours. The reaction mixture was filtered hot and then the filtrate was concentrated in vacuo. The residue, dissolved in chloroform, was washed with water, dried by adding anhydrous sodium sulfate and concentrated in vacuo. The residue was charged on a column of silica gel (C-200) packed with chloroform, and purified by eluting with chloroform-methanol (300:1), (200:1) and (100:1), in this order to obtain the compound 914 as colorless crystals.
Reaction SMILES: N[C:2]1[S:3][C:4]([C:25]2[CH:30]=[CH:29][N:28]=[C:27]([Cl:31])[N:26]=2)=[C:5]([C:7]2[CH:8]=[C:9]([NH:13][S:14]([C:17]3[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=3[F:24])(=[O:16])=[O:15])[CH:10]=[CH:11][CH:12]=2)[N:6]=1.C(ON=O)(C)(C)C>C1COCC1.CCOC(C)=O>[Cl:31][C:27]1[N:26]=[C:25]([C:4]2[S:3][CH:2]=[N:6][C:5]=2[C:7]2[CH:8]=[C:9]([NH:13][S:14]([C:17]3[C:18]([F:24])=[CH:19][CH:20]=[CH:21][C:22]=3[F:23])(=[O:16])=[O:15])[CH:10]=[CH:11][CH:12]=2)[CH:30]=[CH:29][N:28]=1
Reactant: Nc1nc(-c2cccc(NS(=O)(=O)c3c(F)cccc3F)c2)c(-c2ccnc(Cl)n2)s1
Agent: CC(C)(C)ON=O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: O=S(=O)(Nc1cccc(-c2ncsc2-c2ccnc(Cl)n2)c1)c1c(F)cccc1F
Temperature: 25 °C
Reaction time: 1 h
Yield: 68.3 %

Procedure:
To N-{3-[2-amino-5-(2-chloro-4-pyrimidinyl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzene sulfonamide (0.8 g, 1.67 mmol) in 10 mL THF was added t-butylnitrite (0.4 mL, 4 mmol) by syringe. The mixture stirred at rt for 1 h. More t-butylnitrite (0.2 mL, 2 mmol) was added and the mixture heated to 80° C. for 1 h. The mixture was cooled, diluted with 100 mL EtOAc, washed with 20 mL water, filtered through Whatman 1 PS (phase separating) paper and concentrated under vacuum. The crude product was then purified by flash chromatography to give the title compound of Step B (0.53 g, 1.14 mmol, 65% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.07 (s, 1H), 9.37 (s, 1H), 8.55 (d, J=5.3 Hz, 1H), 7.65-7.75 (m, 1H), 7.40 (t, J=8.0 Hz, 1H), 7.23-7.32 (m, 5H), 7.03 (d, J=5.3 Hz, 1H).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([C:10]1[C:23]2[C:14](=[CH:15][C:16]3[C:21]([CH:22]=2)=[C:20]([CH2:24][CH2:25][CH3:26])[C:19]([CH2:27][CH2:28][CH3:29])=[C:18]([CH2:30][CH2:31][CH3:32])[C:17]=3[CH2:33][CH2:34][CH3:35])[C:13]([CH2:36][CH2:37][CH3:38])=[C:12]([C:39](OC)=[O:40])[C:11]=1[C:43](OC)=[O:44])[CH2:8][CH3:9].O.S(=O)(=O)(O)O>C(OCC)C>[OH:40][CH2:39][C:12]1[C:11]([CH2:43][OH:44])=[C:10]([CH2:7][CH2:8][CH3:9])[C:23]2[C:14](=[CH:15][C:16]3[C:21]([CH:22]=2)=[C:20]([CH2:24][CH2:25][CH3:26])[C:19]([CH2:27][CH2:28][CH3:29])=[C:18]([CH2:30][CH2:31][CH3:32])[C:17]=3[CH2:33][CH2:34][CH3:35])[C:13]=1[CH2:36][CH2:37][CH3:38]
Reactant: CCCc1c(CCC)c(CCC)c2cc3c(CCC)c(C(=O)OC)c(C(=O)OC)c(CCC)c3cc2c1CCC
Agent: O=S(=O)(O)O
Agent: [Al+3]
Agent: [H-]
Solvent: O
Solvent: CCOCC
Product: CCCc1c(CCC)c(CCC)c2cc3c(CCC)c(CO)c(CO)c(CCC)c3cc2c1CCC
Temperature: 25 °C
Yield: 98 %

Procedure:
Dimethyl 1,4,5,6,7,8-hexapropylanthracene-2,3-dicarboxylate obtained in REFERENCE EXAMPLE 2 was used. After lithium aluminum hydride was added to the solution of dimethyl 1,4,5,6,7,8-hexapropylanthracene-2,3-dicarboxylate in diethyl ether at 0° C., the mixture was warmed to room temperature and stirred for an hour. At room temperature, water was added to terminate the reaction. Next, the reaction mixture was rendered slightly acidic with 2N sulfuric acid and extracted with ether. After washing with brine, the extract was dried over anhydrous magnesium sulfate. Column chromatography with silica gel as the packing material was performed using hexane. Recrystallization from hexane gave 6.637 g (13.846 mmols) of the title compound as a light yellow solid. The isolation yield was 98%.
Reaction SMILES: [S:1](S([O-])=O)([O-:3])=[O:2].[Na+].[Na+].Cl[CH2:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1.O>CN(C=O)C>[C:11]1([CH2:10][S:1]([CH2:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:14]=[CH:13][CH:12]=2)(=[O:3])=[O:2])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1
Reactant: ClCc1cccc2ccccc12
Reactant: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=S(=O)(Cc1cccc2ccccc12)Cc1cccc2ccccc12
Temperature: 25 °C
Reaction time: 12 h
Yield: 100.3 %

Procedure:
To a well-stirred suspension of 7.3 grams (42 mmol) of sodium hydrosulfite (Na2S2O4) in 30 ml DMF was added 5.0 grams (28.3 retool) of 1-chloromethylnaphthalene. The mixture was stirred at room temperature for 12 hours, then brought to 85° C. for 24 hours. The warm mixture was poured onto 400 ml crushed ice, and the total volume brought to 700 ml with water. The precipitated solids were filtered to give 4.91 grams (14.2 mmol, 100% yield) of bis(1-naphthylmethyl) sulfone. Pure material was obtained by recrystallization from toluene (mp 220° C.).
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5]Br.C([O-])([O-])=O.[K+].[K+].[C:19]([O:23][C:24](=[O:49])[CH2:25][N:26]1[C:30]2[CH:31]=[CH:32][C:33]([NH:35][S:36]([C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=3)(=[O:38])=[O:37])=[CH:34][C:29]=2[N:28]=[C:27]1[CH2:46][CH2:47][CH3:48])([CH3:22])([CH3:21])[CH3:20]>CC#N.CCOC(C)=O.O>[C:19]([O:23][C:24](=[O:49])[CH2:25][N:26]1[C:30]2[CH:31]=[CH:32][C:33]([N:35]([CH2:5][C:4]3[CH:7]=[CH:8][CH:9]=[CH:10][C:3]=3[C:2]([F:12])([F:11])[F:1])[S:36]([C:39]3[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=3)(=[O:37])=[O:38])=[CH:34][C:29]=2[N:28]=[C:27]1[CH2:46][CH2:47][CH3:48])([CH3:22])([CH3:21])[CH3:20]
Reactant: CCCc1nc2cc(NS(=O)(=O)c3ccc(F)cc3)ccc2n1CC(=O)OC(C)(C)C
Reactant: FC(F)(F)c1ccccc1CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC#N
Solvent: O
Product: CCCc1nc2cc(N(Cc3ccccc3C(F)(F)F)S(=O)(=O)c3ccc(F)cc3)ccc2n1CC(=O)OC(C)(C)C
Temperature: 80 °C
Reaction time: 8 h

Procedure:
2-Trifluoromethylbenzyl bromide (0.27 mmol) and K2CO3 (63 mg, 0.45 mmol) were added to a solution of [5-(4-fluoro-benzenesulfonylamino)-2-propyl-benzoimidazol-1-yl]-acetic acid tert-butyl ester (40 mg, 0.09 mmol) in CH3CN (1 mL), and stirred overnight at 80° C. The reaction mixture was diluted with EtOAc and H2O, and then filtered through an Extrelut column. The column was washed with EtOAc, and the filtrate was concentrated. The crude product was carried onto the next reaction without any further purification or characterization.
Reaction SMILES: Cl[C:2]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[F:16][C:17]1[CH:18]=[C:19]([OH:24])[CH:20]=[CH:21][C:22]=1[F:23]>>[N+:13]([C:10]1[CH:11]=[CH:12][C:2]([O:24][C:19]2[CH:20]=[CH:21][C:22]([F:23])=[C:17]([F:16])[CH:18]=2)=[C:3]([CH:9]=1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])([O-:15])=[O:14]
Reactant: Oc1ccc(F)c(F)c1
Reactant: CCOC(=O)c1cc([N+](=O)[O-])ccc1Cl
Product: CCOC(=O)c1cc([N+](=O)[O-])ccc1Oc1ccc(F)c(F)c1
Yield: 94.7 %

Procedure:
Using the method described in Example 21.2, ethyl 2-chloro-5-nitrobenzoate (0.6 g) and 3,4-difluorophenol (0.34 g) were combined to provide 0.8 g of the title compound as an oil.
Reaction SMILES: Cl[CH2:2][C:3]1[C:11]([CH:12]([CH3:14])[CH3:13])=[CH:10][C:6]2[O:7][CH2:8][O:9][C:5]=2[CH:4]=1.[C-:15]#[N:16].[Na+]>CS(C)=O>[C:15]([CH2:2][C:3]1[C:11]([CH:12]([CH3:14])[CH3:13])=[CH:10][C:6]2[O:7][CH2:8][O:9][C:5]=2[CH:4]=1)#[N:16]
Reactant: [C-]#N
Reactant: CC(C)c1cc2c(cc1CCl)OCO2
Agent: [Na+]
Solvent: CS(C)=O
Product: CC(C)c1cc2c(cc1CC#N)OCO2
Temperature: 25 °C
Reaction time: 3 h
Yield: 94.9 %

Procedure:
6.9 g of 5-chloromethyl-6-isopropyl-1,3-benzodioxole was dissolved in 100 ml of dimethyl sulfoxide, followed by the addition of3.12 g of sodium cyanide. The obtained mixture was stirred at a room temperature for 3 hours and distilled to remove the solvent. Ethyl acetate was added to the residue and the obtained mixture was washed with water and a saturated aqueous solution of common salt successively, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated to obtain 6.26 g of the title compound as a crude oil.
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][N+:4]([CH2:7][C:8]([NH:10][NH2:11])=[O:9])=[CH:3][CH:2]=1.[Cl-:12].[C:13]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)(=O)[CH3:14]>>[Cl-:12].[N:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[C:13](=[N:11][NH:10][C:8]([CH2:7][N+:4]1[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=1)=[O:9])[CH3:14]
Reactant: NNC(=O)C[n+]1ccccc1
Reactant: CC(=O)c1ccccn1
Agent: [Cl-]
Product: CC(=NNC(=O)C[n+]1ccccc1)c1ccccn1

Procedure:
Following the general method of Example 2 and making non-critical variations, 5.63 gm (0.03 mole) of Girard's Reagent P and 3.63 gm (0.03 mole) of 2-acetylpyridine yield 5.70 gm (65%) of the title compound; mp 183.7° (decomp).
Reaction SMILES: [C:1]([NH2:9])(=[S:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:10][CH2:11][C:12]([CH2:14]Cl)=O.C([O-])([O-])=O.[K+].[K+]>C(O)C>[Cl:10][CH2:11][C:12]1[N:9]=[C:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[S:8][CH:14]=1
Reactant: NC(=S)c1ccccc1
Reactant: O=C(CCl)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: ClCc1csc(-c2ccccc2)n1
Reaction time: 1 h

Procedure:
A solution of thiobenzamide (1.37 g, 10 mmol) and 1,3-dichloro-acetone (1.27 g, 10 mmol) in ethanol (25 mL) is warmed to 75° C. and stirred at this temperature for 1 h. The resulting solution is cooled, poured into ice then brought to pH 8 with K2CO3 solution (sat.). This mixture is extracted with ethyl acetate, dried over MgSO4 and concentrated to give the title compound. This product is used without further purification. MS (ESI) 210 (M+H)+.