Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]([OH:12])=O)=[N:8][CH:9]=1)([O-:3])=[O:2].Cl.[NH2:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]2[CH:27]=[C:26]([CH3:28])[N:25]=[C:24]([NH2:29])[N:23]=2)=[CH:17][CH:16]=1.C(N(CC)C1C=CC=CC=1)C>O=P(Cl)(Cl)Cl>[NH2:29][C:24]1[N:23]=[C:22]([NH:21][C:18]2[CH:19]=[CH:20][C:15]([NH:14][C:10]([C:7]3[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][N:8]=3)=[O:12])=[CH:16][CH:17]=2)[CH:27]=[C:26]([CH3:28])[N:25]=1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cn1
Reactant: Cc1cc(Nc2ccc(N)cc2)nc(N)n1
Agent: Cl
Solvent: O=P(Cl)(Cl)Cl
Solvent: CCN(CC)c1ccccc1
Product: Cc1cc(Nc2ccc(NC(=O)c3ccc([N+](=O)[O-])cn3)cc2)nc(N)n1
Temperature: 20 °C
Reaction time: 72 h
Yield: 33.9 %

Procedure:
5-Nitropyridine-2-carboxylic acid 18 (1.06 g, 6.31 mmol) was refluxed in POCl3 (10 mL) for 1 h. (clear solution obtained), cooled to 20° C. and excess POCl3 was removed under vacuum. The resulting residue was dissolved in 1,4-dioxane ((20 mL) and added slowly to a suspension of 17 (1.44 g, 5.72 mmol) and N,N-diethylaniline (2.0 mL, 12.62 mmol) in 1,4-dioane (20 mL). The reaction mixture was stirred at 20° C. for 3 days. The resulting white precipitate was filtered and washed with more 1,4-dioxane. The solid was stirred in aqueous NH3 (20 mL) and the resulting red precipitate was filtered, washed with water and recrystallized from MeOH to give 20 (708 mg, 31%); mp (MeOH)>290° C.; 1H NMR ([(CD3)2SO] δ 10.74 (1 H, NH), 9.43 (dd, J=2.6, 0.5 Hz, 1 H, H-6), 8.96 (s, 1 H, NH), 8.81 (dd, J=8.6, 2.6 Hz, 1 H, H-4), 8.38 (dd, J=8.6, 0.6 Hz, 1 H, H-3), 7.81 (d, J=9.0 Hz, 2 H, H-2′ H-6′), 7.70 (d, J=9.1 Hz, 2 H, H-3′,5′), 6.09 (s, 2 H, NH2), 5.87 (s, 1 H, H-5″), 2.09 (s, 3 H, CH3); HRMS (FAB+) calc. for C17H16N7O3 (M+1) m/z 366.1315, found 366.1314; Anal. calc. for C17H15N7O3.0.25 MeOH: C, 55.5; H, 4.4: N, 26.3; found, C, 55.7; H, 4.5; N, 26.2%.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH2:7]Cl.[C:13]1(=[O:20])[CH2:18][CH2:17][CH2:16][C:15](=[O:19])[CH2:14]1.[OH-].[K+]>CO>[Cl:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH2:7][CH:14]1[C:15](=[O:19])[CH2:16][CH2:17][CH2:18][C:13]1=[O:20]
Reactant: O=C1CCCC(=O)C1
Reactant: ClCCCc1ccccc1CCl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: O=C1CCCC(=O)C1Cc1ccccc1CCCCl

Procedure:
A solution of 155 g (0.75 mol) of 2-(3-chloropropyl)benzyl chloride 2 [Page, et al., J. Amer. Chem. Soc. 75:2053 (1953)], 91 g (0.81 mol) of 1,3-cyclohexanedione 1[Aldrich Chem. Co. 10,160-5; Beilstein 7, 554], and 47 g of 85% KOH in 400 ml of methanol was refluxed 16 hours. After concentrating, the residue was partitioned between benzene and dilute aqueous NaOH solution. Acidification of the aqueous phase gave a solid that was recrystallized from ethyl acetate to give 34 g of the dione, 3, mp 143°-145° C.
Reaction SMILES: [C:1]([O-:4])(=O)[CH3:2].C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4].FC(F)(F)C(O)=O.[Br:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28](C=C)[CH:27]=1.O>ClCCl>[Br:25][C:26]1[CH:27]=[C:28]([CH2:2][CH:1]=[O:4])[CH:29]=[CH:30][CH:31]=1
Reactant: CC(=O)[O-]
Reactant: C=Cc1cccc(Br)c1
Agent: [Pb+4]
Solvent: O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=CCc1cccc(Br)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of lead tetraacetate (3.6 g, 8.2 mmol) and trifluoroacetic acid (8.25 mL) at 0° C. is treated dropwise with a solution of 1-bromo-3-vinylbenzene (1.5 g, 8.2 ml) in dichloromethane, allowed to warm to room temperature, stirred for 2 h at room temperature, diluted with dichloromethane, poured into water, stirred vigorously and filtered through a pad of celite. The filtrate is separated. The filtercake is rinsed with additional portions of dichloromethane. The combined organic phases are washed sequentially with water, NaHCO3 and brine, dried over MgSO4 and concentrated in vacuo to afford (3-bromophenyl)acetaldehyde.
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=1)[CH2:11]Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.NC(N)=[S:18].N.Cl>C(O)(C)C.O>[O:1]([C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=1)[CH2:11][SH:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: BrCc1cccc(Oc2ccccc2)c1
Reactant: NC(N)=S
Agent: Cl
Agent: N
Solvent: CC(C)O
Solvent: O
Product: SCc1cccc(Oc2ccccc2)c1

Procedure:
A solution of 30.8 g of m-phenoxybenzyl bromide in 70 ml of isopropanol is reacted with 9.5 g of thiourea in 30 ml of water and the reaction mixture is refluxed briefly. After cooling, 25 ml of a 25% ammonia solution are added and the mixture is heated briefly to reflux and then allowed to cool, whereupon it is acidified with 18% hydrochloric acid and extracted with methylene chloride. The extract is dried over magnesium sulfate and concentrated, affording the compound of the formula ##STR7## with a boiling point of 114°-116° C.'0.05 mm Hg.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[C:18]([CH3:23])[C:17]=1[CH3:24].Cl[C:26](Cl)([O:28][C:29](=[O:35])OC(Cl)(Cl)Cl)Cl.[CH:37]1(CO)[CH2:41][CH2:40][CH2:39][CH2:38]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:29](=[O:35])[O:28][CH2:26][CH:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)=[C:18]([CH3:23])[C:17]=1[CH3:24]
Reactant: OCC1CCCC1
Reactant: COc1cc2nccc(Oc3ccc(N)c(C)c3C)c2cc1OC
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COc1cc2nccc(Oc3ccc(NC(=O)OCC4CCCC4)c(C)c3C)c2cc1OC
Yield: 69.1 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopentylmethanol (23 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 66%).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:23])=[C:6]([CH:22]=1)[CH2:7][C:8]1[CH:21]=[CH:20][C:11]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])=[CH:10][CH:9]=1.[Li]CCCC.[Si:29]([O:36][C@H:37]1[C@H:44]2[C@H:40]([O:41][C:42]([CH3:46])([CH3:45])[O:43]2)[O:39][C@H:38]1[CH:47]=[O:48])([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]>C1COCC1>[Si:29]([O:36][C@H:37]1[C@H:44]2[C@H:40]([O:41][C:42]([CH3:46])([CH3:45])[O:43]2)[O:39][C@H:38]1[CH:47]([C:2]1[CH:3]=[CH:4][C:5]([Cl:23])=[C:6]([CH2:7][C:8]2[CH:21]=[CH:20][C:11]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])=[CH:10][CH:9]=2)[CH:22]=1)[OH:48])([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:30])[CH3:31]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(Cc2cc(Br)ccc2Cl)cc1
Reactant: CC1(C)O[C@@H]2O[C@@H](C=O)[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]2O1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC1(C)O[C@@H]2O[C@@H](C(O)c3ccc(Cl)c(Cc4ccc(O[Si](C)(C)C(C)(C)C)cc4)c3)[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]2O1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 25 %

Procedure:
A solution of (4-(5-bromo-2-chlorobenzyl)phenoxy)(tert-butyl)dimethylsilane (14.2 g, 34.57 mmol, prepared following the procedure given in US20070049537) in dry THF (90 mL) was cooled to −78° C. and nBuLi (30.7 mL, 46.05 mmol, 1.5 M solution in hexane) was added drop wise while stirring and stirring was continued for further 30 min. A solution of (3aS,5R,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carbaldehyde (7.0 g, 23.05 mmol, prepared according to the procedure given in NUCLEOSIDE, NUCLOETIDES & NUCLEIC ACIDS, 20(4-7), 649-652 (2001)) in dry THF (13 mL) was added dropwise to the reaction mixture and stirred at the same temperature for 2 h. Reaction temperature was raised slowly to 0° C. and then stirred at r.t. for 16 h. After completion of reaction, as confirmed by TLC, reaction mixture was quenched by the addition of saturated NH4Cl solution and extracted with ethyl acetate (3×300 mL). The combined organic layers were dried over Na2SO4 and the volatiles were evaporated in vacuo. The residue obtained was purified by column chromatography (silica gel, 0.2:9.8 Acetone:Pet. Ether) to afford the title compound (3.66 g, 25%)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)[N:9]=[CH:8][N:7]=[C:6]2[O:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][CH:26]=[C:25]2[CH3:31].CCN(C(C)C)C(C)C.[Cl:41][CH2:42][C:43](Cl)=[O:44]>ClCCl.CO>[Cl:41][CH2:42][C:43]([N:18]1[CH2:19][CH2:20][CH:15]([CH2:14][O:13][C:12]2[CH:11]=[C:10]3[C:5]([C:6]([O:21][C:22]4[CH:23]=[C:24]5[C:28](=[CH:29][CH:30]=4)[NH:27][CH:26]=[C:25]5[CH3:31])=[N:7][CH:8]=[N:9]3)=[CH:4][C:3]=2[O:2][CH3:1])[CH2:16][CH2:17]1)=[O:44]
Reactant: COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCNCC1
Reactant: O=C(Cl)CCl
Solvent: CO
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCN(C(=O)CCl)CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-[(piperidin-4-yl)methoxy]quinazoline (0.4 g), prepared as described for the starting material in Example 1, was dissolved in dichloromethane (15 ml). PS-DIEA resin (0.6 g; 4 mmol/g) was added followed by chloroacetyl chloride (0.091 ml). The reaction mixture was stirred at ambient temperature for 3 hours then diluted with methanol and the resin removed by filtration. The solvent was evaporated under vacuum and the residue was purified by column chromatography on silica using increasingly polar solvent mixtures, starting with dichloromethane and ending with dichloromethane/methanol (92/8). Removal of the solvents by evaporation gave 7-{[1-(chloroacetyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline (0.237 g) as a solid foam.
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)[N:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[CH:7]=1.[N-:25]=[N+:26]=[N-:27].[Na+]>CN(C)C=O>[N:25]([CH2:2][C:3]1[N:4]=[C:5]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)[N:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[CH:7]=1)=[N+:26]=[N-:27]
Reactant: CS(=O)(=O)c1ccc(-n2cc(CCl)nc2-c2ccc(Cl)cc2)cc1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1ccc(-n2cc(CN=[N+]=[N-])nc2-c2ccc(Cl)cc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 97.6 %

Procedure:
A mixture of 4-chloromethyl-2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole (Example 159, Step 1) (500 mg, 1.31 mmol) and sodium azide (256 mg, 3.94 mmol) in 5 ml of dimethylformamide was stirred overnight at room temperature. The mixture was warmed to 80° C. for one hour and then cooled. The mixture was partitioned between ethyl acetate and water, and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated. Chromatography of the residue over silica gel using 50% ethyl acetate in hexane as the eluent gave the title compound as a pure white crystalline solid (496 mg):mp (DSC) 186° C. Anal. Calc'd. for C17H14ClN5O2S (MW 387.85): C, 52.64; H, 3.64; N, 18.06. Found: C, 52.46; H, 3.77; N, 17.84.
Reaction SMILES: [CH3:1][C:2]1([CH3:30])[C:11]2[CH:10]=[CH:9][C:8](C#CC3C=CC(C(OCC)=O)=CC=3)=[CH:7][C:6]=2[C:5]([C:25]2[S:26][CH:27]=[CH:28][N:29]=2)=[CH:4][CH2:3]1.FC(F)(F)S(OC1C2C=CC([C:49]#[C:50][C:51]3[CH:61]=[CH:60][C:54]([C:55]([O:57][CH2:58][CH3:59])=[O:56])=[CH:53][CH:52]=3)=CC=2C(C)(C)CC=1)(=O)=O>C1COCC1>[CH3:30][C:2]1([CH3:1])[C:11]2[CH:10]=[C:9]([C:49]#[C:50][C:51]3[CH:61]=[CH:60][C:54]([C:55]([O:57][CH2:58][CH3:59])=[O:56])=[CH:53][CH:52]=3)[CH:8]=[CH:7][C:6]=2[C:5]([C:25]2[S:26][CH:27]=[CH:28][N:29]=2)=[CH:4][CH2:3]1
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2nccs2)=CCC3(C)C)cc1
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(C)(C)CC=C3OS(=O)(=O)C(F)(F)F)cc1
Solvent: C1CCOC1
Product: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(C)(C)CC=C3c2nccs2)cc1

Procedure:
Employing the same general procedure as for the preparation of ethyl 4-[(7,8-dihydro-8,8-dimethyl-5-(2-thiazolyl)naphth-3-yl)ethynyl]benzoate (Compound 67), 400 mg (0.84 mmol) of ethyl 4-[(5-trifluoromethylsulfonyloxy-7,8-dihydro-8,8-dimethylnaphth-2-yl)ethynyl]benzoate (Compound 87) in 2 ml of THF was converted into the title compound (white solid) using a solution of 82 mg (1.26 mmol) of thiazole in 2 ml of THF, 81 mg (0.84 ml, 1.26 mmol) of n-butyllithium (1.5M solution in hexanes), 228 mg (3.36 ml, 1.68 mmol) of zinc chloride (0.5M solution in THF) and 10 mg (0.01 mmol) of tetrakis(triphenylphosphine)palladium (0).
Reaction SMILES: [CH3:1][S:2]([O:5][CH2:6][CH2:7][CH:8]([C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=1)[CH2:9][N:10]1[CH:14]=[CH:13][N:12]=[C:11]1[C:15](=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[O:22][CH3:23])(=[O:4])=[O:3].[CH3:33][C:34]1[CH:35]=[C:36]([C:41]23[CH2:48][CH2:47][N:44]([CH2:45][CH2:46]2)[CH2:43][CH2:42]3)[CH:37]=[C:38]([CH3:40])[CH:39]=1>C(#N)C>[CH3:1][S:2]([O-:5])(=[O:4])=[O:3].[CH3:40][C:38]1[CH:37]=[C:36]([C:41]23[CH2:46][CH2:45][N+:44]([CH2:6][CH2:7][CH:8]([C:25]4[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=4)[CH2:9][N:10]4[CH:14]=[CH:13][N:12]=[C:11]4[C:15](=[O:24])[C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[O:22][CH3:23])([CH2:47][CH2:48]2)[CH2:43][CH2:42]3)[CH:35]=[C:34]([CH3:33])[CH:39]=1
Reactant: Cc1cc(C)cc(C23CCN(CC2)CC3)c1
Reactant: COc1ccccc1C(=O)c1nccn1CC(CCOS(C)(=O)=O)c1ccc(Cl)c(Cl)c1
Solvent: CC#N
Product: COc1ccccc1C(=O)c1nccn1CC(CC[N+]12CCC(c3cc(C)cc(C)c3)(CC1)CC2)c1ccc(Cl)c(Cl)c1
Product: CS(=O)(=O)[O-]
Yield: 87.6 %

Procedure:
1Methanesulphonyloxy-3-(3,4-dichlorophenyl)-4-[2-(2-methoxybenzoyl)imidazol-1-yl]butane (0.55 g) (see Preparation 84) and 4-(3,5-dimethylphenyl)quinuclidine (0.28 g) (see Preparation 12) were dissolved in acetonitrile (10 ml) and heated under reflux for 2.5 hours. The solvent was removed under reduced pressure, the resulting residue dissolved in dichloromethane and the solvent removed under reduced pressure. The residue was chromatographed on silica gel eluting with a solvent gradient of 95:5 changing to 90:10, by volume, dichloromethane:methanol to give 4-(3,5-dimethylphenyl)-1-(3-[3,4-dichlorophenyl]-4-[2-(2-methoxybenzoyl)imidazol-1-yl]butyl)quinuclidinium methanesulphonate (0.69 g) as a white foam.
Reaction SMILES: Br[C:2]1[C:11]2[NH:10][C:9](=[O:12])[C:8]3[S:13][CH:14]=[CH:15][C:7]=3[C:6]=2[C:5]([C:16]2[CH:21]=[CH:20][C:19]([CH:22]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH3:23])=[CH:18][CH:17]=2)=[C:4]([O:32][CH3:33])[CH:3]=1.[CH3:34]B1OB(C)OB(C)O1>>[CH3:33][O:32][C:4]1[CH:3]=[C:2]([CH3:34])[C:11]2[NH:10][C:9](=[O:12])[C:8]3[S:13][CH:14]=[CH:15][C:7]=3[C:6]=2[C:5]=1[C:16]1[CH:17]=[CH:18][C:19]([CH:22]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH3:23])=[CH:20][CH:21]=1
Reactant: CB1OB(C)OB(C)O1
Reactant: COc1cc(Br)c2[nH]c(=O)c3sccc3c2c1-c1ccc(C(C)NC(=O)OC(C)(C)C)cc1
Product: COc1cc(C)c2[nH]c(=O)c3sccc3c2c1-c1ccc(C(C)NC(=O)OC(C)(C)C)cc1
Yield: 71.7 %

Procedure:
Following General Procedure J, tert-butyl 1-(4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethylcarbamate (32 mg, 0.060 mmol) was reacted with trimethylboroxine (8 mg, 0.060 mmol) to afford the desired product (20 mg, 61%) as a grey solid: ESI MS m/z 465 [C26H28N2O4S+H]+.
Reaction SMILES: Cl[C:2]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-].[NH4+:16]>[Cu]>[NH2:16][C:2]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: [NH4+]
Reactant: CS(=O)(=O)c1ccc(Cl)c(C(=O)O)c1
Agent: [Cu]
Agent: [OH-]
Product: CS(=O)(=O)c1ccc(N)c(C(=O)O)c1
Temperature: 127.5 °C
Reaction time: 18 h

Procedure:
A mixture of 4.26 mmol 2-chloro-5-methanesulfonyl-benzoic acid, 0.39 mmol Copper powder and 10 ml ammonium hydroxide 25% was heated at 125-130° C. with stirring for 18 hours. Mixture was cooled to room temperature and filtered. The solid was washed with methanol. The filtrate was concentrated in vacuo. The residue was acidified with HCl 1N to pH=2. The obtained solid was washed with water and dried (HV, 50° C., 1 hour) to yield the title compound MS (m/e): 214.1 (M−H, 100%)
Reaction SMILES: [S].N.[SH2:3].[CH2:4](Cl)[CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]>CO>[CH2:4]([S:3][S:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])[CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: S
Reactant: CCCCCCCl
Agent: N
Agent: [S]
Solvent: CO
Product: CCCCCCSSCCCCCC
Reaction time: 2 h
Yield: 83.5 %

Procedure:
1.5 mole sulfur, 6 moles of ammonia and 1.5 mole of hydrogen sulfide were charged into a 3 liter stainless steel autoclave and heated to 70° C. as 3 moles of n-hexyl chloride and 250 ml. of methanol were pumped into the vessel. After 2 hours at 70° C., the mixture was filtered free of ammonium chloride and the filtrate was distilled to give an 83.5 percent yield of di-n-hexyl disulfide, boiling point 120° - 122° C. and 1 mm. n D25 1.4864, d 425 0.9145, RD 0.341, calculated RD 0.315.
Reaction SMILES: C[C:2](C)([O-:4])C.[K+].[CH3:7][CH:8]1[CH2:16][C:15]2[C:10](=[C:11]([Cl:26])[C:12]([Cl:25])=[C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:14]=2)[C:9]1=[O:27].[CH:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.O>C(O)(C)(C)C>[CH3:2][O:4][C:28]1[CH:33]=[CH:32][C:31]([C:8]2([CH3:7])[CH2:16][C:15]3[C:10](=[C:11]([Cl:26])[C:12]([Cl:25])=[C:13]([O:17][CH2:18][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH:14]=3)[C:9]2=[O:27])=[CH:30][CH:29]=1
Reactant: CC(C)(C)[O-]
Reactant: CC1Cc2cc(OCc3ccccc3)c(Cl)c(Cl)c2C1=O
Reactant: c1ccccc1
Agent: [K+]
Solvent: CC(C)(C)O
Solvent: O
Product: COc1ccc(C2(C)Cc3cc(OCc4ccccc4)c(Cl)c(Cl)c3C2=O)cc1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
Potassium tert-butoxide (8.42 g., 0.075 mole) dissolved in tert-butanol (450 ml.) is added to a refluxing solution of 2-methyl-5-benzyloxy-6,7-dichloro-1-indanone (16.1 g., 0.05 mole) in tert-butanol (150 ml.)-benzene (600 ml.), refluxing is continued for 2.5 hrs., then 4,4'-dimethoxydiphenyliodonium chloride (37.66 g., 0.10 mole) is added and refluxing is continued for 3 hrs. The reaction mixture is cooled to 25° C., 500 ml. water added, and the mixture concentrated in vacuo to give a brown oil which on ether extraction, drying over anhydrous magnesium sulfate, removal of the ether and chromatographing of the residue on silica gel with chloroform gives 3.44 g. of 2-(4-methoxyphenyl)-2-methyl-5-benzyloxy-6,7-dichloro-1-indanone which melts at 115°-119° C. and is used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[NH2:11][C:12]1[CH:16]=[CH:15][NH:14][N:13]=1.O=[C:18]([CH2:25][CH2:26][CH3:27])[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21]>>[Cl:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]1[C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:18]([CH2:25][CH2:26][CH3:27])[NH:11][C:12]2=[N:13][NH:14][CH:15]=[C:16]12
Reactant: Nc1cc[nH]n1
Reactant: O=Cc1ccc(F)cc1Cl
Reactant: CCCC(=O)CC(=O)OCC
Product: CCCC1=C(C(=O)OCC)C(c2ccc(F)cc2Cl)c2c[nH]nc2N1

Procedure:
The title compound was prepared from 2-chloro-4-fluorobenzaldehyde, 3-aminopyrazole and ethyl 3-ketohexanoate in the same manner as in Example 25.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:10]=[C:9]([CH3:11])[N:8]([C:12]2[CH:13]=[C:14]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[O:24][C:25]([F:28])([F:27])[F:26])[CH:15]=[CH:16][CH:17]=2)[N:7]=1)=O)C.CC(C[AlH]CC(C)C)C.C1(C)C=CC=CC=1>ClCCl>[CH3:11][C:9]1[N:8]([C:12]2[CH:13]=[C:14]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[O:24][C:25]([F:27])([F:28])[F:26])[CH:15]=[CH:16][CH:17]=2)[N:7]=[C:6]([CH:4]=[O:3])[CH:10]=1
Reactant: CCOC(=O)c1cc(C)n(-c2cccc(-c3ccccc3OC(F)(F)F)c2)n1
Agent: CC(C)C[AlH]CC(C)C
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: Cc1cc(C=O)nn1-c1cccc(-c2ccccc2OC(F)(F)F)c1
Reaction time: 0.33 h

Procedure:
To a solution of ethyl 5-methyl-1-[2′-(trifluoromethoxy)-1,1′-biphenyl-3-yl]-1H-pyrazole-3-carboxylate (from EXAMPLE 3) (1.1 g, 2.82 mmol) in anhydrous dichloromethane (10 mL) was added DIBAL-H in toluene solution (1.0M, 6.8 mL, 6.8 mmol) at −78° C. After stirring for 20 min at that temperature, the reaction was quenched with methanol as described above in EXAMPLE 123. Further work-up and purification, as described in EXAMPLE 123, produced the titled compound.
Reaction SMILES: O[C:2]1[N:3]2[C:7]([N:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=1)=[N:6][CH:5]=[N:4]2.P(Cl)(Cl)([Cl:17])=O>>[Cl:17][C:2]1[N:3]2[C:7]([N:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=1)=[N:6][CH:5]=[N:4]2
Reactant: CC(C)(C)c1cc(O)n2ncnc2n1
Reactant: O=P(Cl)(Cl)Cl
Product: CC(C)(C)c1cc(Cl)n2ncnc2n1

Procedure:
A mixture of 20 g of 4-hydroxy-6-t-butyl-1,3,3a,7-tetrazaindene and 80 ml of phosphorus oxychloride was refluxed for 3 to 4 hours at a temperature kept at 140° to 150° C. by means of an oil bath. After excess phosphorus oxychloride was distilled away under reduced pressure, the reaction mixture was poured into ice water. The reaction product was extracted with methylene chloride and dried over anhydrous sodium sulfate. After the removal of methylene chloride by distillation, pale yellow crystals were obtained. Yield 16 g.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[OH:5][C:6]1[CH:14]=[CH:13][C:9]([CH2:10][CH2:11][Cl:12])=[CH:8][CH:7]=1.O>C(O)(=O)C>[OH:5][C:6]1[CH:14]=[CH:13][C:9]([CH2:10][CH2:11][Cl:12])=[CH:8][C:7]=1[N+:1]([O-:4])=[O:2]
Reactant: Oc1ccc(CCCl)cc1
Reactant: O=[N+]([O-])O
Solvent: CC(=O)O
Solvent: O
Product: O=[N+]([O-])c1cc(CCCl)ccc1O
Reaction time: 3.5 h
Yield: 55 %

Procedure:
A solution of concentrated nitric acid (1.8 ml) in acetic acid (4 ml) was added to a stirred solution of 4-hydroxyphenethyl chloride (4.5 g) in acetic acid (25 ml), keeping the temperature below 15°. The mixture was then stirred at 10° for 3.5 hours, poured into water, and extracted into ethyl acetate. The organic extract was washed with 5% aqueous sodium carbonate solution, dried over magnesium sulphate and evaporated. The residue was purified by chromatography on silica (50 g) using hexane plus 0-10% ethyl acetate as the eluant. Appropriate fractions were combined and evaporated to give the title compound as a colourless solid (3.2 g, 55%), m.p. 53°-55°.