Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O[C@@H:2]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)[CH3:3].C(N(CC)CC)C.[F:26]C(F)(S(F)(=O)=O)C(F)(F)C(F)(F)C(F)(F)F>CC#N.O>[F:26][C@H:2]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)[CH3:3]
Reactant: O=S(=O)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reactant: COc1ccc(CN2C(=O)OC[C@@H]2[C@@H](C)O)cc1
Solvent: CC#N
Solvent: O
Solvent: CCN(CC)CC
Product: COc1ccc(CN2C(=O)OC[C@@H]2[C@H](C)F)cc1
Temperature: 0 °C
Reaction time: 1.17 h
Yield: 95.7 %

Procedure:
To a cooled (0° C.) solution of (R)-4-((R)-1-hydroxyethyl)-3-(4-methoxybenzyl)oxazolidin-2-one (2.27 g, 9.04 mmol) in 30 mL MeCN were added triethylamine (11.4 mL, 82 mmol) followed by perfluoro-1-butanesulfonyl fluoride (4.9 mL, 27.3 mmol) and NEt3(HF)3 (4.5 mL, 27.6 mmol) and the resulting mixture was stirred at 0° C. for 70 min. The reaction mixture was diluted with water (60 mL) and extracted with EtOAc (3×60 mL). Combined organics were washed with water (70 mL), brine (70 mL), dried over Na2SO4, filtered and concentrated. Flash column chromatography (EtOAc/heptane 5 to 70%) gave 2.19 g (R)-4-((S)-1-fluoroethyl)-3-(4-methoxybenzyl)oxazolidin-2-one. 1H NMR (400 MHz, CDCl3) δ 7.25-7.20 (m, 2H), 6.92-6.83 (m, 2H), 4.87 (d, J=15.1 Hz, 1H), 4.75 (dqd, J=47.6, 6.6, 2.1 Hz, 1H), 4.26 (td, J=9.2, 1.4 Hz, 1H), 4.17-4.05 (m, 2H), 3.81 (s, 3H), 3.71 (dddd, J=19.8, 9.5, 5.8, 2.1 Hz, 1H), 1.29 (dd, J=23.1, 6.2 Hz, 3H). MS m/z 254.5 (M+H).
Reaction SMILES: [OH:1][C:2]1[C:7]2[CH:8]=[CH:9][S:10][C:6]=2[C:5](/[CH:11]=[CH:12]/[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:4][CH:3]=1>[C].[Pd].C(O)C>[OH:1][C:2]1[C:7]2[CH:8]=[CH:9][S:10][C:6]=2[C:5]([CH2:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:4][CH:3]=1
Reactant: CCOC(=O)/C=C/c1ccc(O)c2ccsc12
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)CCc1ccc(O)c2ccsc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Into a 100-mL round-bottom flask purged and maintained with an inert atmosphere of H2, was placed ethyl (2E)-3-(4-hydroxy-1-benzothiophen-7-yl)prop-2-enoate (200 mg, 0.68 mmol, 1.00 equiv, 85%), Palladium carbon (100 mg), ethanol (4 mL). The resulting solution was stirred overnight at 25° C. The solids were filtered out. The resulting mixture was concentrated under vacuum. The residue was purified by thin layer chromatography developed with ethyl acetate/petroleum ether (1:5). This resulted in 150 mg (79%) of ethyl 3-(4-hydroxy-1-benzothiophen-7-yl)propanoate as colorless oil.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:19]=[CH:18][C:17]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([C:20]3[CH:32]=[CH:31][C:30]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[NH:23][C:22]=4[CH:21]=3)[C:9]=2[CH:8]=1.Cl[C:34]1[CH:39]=[C:38]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:37]=[CH:36][N:35]=1.CC(P(C(C)(C)C)C1C(C2C=CC=CC=2)=CC=CC=1)(C)C.CC([O-])(C)C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:40]1([C:38]2[CH:39]=[CH:34][N:35]=[C:36]([N:23]3[C:22]4[CH:21]=[C:20]([N:10]5[C:9]6[CH:8]=[C:7]([C:2]7[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=7)[CH:19]=[CH:18][C:17]=6[C:16]6[C:11]5=[CH:12][CH:13]=[CH:14][CH:15]=6)[CH:32]=[CH:31][C:30]=4[C:29]4[C:24]3=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:37]=2)[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1
Reactant: Clc1cc(-c2ccccc2)ccn1
Reactant: c1ccc(-c2ccc3c4ccccc4n(-c4ccc5c(c4)[nH]c4ccccc45)c3c2)nc1
Agent: [Pd]
Agent: CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C
Agent: CC(C)(C)[O-]
Product: c1ccc(-c2ccnc(-n3c4ccccc4c4ccc(-n5c6ccccc6c6ccc(-c7ccccn7)cc65)cc43)c2)cc1
Temperature: 100 °C
Reaction time: 48 h

Procedure:
To a dry pressure Schlenk tube equipped with a magnetic stir bar was added 2′-(pyridin-2-yl)-9H-2,9′-bicarbazole (409 mg, 1.0 mmol, 1.0 eq), 2-chloro-4-phenylpyridine (228 mg, 1.2 mmol, 1.2 eq), Pd2(dba)3 (36 mg, 0.04 mmol, 0.04 eq), JohnPhos (48 mg, 0.16 mmol, 0.16 eq) and tBuONa (154 mg, 1.6 mmol, 1.6 eq). Then the tube was evacuated and back-filled with nitrogen, the evacuation and back-fill procedure was repeated twice. Then dry solvent toluene (4 mL) and dioxane (4 mL) were added under the protection of nitrogen. The tube was sealed and the mixture was stirred in an oil bath at a temperature of 95-105° C. for 2 days. Then the mixture was cooled to ambient temperature. The solvent was removed under reduced pressure and the residue was purified through column chromatography on silica gel using hexane and ethyl acetate (10:1-5:1-3:1) as an eluent to obtain the desired product, 9-(4-phenylpyridin-2-yl)-2′-(pyridin-2-yl)-9H-2,9′-bicarbazole Ligand N3NPh, as a brown solid (561 mg in 99.7% yield). 1H NMR (DMSO-d6, 400 MHz): δ 7.29-7.34 (m, 2H), 7.41-7.48 (m, 5H), 7.53-7.60 (m, 2H), 7.64 (dd, J=8.0, 1.2 Hz, 1H), 7.76 (d, J=4.8 Hz, 1H), 7.82-7.88 (m, 3H), 7.97 (d, J=8.0 Hz, 1H), 8.05 (d, J=8.4 Hz, 1H), 8.10 (s, 1H), 8.19 (s, 1H), 8.26 (s, 1H), 8.30 (d, J=7.6 Hz, 1H), 8.36 (d, J=8.4 Hz, 1H), 8.42 (d, J=8.0 Hz, 1H), 8.59-8.61 (m, 2H), 8.70 (d, J=5.6 Hz, 1H). 13C NMR (DMSO-d6, 100 MHz): δ 107.61, 109.87, 110.25, 111.57, 116.34, 118.65, 119.76, 119.97, 120.25, 120.35, 120.77, 120.81, 120.88, 121.48, 122.05, 122.39, 122.42, 123.07, 123.13, 123.38, 126.70, 126.98, 127.09, 129.16, 129.66, 134.83, 136.48, 136.74, 137.22, 139.79, 139.80, 141.25, 141.50, 149.46, 150.17, 150.40, 151.30, 156.16.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][CH:10]([N:13]([CH3:15])[CH3:14])[CH2:9]2)=[CH:4][CH:3]=1.[CH3:16][O:17][C:18](=[O:28])[C:19]1[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=1>>[CH3:16][O:17][C:18](=[O:28])[C:19]1[CH:27]=[CH:26][C:22]([C:23]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH2:12][CH2:11][CH:10]([N:13]([CH3:15])[CH3:14])[CH2:9]3)=[CH:4][CH:3]=2)=[O:24])=[CH:21][CH:20]=1
Reactant: COC(=O)c1ccc(C(=O)O)cc1
Reactant: CN(C)C1CCN(c2ccc(N)cc2)C1
Product: COC(=O)c1ccc(C(=O)Nc2ccc(N3CCC(N(C)C)C3)cc2)cc1

Procedure:
[1-(4-Aminophenyl)pyrrolidin-3-yl]dimethylamine was reacted with terephthalic acid monomethyl ester by method E. This resulted in the product with the molecular weight of 367.45 (C21H25N3O3); MS (ESI): 368 (M+H+).
Reaction SMILES: [NH2:1][CH2:2][CH:3]([OH:6])[CH2:4][OH:5].C([O-])([O-])=O.[K+].[K+].[CH3:13][C:14]([C:16](Cl)=[O:17])=[CH2:15]>CN(C)C=O.CO>[OH:6][CH:3]([CH2:4][OH:5])[CH2:2][NH:1][C:16](=[O:17])[C:14]([CH3:15])=[CH2:13]
Reactant: C=C(C)C(=O)Cl
Reactant: NCC(O)CO
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: CN(C)C=O
Product: C=C(C)C(=O)NCC(O)CO
Temperature: 0 °C

Procedure:
4.56 g of 3-amino-1,2-propanediol (0.05 mol) were dissolved in 30 ml of dimethylformamide (anhydrous). This solution, and also 13.8 g of K2CO3, were transferred to a 100 ml three-necked flask fitted with dropping funnel and gas inlet and gas outlet pipe. The mixture was cooled to 0° C. in an ice bath. 6.18 ml of methacryl chloride (0.06 mol), dissolved in 30 ml of dimethylformamide, were added dropwise over 30 minutes with moderate stirring and gentle passage of nitrogen. After stirring for a further hour with ice cooling, the mixture was allowed to warm to room temperature and was stirred for a further 30 minutes. The reaction batch was filtered through a fluted filter, and the residue was discarded. The filtrate was concentrated in a rotary evaporator until a viscous oil was produced. This oil was dissolved in 30 ml of methanol and filtered a second time, and the filtrate was again concentrated in a rotary evaporator. The residual amounts of solvent were removed in a high vacuum. The yield was 8.52 g.
Reaction SMILES: [CH2:1]([C:3]([OH:33])([CH2:31][CH3:32])[CH2:4][CH2:5]/[CH:6]=[C:7](/[C:9]1[CH:10]=[C:11]([CH:28]=[CH:29][CH:30]=1)[O:12][CH2:13][C:14]1[CH:15]=[C:16]([C:24](OC)=[O:25])[C:17](=[CH:22][CH:23]=1)[C:18](OC)=[O:19])\[CH3:8])[CH3:2].[BH4-].[Li+]>>[OH:25][CH2:24][C:16]1[CH:15]=[C:14]([CH:23]=[CH:22][C:17]=1[CH2:18][OH:19])[CH2:13][O:12][C:11]1[CH:10]=[C:9](/[C:7](/[CH3:8])=[CH:6]/[CH2:5][CH2:4][C:3]([CH2:31][CH3:32])([OH:33])[CH2:1][CH3:2])[CH:30]=[CH:29][CH:28]=1
Reactant: CCC(O)(CC)CC/C=C(\C)c1cccc(OCc2ccc(C(=O)OC)c(C(=O)OC)c2)c1
Agent: [BH4-]
Agent: [Li+]
Product: CCC(O)(CC)CC/C=C(\C)c1cccc(OCc2ccc(CO)c(CO)c2)c1

Procedure:
In a manner similar to Example 53(e), by reacting 131 mg (0.29 mmol) of dimethyl 4-[3-((E)-5-ethyl-5-hydroxy-1-methylhept-1-enyl)phenoxymethyl]phthalate with 25 mg (1.15 mmol) of lithium borohydride, a colourless oil is obtained (m=89 mg; Y=78%).
Reaction SMILES: [F:1][C:2]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[N:4]2[CH2:11][CH2:12][N:13]([C:16]3[N:23]=[CH:22][CH:21]=[C:20]([C:24]4[CH:29]=[C:28]([NH:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=5)[C:27](=[O:37])[N:26]([CH3:38])[CH:25]=4)[C:17]=3[CH:18]=[O:19])[C:14](=[O:15])[C:3]=12.[BH4-].[Na+]>CO>[F:1][C:2]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[N:4]2[CH2:11][CH2:12][N:13]([C:16]3[C:17]([CH2:18][OH:19])=[C:20]([C:24]4[CH:29]=[C:28]([NH:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=5)[C:27](=[O:37])[N:26]([CH3:38])[CH:25]=4)[CH:21]=[CH:22][N:23]=3)[C:14](=[O:15])[C:3]=12
Reactant: Cn1cc(-c2ccnc(N3CCn4c5c(c(F)c4C3=O)CCCC5)c2C=O)cc(Nc2ccccn2)c1=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: Cn1cc(-c2ccnc(N3CCn4c5c(c(F)c4C3=O)CCCC5)c2CO)cc(Nc2ccccn2)c1=O
Temperature: 20 °C
Reaction time: 2 h
Yield: 26.3 %

Procedure:
A mixture of 183a (160 mg, 0.31 mmol) and NaBH4 (59 mg, 1.55 mmol) in methanol (20 mL) was stirred at 20° C. for 2 h. The reaction was then quenched with water and evaporated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 183 (42 mg, 26%) as an off-white solid. MS-ESI: [M+H]+ 515.3. 1H NMR (500 MHz, DMSO-d6) δ 8.74 (d, J=2.5 Hz, 1H), 8.65 (s, 1H), 8.50 (d, J=5.0 Hz, 1H), 8.18-8.17 (m, 1H), 7.61-7.58 (m, 1H), 7.53 (d, J=2.0 Hz, 1H), 7.36 (d, J=5.0 Hz, 1H), 7.31 (d, J=8.5 Hz, 1H), 6.81-6.79 (m, 1H), 4.95 (t, J=5.0 Hz, 1H), 4.49-4.40 (m, 2H), 4.22-4.14 (m, 2H), 4.10-4.05 (m, 1H), 3.87-3.85 (m, 1H), 3.62 (s, 3H), 2.64-2.60 (m, 1H), 2.57-2.53 (m, 1H), 2.43-2.41 (m, 2H), 1.81-1.75 (m, 2H), 1.71-1.67 (m, 2H).
Reaction SMILES: [CH3:1][S:2][C:3]1[NH:8][C:7](=[O:9])[C:6]([CH:10]([NH:12][C:13](=[O:18])[CH2:14][CH:15](C)[CH3:16])[CH3:11])=[N:5][N:4]=1.SC1NC(=O)C(C(NC(=O)CC(C)C)C)=NN=1>>[CH3:1][S:2][C:3]1[NH:8][C:7](=[O:9])[C:6]([CH:10]([NH:12][C:13](=[O:18])[CH2:14][CH2:15][CH3:16])[CH3:11])=[N:5][N:4]=1
Reactant: CSc1nnc(C(C)NC(=O)CC(C)C)c(=O)[nH]1
Agent: CC(C)CC(=O)NC(C)c1nnc(S)[nH]c1=O
Product: CCCC(=O)NC(C)c1nnc(SC)[nH]c1=O

Procedure:
In a similar manner was prepared N-[1-(3-methylthio-4,5-dihydro-5-oxo-1,2,4-triazin-6-yl)ethyl]-3-methylbutyramide (1.0 g) m.p. 193°-194° (from ethyl acetate) from N-[1-(3-mercapto-4,5-dihydro-5-oxo-1,2,4-triazin-6-yl)ethyl]-3-methylbutyramide (2.0 g).
Reaction SMILES: [OH:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.[CH2:17](O)[CH2:18][OH:19].C([O-])([O-])OC>C(OCC)(=O)C>[OH:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]2([C:8]3[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=3)[O:19][CH2:18][CH2:17][O:7]2)=[CH:4][CH:3]=1.[OH:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1
Reactant: OCCO
Agent: COC([O-])[O-]
Agent: O=C(c1ccc(O)cc1)c1ccc(O)cc1
Solvent: CCOC(C)=O
Product: Oc1ccc(C2(c3ccc(O)cc3)OCCO2)cc1

Procedure:
In a flask equipped with a stirring blade and a thermometer, montmorillonite clay K10 (750 g) and 495 g of 4,4′-dihydroxybenzophenone were charged, and the atmosphere in the flask was replaced by nitrogen. 1,200 mL of ethylene glycol and 500 mL of methyl orthoformate were added and the reaction was carried out at a bath temperature of 110° C. for 8 hours while distilling off by-products produced. 500 mL of methyl orthoformate was added, followed by the reaction for 8 hours, namely, 16 hours in total. The reaction solution was diluted by adding 1 L of ethyl acetate and clay was removed by filtration, and then solution was extracted with an aqueous 2% sodium hydrogen carbonate solution four times. The extract solution was concentrated and the resulting slurry-like compound was washed with dichloroethane to obtain a 2,2-bis(4-hydroxyphenyl)-1,3-dioxolane/4,4′-dihydroxybenzophenone mixture (=85.5/14.5 mol %). The structure was confirmed by 1H-NMR. Other impurities could not be recognized by gas chromatography.
Reaction SMILES: [OH:1][C:2]([C:9]1[CH:10]=[C:11]([CH:34]=[CH:35][CH:36]=1)[O:12][C:13]1[C:18]([NH:19][C:20]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=2)=[O:21])=[CH:17][CH:16]=[CH:15][N:14]=1)([CH2:6][CH:7]=[CH2:8])[CH2:3][CH:4]=[CH2:5].S(=O)(=O)(O)O.[C:42](=O)(O)[O-].[Na+]>CO>[CH3:42][O:1][C:2]([C:9]1[CH:10]=[C:11]([CH:34]=[CH:35][CH:36]=1)[O:12][C:13]1[C:18]([NH:19][C:20]([NH:22][C:23]2[CH:24]=[CH:25][C:26]([O:29][C:30]([F:33])([F:31])[F:32])=[CH:27][CH:28]=2)=[O:21])=[CH:17][CH:16]=[CH:15][N:14]=1)([CH2:6][CH:7]=[CH2:8])[CH2:3][CH:4]=[CH2:5]
Reactant: O=C([O-])O
Reactant: C=CCC(O)(CC=C)c1cccc(Oc2ncccc2NC(=O)Nc2ccc(OC(F)(F)F)cc2)c1
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CO
Product: C=CCC(CC=C)(OC)c1cccc(Oc2ncccc2NC(=O)Nc2ccc(OC(F)(F)F)cc2)c1
Temperature: 100 °C

Procedure:
To a solution of Example 640 (120 mg, 0.24 mmol) in dry methanol (15 mL) was added concentrated sulfuric acid (2 mL) at rt. The mixture was heated to 100° C. for 72 h and cooled down to rt. A saturated solution of sodium bicarbonate was slowly added and the mixture was extracted with dichloromethane. Evaporation afforded a residue which was purified by reverse phase preparative HPLC. (M+H)+=514. 1H NMR (400 MHz, DMSO-d6) ppm 2.62 (m, 4H), 3.08 (s, 3H), 5.03 (m, 4H), 5.55 (m, 2H), 7.31 (m, 7H), 7.57 (d, 2H, J=9.1 Hz), 7.70 (dd, J=5.0, 1.7 Hz, 1H), 8.55 (dd, J=7.8, 1.5 Hz, 1H), 8.72 (s, 1H), 9.56 (s, 1H).
Reaction SMILES: C(O[C:4]1[C:5](=[O:16])[C:6](=[O:15])[C:7]=1[NH:8][C:9]1[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=1)C.[O:17]([C:24]1[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][NH2:32])=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[O:17]([C:24]1[CH:25]=[CH:26][C:27]([CH2:30][CH2:31][NH:32][C:4]2[C:5](=[O:16])[C:6](=[O:15])[C:7]=2[NH:8][C:9]2[CH:10]=[CH:11][N:12]=[CH:13][CH:14]=2)=[CH:28][CH:29]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CCOc1c(Nc2ccncc2)c(=O)c1=O
Reactant: NCCc1ccc(Oc2ccccc2)cc1
Product: O=c1c(NCCc2ccc(Oc3ccccc3)cc2)c(Nc2ccncc2)c1=O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
The title compound was prepared according to the procedure described in example 1B starting from 3-ethoxy-4-(pyridin-4-yl-amino)-3-cyclobutene-1,2-dione prepared according to example 7A and 2-(4-phenoxyphenyl)-ethylamine. The reaction mixture was heated to reflux for 2 hours instead of stirring 18 h at r.t.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH2:10](Br)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[CH2:10]([O:9][C:4]1[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([Br:1])[CH:3]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Oc1cc(F)cc(Br)c1
Reactant: BrCc1ccccc1
Product: Fc1cc(Br)cc(OCc2ccccc2)c1

Procedure:
Prepared as described for 1-bromo-2-fluoro-3-isopropoxy-benzene SM23 using 3-bromo-5-fluorophenol and benzylbromide.
Reaction SMILES: [CH:1]1([C:4]2[NH:5][C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=3[C:12]3[C:13]=2[C:14](=[O:26])[N:15]([C:17]2[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][CH:18]=2)[N:16]=3)[CH2:3][CH2:2]1.C(Cl)(=O)C([Cl:30])=O.CN(C)C=O>ClCCl>[CH:1]1([C:4]2[NH:5][C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=3[C:12]3[C:13]=2[C:14](=[O:26])[N:15]([C:17]2[CH:25]=[CH:24][C:20]([C:21]([Cl:30])=[O:22])=[CH:19][CH:18]=2)[N:16]=3)[CH2:3][CH2:2]1
Reactant: O=C(O)c1ccc(-n2nc3c4ccccc4[nH]c(C4CC4)c-3c2=O)cc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)c1ccc(-n2nc3c4ccccc4[nH]c(C4CC4)c-3c2=O)cc1
Temperature: 45 °C
Reaction time: 8 h

Procedure:
To a suspension of finely ground 4-(4-cyclopropyl-3-oxo-3,5-dihydro-pyrazolo[4,3-c]quinolin-2-yl)-benzoic acid (0.19 g. 0.55 mmol) in dichloromethane (4 ml) was added oxalyl chloride (1.6 ml, 0.01 mol) followed by a drop of dimethyl formamide. The mixture was stirred under nitrogen at 45° C. for 8 h. The solvent was removed in vacuo to yield 4-(4-cyclopropyl-3-oxo-3,5-dihydro-pyrazolo[4,3-c]quinolin-2-yl)-benzoyl chloride as a pale yellow solid, LCMS m/z [M+MeOH—Cl]+ @ RT 1.46 min: 95% purity. Used without further purification. Step 5 N-(3-Dimethylamino propyl)-4-(4-cyclopropyl-3-oxo-3,5-dihydro-pyrazolo[4,3-c]quinolin-2-yl]-benzamide
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[S:21]([CH3:23])=[O:22].Cl.CN[OH:27].C(N(CC)CC)C>CO>[NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:15])([F:16])[F:17])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([CH:19]=[N:20][OH:27])[C:3]=1[S:21]([CH3:23])=[O:22]
Reactant: CNO
Reactant: CS(=O)c1c(C#N)nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c1N
Agent: Cl
Solvent: CO
Solvent: CCN(CC)CC
Product: CS(=O)c1c(C=NO)nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c1N
Yield: 33.4 %

Procedure:
A mixture of 5-amino-3-cyano 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole (1 g), methylhydroxylamine hydrochloride (0.26 g) and triethylamine (0.4 g) was stirred in methanol at ambient temperature for 2 hours, evaporated, washed (water) extracted with ethyl acetate to give 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime (0.35 g) as a white solid m.p. about 190° C. Compound 2 was prepared in a similar manner from fipronil.
Reaction SMILES: [N:1]1([S:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[CH3:23][C:24]1[N:29]=[C:28]([NH2:30])[CH:27]=[CH:26][CH:25]=1>>[N:1]1([S:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:30][C:28]3[CH:27]=[CH:26][CH:25]=[C:24]([CH3:23])[N:29]=3)=[O:19])=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: O=C(O)c1ccc(S(=O)(=O)N2CCCc3ccccc32)cc1
Reactant: Cc1cccc(N)n1
Product: Cc1cccc(NC(=O)c2ccc(S(=O)(=O)N3CCCc4ccccc43)cc2)n1

Procedure:
4-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)benzoic acid (1) (100 mg, 0.32 mmol) was treated with 6-methylpyridin-2-amine (28 mg, 0.26 mmol) using method C. The residue was purified using flash chromatography eluting with 0-30% EtOAc in hexanes. The resulting solid was triturated with dichloromethane/hexanes to give 4-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)-N-(6-methylpyridin-2-yl)benzamide as a white solid. Yield: 14 mg (13%). 1H-NMR: 10.95 (s, 1H), 8.08 (d, J=8.5 Hz, 2H), 7.96 (d, J=8.5 Hz, 1H), 7.73 (t, J=8.0 Hz, 1H), 7.69 (d, J=8.5 Hz, 2H), 7.62 (d, J=8.5 Hz, 1H), 7.24-7.18 (m, 1H), 7.12-7.07 (m, 2H), 7.04 (d, J=7.5 Hz, 1H), 3.82-3.78 (m, 2H), 2.47-2.42 (m, 5H), 1.65-1.57 (m, 2H).
Reaction SMILES: [S:1]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([NH2:21])[C:13]=1[O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:8]([OH:10])=[O:9])(=[O:4])(=[O:3])[NH2:2].[CH2:22]([CH2:26][C:27](=O)[CH3:28])[C:23]([CH3:25])=O>C(O)(=O)C>[S:1]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([N:21]2[C:27]([CH3:28])=[CH:26][CH:22]=[C:23]2[CH3:25])[C:13]=1[O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:8]([OH:10])=[O:9])(=[O:3])(=[O:4])[NH2:2]
Reactant: Nc1cc(C(=O)O)cc(S(N)(=O)=O)c1Oc1ccccc1
Reactant: CC(=O)CCC(C)=O
Solvent: CC(=O)O
Product: Cc1ccc(C)n1-c1cc(C(=O)O)cc(S(N)(=O)=O)c1Oc1ccccc1

Procedure:
A mixture of 3-sulphamoyl-4-phenoxy-5-aminobenzoic acid (1.54 g=5 mmols; P. W. Feit, J. Med. Chem. 14, 432 (1971)), acetonylacetone (0.57 g=5 mmols) and 10 ml of glacial acetic acid is refluxed under N2 for 30 minutes, the red reaction solution is evaporated in vacuo and freed from residues of glacial acetic acid and water by adding benzene and evaporating azeotropically, the residue is dissolved in acetone, the solution is boiled with silica gel and filtered through a fine filter and the solution is concentrated to 50 ml and, after adding 50 ml of ethyl acetate, freed from acetone residues in vacuo, whereupon crystallisation takes place. After the purification procedure has been repeated, beige-coloured crystals with a melting point of 283°-286° (decomposition) result.
Reaction SMILES: [Na].[CH:2]1[C:15]([OH:16])=[CH:14][C:5]2[CH:6]=[CH:7][C:8](S(O)(=O)=O)=[CH:9][C:4]=2[CH:3]=1>>[CH:14]1[C:5]2[C:4](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:3]=[CH:2][C:15]=1[OH:16]
Reactant: O=S(=O)(O)c1ccc2cc(O)ccc2c1
Agent: [Na]
Product: Oc1ccc2ccccc2c1

Procedure:
Schaeffer's Salt is the common name for the sodium salt of 2-naphthol-6-sulfonic acid. As indicated, this product is obtained by sulfonation of 2-naphthol and forming the sodium salt of the intermediate 2-naphthol-6-sulfonic acid. In preparing Schaeffer's Salt, 2-naphthol is sulfonated directly with concentrated sulfuric acid at a temperature of about 100° C. under conditions such as to provide the maximum amount of 2-naphthol-6-sulfonic acid and follows conventional procedures. After the sulfonation is substantially complete, the resulting mixture is conventionally referred to as a sulfonation mixture. The sulfonation mixture will contain unreacted 2-naphthol, 2-naphthol-6-sulfonic acid, by-product 6,6'-oxybis(2-naphthalene sulfonic acid) and by-product 2-naphthol-3,6-disulfonic acid, with the major product being 2-naphthol-6-sulfonic acid. Preparation of the sulfonation mixture follows conventional procedure and forms no part of the present invention per se.
Reaction SMILES: [Cl:1][C:2]1[C:11]([Cl:12])=[CH:10][C:5]2[NH:6][C:7](=O)[NH:8][C:4]=2[CH:3]=1.O.N.P(Cl)(Cl)([Cl:17])=O>>[Cl:17][C:7]1[NH:6][C:5]2[CH:10]=[C:11]([Cl:12])[C:2]([Cl:1])=[CH:3][C:4]=2[N:8]=1
Reactant: O=c1[nH]c2cc(Cl)c(Cl)cc2[nH]1
Reactant: O=P(Cl)(Cl)Cl
Agent: N
Solvent: O
Product: Clc1nc2cc(Cl)c(Cl)cc2[nH]1
Temperature: 120 °C
Reaction time: 24 h

Procedure:
5,6-Dichloro-1,3-dihydro-2H-benzimidazol-2-one (11.5 g) was suspended in phosphorus oxychloride (40 mL), and the mixture was stirred at 120° C. for 24 hours. After cooling the reaction mixture, water was added to the reaction mixture, and to the mixture was added 28% aqueous ammonia solution to alkalize. The solid was collected by filtration and dried to give the title compound (5.0 g).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=1.N1C=CN=C1.[Si:15](Cl)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]>ClCCl.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])=[CH:4][CH:3]=1
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCc1ccc(Br)cc1
Agent: c1c[nH]cn1
Solvent: ClCCl
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCc1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (4-bromophenyl)methanol (3.0 g, 16.04 mmol) and imidazole (1.42 g, 20.85 mmol) in dichloromethane was added tert-butyl dimethylsilyl chloride (3.14 g, 20.85 mmol) and the mixture was stirred at room temperature overnight. The reaction was diluted with water, extracted with ethyl acetate (2×) and concentrated. The residue was absorbed onto silica and purified by flash column chromatography (silica gel, ethyl acetate/hexanes) to give the desired product. 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.3 Hz, 2H), 4.68 (s, 2H), 0.94 (s, 9H), 0.09 (s, 6H).