Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: BrCCCCC.[CH2:7]([PH:12](=O)[CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH2:8][CH2:9][CH2:10][CH3:11].P(Cl)(Cl)[Cl:20]>>[Cl:20][P:12]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: CCCCC[PH](=O)CCCCC
Reactant: ClP(Cl)Cl
Solvent: CCCCCBr
Product: CCCCCP(Cl)CCCCC

Procedure:
Following the procedure of Example 3, 1-bromopentane (181.2 g) was used as starting material to prepare di-n-pentylphosphine oxide (22.4 g), and this compound was further reacted with phosphorus trichloride to give chloro di-n-pentylphosphine, b.p. 88° C. at a pressure of 0.3 mm of mercury. This compound (10.4 g) was added to a solution of hexamethyldisilazane (4.02 g) in dry toluene (10 cm3) under nitrogen, and the solution was heated at 100° C. for 5 hr. with distillation of chlorotrimethylsilane. The solution was cooled to 25° C. and sulphur (1.6 g) was added causing the temperature to rise to 60° C. The solution was heated to 100° C. for 4 hr. and then allowed to cool. Work up as described in Example 3 gave a crude product (10.6 g) which was also titrated in the presence of zinc and found to have a purity of 55% of theoretical (in this case based on MW 425). Further purification by chromatography on silica gel using hexane with increasing amounts of ethyl acetate (0-30% by volume) as eluent gave N-(di-n-pentylphosphinothioyl)-P,P-di-n-pentylphosphinothioic amide (2.4 g) of 95% purity, m.p. 59-63,5° C. (MS:m/z 426, 31 p NMR in CDCl3, singlet 68.3 ppm downfield of H3PO4). The compound of Formula I in which R1 =R2 =R3 =R4 =n-pentyl was tested by the procedure of Test 1. The results show that the product of this Example is a weak extractant for zinc at pH 1.7 but that it extracts zinc selectively in the presence of iron and has good solubility in ESCAID 100.
Reaction SMILES: NC(N)=O.[CH:5]12[O:12][CH:9](CC1)[CH2:8][N:7]([C:13]1[N:18]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26]([NH:28][CH2:29][CH3:30])=[O:27])=[CH:21][CH:20]=3)[N:16]=[C:15]3[N:31]([CH:34]4CCN(C(OCC)=O)C[CH2:35]4)[N:32]=[CH:33][C:14]=13)[CH2:6]2.[CH:45]1(N)C[CH2:46]1.N[C:50]1C=CC=CC=1>>[CH:8]12[N:7]([C:13]3[N:18]=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([NH:25][C:26]([NH:28][CH:29]5[CH2:50][CH2:30]5)=[O:27])=[CH:21][CH:20]=4)[N:16]=[C:15]4[N:31]([CH2:34][CH3:35])[N:32]=[CH:33][C:14]=34)[CH:6]([CH2:45][CH2:46]1)[CH2:5][O:12][CH2:9]2
Reactant: CCNC(=O)Nc1ccc(-c2nc(N3CC4CCC(C3)O4)c3cnn(C4CCN(C(=O)OCC)CC4)c3n2)cc1
Reactant: NC1CC1
Reactant: Nc1ccccc1
Agent: NC(N)=O
Product: CCn1ncc2c(N3C4CCC3COC4)nc(-c3ccc(NC(=O)NC4CC4)cc3)nc21

Procedure:
A urea formation procedure similar to that used for the synthesis of ethyl 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-(4-(3-ethylureido)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate is used, utilizing cyclopropylamine as the aniline component. (47%, MS=434.4 (M+H))
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].Cl[CH2:15][C:16]1[N:17]=[C:18]([C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([C:28]([F:31])([F:30])[F:29])[CH:22]=2)[O:19][CH:20]=1.[I-].[Na+]>CN(C)C=O.O>[F:27][C:25]1[CH:24]=[C:23]([C:28]([F:29])([F:30])[F:31])[CH:22]=[C:21]([C:18]2[O:19][CH:20]=[C:16]([CH2:15][CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])[N:17]=2)[CH:26]=1
Reactant: CCOC(=O)CC(=O)OCC
Reactant: Fc1cc(-c2nc(CCl)co2)cc(C(F)(F)F)c1
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)C(Cc1coc(-c2cc(F)cc(C(F)(F)F)c2)n1)C(=O)OCC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
In a 50 mL round bottomed flask was placed diethyl malonate (3.72 g, 23.25 mmol, 5 equiv.) and N,N-dimethylformamide (10 mL). To the solution was added sodium hydride (60% suspension in mineral oil, 744.0 mg, 18.6 mmol, 4.0 equiv.) at room temperature portionwise over 10 minutes. After stirring for 30 minutes a solution of 4-(chloromethyl)-2-[5-fluoro-3-(trifluoromethyl)phenyl]-1,3-oxazole (1.30 g, 4.65 mmol) in N,N-dimethylformamide (10 mL) was added at 0° C. over 15 minutes, and the reaction mixture allowed to warm up to ambient temperature. To the mixture was added sodium iodide (697.0 mg, 4.65 mmol, 1 equiv) at room temperature. The reaction mixture was stirred at the same temperature for 2 hours. Water was then added to the reaction mixture (30 mL) and the whole was extracted with ethyl acetate (30 mL×3). The organic layers were combined, washed with brine (30 mL) and dried with sodium sulfate. After removal of the solvent under reduced pressure the crude mixture was purified by a silica-gel column chromatography (SiO2=80 g, hexane:EtOAc=7:1) repeatedly. The desired product, diethyl 2-({2-[5-fluoro-3-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}methyl)propane-1,3-dioate, was obtained as colorless powder (1.75 g).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][S:9]([N:12]([CH3:14])[CH3:13])(=[O:11])=[O:10])=[CH:4][CH:3]=1.[N:15]([O-])=O.[Na+].[ClH:19]>O>[ClH:19].[NH:1]([C:2]1[CH:7]=[CH:6][C:5]([CH2:8][S:9]([N:12]([CH3:14])[CH3:13])(=[O:11])=[O:10])=[CH:4][CH:3]=1)[NH2:15]
Reactant: CN(C)S(=O)(=O)Cc1ccc(N)cc1
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CN(C)S(=O)(=O)Cc1ccc(NN)cc1
Temperature: 0 °C
Yield: 94 %

Procedure:
To a suspension of 4.30 g (20.1 mmol, 1.0 equiv.) of 4-amino-N,N-dimethylbenzenemethanesulfonamide in 40 mL of concentrated aqueous hydrochloric acid and 20 mL of water cooled to 0° C. was added a solution of 1.38 g (20.1 mmol, 1.0 equiv.) of sodium nitrite in 20 mL of water dropwise. The reaction mixture became homogeneous during the addition. The reaction was stirred for fifteen minutes at 0° C. after the addition was complete. Meanwhile a solution of 22.6 g (100 mmol, 5.0 equiv.) of stannous chloride dihydrate in 40 mL of concentrated aqueous hydrochloric acid was prepared and cooled to -40° C. The solution of the diazonium salt was filtered into the stannous chloride solution. The reaction was allowed to warm to room temperature over the course of one hour. The reaction was then recooled to 0° C. and the precipitated product was collected by filtration. The solid was dried at 65° C. at 0.05 mm Hg for 45 minutes to yield 5.02 g (94%) of 4 -hydrazinyl-N,N-dimethylbenzenemethanesulfonamide hydrochloride.
Reaction SMILES: [CH2:1]([C:3]1[C:7]([CH2:8][CH3:9])=[CH:6][NH:5][CH:4]=1)[CH3:2].[CH2:10]([O:17][C:18]([C:20]1[NH:21][C:22]([CH2:28]OC(=O)C)=[C:23]([CH2:26][CH3:27])[C:24]=1[CH3:25])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[CH2:10]([O:17][C:18]([C:20]1[NH:21][C:22]([CH2:28][C:4]2[NH:5][C:6]([CH2:28][C:22]3[NH:21][C:20]([C:18]([O:17][CH2:10][C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=4)=[O:19])=[C:24]([CH3:25])[C:23]=3[CH2:26][CH3:27])=[C:7]([CH2:8][CH3:9])[C:3]=2[CH2:1][CH3:2])=[C:23]([CH2:26][CH3:27])[C:24]=1[CH3:25])=[O:19])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CCc1c[nH]cc1CC
Reactant: CCc1c(COC(C)=O)[nH]c(C(=O)OCc2ccccc2)c1C
Product: CCc1c(Cc2[nH]c(Cc3[nH]c(C(=O)OCc4ccccc4)c(C)c3CC)c(CC)c2CC)[nH]c(C(=O)OCc2ccccc2)c1C

Procedure:
condensing 3,4-diethylpyrrole with two molecular equivalents of benzyl-5-(acetoxymethyl)-4-ethyl-3-methylpyrrole-2-carboxylate to produce 2,5-bis(5-benzyloxycarbonyl-3-ethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole;
Reaction SMILES: [C:1](=[O:19])(SC1C=CC=CC=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11].C(=O)[CH2:21][CH2:22][CH2:23][C:24]#[CH:25].[C:27](=O)=[O:28].[NH4+].[Cl-]>C1COCC1>[CH2:3]([C@H:2]1[C@H:1]([CH2:25][CH2:24][CH2:23][C:22]#[CH:21])[O:19][C:27]1=[O:28])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11]
Reactant: C=CCCCCCCCCC(=O)Sc1ccccc1
Reactant: O=C=O
Reactant: C#CCCCC=O
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: C#CCCC[C@@H]1OC(=O)[C@H]1CCCCCCCC=C
Temperature: -78 °C
Reaction time: 2 h

Procedure:
Thereafter the ice bath was replaced with an acetone-dry ice bath and the reaction mixture was cooled to −78° C. A solution of S-phenyl 10-undecenethioate 2 (55.3 mg, 0.20 mmol) in 250 THF was added dropwise via a syringe over 5 min. After stirring the mixture for 2 h at −78° C., a solution of 5-hexynal 1 (19.2 mg, 0.20 mmol) in 250 μL THF was added dropwise over 25 min via a syringe which was cooled externally by a rubber tube filled with dry ice. The reaction mixture was stirred for 30 min and then gradually warmed up to 0° C. within 75 min. Then 1 mL half-saturated NH4Cl solution was added.
Reaction SMILES: [C:1]1(=[O:8])[CH2:6][CH2:5][CH2:4][C:3](=[O:7])[CH2:2]1.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]=[C:17]=[O:18])=[CH:12][CH:11]=1.C(N(CC)CC)C.[N-]=C=O>CC(C)=O>[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]([C:2]2[C:3](=[O:7])[CH2:4][CH2:5][CH2:6][C:1]=2[OH:8])=[O:18])=[CH:12][CH:11]=1
Reactant: O=C1CCCC(=O)C1
Reactant: O=C=Nc1ccc(Cl)cc1
Agent: [N-]=C=O
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Product: O=C1CCCC(O)=C1C(=O)Nc1ccc(Cl)cc1

Procedure:
A solution containing 8.5 parts of cyclohexane-1,3-dione, 11.5 parts of p-chlorophenylisocyanate and 7.6 parts of triethylamine in 200 parts of acetone is stirred and refluxed for two hours. The infrared spectrum then shows no isocyanate (band at 2270 cm-1). The solution is concentrated under reduced pressure to about 50 parts, with separation of a few crystals, and poured with stirring into 500 parts of 2-normal hydrochloric acid. The precipitated solid is collected by filtration and dried. The resulting solid is mixed with chloroform, 250 parts by volume, and filtered from 6.5 parts of insoluble by-product. Removal of chloroform from the filtrate leaves a light pink solid which is crystallized from alcohol to give 6.7 parts of nearly white solid, melting point 113°C.-114°C.
Reaction SMILES: Cl[S:2]([C:5]1[S:6][C:7]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][CH:11]=2)=[CH:8][CH:9]=1)(=[O:4])=[O:3].[NH2:20][C:21]1[O:25][N:24]=[C:23]([CH3:26])[C:22]=1[Br:27]>>[Br:27][C:22]1[C:23]([CH3:26])=[N:24][O:25][C:21]=1[NH:20][S:2]([C:5]1[S:6][C:7]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][CH:11]=2)=[CH:8][CH:9]=1)(=[O:4])=[O:3].[C:10]1([C:7]2[S:6][C:5]([S:2]([NH2:20])(=[O:4])=[O:3])=[CH:9][CH:8]=2)[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1.[Br:27][C:22]1[C:23]([CH3:26])=[N:24][O:25][C:21]=1[NH:20][S:2]([C:5]1[S:6][C:7]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][CH:11]=2)=[CH:8][CH:9]=1)(=[O:4])=[O:3]
Reactant: Cc1noc(N)c1Br
Reactant: O=S(=O)(Cl)c1ccc(-c2cccc3ccccc23)s1
Product: Cc1noc(NS(=O)(=O)c2ccc(-c3cccc4ccccc34)s2)c1Br
Product: NS(=O)(=O)c1ccc(-c2cccc3ccccc23)s1

Procedure:
N-14-bromo-3-methyl-5-isoxazolyl)-5-(1-naphthyl)thiophene-sulfonamide N-(4-bromo-3-methyl-5-isoxazolyl)-5-(1-naphthyl)thiophene-sulfonamide was prepared in the same manner as described in Example 2. Reaction of 2-chlorosulfonyl-5-(1-naphthyl)thiophene (200 mg, 0.65 mmol) with 5-amino-4-bromo-3-methylisoxazole (0.65 mmol), after purification by column chromatography using 1% MeOH/CHCl3, gave 65.3 mg of pure N-(4-bromo-3-methyl-5-isoxazolyl)-5-(1-naphthyl)thiophene-sulfonamide as a brown solid, (22% yield, m.p. 118° C.).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](Cl)[CH:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:11](=[O:21])[C@@H:12]1[C:16]([CH3:18])([CH3:17])[CH2:15][C:14](=[O:19])[N:13]1[CH3:20].ClC1C([C:29]([F:32])([F:31])[F:30])=CC=CC=1C[N+]#[C-]>>[Cl:1][C:2]1[C:7]([C:29]([F:32])([F:31])[F:30])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:11](=[O:21])[C@@H:12]1[C:16]([CH3:18])([CH3:17])[CH2:15][C:14](=[O:19])[N:13]1[CH3:20]
Reactant: [C-]#[N+]Cc1cccc(C(F)(F)F)c1Cl
Reactant: CN1C(=O)CC(C)(C)[C@H]1C(=O)NCc1ccc(Cl)cc1Cl
Product: CN1C(=O)CC(C)(C)[C@H]1C(=O)NCc1cccc(C(F)(F)F)c1Cl

Procedure:
N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-1,3,3-trimethyl-5-oxoprolinamide was prepared in a manner analogous to that described above for the synthesis of N-[(2,4-dichlorophenyl)methyl]-1,3,3-trimethyl-5-oxoprolinamide (E127) but using [2-chloro-3-(trifluoromethyl)phenyl]methyl isocyanide (prepared as described in example 40) in the place of (2,4-dichlorophenyl)methyl isocyanide.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[C:12](I)=[C:13]([C:15]([NH2:17])=[O:16])[N:14]=[C:7]3[C:6]=2[CH:19]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[N:30][N:31](C(OC(C)(C)C)=O)[CH:32]=2)O1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[C:12]([C:28]4[CH:29]=[N:30][NH:31][CH:32]=4)=[C:13]([C:15]([NH2:17])=[O:16])[N:14]=[C:7]3[C:6]=2[CH:19]=1
Reactant: NC(=O)c1nc2n(c1I)CCOc1ccc(Br)cc1-2
Reactant: CC(C)(C)OC(=O)n1cc(B2OC(C)(C)C(C)(C)O2)cn1
Product: NC(=O)c1nc2n(c1-c1cn[nH]c1)CCOc1ccc(Br)cc1-2

Procedure:
10-Bromo-3-iodo-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide (0.1 g) was reacted with tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-1-carboxylate similar to as described in Example 4 and triturated from water to give 86 mg of 10-bromo-3-(1H-pyrazol-4-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide. This intermediate was reacted with 2-Methyl-3-butyne-ol similar to as described in Procedure E to afford 5.5 mg of 10-(3-hydroxy-3-methyl-but-1-ynyl)-3-(1H-pyrazol-4-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide following reverse phase hplc purification. MS (Q1) 378 (M)+. NMR (400 MHz, DMSO) δ 13.10 (s, 1H), 8.57 (d, J=2.1 Hz, 1H), 8.11 (s, 1H), 7.81 (s, 1H), 7.54 (s, 1H), 7.29 (dd, J=8.4, 2.1 Hz, 1H), 7.10-6.95 (m, 2H), 5.43 (s, 1H), 4.49-4.40 (m, 2H), 4.35-4.25 (m, 2H), 1.49 (s, 6H).
Reaction SMILES: [N+]([CH2:4][C@H:5]([C@@H:7]([C@H:9]([C@H:11]([CH2:13][OH:14])[OH:12])[OH:10])[OH:8])[OH:6])([O-])=O.[OH-].[Na+].S(=O)(=O)(O)[OH:18].[OH-].[Ba+2].[OH-]>O>[O:18]=[CH:4][C@H:5]([C@@H:7]([C@H:9]([C@H:11]([CH2:13][OH:14])[OH:12])[OH:10])[OH:8])[OH:6]
Reactant: O=[N+]([O-])C[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)CO
Reactant: O=S(=O)(O)O
Agent: [Ba+2]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)CO

Procedure:
A solution of 5 grams of 1-deoxy-1-nitro-L-glucitol dissolved in 15 ml. of 2 N sodium hydroxide was added dropwise to a stirred solution of 7.5 ml. of sulfuric acid in 9 ml. of water at room temperature. After dilution with 200 ml. of water, the solution was neutralized to Congo red indicator with warm barium hydroxide solution and the remaining sulfate ion precipitated with barium acetate solution. The barium sulfate was removed by filtration and the filtrate de-ionized by passage through 50 ml. of Dowex-50(H+) resin. The effluent and washings were concentrated at reduced pressure to a syrup. This syrup was diluted with a few drops of ethanol and allowed to crystallize. The resulting β-L-glucose was filtered with the aid of ethanol; yield 2.5 grams, mp 146°-147° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:34])[CH2:9][CH2:10][N:11]1[C:15]2[CH:16]=[CH:17][C:18]([C:20](O)=[O:21])=[CH:19][C:14]=2[N:13]=[C:12]1[NH:23][C:24]1[S:25][C:26]2[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:27]=2[N:28]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:35][CH2:36][C:37]([N:39]([CH3:41])[CH3:40])=[O:38].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[N:8]([CH2:9][CH2:10][N:11]1[C:15]2[CH:16]=[CH:17][C:18]([C:20](=[O:21])[NH:35][CH2:36][C:37](=[O:38])[N:39]([CH3:41])[CH3:40])=[CH:19][C:14]=2[N:13]=[C:12]1[NH:23][C:24]1[S:25][C:26]2[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:27]=2[N:28]=1)[CH3:34])([CH3:4])([CH3:2])[CH3:3]
Reactant: CN(CCn1c(Nc2nc3ccc(Cl)cc3s2)nc2cc(C(=O)O)ccc21)C(=O)OC(C)(C)C
Reactant: CN(C)C(=O)CN
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CN(C)C(=O)CNC(=O)c1ccc2c(c1)nc(Nc1nc3ccc(Cl)cc3s1)n2CCN(C)C(=O)OC(C)(C)C
Yield: 41.1 %

Procedure:
{2-[2-(6-Chloro-benzothiazol-2-ylamino)-5-(dimethylcarbamoylmethyl-carbamoyl)-benzoimidazol-1-yl]ethyl}-methyl-carbamic acid tert-butyl ester (70 mg) was prepared by following General Procedure F starting from 1-[2-(tert-butoxycarbonyl-methyl-amino)-ethyl]-2-(6-chloro-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (146 mg), 2-amino-N,N-dimethyl-acetamide (50 mg), HBTU (125 mg), and DIEA (100 uL) in DMF (1 mL).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([N+:13]([O-:15])=[O:14])[CH:12]=1)[C:6]([O:8][CH3:9])=[O:7])#[CH:2].I[C:17]1[CH:18]=[C:19]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:20]=[CH:21][CH:22]=1.C(N(CC)C(C)C)(C)C>C1COCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:26]([O:25][C:24]([NH:23][C:19]1[CH:18]=[C:17]([C:2]#[C:1][C:3]2[CH:4]=[C:5]([CH:10]=[C:11]([N+:13]([O-:15])=[O:14])[CH:12]=2)[C:6]([O:8][CH3:9])=[O:7])[CH:22]=[CH:21][CH:20]=1)=[O:30])([CH3:29])([CH3:27])[CH3:28]
Reactant: CC(C)(C)OC(=O)Nc1cccc(I)c1
Reactant: C#Cc1cc(C(=O)OC)cc([N+](=O)[O-])c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1cc(C#Cc2cccc(NC(=O)OC(C)(C)C)c2)cc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 65.9 %

Procedure:
A solution of methyl 3-ethynyl-5-nitrobenzoate (1.45 g, 7.08 mmol), tert-butyl (3-iodophenyl)carbamate (2.26 g, 7.08 mmol) in THF (28 mL) was treated with bis(triphenylphosphine)palladium(II) chloride (248 mg, 0.354 mmol), copper(I) iodide (108 mg, 0.566 mmol) and N,N-diisopropylethylamine (2.47 mL, 14.2 mmol) and stirred at 25° C. overnight. The reaction was diluted with water and extracted with ethyl acetate three times. The combined organic solutions were dried with sodium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by flash column chromatography to yield the desired product (1.85 g, 66%). LCMS for C21H20N2O6Na (M+Na)+: m/z=419.3.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH:18]OS([O-])=O.[K+].[OH2:24]>CO>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)(=[O:18])=[O:24])=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16]
Reactant: Cc1ccc(Sc2ccccc2)cc1[N+](=O)[O-]
Reactant: O
Reactant: O=S([O-])OO
Agent: [K+]
Solvent: CO
Product: Cc1ccc(S(=O)(=O)c2ccccc2)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 6 h
Yield: 82 %

Procedure:
A solution of 1-methyl-2-nitro-4-(phenylthio)benzene (Intermediate 111; 745 mg; 3.04 mmol) in MeOH (11 ml) and water (11 ml) was treated with Oxone® (5.60 g; 9.11 mmol) and the reaction mixture was stirred at RT for 6 hours. Water was added and the reaction mixture was extracted 2 times with DCM. The combined organic extracts were dried over MgSO4, filtered and concentrated to dryness affording the title compound as a beige solid (690 mg, 82%).
Reaction SMILES: Cl[CH2:2][C:3]1[S:7][C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][C:11]=3[NH:17][S:18]([C:21]2[S:22][CH:23]=[CH:24][CH:25]=2)(=[O:20])=[O:19])=[N:5][CH:4]=1.[N:26]1([CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C(N(CC)CC)C.[Cl-].[NH4+]>CN(C)C=O>[S:22]1[CH:23]=[CH:24][CH:25]=[C:21]1[S:18]([NH:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:10]=1[NH:9][C:8]([C:6]1[S:7][C:3]([CH2:2][N:29]3[CH2:28][CH2:27][N:26]([CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:31][CH2:30]3)=[CH:4][N:5]=1)=[CH:16]2)(=[O:19])=[O:20]
Reactant: O=S(=O)(Nc1cccc2cc(-c3ncc(CCl)s3)[nH]c12)c1cccs1
Reactant: CCOC(=O)CN1CCNCC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCOC(=O)CN1CCN(Cc2cnc(-c3cc4cccc(NS(=O)(=O)c5cccs5)c4[nH]3)s2)CC1
Temperature: 25 °C
Reaction time: 15 h
Yield: 82.8 %

Procedure:
To a solution of N-{2-[5-(chloromethyl)-1,3-thiazol-2-yl]-1H-indol-7-yl}thiophene-2-sulfonamide (0.460 g) in N,N-dimethylformamide (12 ml) were added ethyl piperazin-1-ylacetate (0.385 g) and triethylamine (0.31 ml), and the mixture was stirred at room temperature for 15 hr. Saturated aqueous ammonium chloride solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from tetrahydrofuran-hexane to give the title compound (0.507 g, yield 83%) as colorless crystals.
Reaction SMILES: [CH2:1]([O:13][C:14]1[CH:15]=[C:16]([C:33]2([CH:39]([C:41]3[CH:46]=[CH:45][C:44]([I:47])=[CH:43][CH:42]=3)[OH:40])SCCCS2)[CH:17]=[CH:18][C:19]=1[O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C1C(=O)N(Br)C(=[O:51])C1.[O-]S([O-])=O.[Na+].[Na+].C(Cl)Cl>CC(C)=O.O.CC(C)=O>[CH2:1]([O:13][C:14]1[CH:15]=[C:16]([C:33](=[O:51])[C:39]([C:41]2[CH:46]=[CH:45][C:44]([I:47])=[CH:43][CH:42]=2)=[O:40])[CH:17]=[CH:18][C:19]=1[O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCOc1ccc(C2(C(O)c3ccc(I)cc3)SCCCS2)cc1OCCCCCCCCCCCC
Reactant: O=C1CCC(=O)N1Br
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: CC(C)=O
Product: CCCCCCCCCCCCOc1ccc(C(=O)C(=O)c2ccc(I)cc2)cc1OCCCCCCCCCCCC
Temperature: 12.5 °C
Reaction time: 0.5 h
Yield: 25.3 %

Procedure:
A solution of [2-(3,4-bis-dodecyloxy-phenyl)-[1,3]dithian-2-yl]-(4-iodo-phenyl)-methanol (JYC-II-020-A) (8.2 g, 10.3 mmol) in 400 mL of acetone was added dropwise to a solution of NBS (31.86 g, 17.9 mmol) in 3% water/acetone (v/v) at 0° C. The reaction mixture was stirred at 0-25° C. for 30 min. It was then poured into a saturated aqueous Na2SO3 solution (400 mL) and CH2Cl2 (400 mL) mixture. The resulting mixture was stirred at room temperature for additional 10 min. The organic layer was washed with H2O and dried over anhydrous MgSO4. The solvent was removed under reduced pressure. The crude product was recrystallized from hexanes. The product was further purified by column chromatography (silica gel, hexanes:dichloromethane=2:1 (v/v)) to give a light yellow solid (1.84 g, 25.4%). 1H NMR (300 MHz, CDCl3, δ): 7.85 (d, J=8.5 Hz, 2H), 7.65 (d, J=8.5 Hz, 2H), 7.53 (d, J=1.9 Hz, 1H), 7.38 (dd, J=8.5 Hz, 1.9 Hz, 1H), 6.83 (d, J=8.2 Hz, 1H), 4.04 (t, J=6.6 Hz, 2H), 4.03 (t, J=6.6 Hz, 2H), 1.76-1.86 (m, 4H), 1.20-1.51 (m, 36H), 0.86 (t, J=6.3 Hz, 6H). 13C {1H} NMR (75 MHz, CDCl3, δ): 193.77, 192.45, 155.19, 149.28, 138.17, 132.46, 130.90, 126.16, 125.47, 111.94, 111.46, 103.28, 69.21, 69.15, 32.00, 29.75, 29.70, 29.66, 29.45, 29.40, 29.10, 28.94, 26.06, 25.98, 22.78, 14.24. HRMS-EI (m/z): [M]+ calcd for C38H57IO4, 704.33016; found, 704.32941. Anal. calcd for C38H57IO4: C, 64.76; H, 8.15. Found: C, 64.81; H, 8.15.