Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]2.CC[O-].[Na+].[I-].[Na+].[CH2:19]([N:21]([CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH:30]1[CH3:35])[C:22](=[O:28])[CH2:23][CH:24]([CH3:27])[CH2:25]Cl)C.[Na+].[Cl-]>C(O)C>[CH3:19][N:21]([CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH:30]1[CH3:35])[C:22]([CH2:23][CH:24]([CH3:27])[CH2:25][O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]2)=[O:28]
Reactant: CCN(C(=O)CC(C)CCl)C1CCCCC1C
Reactant: O=c1ccc2cc(O)ccc2[nH]1
Agent: CC[O-]
Agent: [Cl-]
Agent: [I-]
Solvent: CCO
Product: CC(COc1ccc2[nH]c(=O)ccc2c1)CC(=O)N(C)C1CCCCC1C

Procedure:
1.6 Grams of 6-hydroxycarbostyril, 0.7 g of sodium ethylate, 1.6 g of sodium iodide and 3.3 g of N-ethyl-N-(4-chloro-3-methylbutyryl)-2-methylcyclohexylamine are added to 30 ml of ethanol and the mixture is refluxed under agitation for 5 hours. After the reaction, the reaction solution is poured into 200 ml of saturated NaCl solution and the precipitated crystals are filtered out and washed with water. The resultant crude crystals are recrystallized from benzene-ligroin to obtain 1.4 g of 6-{3-[N-methyl-N-(2-methylcyclohexyl)aminocarbonyl]-2-methylpropoxy}carbostyril with melting point of 146°-149° C.
Reaction SMILES: [C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4])[OH:2].[CH3:9][C:10](=O)[CH2:11][CH3:12].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>C(Cl)Cl>[CH2:10]([C:11]1([CH3:12])[O:4][C:3]2[CH:5]=[CH:6][CH:7]=[CH:8][C:1]=2[O:2]1)[CH3:9]
Reactant: CCC(C)=O
Reactant: Oc1ccccc1O
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Solvent: ClCCl
Product: CCC1(C)Oc2ccccc2O1

Procedure:
Following Intermediate Method 3, the reaction of catechol with 2-butanone and phosphorus pentoxide in methylene chloride produces 2-ethyl-2-methyl-1,3-benzodioxole, (XVI). Nitration of (XVI) with nitric and sulfuric acid in methylene chloride yields 2-ethyl-2-methyl-5-nitro-1,3-benzodioxole, (XVII). Subsequent hydrogenation of the compound (XVII) with platinum oxide in ethanol produces 5-amino-2-ethyl-2-methyl-1,3-benzodioxole, (XVIII). ##STR30##
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=2[CH3:20])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[C:21](N=C(N(C)C)N(C)C)([CH3:24])([CH3:23])[CH3:22].BrCC(C)C>C(#N)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([C:12]2[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=2[CH3:20])[CH2:22][CH:21]([CH3:24])[CH3:23])(=[O:9])=[O:10])=[CH:4][CH:3]=1
Reactant: CN(C)C(=NC(C)(C)C)N(C)C
Reactant: COc1ccc(C)c(NS(=O)(=O)c2ccc(F)cc2)c1
Solvent: CC#N
Solvent: CC(C)CBr
Product: COc1ccc(C)c(N(CC(C)C)S(=O)(=O)c2ccc(F)cc2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 4-fluoro-N-[2-methyl-5-(methyloxy)phenyl]benzenesulfonamide (185.8 mg, 0.629 mmol) in Acetonitrile (5 mL) was added neat Barton's base (2-(tert-butyl)-1,1,3,3-tetramethylguanidine) (0.131 mL, 0.629 mmol). The reaction mixture was stirred at room temperature for 1 hour. 1-bromo-2-methylpropane (0.137 mL, 1.258 mmol) was then added. The reaction vessel was sealed and heated in Biotage Initiator microwave using initial high absorbance power setting to 150° C. for 25 min. The solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus. The sample was loaded in dichloromethane and purified on automated normal chromatograph on silica (Si) 50 g using a 0-50% ethyl acetate-cyclohexane over 40 mins. The appropriate fractions were combined and dried under a stream of nitrogen in the Radleys blowdown apparatus to give the required product 171 mg as a white solid.
Reaction SMILES: [Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([OH:12])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.O>CN(C)C=O>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:4][CH:3]=1
Reactant: Oc1ccc(Br)c2ccccc12
Reactant: ClCCN1CCCCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Brc1ccc(OCCN2CCCCC2)c2ccccc12
Temperature: 60 °C
Reaction time: 1 h
Yield: 96.5 %

Procedure:
To a solution of 4-bromonaphthalen-1-ol (1.1 g) in N,N-dimethylformamide (30 ml) were sequentially added potassium carbonate (1.0 g) and 1-(2-chloroethyl)piperidine (1.1 g), and the solution was stirred for 1 hour at 60° C. Water was added thereto followed by stirring, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and the solvent was then evaporated in vacuo. The residue was purified by NH silica gel column chromatography (hexane-ethyl acetate system) to obtain 1-[2-(4-bromonaphthalen-1-yloxy)ethyl]piperidine (1.59 g). This compound (800 mg) was used according to an analogous synthetic method to Preparation Example 51 to provide the title compound (518 mg).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[NH:14][CH2:15][CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:4][CH:3]=1.[CH2:21]([O:23][C:24]([C:26]1([C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:31][CH:30]=2)[CH2:28][CH2:27]1)=[O:25])[CH3:22]>>[CH2:21]([O:23][C:24]([C:26]1([C:29]2[CH:34]=[CH:33][C:32]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[O:12][N:11]=[C:10]([CH3:13])[C:9]=4[NH:14][CH2:15][CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:4][CH:3]=3)=[CH:31][CH:30]=2)[CH2:27][CH2:28]1)=[O:25])[CH3:22]
Reactant: CCOC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Reactant: Cc1noc(-c2ccc(Br)cc2)c1NCCC(C)(C)C
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4NCCC(C)(C)C)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 1, Step 7, using [5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-(3,3-dimethyl-butyl)-amine and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH2:11])[N:2]=1.C(O)(C(F)(F)F)=O>[Pt](=O)=O>[CH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[C:3]([NH2:11])[N:2]=1
Reactant: Nc1cc2ccccc2cn1
Agent: O=[Pt]=O
Solvent: O=C(O)C(F)(F)F
Product: Nc1cc2c(cn1)CCCC2
Reaction time: 3 h
Yield: 56.8 %

Procedure:
A mixture of isoquinolin-3-amine (239 mg, 1.66 mmol), platinum(IV)oxide (28 mg, 0.123 mmol), and TFA (6 mL) was hydrogenated in the Parr apparatus for 3 hrs. The reaction mixture was filtered with the aid of ethyl acetate. The filtrate was evaporated in vacuo and the residue was partitioned between 10% aqueous sodium carbonate and ethyl acetate. The layers were separated, the aqueous phase was washed again with ethyl acetate, and the combined organic layers were washed with brine and dried over magnesium sulfate. The drying agent was filtered off and the solvent evaporated. The material was purified by column chromatography in ethyl acetate to give 139.8 mg (57%) 5,6,7,8-tetrahydroisoquinolin-3-amine as a yellow-white solid. LCMS RT 0.75 min, MH+=149.1 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.78 (1H, s), 6.26 (1H, s), 4.29 (2H, br. s.), 2.64 (4H, ddd, J=10.6, 5.8, 5.5 Hz), 1.64-1.87 (4H, m).
Reaction SMILES: [CH2:1]([NH:8][S:9]([C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]([OH:22])=O)[CH:15]=[CH:16][CH:17]=1)(=[O:11])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:23]CCl>CN(C)C=O>[CH2:1]([NH:8][S:9]([C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]([Cl:23])=[O:22])[CH:15]=[CH:16][CH:17]=1)(=[O:11])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)C=Cc1cccc(S(=O)(=O)NCc2ccccc2)c1
Reactant: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)C=Cc1cccc(S(=O)(=O)NCc2ccccc2)c1
Temperature: 40 °C
Reaction time: 1 h
Yield: 97.4 %

Procedure:
To a suspension of 3-(3-(benzylsulfamoyl-phenyl)-acrylic acid (5g) (0.16 g, 0.52 mmol) in dichloromethane (2.0 ml) oxalyl chloride (0.16 ml, 1.79 mmol) and one drop of dimethylformamide were added, The reaction mixture was stirred at 40° C. for one hour and concentrated under reduced pressure to give crude title compound (0.17 g).
Reaction SMILES: C([O:3][C:4](=[O:33])[CH:5]([O:18][C:19]1[CH:24]=[CH:23][C:22]([NH:25][S:26]([CH2:29][CH2:30][CH2:31][CH3:32])(=[O:28])=[O:27])=[CH:21][CH:20]=1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])C.C(O)C.[OH-].[Na+].Cl>O>[CH2:29]([S:26]([NH:25][C:22]1[CH:23]=[CH:24][C:19]([O:18][CH:5]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[C:4]([OH:33])=[O:3])=[CH:20][CH:21]=1)(=[O:28])=[O:27])[CH2:30][CH2:31][CH3:32]
Reactant: CCCCCCCCCCCCC(Oc1ccc(NS(=O)(=O)CCCC)cc1)C(=O)OCC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCCCCCCCCCCCC(Oc1ccc(NS(=O)(=O)CCCC)cc1)C(=O)O
Temperature: 25 °C

Procedure:
92 g (0.19 mol) of ethyl-α-[p-butylsulfonylaminophenoxy]tetradecanoate (Intermediate II) obtained in Step B, and 500 ml of ethyl alcohol were placed in a 3-necked flask. A solution of 20 g of sodium hydroxide (dissolved in a minimum amount of water) was added with good stirring. The reaction mixture was refluxed for 3 hours, allowed to cool to room temperature, poured into ice water and acidified with concentrated hydrochloric acid. The oil was extracted with ether, washed with water and saturated sodium chloride solution. The ether was removed under vacuo to give a gummy solid. After trituration with ligroine (boiling point: 35°-60° C.), the solid was collected. Yield was 50 g of Intermediate III, m.p. 80°-82° C. TLC analysis (benzene) showed one product.
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4]([N:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:9][CH2:8]2)=[N:5][N:6]=1.[CH3:18][CH2:19][CH2:20][C:21](=O)[CH2:22][C:23](=O)[CH2:24][CH2:25][CH3:26]>C(O)(=O)C>[CH2:20]([C:21]1[CH:22]=[C:23]([CH2:24][CH2:25][CH3:26])[N:6]2[N:5]=[C:4]([N:7]3[CH2:8][CH2:9][N:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:11][CH2:12]3)[N:3]=[C:2]2[N:1]=1)[CH2:19][CH3:18]
Reactant: CCCC(=O)CC(=O)CCC
Reactant: CCOC(=O)N1CCN(c2nnc(N)[nH]2)CC1
Solvent: CC(=O)O
Product: CCCc1cc(CCC)n2nc(N3CCN(C(=O)OCC)CC3)nc2n1
Yield: 93.9 %

Procedure:
A mixture of 4.48 g (0.02 moles) of 4-(5-amino-4H-1,2,4-triazol-3-yl)-1-piperazinecarboxylic acid, ethyl ester, 3.12 g (0.02 moles) of 4,6-nonanedione and 50 ml of glacial acetic acid was refluxed for 12 hours. The resulting solution was evaporated to dryness in vacuo. The residue was partitioned and treated as described in Example 12 and gave 6.77 g of the desired product as colorless crystals, mp 130°-132° C.
Reaction SMILES: [N:1]([C:4]1[N:12]=[C:11]([F:13])[N:10]=[C:9]2[C:5]=1[NH:6][CH:7]=[N:8]2)=[N+]=[N-].[BH4-].[Na+].Cl.C([O-])([O-])=O.[K+].[K+]>CC(O)C.O>[F:13][C:11]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([NH2:1])[N:12]=1
Reactant: [N-]=[N+]=Nc1nc(F)nc2nc[nH]c12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [BH4-]
Solvent: CC(C)O
Solvent: O
Product: Nc1nc(F)nc2nc[nH]c12
Temperature: 25 °C
Yield: 52 %

Procedure:
A sample of 6-azido-2-fluoropurine (0.18 g) was dissolved in warm 2-propanol (3 mL) and then cooled to ambient temperature. Sodium borohydride (38 mg) was added in small portions. The vigorous gas evolution was allowed to subside between additions. After the addition was complete the mixture was stirred at ambient temperature and then was heated at 72° C. for 1.5 h. The mixture was then cooled to ambient temperature and diluted with water (10 mL) and the pH was adjusted to 6-7 with 1N hydrochloric acid (HCl) and saturated K2CO3 and then the mixture was concentrated to dryness under vacuum. The residue was triturated in 20 mL of hot water then allowed to cool to ambient temperature. The precipitate was collected by filtration, washed with water and dried to obtain 0.08 g of the title compound as an off-white solid, mp>300° C. This material was identical to an authentic sample by TLC, and IR.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3=[CH:14][C:15]4[O:19][CH2:18][O:17][C:16]=4[CH:20]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:21].BrC1C=CC=C2C=1C1(C3=CC4OCOC=4C=C3OC1)C(=O)N2.Br[CH2:45][CH2:46][CH2:47][CH2:48][C:49]([O:51][CH2:52][CH3:53])=[O:50].BrCC1OC(C(F)(F)F)=CC=1>>[O:21]=[C:2]1[C:3]2([C:13]3=[CH:14][C:15]4[O:19][CH2:18][O:17][C:16]=4[CH:20]=[C:12]3[O:11][CH2:10]2)[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:1]1[CH2:45][CH2:46][CH2:47][CH2:48][C:49]([O:51][CH2:52][CH3:53])=[O:50]
Reactant: CCOC(=O)CCCCBr
Reactant: O=C1Nc2ccccc2C12COc1cc3c(cc12)OCO3
Agent: FC(F)(F)c1ccc(CBr)o1
Agent: O=C1Nc2cccc(Br)c2C12COc1cc3c(cc12)OCO3
Product: CCOC(=O)CCCCN1C(=O)C2(COc3cc4c(cc32)OCO4)c2ccccc21

Procedure:
Following the procedure described in EXAMPLE 10.47, and making non-critical variations using spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one to replace 4′-bromospiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one, and ethyl 5-bromovalerate to replace 2-(bromomethyl)-5-(trifluoromethyl)furan, the title compound was obtained (62%) as a gummy material: 1H NMR (300 MHz, CDCl3) δ 7.28 (t, 1H), 7.14 (d, 1H), 7.03 (t, 1H), 6.88 (d, 1H), 6.48 (s, 1H), 6.13 (s, 1H), 5.84 (d, 2H), 4.76 (ABq, 2H), 4.07 (q, 2H), 3.87-3.65 (m, 2H), 2.35 (t, 2H), 1.80-1.64 (m, 4H), 1.20 (t, 3H); 13C NMR (75 MHz, CDCl3) δ 177.4, 173.1, 155.9, 148.8, 142.3, 142.2, 132.5, 128.9, 124.04, 123.3, 119.5, 108.6, 103.0, 101.5, 93.6, 80.5, 60.4, 58.2, 39.9, 33.7, 26.8, 22.2, 14.2; MS (ES+) m/z 432.09 (M+23).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:10][NH2:11])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[C:12]([C:16]1[C:17]([C:28](Cl)=[O:29])=[N:18][C:19]2[C:24]([C:25]=1[OH:26])=[CH:23][CH:22]=[C:21]([Cl:27])[CH:20]=2)(OC)=[O:13]>O1CCCC1.O.Cl>[Cl:27][C:21]1[CH:22]=[CH:23][C:24]2[C:25](=[O:26])[C:16]3[C:12]([OH:13])=[N:11][N:10]([C:4]4[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([Cl:1])[CH:3]=4)[C:28](=[O:29])[C:17]=3[NH:18][C:19]=2[CH:20]=1
Reactant: COC(=O)c1c(C(=O)Cl)nc2cc(Cl)ccc2c1O
Reactant: COc1ccc(NN)cc1Cl
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc(-n2nc(O)c3c(=O)c4ccc(Cl)cc4[nH]c3c2=O)cc1Cl
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 48.2 %

Procedure:
To a solution of 3-chloro-4-methoxyphenylhydrazine (4.26 g, 24.7 mM) in 35b.) in tetrahydrofuran (200 mL) was added a solution of 3-carbomethoxy-7-chloro-4-hydroxyquinoline-2-carbonyl chloride (3.54 g, 11.8 mM, as prepared in Example 35b.) in tetrahydrofuran (100 mL) at 0° C. The resulting yellow suspension was stirred at 0° C. for 30 minutes and diluted with water (200 mL) to give a yellow solution. This solution was further diluted with hydrochloric acid (600 mL, 1N) to give a tan suspension which was stirred for 1 hour. The suspension was filtered (the filtrate was saved) and the collected solids were washed with water and then ether to give the title compound (2.30 g, 45%) as a tan powder, MS(CI): 436 (M+H), which was used above in the synthesis described for 7-chloro-3-(3-chloro-4-methoxyphenyl)-1-hydroxy-3,4,5,10-tetrahydropyridazino[4,5-b]quinoline-4,10-dione. 1H NMR 12.69 (s, 1H, exchangeable), 10.72 (s, 1H, exchangeable), 8.14 (d, J=8.50 Hz, 1H), 8.00 (br s, 1H, exchangeable), 7.76 (s, 1H), 7.48 (d, J=8.50 Hz, 1H), 7.05 (d, J=8.80 Hz, 1H), 6.98 (d, J=2.28 Hz, 1H), 6.85 (dd, J=2.28, 8.80 Hz, 1H), 3.78 (s, 3H), 3.70 (s, 3H). After sitting for five days, further precipitation occurred in the above saved acidic filtrate. The solids were collected to provide material (1.80 g) consisting of a mixture of the title compound (60%), 7-chloro-2-(3-chloro-4-methoxyphenyl)-1-hydroxy-1,2,5,10-tetrahydropyridazino[4,5-b]quinoline-1,10-dione (35%) and 7-chloro-3-(3-chloro-4-methoxyphenyl)-1-hydroxy-3,4,5,10-tetrahydropyridazino[4,5-b]quinoline-4,10-dione (5%).
Reaction SMILES: [C:1](=O)([O-])[O-].[K+].[K+].CB1OB(C)OB(C)O1.Br[C:17]1[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[C:20]([O:26][CH3:27])=[C:19]([F:28])[CH:18]=1.O.C(=O)(O)[O-].[Na+]>O1CCOCC1>[F:28][C:19]1[CH:18]=[C:17]([CH3:1])[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[C:20]=1[O:26][CH3:27]
Reactant: COc1c(F)cc(Br)cc1[N+](=O)[O-]
Reactant: O=C([O-])[O-]
Agent: CB1OB(C)OB(C)O1
Agent: O=C([O-])O
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: COc1c(F)cc(C)cc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 73.5 %

Procedure:
Under nitrogen atmosphere, potassium carbonate (218 mg, 1.58 mmol), tetrakistriphenylphosphine palladium(0) (58 mg, 50 μmol), trimethylboroxine (77 μl, 0.55 mmol) were added to a 1,4-dioxane (5 ml) solution of 4-bromo-2-fluoro-6-nitroanisole (125 mg, 0.5 mmol), followed by stirring with heating under reflux for 1 hour and a half. After cooling to room temperature, saturated sodium bicarbonate water was added to the reaction liquid, followed by extraction three times with ethyl acetate, the organic layer was washed with saturated brine, then dried over anhydrous magnesium sulfate. After filtration and concentration under reduced pressure, the resulting residue was subjected to column chromatography, and the eluate with n-hexane:ethyl acetate (20:1) was concentrated under reduced pressure to obtain the entitled compound (68 mg, 70%) as an orange oily substance.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:17]=[C:16]3[C:12]([CH2:13][C:14](=[O:31])[N:15]3[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([S:25]([N:28]([CH3:30])[CH3:29])(=[O:27])=[O:26])=[CH:21][CH:20]=3)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)#[N:2].Cl[CH2:33][C:34]1[N:35]=[CH:36][N:37]([C:39]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:38]=1>C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:17]=[C:16]3[C:12]([C:13]([CH2:33][C:34]4[N:35]=[CH:36][N:37]([C:39]([C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=5)([C:46]5[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=5)[C:52]5[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=5)[CH:38]=4)([CH2:33][C:34]4[N:35]=[CH:36][N:37]([C:39]([C:52]5[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=5)([C:46]5[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=5)[C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=5)[CH:38]=4)[C:14](=[O:31])[N:15]3[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([S:25]([N:28]([CH3:29])[CH3:30])(=[O:27])=[O:26])=[CH:21][CH:20]=3)=[CH:11][CH:10]=2)=[CH:7][CH:8]=1)#[N:2]
Reactant: ClCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Reactant: CN(C)S(=O)(=O)c1ccc(CN2C(=O)Cc3ccc(-c4ccc(C#N)cc4)cc32)cc1
Solvent: C1CCOC1
Product: CN(C)S(=O)(=O)c1ccc(CN2C(=O)C(Cc3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)(Cc3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)c3ccc(-c4ccc(C#N)cc4)cc32)cc1
Reaction time: 8 h
Yield: 55.6 %

Procedure:
4-[6-(4-Cyano-phenyl)-2-oxo-2,3-dihydro-indol-1-ylmethyl]-N,N-dimethyl-benzenesulfonamide (216 mg, 0.501 mmol) and 4-chloromethyl-1-trityl-1H-imidazole compound (402 mg, 1.12 mmol) were dissolved in 5 ml of anhydrous THF under an atmosphere of dry N2. To this solution was added 95% potassium hexamethyldisilylamide (KHMDS) (230 mg, 1.10 mmol) and the reaction mixture was subsequently stirred overnight. The reaction mixture was partitioned between DCM and saturated aqueous NaHCO3. The DCM layer was dried over sodium sulfate (Na2SO4), filtered and concentrated under vacuum to give a purple foam which was chromatographed on flash silica gel eluting with a gradient of chloroform (CHCl3) to CHCl3/MeOH/NH4OH (98/2/0.01) to give 300 mg of the titled compound as a pink oil.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][CH2:9][CH:8]([CH2:11][CH2:12]O)[N:7]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:5])[CH3:2].[N+:21]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[Se:30]C#N)([O-:23])=[O:22].C1COCC1.C(P(CCCC)CCCC)CCC>CC(OC)(C)C.N1C=CC=CC=1>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][CH2:9][CH:8]([CH2:11][CH2:12][Se:30][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[N+:21]([O-:23])=[O:22])[N:7]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:5])[CH3:2]
Reactant: N#C[Se]c1ccccc1[N+](=O)[O-]
Reactant: CCOC(=O)[C@@H]1CCC(CCO)N1C(=O)OC(C)(C)C
Agent: CCCCP(CCCC)CCCC
Solvent: c1ccncc1
Solvent: C1CCOC1
Solvent: COC(C)(C)C
Product: CCOC(=O)[C@@H]1CCC(CC[Se]c2ccccc2[N+](=O)[O-])N1C(=O)OC(C)(C)C
Reaction time: 1 h
Yield: 83.8 %

Procedure:
497 mg of alcohol 170 (1.73 mmol) was dissolved and 432 mg of ortho-nitrophenyl selenocyanate (1.90 mmol, 1.1 eq.) suspended in a solvent mixture consisting of 10 ml of anhydrous THF and 3 ml of anhydrous pyridine. This was followed by careful dropwise addition of 0.56 ml of tri-n-butylphosphine (2.25 mmol, 1.3 eq.) at 0° C. to obtain a dark-red solution. After one hour, the batch was diluted with 30 ml of MTBE, filtered over a small amount of silica gel and concentrated. The brown residue was purified using column chromatography over silica gel (EE/CH 1:3), thereby obtaining 685 mg of selenyl ether 171 (1.45 mmol, 84%) as an intensely yellow-colored oil.
Reaction SMILES: [Br-].[CH3:2][N:3]([CH3:25])[CH2:4][CH2:5][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Li]CCCC.[Br:31][C:32]1[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][CH:33]=1.Cl>O1CCCC1>[Br:31][C:32]1[CH:39]=[CH:38][C:35](/[CH:36]=[CH:5]/[CH2:4][N:3]([CH3:25])[CH3:2])=[CH:34][CH:33]=1
Reactant: O=Cc1ccc(Br)cc1
Reactant: CN(C)CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Agent: [Br-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CN(C)C/C=C/c1ccc(Br)cc1
Temperature: 60 °C
Reaction time: 8 h

Procedure:
To a stirred solution of (2-dimethylaminoethyl)triphenylphosphonium bromide (1.12 g, 2.7 mmol) in tetrahydrofuran (10 ml) was added 2.5 M n-BuLi in hexanes (1.08 ml, 2.7 mmol) under nitrogen at 0° C. After 30 minutes 4-bromobenzaldehyde (0.5 g, 2.7 mmol) was added slowly and the reaction mixture was stirred at 60° C. overnight. The reaction mixture was acidified with 2M hydrochloric acid and extracted with toluene. The aqueous layer was then made alkaline with 2N sodium hydroxide and extracted twice with ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give the product as yellow oil. Yield 0.41 g, 63%. LCMS method: 2, RT: 2.62 min; MI: 240-242 [M+1].
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[C:14]([F:16])[C:13]([N:17]2[C:22](=[O:23])[CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[N:19]([CH3:28])[C:18]2=[O:29])=[CH:12][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8](=[O:11])[NH:9][CH:10]=1.[C:30]([O:35][CH3:36])(=[O:34])[CH:31]([CH3:33])O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1(C)C=CC=CC=1.O.O1CCCC1>[Cl:1][C:2]1[CH:15]=[C:14]([F:16])[C:13]([N:17]2[C:22](=[O:23])[CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[N:19]([CH3:28])[C:18]2=[O:29])=[CH:12][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([O:11][CH:31]([C:30]([O:35][CH3:36])=[O:34])[CH3:33])=[N:9][CH:10]=1
Reactant: COC(=O)C(C)O
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2cc(Oc3ccc(=O)[nH]c3)c(Cl)cc2F)c1=O
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: COC(=O)C(C)Oc1ccc(Oc2cc(-n3c(=O)cc(C(F)(F)F)n(C)c3=O)c(F)cc2Cl)cn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 27.8 %

Procedure:
To a mixture of 60 mg of 5-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridone, 1.0 ml of tetrahydrofuran, 25 mg of methyl lactate, and 64 mg of triphenylphosphine, 123 mg of a 40% solution of diisopropyl azodicarboxylate in toluene, and the mixture was stirred for 2 hours at room temperature. The reaction solution was poured into water, and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography to obtain 20 mg of 5-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-{1-(methoxycarbonyl)ethoxy}pyridine [present compound 7-12].