Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I([O-])(=O)(=O)=O.[Na+].[OH2:7].[P:8](=[O:22])([S:15][CH2:16][S:17][C:18]([CH3:21])([CH3:20])[CH3:19])([O:12][CH2:13][CH3:14])[O:9][CH2:10][CH3:11].CO>C(Cl)Cl>[P:8](=[O:22])([S:15][CH2:16][S:17]([C:18]([CH3:20])([CH3:19])[CH3:21])=[O:7])([O:12][CH2:13][CH3:14])[O:9][CH2:10][CH3:11]
Reactant: CCOP(=O)(OCC)SCSC(C)(C)C
Reactant: O
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: ClCCl
Solvent: CO
Product: CCOP(=O)(OCC)SCS(=O)C(C)(C)C
Temperature: 0 °C

Procedure:
To a suspension of sodium periodate (11.8 grams, 0.055 mole, 10% excess) in 115 ml. of water, cooled to 0° to 5°C., is added O,O-diethyl S-(tert-butylthio)methyl phosphorothioate (13.6 grams, 0.050 mole) and 5.0 ml. of methanol. The reaction mixture, in an ice bath contained in an insulated bucket, is stirred overnight, during which time the ice melts and the mixture attains room temperature. Fifty ml. of methylene chloride is stirred into the mixture and the solids are filtered and washed with an additional 50 ml. of methylene chloride. The filtrate is separated and the aqueous phase extracted with two 50-ml. portions of methylene chloride. The organic solutions are combined, washed with 25-ml. portions of saturated NaCl, 5% KOH, and saturated NaCl (X2), and then dried (MgSO4). Reduced-pressure evaporation of the solvent from the dried solution gives 13.9 grams (96.5%) of clear, colorless oil which slowly crystallizes, melting point 34.5° to 36.0°C. Attempts to effect recrystallization are not successful. TLC shows the presence of only a trace amount of a contaminant.
Reaction SMILES: [H-].[Na+].[CH2:3]([P:14](=[O:23])([O:19][CH:20]([CH3:22])[CH3:21])[O:15][CH:16]([CH3:18])[CH3:17])[P:4](=[O:13])([O:9][CH:10]([CH3:12])[CH3:11])[O:5][CH:6]([CH3:8])[CH3:7].[CH2:24](Br)/[CH:25]=[C:26](/[CH2:28][CH2:29]/[CH:30]=[C:31](/[CH2:33][CH2:34][CH:35]=[C:36]([CH3:38])[CH3:37])\[CH3:32])\[CH3:27].O>C(COC)OC>[CH2:24]([CH:3]([P:4](=[O:13])([O:9][CH:10]([CH3:11])[CH3:12])[O:5][CH:6]([CH3:8])[CH3:7])[P:14](=[O:23])([O:15][CH:16]([CH3:18])[CH3:17])[O:19][CH:20]([CH3:22])[CH3:21])/[CH:25]=[C:26](/[CH2:28][CH2:29]/[CH:30]=[C:31](/[CH2:33][CH2:34][CH:35]=[C:36]([CH3:37])[CH3:38])\[CH3:32])\[CH3:27]
Reactant: CC(C)OP(=O)(CP(=O)(OC(C)C)OC(C)C)OC(C)C
Reactant: CC(C)=CCC/C(C)=C/CC/C(C)=C/CBr
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: CC(C)=CCC/C(C)=C/CC/C(C)=C/CC(P(=O)(OC(C)C)OC(C)C)P(=O)(OC(C)C)OC(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 60.7 %

Procedure:
Oily sodium hydride (60%, 0.24 g) was added to a solution of tetraisopropyl methylenebisphosphonate (3.44 g) in dimethoxyethane (25 ml). The mixture was stirred at room temperature for 1 hour. Then, a solution of (E,E)-farnesyl bromide (1.43 g) in dimethoxyethane (5 ml) was added dropwise at 0° C. The reaction mixture was stirred at room temperature for 1 hour, then poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried (MgSO4), and then the solvent was distilled off under reduced pressure. The oily residue was subjected to column chromatography on silica gel. Tetraisopropyl (E,E)-farnesylmethylenebisphosphonate (1.67 g, 60.9%) was obtained as an oil from the fractions obtained by elution with ethyl acetate-chloroform (1:1, v/v).
Reaction SMILES: [Na].[CH3:2][O:3][C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:14]C)=[CH:11][CH:12]=2)[CH:7]=[CH:6][CH:5]=1.O>C(O)C>[CH3:2][O:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[CH2:12][CH2:11][C:10](=[O:14])[CH2:9]2
Reactant: COc1ccc2c(OC)cccc2c1
Agent: [Na]
Solvent: CCO
Solvent: O
Product: COc1cccc2c1CCC(=O)C2
Temperature: 70 °C
Reaction time: 0.5 h

Procedure:
1,6-Dihydroxynaphthalene (44 g (0.247 mole)) was mixed with 245 mL of 2N NaOH and 55 mL of methyl sulfate. The mixture was stirred at room temperature. When the pH of the mixture was 6, 124 mL of 2N NaOH and 26.4 mL of methyl sulfate were added and stirred until 1,6-dihydroxynaphthalene was disappeared. Excess of methyl sulfate was destroyed by heating for 30 minutes at 100° C. The warm liquid was acidified and extracted with CH2Cl2. The CH2Cl2 layer was washed twice with 2N NaOH and evaporated. A yield of 47.73 g (92%) of 1,6-dimethoxynaphthanene was obtained. Sodium (19 g) was added to a solution of 22.5 of crude 1,6-dimethoxynaphthalene in 190 mL of boiling ethanol. Ethanol (40 mL) was then added and heating continued under reflux until the Na had disappeared (about 40 minutes). Water (60 mL) was added cautiously and then most of the ethanol was removed under reduced pressure. The residue was mixed with 30 mL of water and the lower aqueous layer was separated and extracted twice with dioxane, which was then combined with the oily upper layer. Water (25 mL) and then hydrochloric acid (density of 1.18 g/mL) until the mixture was acidic (pH 2-3). Then, 3 mL more of HCl was added and the liquid was stirred at about 70° C. for 30 minutes. The lower oily layer was separated, the aqueous layer was diluted with 100 mL of water, separated from more oil, and extracted thrice with methylene chloride. The combined oil and methylene chloride extracts were stirred with 50 mL of saturated aqueous sodium bisulfite until crystallization began. The solid was triturated with ether, then washed with ether and dried. Free 5-methoxy-2-tetralone was obtained by treating the bisulfite addition compound with excess 10% Na2CO3 and extracting the resulting mixture with methylene chloride. The extract was washed with 10% HCl and then with water and dried with Na2SO4. Volatiles were removed under reduced pressure to leave 17 g (81% yield) of liquid. On keeping, the 3,4-Dihydro-5-methoxy-2-(1H)-naphthalenone (hereinafter, "Compound 20") solidified in massive prisms with a melting point of 25°-36° C.
Reaction SMILES: [NH2:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4].[C:11]1([CH3:21])[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1.O>N1C=CC=CC=1>[C:11]1([CH3:21])[CH:16]=[CH:15][C:14]([S:17]([NH:1][CH2:2][C:3]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:4])(=[O:19])=[O:18])=[CH:13][CH:12]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: NCC(=O)c1ccccc1
Solvent: c1ccncc1
Solvent: O
Product: Cc1ccc(S(=O)(=O)NCC(=O)c2ccccc2)cc1
Temperature: 45 °C
Reaction time: 2 h
Yield: 52.5 %

Procedure:
To a solution of 2-aminoacetophenone (7.0 g, 0.05 mol) in 30 mL of pyridine was added p-toluenesulfonyl chloride (11.8 g, 120 mol %). The reaction mixture was refluxed with stirring for 2 h, cooled to 40-50° C. and poured in the cold water (150 mL). The mixture was stirred at rt for 1 h, filtered, washed with warm (~40° C.) water and then dried. Recrystallization from EtOH afforded 7.6 g (51%) of the title compound, mp 148.2-149.3° C. [lit 147-148° C. (Kemter, G.; Noack, H.; Russ, G. Z. Chem. 1963, 3, 352)]; 1H NMR (CDCl3) δ 11.48 (s, 1H, NH), 7.79 (dd, 1H, J=1.2, J=6.8), 7.72 (d, 1H, J=8.4), 7.67 (d, 1H, J=8.4), 7.44 (t, 1H, J=8), 7.21 (d, 1H, J=8), 7.02 (t, 1H, J=6), 2.55 (s, 3H), 2.36 (s, 3H); 13C NMR (CDCl3) δ 202.37, 143.83, 139.94, 136.47, 134.82, 131.87, 129.57, 127.16, 122.55, 122.18, 118.92, 28.04, 21.42; MS (EI, m/z) 289 (M+).
Reaction SMILES: [Br:1][C@@H:2]1[C@:6](C(=O)C)([OH:7])[C@@H:5]([CH2:11][O:12][C:13](=[O:15])[CH3:14])[O:4][C@H:3]1[N:16]1[CH:23]=[C:22]([CH3:24])[C:20](=[O:21])[NH:19][C:17]1=[O:18].O.NN.Cl>O.C(#N)C>[Br:1][C@@H:2]1[C@H:6]([OH:7])[C@@H:5]([CH2:11][O:12][C:13](=[O:15])[CH3:14])[O:4][C@H:3]1[N:16]1[CH:23]=[C:22]([CH3:24])[C:20](=[O:21])[NH:19][C:17]1=[O:18]
Reactant: CC(=O)OC[C@H]1O[C@@H](n2cc(C)c(=O)[nH]c2=O)[C@H](Br)[C@@]1(O)C(C)=O
Agent: Cl
Agent: NN
Solvent: CC#N
Solvent: O
Product: CC(=O)OC[C@H]1O[C@@H](n2cc(C)c(=O)[nH]c2=O)[C@H](Br)[C@@H]1O
Temperature: 0 °C
Yield: 92.9 %

Procedure:
400 ml of acetonitrile and 2.16 g (3 equivalents) of water were added to 16.2 g (40.0 mmol) of 2'-deoxy-2'-bromo-3',5'-O-diacetyl-5-methyluridine, and the mixture was stirred. The resulting solution was cooled to 0° C., 6.01 g (3 equivalents) of hydrazine monohydrate were added thereto, and the mixture was reacted for 20 hours at that temperature. 100 ml of water were added to the reaction mixture, which was then neutralized to a pH of 6.8 by adding 6 N-hydrochloric acid thereto. The acetonitrile layer was separated, washed with saturated saline solution, dried with anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain 13.5 g of 2'-deoxy-2'-bromo-5'-O-acetyl-5-methyluridine. Its purity was 81.8%. Its yield was 76.0%.
Reaction SMILES: [H-].[Na+].[CH:3](=[C:5](/[C:10]1[CH:35]=[C:34]2[C:13]([NH:14][C:15]3[C:16]2=[CH:17][CH:18]=[C:19]2[C:27]=3[NH:26][C:25]3[C:20]2=[CH:21][C:22]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:23][CH:24]=3)=[CH:12][CH:11]=1)\[CH:6]=[CH:7]/[CH:8]=C)\[CH3:4].C1OCCOCCOCCOCCOC1.[Br:51][C:52]1[CH:60]=[CH:59][CH:58]=[CH:57][C:53]=1[C:54](Cl)=[O:55]>C1COCC1>[Br:51][C:52]1[CH:60]=[CH:59][CH:58]=[CH:57][C:53]=1[C:54]([N:26]1[C:27]2[C:19](=[CH:18][CH:17]=[C:16]3[C:34]4[C:13](=[CH:12][CH:11]=[C:10]([C:5]5[CH:6]=[CH:7][CH:8]=[CH:4][CH:3]=5)[CH:35]=4)[NH:14][C:15]3=2)[C:20]2[C:25]1=[CH:24][CH:23]=[C:22]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH:21]=2)=[O:55]
Reactant: C=C/C=C\C(=C/C)c1ccc2[nH]c3c(ccc4c5cc(-c6ccccc6)ccc5[nH]c43)c2c1
Reactant: O=C(Cl)c1ccccc1Br
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C(c1ccccc1Br)n1c2ccc(-c3ccccc3)cc2c2ccc3c4cc(-c5ccccc5)ccc4[nH]c3c21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2.1 g (52.5 mmol) of NaH (60% in mineral oil) are dissolved in 500 ml of THF under a protective atmosphere. 20 g (50 mmol) of 3-[(Z)-1-eth-(E)-ylidenepenta-2,4-dienyl]-8-phenyl-11,12-dihydro-11,12-diazaindeno[2,1-a]-fluorene and 11.5 g (52.5 mmol) of 15-crown-5 dissolved in 200 ml of THF are added. After 1 h at room temperature, a solution of 12 g (55 mmol) of 2-bromobenzoyl chloride in 250 ml of THF is added dropwise. The reaction mixture is stirred at room temperature for 18 h. After this time, the reaction mixture is poured onto ice and extracted three times with dichloromethane. The combined organic phases are dried over Na2SO4 and evaporated. The residue is extracted with hot toluene and recrystallised from toluene/n-heptane. The yield is 22 g (75%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:9]([CH2:20][C:21]([C:23]2[O:24][CH:25]=[CH:26][CH:27]=2)=O)[CH2:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])=O)[CH:5]=[CH:6][C:7]=1[F:8].CC(O)=O.C[N:33](C)C=O>>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:20]=[C:21]([C:23]3[O:24][CH:25]=[CH:26][CH:27]=3)[N:33]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[OH:19])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: O=C(CC(CC(=O)c1ccccc1O)c1ccc(F)c(F)c1)c1ccco1
Reactant: CN(C)C=O
Solvent: CC(=O)O
Product: Oc1ccccc1-c1cc(-c2ccc(F)c(F)c2)cc(-c2ccco2)n1
Temperature: 100 °C

Procedure:
A mixture of 3-(3,4-difluorophenyl)-5-(furan-2-yl)-1-(2-hydroxyphenyl)-1,5-pentanedione on Wang resin (2.0 g, 1.76 mmol), NH4OAc (0.80 g), and AcOH (1.0 mL) in dimethylformamide (20 mL) was heated at 100° C. for 18 h. The resin was filtered, and washed with dimethylformamide (×2) and alternating MeOH and CH2Cl2 (×5), and dried under high vacuum overnight. The dried resin was treated with 50% TFA/CH2Cl2 (15 mL) for 1 h. After filtration of the reaction mixture, the filtrate was concentrated to dryness. The residue was repeatedly dissolved in CH2Cl2 (10 mL) and concentrated to remove traces of TFA. Purification by flash chromatography gave 2-[4-(3,4-difluoro-phenyl)-6-furan-2-yl-pyridin-2-yl]-phenol; mp 147-148° C.; 1H NMR (DMSO-d6) d 6.78 (m, 1H), 6.98 (m, 2H), 7.37 (m, 1H), 7.43 (m, 1H), 7.67 (m, 1H), 8.00 (m, 2H), 8.15 (d, J=1.3 Hz, 1H), 8.31 (m, 2H), 8.39 (d, J=1.3 Hz, 1H), 14.26, (s, 1H); IR (KBr) 1605 cm−1; MS [M+H]+ m/z=350. Anal. calcd for C21H13F2NO2: C, 72.20; H, 3.75; N, 4.01; Found: C, 71.94; H, 3.62; N, 3.74.
Reaction SMILES: C(O)C.Cl.[CH:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][C:6]=1[O:15][CH:16]([NH:21][C:22](=[O:33])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[O:29]C(=O)C)[C:17]([Cl:20])([Cl:19])[Cl:18]>O>[CH:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][C:6]=1[O:15][CH:16]([NH:21][C:22](=[O:33])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[OH:29])[C:17]([Cl:19])([Cl:20])[Cl:18]
Reactant: CC(=O)Oc1ccccc1C(=O)NC(Oc1ccc2ccccc2c1)C(Cl)(Cl)Cl
Agent: Cl
Solvent: CCO
Solvent: O
Product: O=C(NC(Oc1ccc2ccccc2c1)C(Cl)(Cl)Cl)c1ccccc1O
Yield: 52.5 %

Procedure:
50 ml of ethanol and 1 ml of concentrated hydrochloric acid were added to 4.2 g of N-(1'-β-naphthoxy-2',2',2'-trichloroethyl)-2-acetoxybenzamide synthesized in Preparation Example 5. The whole was refluxed for about three hours. After cooling, the reaction mixture was poured into water and the resulting crystals were recrystallized from N-hexane/benzene (2:1) to obtain 2.0 g of N-(1'-β-naphthoxy-2',2',2'-trichloroethyl)-2-hydroxybenzamide as white crystals.
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[C:9]2[NH:10][C:11]([CH3:13])=[N:12][C:8]=2[CH:7]=[C:6]([C:14]([O:16]C)=[O:15])[CH:5]=1>CO>[Cl:3][C:4]1[C:9]2[NH:10][C:11]([CH3:13])=[N:12][C:8]=2[CH:7]=[C:6]([C:14]([OH:16])=[O:15])[CH:5]=1
Reactant: COC(=O)c1cc(Cl)c2[nH]c(C)nc2c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: Cc1nc2cc(C(=O)O)cc(Cl)c2[nH]1
Temperature: 65 °C
Reaction time: 16 h
Yield: 71.8 %

Procedure:
Add 2N sodium hydroxide (5 mL, 5 mmol) to a solution of methyl 7-chloro-2-methyl-1H-benzo[d]imidazole-5-carboxylate (280 mg, 1.25 mmol) in methanol (7.5 mL). Stir at 65° C. for 16 hours. The methanol was concentrated in vacuo and the remaining aqueous layer was extracted with ethyl acetate (10 mL). Acidify the aqueous layer to pH ˜4 with 1N hydrochloric acid (˜5 mL). A colorless precipitate was filtered and dried under high vacuum to yield the title compound (189 mg, 72%). 1H NMR (400 MHz, CD3OD) δ ppm 2.61 (s, 3 H), 7.86 (d, J=1.37 Hz, 1 H), 8.08 (d, J=1.17 Hz, 1 H).
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].S(O)(O)(=O)=O.[CH3:17][S:18][C:19](=[NH:21])[NH2:20]>ClCCl>[CH2:5]([O:4][C:2]([NH:21][C:19](=[N:20][C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3])[S:18][CH3:17])=[O:3])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CSC(=N)N
Agent: O=S(=O)(O)O
Solvent: ClCCl
Product: CSC(=NC(=O)OCc1ccccc1)NC(=O)OCc1ccccc1
Temperature: 25 °C
Yield: 82.2 %

Procedure:
2 ml (14.4 mol) of benzyl chloroformate are added dropwise, under vigorous stirring, to a solution of 1 g (3.60 mmol) of S-methylisothiourea sulphate in 40 ml of a diphasic mixture of dichloromethane/saturated aqueous sodium bicarbonate solution (1:1). Stirring is maintained at ambient temperature for 25 hours. After which, the aqueous phase is extracted 3 times with dichloromethane. The combined organic phases are then washed with water, then dried over sodium sulphate and evaporated under reduced pressure. The residue obtained is purified by chromatography on a silica column (DCM) in order to produce 1.06 g (82%) of product in the form of a yellow oil.
Reaction SMILES: [CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=O)[CH:4]=[CH:3]1.COC1C=CC(P2(=S)SP(C3C=CC(OC)=CC=3)(=S)[S:22]2)=CC=1>C1C=CC=CC=1>[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[S:22])[CH:4]=[CH:3]1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: Cn1ccc(=O)c2ccccc21
Solvent: c1ccccc1
Product: Cn1ccc(=S)c2ccccc21
Reaction time: 1 h
Yield: 165.4 %

Procedure:
Under an inert atmosphere, 1 g of 1-methyl-4-quinolone was dissolved in 20 ml of benzene and then under bigorous stirring, 1.27 g of 2,4-bis-(4-methoxyphenyl)-2,4-dithioxo-1,3,2,4-dithiadiphosphetane (Lawesson's reagent) was added all at once with stirring for 1 hour at reflux. After cooling and concentrating to dryness by distilling under reduced pressure, the 2.5 g of residue were chromatographed on silica and eluted with a mixture of methyl chloride and methanol (9/1) to obtain 910 mg of the expected product melting at 208°-210° C.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][N:9]2[CH2:12][CH2:13][N:14]([CH3:16])[CH3:15])=[CH:4][CH:3]=1.[C:17]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:22]=[CH:21][C:20]([C:23](O)=[O:24])=[CH:19][CH:18]=1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:15][N:14]([CH3:16])[CH2:13][CH2:12][N:9]1[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([NH:1][C:23]([C:20]3[CH:21]=[CH:22][C:17]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)=[CH:18][CH:19]=3)=[O:24])[CH:11]=2)[CH2:6][CH2:7][CH2:8]1
Reactant: O=C(O)c1ccc(-c2ccccc2)cc1
Reactant: CN(C)CCN1CCCc2ccc(N)cc21
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: CN(C)CCN1CCCc2ccc(NC(=O)c3ccc(-c4ccccc4)cc3)cc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 7-amino-1-(2-dimethylaminoethyl)-1,2,3,4-tetrahydroquinoline (D14) (38 mg, 0.152 mmol) in DCM (1 ml) was added 4-biphenylcarboxylic acid (45 mg, 0.22 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (42 mg, 0.22 mmol) and 4-dimethylaminopyridine (2.8 mg, 0.022 mmol) and the reaction stirred at ambient temperature overnight. The crude reaction mixture was loaded directly onto a silica SPE column and elution with EtOAc followed by 1% triethylamine/EtOAc gave the title compound as a red gum. 1H NMR (250 MHz, CDCl3) δ (ppm): 7.94 (d, 2H), 7.75 (br, 1H), 7.70 (d, 2H), 7.64 (d, 2H), 7.47 (t, 2H), 7.39 (t, 1H), 7.01 (d, 1H), 6.92 (d, 1H), 6.82 (dd, 1H), 3.43 (m, 2H), 3.33 (m, 2H), 2.73 (t, 2H), 2.55 (m, 2H), 2.33 (s, 6H), 1.95 (m, 2H).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][CH:10]=[N:11]2)=[CH:6][CH:5]=1)([O-])=O>[Pd].CO>[N:11]1[C:12]2[C:7](=[CH:6][CH:5]=[C:4]([NH2:1])[CH:13]=2)[CH:8]=[CH:9][CH:10]=1
Reactant: O=[N+]([O-])c1ccc2cccnc2c1
Agent: [Pd]
Solvent: CO
Product: Nc1ccc2cccnc2c1
Reaction time: 2 h
Yield: 95.9 %

Procedure:
A mixture of 7-nitroquinoline (0.30 g, 0.0017 mol; Specs, Inc.), 10% Pd-C (50 mg), and MeOH (20 mL) was stirred under H2 (1 atm) for 2 h. The mixture was filtered and the filtrate was concentrated to give a yellow solid (235 mg, 95%). LC-MS: 0.33 min, 145.1 (M+1). 1H NMR (DMSO-d6): 8.58 (1H, dd, J=4.4, 1.6 Hz), 8.00 (1H, dd, J=8.0, 1.2 Hz), 7.60 (1H, d, J=8.8 Hz), 7.07 (1H, dd, J=8.0, 4.4 Hz), 6.98 (1H, dd, J=8.8, 2.0 Hz), 6.93 (1H, d, J=2.0 Hz), 5.75 (s, 2H).
Reaction SMILES: [C:1]([C:9]1[CH:20]=[CH:19][CH:18]=[CH:17][C:10]=1[NH:11][C:12](=O)C(Cl)Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C-]#[N:22].[K+]>C(O)C.O>[NH2:22][C:12]1[C:1]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)([OH:8])[C:9]2[C:10](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:11]=1
Reactant: [C-]#N
Reactant: O=C(c1ccccc1)c1ccccc1NC(=O)C(Cl)Cl
Agent: [K+]
Solvent: O
Solvent: CCO
Product: NC1=Nc2ccccc2C1(O)c1ccccc1
Temperature: 25 °C
Reaction time: 40 h

Procedure:
2'-Benzoyl-2,2-dichloroacetanilide (50 g.) was suspended in 91% ethanol (750 ml) and treated with a solution of potassium cyanide (30 g) in water (50 ml). The reaction was stirred at room temperature for 40 hours. The crystalline precipitate was filtered off and the mother liquors diluted with water to provide further crops of 2-amino-3-phenyl-3H-indol-3-ol. Total 37 g. The product could be recrystallized from acetonitrile or aqueous dimethylformamide and had a m.p. of 204°-6°C (decomp).
Reaction SMILES: [CH:1]1([CH:4]2[O:8][C:7]([C:10]3[CH:11]=[C:12]([S:15][C:16]4[CH:21]=[CH:20][C:19]([C:22](=O)[CH3:23])=[CH:18][CH:17]=4)[S:13][CH:14]=3)([CH3:9])[CH2:6][O:5]2)[CH2:3][CH2:2]1.Cl.[NH2:26][OH:27]>>[CH:1]1([CH:4]2[O:8][C:7]([C:10]3[CH:11]=[C:12]([S:15][C:16]4[CH:21]=[CH:20][C:19]([C:22](=[N:26][OH:27])[CH3:23])=[CH:18][CH:17]=4)[S:13][CH:14]=3)([CH3:9])[CH2:6][O:5]2)[CH2:3][CH2:2]1
Reactant: NO
Reactant: CC(=O)c1ccc(Sc2cc(C3(C)COC(C4CC4)O3)cs2)cc1
Agent: Cl
Product: CC(=NO)c1ccc(Sc2cc(C3(C)COC(C4CC4)O3)cs2)cc1
Yield: 50 %

Procedure:
Using an analogous procedure to that described in Example 68, 4'-[4-(2-cyclopropyl-4-methyl-1,3-dioxolan-4-yl)thien-2-ylthio]acetophenone was reacted with hydroxylamine hydrochloride to give 4'-[4-(2-cyclopropyl-4-methyl-1,3-dioxolan-4-yl)thien-2-ylthio]acetophenone oxime in 50% yield as an oil.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:10][C:11]12S[CH:12]1[CH:13]1[S:18][C:14]1(O)[CH:15]=[CH:16]2.CC(O)=O>C(Cl)Cl.[Zn]>[SH:18][C:14]1[CH:15]=[CH:16][C:11]([NH:10][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:12][CH:13]=1
Reactant: NC12C=CC3(O)SC3C1S2
Reactant: O=C(Cl)c1ccccc1
Agent: [Zn]
Solvent: CC(=O)O
Solvent: ClCCl
Product: O=C(Nc1ccc(S)cc1)c1ccccc1
Reaction time: 8 h

Procedure:
Benzoyl chloride (5.14 mL, 44.28 mL) was added dropwise to a mixture of 4-aminophenol disulfide (5.0 g, 20.13 mmol) and TEA (7.01 mL, 50.3 mmol) in 60 mL DCM at 0° C. The reaction was allowed to stir overnight. The resulting precipitate was collected by filtration. The solid was washed with MeOH and water and then dried. The solid was combined with 200 mL of concentrated HOAc, and 5.0 equiv of zinc powder was added. The reaction was monitored by LCMS. When the reaction was complete, the acetic acid solution was concentrated to approximately 20 mL in volume. The crude mixture was then extracted with water and EtOAc. The organic layer was dried with MgSO4 then concentrated. MS: 228 [M+H]+; 1H NMR (DMSO-d6): 10.23 (s, 1H), 7.94 (d, 2H), 7.81 (d, 2H), 7.56 (m, 3H), 7.28 (d, 2H), 5.31 (s, 1H).
Reaction SMILES: [CH2:1]([CH:8]1[S:13][CH2:12][CH2:11][CH2:10][S:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:14][Si:15](Cl)([CH3:17])[CH3:16]>>[CH2:1]([C:8]1([Si:15]([CH3:17])([CH3:16])[CH3:14])[S:9][CH2:10][CH2:11][CH2:12][S:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C[Si](C)(C)Cl
Reactant: c1ccc(CC2SCCCS2)cc1
Product: C[Si](C)(C)C1(Cc2ccccc2)SCCCS1
Yield: 75 %

Procedure:
The title compound of this step was prepared in 75% yield, by the procedure described in JACS 89, (1967), 4347 by E. J. Corey, et al., using 2-benzyl-1,3-dithiane and trimethylsilyl chloride. The product was recrystallized from diethyl ether/pentane.
Reaction SMILES: Cl[C:2]1[C:7]([CH2:8][CH2:9]Cl)=[C:6]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=2)[N:5]=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[N:3]=1.[NH:25]1[C:33]2[C:28](=[CH:29][C:30]([NH2:34])=[CH:31][CH:32]=2)[CH:27]=[N:26]1>>[NH:25]1[C:33]2[C:28](=[CH:29][C:30]([N:34]3[C:2]4[N:3]=[C:4]([N:19]5[CH2:24][CH2:23][O:22][CH2:21][CH2:20]5)[N:5]=[C:6]([C:11]5[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=5)[C:7]=4[CH2:8][CH2:9]3)=[CH:31][CH:32]=2)[CH:27]=[N:26]1
Reactant: Nc1ccc2[nH]ncc2c1
Reactant: COc1cccc(-c2nc(N3CCOCC3)nc(Cl)c2CCCl)c1
Product: COc1cccc(-c2nc(N3CCOCC3)nc3c2CCN3c2ccc3[nH]ncc3c2)c1

Procedure:
In the same manner as Example 1-A-01, from 4-[4-chloro-5-(2-chloroethyl)-6-(3-methoxyphenyl)-pyrimidin-2-yl]-morpholine and 1H-indazol-5-ylamine, the desired compound was obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:15]=[CH:14][C:11]([CH:12]=[O:13])=[C:10]([N+:16]([O-])=O)[CH:9]=2)=[CH:4][CH:3]=1.S(S([O-])=O)([O-])=O.[Na+].[Na+].O>C1COCC1>[NH2:16][C:10]1[CH:9]=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)[CH:15]=[CH:14][C:11]=1[CH:12]=[O:13]
Reactant: Cc1ccc(-c2ccc(C=O)c([N+](=O)[O-])c2)cc1
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1ccc(-c2ccc(C=O)c(N)c2)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 50.3 %

Procedure:
Into a solution of 4-(4-methylphenyl)-2-nitrobenzaldehyde (590 mg) in THF (50 ml) was added a solution of sodium hydrosulfite (2.66 g)/water (25 ml). After being stirred at room temperature for 10 minutes, the reaction mixture was extracted with ethyl acetate, and the extract was washed with an aqueous solution of sodium chloride. The extract was dried (anhydrous magnesium sulfate) and was then concentrated to obtain 2-amino-4-(4-methylphenyl)benzaldehyde (0.26 g) as a light brown powder.