Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH3:9])=[CH:4][C:3]=1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[CH2:13][CH2:12]1.[C:23](N1C=CN=C1)(N1C=CN=C1)=[O:24].[ClH:35]>ClCCl.O1CCOCC1>[ClH:35].[CH2:8]([C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:23](=[O:24])[N:10]([CH:11]3[CH2:12][CH2:13][N:14]([CH:17]4[CH2:18][CH2:19][O:20][CH2:21][CH2:22]4)[CH2:15][CH2:16]3)[C:3]=2[CH:4]=1)[CH3:9]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CCc1ccc(N)c(NC2CCN(C3CCOCC3)CC2)c1
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: CCc1ccc2[nH]c(=O)n(C3CCN(C4CCOCC4)CC3)c2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 29 %

Procedure:
To a solution of (2-amino-5-ethylphenyl)[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]amine D26 (251 mg, 0.83 mmol) in dichloromethane (10 mL) was added 1,1′-carbonyldiimidazole (403 mg, 2.49 mmol). The mixture was stirred under room temperature for 1 hour and 2 mL of 4 M HCl in 1,4-dioxane was added. The resulting mixture was stirred for 5 min and concentrated in vacuo. The residue was dissolved in MeOH and purified by using a Gilson preparative HPLC system with a Waters Xterra (C-18) column 100 mm by 50 mm ID, eluting with 10% B to 90% B in 10 min, where A=H2O and B=CH3CN pumped at 150 mL/min to yield 89 mg of the title compound (29% yield). MS (ESI): 330 [M+H]+; 1H NMR (HCl salt) (400 MHz, CDCl3): δ 1.30 (3H, t), 1.99 (5H, m), 2.25 (2H, d), 2.75 (2H, q), 3.03 (2H, m), 3.44 (4H, d), 3.68 (2H, m), 4.14 (2H, d), 4.69 (1H, m), 6.91 (1H, d), 7.00 (1H, d), 7.84 (1H, s), 9.36 (1H, s), 12.91 (1H, br).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH2:6]([S:13][C:14]1[N:19]=[C:18]([NH:20][C@H:21]([CH3:31])[CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH:17]=[C:16]([NH2:32])[N:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.CO>[CH2:6]([S:13][C:14]1[N:15]=[C:16]([NH:32][S:2]([CH3:1])(=[O:4])=[O:3])[CH:17]=[C:18]([NH:20][C@H:21]([CH3:31])[CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:25])[CH3:26])[N:19]=1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: C[C@H](CO[Si](C)(C)C(C)(C)C)Nc1cc(N)nc(SCc2ccccc2)n1
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: ClCCl
Product: C[C@H](CO[Si](C)(C)C(C)(C)C)Nc1cc(NS(C)(=O)=O)nc(SCc2ccccc2)n1

Procedure:
Methanesulfonyl chloride (85 μl) was added to a solution of the subtitle product of step ii) (0.20 g) and N,N-diiosopropylethylamine (0.26 ml) in DCM (10 ml) at 0° C. The ice-bath was removed and stirring maintained for 2 h. The reaction solution was extracted with H2O (2×20 ml) and the organics dried (MgSO4) and concentrated to yield a brown oil. The residue was diluted in methanol (110 ml) and treated with potassium carbonate (0.15 g) for 2 h at room temperature. The volatiles were removed in vacuo and the residue partitioned between EtOAc (20 ml) and H2O (20 ml). The aqueous was further extracted with EtOAc (2×20 ml), the organics combined, dried (MgSO4) and concentrated to yield the subtitle compound as a crude white solid. This material was used directly in the next step. Yield: 0.23 g.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH:14]=[CH:13]1>C(#N)C>[O:9]1[CH:19]2[CH:18]1[CH2:17][C:16]1[C:21]([CH2:20]2)=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: C1=CCc2ccccc2C1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: CC#N
Product: c1ccc2c(c1)CC1OC1C2
Temperature: 25 °C
Reaction time: 6 h
Yield: 65.8 %

Procedure:
A solution of metachloroperbenzoic acid (55%, 22.8 g) in acetonitrile (190 ml) was added dropwise over 15 min to a solution of 1,4 dihydro naphthalene (7.86 g) in acetonitrile (100 ml) at 0° C. The resulting mixture was stirred for 6 hours at room temperature. The mixture was concentrated to about 50 ml under reduced pressure, diluted with methylene chloride and filtered. The filtrate was washed with 10% aqueous sodium sulfite, saturated aqueous sodium hydrogenocarbonate, saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated in vacuo. The resulting solid (8.45 g) was chromatographed (silica gel, 150 g, elution with ethyl acetate:hexane, 1:9) to give the title compound as a solid (5.81 g).
Reaction SMILES: [C:1]1([CH:7]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9](=[O:14])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:15]C1CC(C(C)C)CCC1=O>>[Br:15][CH:10]1[CH2:11][CH2:12][CH2:13][CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:8][C:9]1=[O:14]
Reactant: CC(C)C1CCC(=O)C(Br)C1
Reactant: O=C1CCCCC(c2ccccc2)C1
Product: O=C1CC(c2ccccc2)CCCC1Br

Procedure:
The bromination of 3-phenylcycloheptanone takes place in a manner similar to that described above for the preparation of 2-bromo-4-isopropyl-cyclohexanone. The title compound is reacted as a crude product without further characterization.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[C@@H:15]2[O:16][C:17]([CH3:20])([CH3:19])[O:18][C@@H:14]2[C@@H:13]([CH2:21][CH2:22][S:23](Cl)(=[O:25])=[O:24])[O:12]1.[NH3:27]>CN(C)C=O.CO>[Cl:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[C@@H:15]2[O:16][C:17]([CH3:20])([CH3:19])[O:18][C@@H:14]2[C@@H:13]([CH2:21][CH2:22][S:23]([NH2:27])(=[O:25])=[O:24])[O:12]1
Reactant: N
Reactant: CC1(C)O[C@@H]2[C@H](O1)[C@@H](CCS(=O)(=O)Cl)O[C@H]2n1cnc2c(Cl)ncnc21
Solvent: CN(C)C=O
Solvent: CO
Product: CC1(C)O[C@@H]2[C@H](O1)[C@@H](CCS(N)(=O)=O)O[C@H]2n1cnc2c(Cl)ncnc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 42 %

Procedure:
2-[(3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]ethanesulfonyl chloride (100.0 mg, 0.0002362 mol) was dissolved in N,N-Dimethylformamide (2.0 mL). 7.00 M of Ammonia in Methanol (0.500 mL) was added at 0° C. and the mixture was stirred for 30 minutes, allowing to warm to room temperature. The reaction was concentrated in vacuo and the residue was diluted with brine and extracted with EtOAc. The organic phase was brine washed, water washed and evaporated. The residue was purified by flash chromatography (0 to 100% EtOAc/Hexanes) to yield the product (40 mg, 42%).
Reaction SMILES: [F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([I:19])=[CH:15][C:14]=2[F:20])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=O.C(#N)C.CC1(C)[O:29][C@@H:28]([CH2:30][O:31][NH2:32])[CH2:27][O:26]1.Cl>C1(C)C=CC=CC=1>[OH:29][C@H:28]([CH2:27][OH:26])[CH2:30][O:31][NH:32][C:5](=[O:7])[C:4]1[CH:8]=[CH:9][C:10]([F:11])=[C:2]([F:1])[C:3]=1[NH:12][C:13]1[CH:18]=[CH:17][C:16]([I:19])=[CH:15][C:14]=1[F:20]
Reactant: CC1(C)OC[C@H](CON)O1
Reactant: O=C(O)c1ccc(F)c(F)c1Nc1ccc(I)cc1F
Agent: Cl
Solvent: Cc1ccccc1
Solvent: CC#N
Product: O=C(NOC[C@H](O)CO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F
Reaction time: 1.5 h

Procedure:
To a flask containing 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzoic acid (2.6 kg, 6.6 mol) and N,N′-carbonyldiimidazole (1.1 kg, 6.8 mol) under nitrogen atmosphere, was added 12 L of dry acetonitrile. After stirring at 22°±5° C. for about 90 minutes, a solution of (R)-O-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-hydroxylamine in toluene was added (8.5 L total volume, about 8 moles of amine). The solution was stirred for at least 6 hours at 22°±5 C. Aqueous hydrochloric acid (9 L, 1.5 molar) was added, and after stirring for about 5 minutes, the layers were separated. Aqueous hydrochloric acid (9 L, 1.5 molar) was added to the remaining top layer, and after stirring for about 20 hours, the layers were separated. The remaining top layer was concentrated by vacuum distillation, and then diluted with 15 L toluene and 2 L ethanol. The mixture was warmed to 35–45° C. and diluted with 20 L warm water, then cooled to 0–5° C. The product was collected by filtration and washed with 2 L toluene. The product was recrystallized by dissolving in 12 L toluene and 2 L ethanol (50°±5 C), adding 10 L water and cooling to 0–5° C. After collecting the product by filtration and washing with toluene, the product was dried in a vacuum oven resulting in 2.6 kg of N-[(R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[S:17][CH:18]=[CH:19][CH:20]=3)=[C:12]([F:21])[CH:11]=2)=[CH:6][CH:5]=1)[CH2:2][CH3:3].[Li]CCCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:37])(=O)=O)=CC=1.O>C1COCC1>[F:37][C:18]1[S:17][C:16]([C:13]2[CH:14]=[CH:15][C:10]([C:7]3[CH:6]=[CH:5][C:4]([CH2:1][CH2:2][CH3:3])=[CH:9][CH:8]=3)=[CH:11][C:12]=2[F:21])=[CH:20][CH:19]=1
Reactant: O=S(=O)(c1ccccc1)N(F)S(=O)(=O)c1ccccc1
Reactant: CCCc1ccc(-c2ccc(-c3cccs3)c(F)c2)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Product: CCCc1ccc(-c2ccc(-c3ccc(F)s3)c(F)c2)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
4.0 g (13.5 mmol) of 2-(4′-propyl-3-fluorobiphenyl-4-yl)thiophene (“PGT-3-H”) are initially introduced at −20° C. in THF, and 9.3 ml (14.8 mmol) of n-BuLi (15% solution in hexane) are added dropwise. The mixture is warmed to 0° C. and stirred at this temperature for 30 min. The batch is cooled to −78° C., and a solution of 5.11 g (16.2 mmol) of N-fluorobenzenesulfonimide (NFSI) in THF is metered in. After 30 min at −78° C., the batch is warmed to room temperature. Water is added, and the mixture is extracted a number of times with MTBE. The combined organic phases are washed with water and sat. sodium chloride solution and dried using sodium sulfate. The solution is evaporated to dryness, and the residue is purified by chromatography (SiO2, n-pentane). The further purification is carried out by recrystallisation from ethanol and n-heptane, giving 2-fluoro-5-(3-fluoro-4′-propylbiphenyl-4-yl)thiophene (“PGT-3-F”) as a colourless solid having an m.p. of 64° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][C:4]=1[C:11]1[S:12][CH:13]=[CH:14][CH:15]=1.[C:16]([C:19]1[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=1[C:21]([OH:23])=[O:22])(=[O:18])[CH3:17]>>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6](/[CH:7]=[CH:17]/[C:16]([C:19]2[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=2[C:21]([OH:23])=[O:22])=[O:18])=[CH:5][C:4]=1[C:11]1[S:12][CH:13]=[CH:14][CH:15]=1
Reactant: CC(=O)c1ccccc1C(=O)O
Reactant: COc1ccc(C=O)cc1-c1cccs1
Product: COc1ccc(/C=C/C(=O)c2ccccc2C(=O)O)cc1-c1cccs1
Yield: 44 %

Procedure:
The title compound was prepared by condensing 4-methoxy-3-(thiophen-2-yl)-benzaldehyde (Ex-41A) and 2-acetylbenzoic acid in a similar manner as described in Ex-3. Beige solid with green tint, mp 79–81° C., 44% yield. 1H-NMR (DMSO-D6) δ 8.07 (d, J=2 Hz, 1H), 7.91 (d, J=8 Hz, 1H), 7.73 (dd, J=2, 4 Hz, 1H), 7.67–7.70 (m, 2H), 7.63 (dd, J=2, 7 Hz, 1H), 7.57 (dd, J=2,5 Hz, 1H), 7.50 (d, J=8 Hz, 1H), 7.22 (d, J=2 Hz, 2H), 7.19 (d, J=8 Hz, 1H), 7.12 (dd, J=4, 5 Hz, 1H), 3.96 (s, 3H). HRMS m/z=calc. 365.0848, found 365.0853.
Reaction SMILES: Cl.[F:2][C:3]1[CH:9]=[C:8]([SH:10])[C:7]([CH3:11])=[CH:6][C:4]=1[NH2:5].[Cl:12][C:13]1[CH:14]=[C:15]([C:20]([F:23])([F:22])[F:21])[CH:16]=[CH:17][C:18]=1Cl.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[F:2][C:3]1[CH:9]=[C:8]([S:10][C:18]2[CH:17]=[CH:16][C:15]([C:20]([F:23])([F:22])[F:21])=[CH:14][C:13]=2[Cl:12])[C:7]([CH3:11])=[CH:6][C:4]=1[NH2:5]
Reactant: FC(F)(F)c1ccc(Cl)c(Cl)c1
Reactant: Cc1cc(N)c(F)cc1S
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cc(N)c(F)cc1Sc1ccc(C(F)(F)F)cc1Cl
Reaction time: 6 h
Yield: 73 %

Procedure:
1.00 Gram of 2-fluoro-5-methyl-4-mercaptoaniline hydrochloride, 2.24 g of 3,4-dichlorobenzotrifluoride and 1.59 g of potassium carbonate were dissolved in 10 ml of dimethylformamide, and the resulting solution was stirred for 6 hours at a temperature of from 110° to 120° C. in an oil bath. Thereafter, the reaction solution was poured into water and extracted with two 100-ml portions of diethyl ether. The extract obtained was washed with water, dried, filtered and concentrated. The residue obtained was subjected to chromatography on silica gel to obtain 1.27 g of 2-fluoro-5-methyl-4-[2-chloro-4-(trifluoromethyl)phenylthio]aniline.
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:18]=[CH:17][C:12]([O:13][CH2:14][CH2:15][OH:16])=[CH:11][CH:10]=2)[O:3]1.C(N(CC)CC)C.[S:27](Cl)([C:30]1[CH:36]=[CH:35][C:33](C)=[CH:32][CH:31]=1)(=[O:29])=[O:28]>CN(C)C1C=CN=CC=1.ClCCl>[C:30]1([S:27]([O:16][CH2:15][CH2:14][O:13][C:12]2[CH:17]=[CH:18][C:9]([B:4]3[O:3][C:2]([CH3:19])([CH3:1])[C:6]([CH3:7])([CH3:8])[O:5]3)=[CH:10][CH:11]=2)(=[O:29])=[O:28])[CH:36]=[CH:35][CH:33]=[CH:32][CH:31]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC1(C)OB(c2ccc(OCCO)cc2)OC1(C)C
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC1(C)OB(c2ccc(OCCOS(=O)(=O)c3ccccc3)cc2)OC1(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 90.3 %

Procedure:
Into dichloromethane 100 ml, 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethanol (4.4 g, 16.7 mmol) synthesized in Example 2 (2b) was dissolved, to which triethylamine (4.6 ml, 33.2 mmol), 4-dimethylaminopyridine (400 mg, 3.3 mmol), tosyl chloride (4.8 g, 25.2 mmol) were sequentially added while cooling with ice. The resulting mixture was warmed back to room temperature, followed by further stirring for two hours. The resulting reaction liquid was sequentially washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (hexane:ethyl acetate, 100:0-70:30, V/V) to give the desired title compound (6.1 g, yield 88%).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]2[N:8]([CH3:46])[C:9]([CH2:11][O:12][C:13]3[CH:45]=[CH:44][C:16]([CH2:17][CH:18]4[S:22][C:21](=[O:23])[N:20](C(C5C=CC=CC=5)(C5C=CC=CC=5)C5C=CC=CC=5)[C:19]4=[O:43])=[CH:15][CH:14]=3)=[N:10][C:5]2=[CH:4][CH:3]=1.C(O)(=O)C>O>[Cl:1][C:2]1[N:7]=[C:6]2[N:8]([CH3:46])[C:9]([CH2:11][O:12][C:13]3[CH:45]=[CH:44][C:16]([CH2:17][CH:18]4[S:22][C:21](=[O:23])[NH:20][C:19]4=[O:43])=[CH:15][CH:14]=3)=[N:10][C:5]2=[CH:4][CH:3]=1
Reactant: Cn1c(COc2ccc(CC3SC(=O)N(C(c4ccccc4)(c4ccccc4)c4ccccc4)C3=O)cc2)nc2ccc(Cl)nc21
Solvent: CC(=O)O
Solvent: O
Product: Cn1c(COc2ccc(CC3SC(=O)NC3=O)cc2)nc2ccc(Cl)nc21

Procedure:
A procedure similar to that described in Example 12 was repeated, except that 1.16 g of 5-{4-(5-chloro-3-methylimidazo[5,4-b]pyridin-2-ylmethoxy)benzyl}-3-triphenylmethylthiazolidine-2,4-dione (prepared as described in Preparation 45) and 16 ml of a 3:1 by volume mixture of acetic acid and water were used, to give the title compound as a crude product. The product was crystallized by trituration with ethyl acetate, to give 0.38 g of the title compound, melting at 222°-223° C.
Reaction SMILES: C(=O)([S:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][C@H:11]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:12]([N:14]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[CH3:15])=[O:13])[CH:5]=1)C.[OH-].[K+].C([N:38]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:40]([CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49])=[C:39]1[CH2:53]Br)(=O)C.Cl>C(O)C>[C:28]([O:27][C:25]([NH:24][C@H:11]([C:12]([N:14]([C:16]1[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=1)[CH3:15])=[O:13])[CH2:10][C:6]1[CH:5]=[C:4]([S:3][CH2:53][C:39]2[NH:38][C:46]3[C:41]([C:40]=2[CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:42][CH:43]=[CH:44][CH:45]=3)[CH:9]=[CH:8][CH:7]=1)=[O:26])([CH3:30])([CH3:31])[CH3:29]
Reactant: CCOC(=O)Cc1c(CBr)n(C(C)=O)c2ccccc12
Reactant: COc1ccc(N(C)C(=O)[C@H](Cc2cccc(SC(C)=O)c2)NC(=O)OC(C)(C)C)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CCOC(=O)Cc1c(CSc2cccc(C[C@H](NC(=O)OC(C)(C)C)C(=O)N(C)c3ccc(OC)cc3)c2)[nH]c2ccccc12
Reaction time: 0.17 h
Yield: 75.3 %

Procedure:
To a solution of (S)—S-3-(2-(tert-butoxycarbonylamino)-3-((4-methoxyphenyl)(methyl)amino)-3-oxopropyl)phenyl ethanethioate (335 mg, 0.73 mmol) in ethanol (2 ml) was added potassium hydroxide (82 mg, 1.46 mmol). After 10 minutes, ethyl 2-(1-acetyl-2-(bromomethyl)-1H-indol-3-yl)acetate (I-4A, 272 mg, 0.8 mmol) was added. The reaction was stirred for 2 hours and then neutralized with 1N (aq) HCl then extracted with EtOAc. The organic layer was dried with Na2SO4, filtered and concentrated. The crude product was introduced to a silica gel loading column and purified by column chromatography (1-5% MeOH/DCM) to provide the desired product (347 mg, 0.55 mmol), 75.3%. MS (m/z) 632 [M+H]+.
Reaction SMILES: [N+:1]([C:4]1[CH:41]=[CH:40][C:7]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH:16]([C:23]3[CH:28]=[CH:27][C:26]([C:29](=O)[C:30]4[CH:35]=[CH:34][C:33]([N+:36]([O-:38])=[O:37])=[CH:32][CH:31]=4)=[CH:25][CH:24]=3)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:12][CH:11]=2)=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].ClCCCl.C([SiH](CC)CC)C>O>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][C:10]2[CH:15]=[CH:14][C:13]([CH:16]([C:23]3[CH:28]=[CH:27][C:26]([CH2:29][C:30]4[CH:31]=[CH:32][C:33]([N+:36]([O-:38])=[O:37])=[CH:34][CH:35]=4)=[CH:25][CH:24]=3)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:12][CH:11]=2)=[CH:40][CH:41]=1)([O-:3])=[O:2]
Reactant: CCCCCCC(c1ccc(C(=O)c2ccc([N+](=O)[O-])cc2)cc1)c1ccc(C(=O)c2ccc([N+](=O)[O-])cc2)cc1
Agent: CC[SiH](CC)CC
Solvent: ClCCCl
Solvent: O
Product: CCCCCCC(c1ccc(Cc2ccc([N+](=O)[O-])cc2)cc1)c1ccc(Cc2ccc([N+](=O)[O-])cc2)cc1
Yield: 103 %

Procedure:
In a 1-liter three-necked flask equipped with a stirring device, a thermometer and a nitrogen substituting device, 14.4 g of 1,1-bis(4-(4-nitrobenzoyl)phenyl)heptane, 60 milliliters of 1,2-dichloroethane and 19.4 g of boron trifluoride diethyl ether complex were introduced and heated at reflux. 14.4 g of triethylsilane was added dropwise for 15 minutes with maintaining the temperature. After the end of the reaction was confirmed by a liquid chromatography, the reaction solution was poured in water and extracted with chloroform. The solution was washed with an aqueous solution of sodium hydrogencarbonate and water, and then dried with anhydrous sodium sulfate. After removing off the solvent by a rotary evaporator, the solution was dissolved in toluene and subjected to a separating operation by a column chromatography with silica gel. After removing off the solvent again, 14.08 g of 1,1-bis(4-(4-nitrobenzyl)phenyl) heptane was obtained as red oil.
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:11]=[CH:10][C:6]([C:7](O)=O)=[CH:5][CH:4]=1.[CH3:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([NH2:21])=[C:18]([SH:20])[CH:19]=1.C([O-])([O-])=O.[K+].[K+]>>[CH3:12][O:13][C:14]1[CH:15]=[CH:16][C:17]2[N:21]=[C:7]([C:6]3[CH:10]=[CH:11][C:3]([NH:2][CH3:1])=[CH:4][CH:5]=3)[S:20][C:18]=2[CH:19]=1
Reactant: CNc1ccc(C(=O)O)cc1
Reactant: COc1ccc(N)c(S)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CNc1ccc(-c2nc3ccc(OC)cc3s2)cc1
Temperature: 170 °C
Yield: 22.3 %

Procedure:
A mixture of 4-methylaminobenzoic acid (11.5 g, 76.2 mmol) and 5-methoxy-2-aminothiophenol (12.5, g, 80 mmol) was heated in PPA (˜30 g) to 170° C. under N2 atmosphere for 1.5 hr. The reaction mixture was then cooled to room temperature and poured into 10% K2CO3 solution. The precipitate was filtered under reduced pressure. The crude product was re-crystallized twice from acetone/water and THF/water followed by the treatment with active with carbon to give 4.6 g (21%) of 6-Methoxy-2-(4-methylaminophenyl)benzothiazole as a yellow solid. 1HNMR (300 MHz, acetone-d6) δ: 7.84(d, J=8.7 Hz, 2H, H-2′6′), 7.78(dd, J1=8.8 Hz, J2=1.3 Hz, 1H, H-4), 7.52(d, J=2.4 Hz, 1H, H-7), 7.05(dd, J1=8.8 Hz, J2=2.4 Hz, H-5), 6.70(d, J=7.6 Hz, 2H, H-3′5′), 5.62(s, 1H, NH), 3.88(s, 3H, OCH3), 2.85(d, J=6.2 Hz, 3H, NCH3)
Reaction SMILES: [BH4-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][CH:19]3[CH2:24][C:23](=[O:25])[C:22]4[CH:26]=[CH:27][CH:28]=[CH:29][C:21]=4[S:20]3(=[O:31])=[O:30])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1.O>CO>[F:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][CH:19]3[CH2:24][CH:23]([OH:25])[C:22]4[CH:26]=[CH:27][CH:28]=[CH:29][C:21]=4[S:20]3(=[O:30])=[O:31])[CH2:14][CH2:15]2)=[CH:6][CH:5]=1
Reactant: O=C1CC(CCCN2CCN(c3ccc(F)cc3)CC2)S(=O)(=O)c2ccccc21
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: O=S1(=O)c2ccccc2C(O)CC1CCCN1CCN(c2ccc(F)cc2)CC1
Yield: 61.1 %

Procedure:
340 mg (9 mmol) of sodium borohydride was added to a suspension of 375 mg (0.9 mmol) of the Compound 19 in 15 ml of methanol while stirring under cooling with ice. After stirring for two hours at room temperature, 15 ml of water was added and the mixture was stirred for one hour at room temperature and concentrated under vacuum. Ethyl acetate was added to the residue and the organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The crude product was purified by recrystallizing from ethanol to obtain 230 mg (yield: 61%) of the title compound.
Reaction SMILES: [CH3:1][O:2][CH:3]([O:19][CH3:20])[C@@:4]1([CH3:18])[C@@H:9]2[O:10][C@@H:8]2[C:7]2[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:6]=2[O:5]1.[CH:21]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[NH:30][CH2:31][C:32]1[NH:33][CH:34]=[CH:35][N:36]=1)([CH3:23])[CH3:22]>>[CH3:1][O:2][CH:3]([O:19][CH3:20])[C@@:4]1([CH3:18])[C@H:9]([OH:10])[C@@H:8]([N:30]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[CH:21]([CH3:23])[CH3:22])[CH2:31][C:32]2[NH:36][CH:35]=[CH:34][N:33]=2)[C:7]2[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:6]=2[O:5]1
Reactant: COC(OC)[C@]1(C)Oc2ccc([N+](=O)[O-])cc2[C@H]2O[C@H]21
Reactant: CC(C)c1ccccc1NCc1ncc[nH]1
Product: COC(OC)[C@]1(C)Oc2ccc([N+](=O)[O-])cc2[C@H](N(Cc2ncc[nH]2)c2ccccc2C(C)C)[C@H]1O
Yield: 41.4 %

Procedure:
The title compound (72 mg, 42%) was prepared using (2R,3R,4R)-3,4-dihydro-2-dimethoxymethyl-3,4-epoxy-2-methyl-6-nitro-2H-1-benzopyran (100 mg, 0.35 mmol) and 2-isopropylphenyl-1H-imidazol-2-ylmethylamine (75 mg, 0.35 mmol), according to the same procedure used for the preparation of example 1 above.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([OH:12])=[O:11])[CH:8]=2)[CH:3]=[CH:2]1.S(=O)(=O)(O)O.[CH3:18]O>>[CH3:18][O:11][C:10]([C:7]1[CH:8]=[C:9]2[C:4]([CH:3]=[CH:2][NH:1]2)=[CH:5][CH:6]=1)=[O:12]
Reactant: CO
Reactant: O=C(O)c1ccc2cc[nH]c2c1
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccc2cc[nH]c2c1

Procedure:
A solution of 1H-indole-6-carboxylic acid (10 g) in methanol (300 mL) was treated with concentrated sulfuric acid (0.5 mL) then heated on a steam bath for 10 hours. The solvent was removed under reduced pressure and the residue partitioned between saturated sodium bicarbonate solution (150 mL) and dichloromethane (150 mL). The aqueous layer was further extracted twice with dichloromethane (150 mL). The combined organics were dried over sodium sulfate then evaporated. The residue was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (7:3, v/v) to give the title compound (7.4 g) as a white solid, m.p. 79-81° C. MS: 176 (MH+).