Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][OH:11])[CH:5]=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[C:15](N1C=CN=C1)(N1C=CN=C1)=[O:16].[H-].[Na+]>CC1CCCO1.O.C(OCC)(=O)C>[CH3:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:9][CH2:10][O:11][C:15]2=[O:16])[CH:5]=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]
Reactant: Cc1nc(NCCO)ccc1[N+](=O)[O-]
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC1CCCO1
Solvent: O
Product: Cc1nc(N2CCOC2=O)ccc1[N+](=O)[O-]
Reaction time: 4 h
Yield: 84.4 %

Procedure:
To a solution of 2-((6-methyl-5-nitropyridin-2-yl)amino)ethanol (223 mg, 1.131 mmol) in 2-methyltetrahydrofuran (20 mL) was added 1,1′-carbonyldiimidazole (CDI) (220 mg, 1.357 mmol) and the reaction mixture stirred under nitrogen for 4 hours. The mixture was then left to stand for 20 hours. To this was added sodium hydride (60% wt in mineral oil) (100 mg, 2.488 mmol) and the reaction mixture stirred at room temperature for 2 hours. The reaction mixture was then diluted with water and ethyl acetate and the organic phase separated, washed with brine, then dried over magnesium sulphate. The solvent was removed in vacuo and the residue purified by flash silica (Si) chromatography (0-100% ethyl acetate-cyclohexane gradient) to give the title compound (0.213 g) as an off-white solid. LCMS (2 min, formic) Rt 0.85 min, m/z (ES+) 224 (M+H).
Reaction SMILES: [CH2:1]([C:5]1[NH:6][C:7]2[C:12]([C:13]=1[C:14]1[C:23]3[C:18](=[C:19]([O:24][CH3:25])[CH:20]=[CH:21][CH:22]=3)[CH2:17][CH2:16][CH:15]=1)=[CH:11][CH:10]=[C:9]([C:26]([OH:28])=[O:27])[CH:8]=2)[CH2:2][CH2:3][CH3:4].[H-].[Na+].[CH2:31](Br)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CN(C)C=O>[CH2:31]([N:6]1[C:7]2[C:12](=[CH:11][CH:10]=[C:9]([C:26]([OH:28])=[O:27])[CH:8]=2)[C:13]([C:14]2[C:23]3[C:18](=[C:19]([O:24][CH3:25])[CH:20]=[CH:21][CH:22]=3)[CH2:17][CH2:16][CH:15]=2)=[C:5]1[CH2:1][CH2:2][CH2:3][CH3:4])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: CCCCc1[nH]c2cc(C(=O)O)ccc2c1C1=CCCc2c(OC)cccc21
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCc1c(C2=CCCc3c(OC)cccc32)c2ccc(C(=O)O)cc2n1Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a suspension of 2-butyl-3-(5-methoxy-3,4-dihydro-naphthalen-1-yl)-1H-indole-6-carboxylic acid on Wang resin (100 mg; prepared according to the procedure outlined in Example 9) in dimethylformamide (1.5 mL) was added sodium hydride (60% in mineral oil; 20 mg) and the mixture was stirred at room temperature for 30 min. Benzyl bromide (0.1 mL) was added and the mixture was stirred for 3 h. The mixture was filtered, washed with water (1×1.5 mL), tetrahydrofuran (2×1.5 mL), dichloromethane (2×1.5 mL), and dried. The product was cleaved from the resin by treatment with 1:1 trifluoroacetic acid/dichloromethane for 1 h; 1H NMR (DMSO-d6) δ 0.67 (t, J=7.0 Hz, 3 H), 1.16 (t, J=6.7 Hz, 2 H), 1.34 (t, J=6.7 Hz, 2 H), 2.42 (m, 2 H), 2.55 (m, 2 H), 2.80 (m, 2 H), 3.82 (s, 3 H), 5.59 (s, 2 H), 6.12 (t, 1 H), 6.32 (d, J=7.3 Hz, 1 H), 6.88 (d, J=8.3 Hz, 1 H), 7.00 (m, 3 H), 7.15 (d, J=8.3 Hz, 1 H), 7.30 (m, 3 H), 7.55 (d, J=8.2 Hz, 1 H), 7.94 (s, 1 H).
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[CH2:15](O)[CH3:16]>>[Br:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:15][CH3:16])=[O:9])[CH:5]=[CH:4][CH:3]=1
Reactant: CCO
Reactant: O=C(O)c1cccc(Br)n1
Solvent: O=S(Cl)Cl
Product: CCOC(=O)c1cccc(Br)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a stirring solution of 6-bromopicolinic acid (14.25 g, 70.3 mmol) in anhydrous ethanol (250 ml) was slowly added thionyl chloride (60 ml) at 5° C. After the addition was completed, the ice-bath was removed and the mixture was stirred at 25° C. for 3 hr. The solvent was evaporated under vacuum, the aqueous residue basified with saturated sodium carbonate, and extracted with DCM. The organic phase was dried over Na2SO4 and concentrated to give ethyl 6-bromopicolinate as a white solid (15.75 g).
Reaction SMILES: [CH:1]([C@@H:4]1[CH2:9][CH2:8][C@H:7]([N:10]2[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[F:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1>CCCCC>[F:17][C:18]1[CH:24]=[CH:23][C:21]([N:22]=[C:13]2[CH2:14][CH2:15][N:10]([C@H:7]3[CH2:8][CH2:9][C@@H:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6]3)[CH2:11][CH2:12]2)=[CH:20][CH:19]=1
Reactant: Nc1ccc(F)cc1
Reactant: CC(C)[C@H]1CC[C@@H](N2CCC(=O)CC2)CC1
Solvent: CCCCC
Product: CC(C)[C@H]1CC[C@@H](N2CCC(=Nc3ccc(F)cc3)CC2)CC1

Procedure:
cis-1-(4-Isopropyl-cyclohexyl)-piperidine-4-on (5.0 g, 23.4 mmol), 4-fluoro aniline (3.3 g, 35.3 mmol) and molecular sieves (20 g, 4A) were stirred in 100 ml pentane at room temperature for 6 days. The molecular sieves was filtered off and the solvent was evaporated. The crude product was used without any further purification for the following step.
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([C@H:14]2[CH2:19][CH2:18][C@H:17]([NH:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH2:16][CH2:15]2)=[C:10]([CH2:29][NH:30][CH3:31])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:32][S:33](Cl)(=[O:35])=[O:34]>>[C:1]([O:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([C@H:14]2[CH2:19][CH2:18][C@H:17]([N:20]([CH2:21][C:22]3[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=3)[S:33]([CH3:32])(=[O:35])=[O:34])[CH2:16][CH2:15]2)=[C:10]([CH2:29][NH:30][CH3:31])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CNCc1cc(C(=O)OC(C)(C)C)ccc1[C@H]1CC[C@H](NCc2ccc(F)cc2)CC1
Reactant: CS(=O)(=O)Cl
Product: CNCc1cc(C(=O)OC(C)(C)C)ccc1[C@H]1CC[C@H](N(Cc2ccc(F)cc2)S(C)(=O)=O)CC1

Procedure:
from trans-4-(4-tert.butoxycarbonyl-methylaminomethylphenyl)-N-(4-fluorobenzyl)cyclohexylamine and methanesulphonic acid chloride. Colourless oil.
Reaction SMILES: Cl[C:2]1[C:3]2[N:4]([C:12]([CH2:15][CH3:16])=[N:13][N:14]=2)[C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.Cl[C:18]1[C:19]2[N:20](C=NN=2)[C:21]2C(N=1)=CC=C[CH:22]=2.C(NCC)C.C(NCCC)CC>>[CH2:19]([N:20]([CH2:21][CH3:22])[C:2]1[C:3]2[N:4]([C:12]([CH2:15][CH3:16])=[N:13][N:14]=2)[C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH3:18]
Reactant: CCc1nnc2c(Cl)nc3ccccc3n12
Reactant: Clc1nc2ccccc2n2cnnc12
Solvent: CCCNCCC
Solvent: CCNCC
Product: CCc1nnc2c(N(CC)CC)nc3ccccc3n12
Yield: 69 %

Procedure:
This compound was prepared by the method of Example 11, utilizing 4-chloro-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline (the product of Example 4) as starting material in place of 4-chloro-[1,2,4]triazolo[4,3-a]quinoxaline (the product of Example 2) and diethylamine as reagent in place of di-n-propylamine. The crude product was recrystallized from cyclohexane to afford 3.54 g. (69% yield) of pure 4-diethylamino-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline as a white solid (m.p. 98°-100° C.). Mass spectrum: m/e, 269 (P).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:6]2[N:7]=C(N)[O:9][C:5]=2[CH:4]=1.COC1C=CC([N+]([O-])=O)=C(O)C=1.CC(O)=O>CO.[Pd]>[NH2:7][C:6]1[CH:11]=[CH:12][C:3]([O:2][CH3:1])=[CH:4][C:5]=1[OH:9]
Reactant: COc1ccc2nc(N)oc2c1
Agent: [Pd]
Agent: COc1ccc([N+](=O)[O-])c(O)c1
Solvent: CC(=O)O
Solvent: CO
Product: COc1ccc(N)c(O)c1
Reaction time: 2 h
Yield: 100 %

Procedure:
General experimental procedure for the preparation of 6-methoxybenzo[d]oxazol-2-amine: A mixture of 5-methoxy-2-nitrophenol (0.51 g, 3.02 mmol), Pd/C (10% by weight, 70 mg), and HOAc (cat. amount) in MeOH (30 mL) was hydrogenated under H2 at room temperature for 2 hrs, and then was filtered through a short Celite pad. The filtrate was concentrated in vacuo to provide 2-amino-5-methoxyphenol as a brown solid (0.42 g, 100%). 1H NMR (CDCl3, 400 MHz) δ 6.79 (d, J=8.4 Hz, 1H), 6.44 (d, J=2.8 Hz, 1H), 6.35 (dd, J=8.4, 2.8 Hz, 1H), 3.74 (s, 3H). This product was used directly in the next step without any further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][C:3]=1[NH2:4].ClC(Cl)(O[C:28](=[O:34])OC(Cl)(Cl)Cl)Cl.[F:36][C:37]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:38]=1[CH2:39][NH2:40]>C(Cl)(Cl)Cl.C(N(CC)CC)C>[Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][C:3]=1[NH:4][C:28]([NH:40][CH2:39][C:38]1[CH:41]=[CH:42][C:43]([F:45])=[CH:44][C:37]=1[F:36])=[O:34]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc2ncnc(Oc3ccc(N)c(Cl)c3)c2cc1OC
Reactant: NCc1ccc(F)cc1F
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: COc1cc2ncnc(Oc3ccc(NC(=O)NCc4ccc(F)cc4F)c(Cl)c3)c2cc1OC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 64 %

Procedure:
2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was dissolved in chloroform (5 ml) and triethylamine (1 ml), and a solution of triphosgene (45 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 30 min. Next, 2,4-difluorobenzylamine (22 μl) was added to the reaction solution, and the mixture was stirred at room temperature for additional 30 min. The precipitated crystal was collected by filtration and was washed to give 48 mg (yield 64%) of the title compound.
Reaction SMILES: [N:1]([CH:4]([C:6]1[CH:11]=[C:10]([Cl:12])[C:9]([F:13])=[C:8]([Br:14])[C:7]=1[O:15][CH3:16])[CH3:5])=[N+]=[N-].CP(C)C>C1COCC1.O.CCOC(C)=O>[Br:14][C:8]1[C:7]([O:15][CH3:16])=[C:6]([CH:4]([NH2:1])[CH3:5])[CH:11]=[C:10]([Cl:12])[C:9]=1[F:13]
Reactant: COc1c(C(C)N=[N+]=[N-])cc(Cl)c(F)c1Br
Agent: CP(C)C
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COc1c(C(C)N)cc(Cl)c(F)c1Br
Reaction time: 1 h
Yield: 93.3 %

Procedure:
To the stirred solution of 1-(1-azidoethyl)-3-bromo-5-chloro-4-fluoro-2-methoxybenzene (3.3 g, 11 mmol) in THF (50 mL) and water (10 mL) was added 1.0 M trimethylphosphine in THF (13 mL) at room temperature and the mixture was stirred for 1 hour. The mixture was diluted with EtOAc, washed with saturated sodium bicarbonate solution, water, brine, dried over magnesium sulfate and concentrated to give the desired compound (2.9 g, 95%). LCMS calculated for C9H8BrClFO (M−NH2)+: m/z=264.9, 266.9. found: 265.0, 267.0.
Reaction SMILES: [NH2:1][CH:2]1[C:10]2[C:5](=[CH:6][C:7]([CH2:11][N:12]3[CH:16]=[C:15]([CH2:17][OH:18])[C:14]([C:19]([F:22])([F:21])[F:20])=[N:13]3)=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.C(N(CC)CC)C.[CH3:30][S:31](Cl)(=[O:33])=[O:32]>C(Cl)Cl>[OH:18][CH2:17][C:15]1[C:14]([C:19]([F:22])([F:21])[F:20])=[N:13][N:12]([CH2:11][C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[CH:2]([NH:1][S:31]([CH3:30])(=[O:33])=[O:32])[CH2:3][CH2:4]3)[CH:16]=1
Reactant: CS(=O)(=O)Cl
Reactant: NC1CCc2cc(Cn3cc(CO)c(C(F)(F)F)n3)ccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)NC1CCc2cc(Cn3cc(CO)c(C(F)(F)F)n3)ccc21
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of (1-((1-amino-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)methanol (0.096 mmol, 30 mg) and triethylamine (0.193 mmol, 0.027 mL, 19.50 mg) in DCM (0.9 mL) was added methanesulfonyl chloride (0.096 mmol, 7.46 μL, 11.04 mg) and the whole stirred at room temperature for 3 h. The reaction mixture was concentrated under reduced pressure and the residue purified by RP-HPLC to give a clear film (2.2 mg 5.7 μmol, 5.9%). MS (ESI): m/z [M+H]+ 390.0
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[CH:11][C:10]([C:13]3[CH:26]=[CH:25][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=4)=[CH:15][CH:14]=3)=[N:9]2)=[CH:4][CH:3]=1.Br[C:28]1(CCOCC)C(=O)NC(=O)NC1=O>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:12]=[CH:11][C:10]([C:13]3[CH:26]=[CH:25][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([O:24][CH3:28])=[CH:20][CH:19]=4)=[CH:15][CH:14]=3)=[N:9]2)=[CH:6][CH:7]=1
Reactant: Oc1ccc(Oc2ccc(-c3ccn(-c4ccc(Cl)cc4)n3)cc2)cc1
Reactant: CCOCCC1(Br)C(=O)NC(=O)NC1=O
Product: COc1ccc(Oc2ccc(-c3ccn(-c4ccc(Cl)cc4)n3)cc2)cc1

Procedure:
By the same procedure as Example 1, Part C, 4-{4-[1-(4-Chloro-phenyl)-1H-pyrazol-3-yl]-phenoxy}-phenol and 5-bromo-5-(2-methoxyethyl)-pyrimidine-2,4,6-trione (from Preparation 3B) were converted to the title compound. MS m/z: ESI+ 547.1 (M+H)+, ESI− 545.3 (M−H)−.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:23]=[CH:22][C:9]2[N:10]([CH2:20][CH3:21])[C:11](=[O:19])[C:12]([CH3:18])([CH3:17])[C:13](=[O:16])[N:14]([CH3:15])[C:8]=2[CH:7]=1.[I-:24].[Na+].CC(C)=O>O>[CH2:20]([N:10]1[C:11](=[O:19])[C:12]([CH3:18])([CH3:17])[C:13](=[O:16])[N:14]([CH3:15])[C:8]2[CH:7]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][I:24])[CH:23]=[CH:22][C:9]1=2)[CH3:21]
Reactant: [I-]
Reactant: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(OCCCCl)ccc21
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(OCCCI)ccc21
Temperature: 25 °C
Yield: 99.7 %

Procedure:
7-(3-Chloropropoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione (2.18 g) and sodium iodide (4.8 g) were added to acetone (50 ml), and heated under reflux for 8.5 hours. The reaction mixture was cooled to room temperature, water was added, and extraction with ethyl acetate was performed. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1). The purified product was concentrated under reduced pressure to give the title compound (2.76 g) as a colorless oil.
Reaction SMILES: [C:1]([OH:8])(=O)/[CH:2]=[CH:3]\[C:4]([OH:6])=[O:5].Br[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1.O>O1CCCC1>[C:18]1([C:1](=[O:8])[CH:2]=[CH:3][C:4]([OH:6])=[O:5])[C:19]2[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:15]=[CH:16][CH:17]=1
Reactant: Brc1cccc2ccccc12
Reactant: O=C(O)/C=C\C(=O)O
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)C=CC(=O)c1cccc2ccccc12
Temperature: 78 °C
Reaction time: 0.08 h
Yield: 30 %

Procedure:
5.88 g(60 mmol) of dry maleic acid was dissolved in 100 ml of dry tetrahydrofuran and the mixture was cooled down to 78° C. 4.14 g(20 mmol) of 1-bromonaphthalene was dissolved in 100 ml of dry tetrahydrofuran and 13.8 ml of 1.6N n-butyllithium-hexane solution was added thereto at 78° C. This reaction solution was stirred for 5 minutes and then it was added to the dry maleic acid solution prepared in advance using cannula. The resulting mixture was stirred for 10 minutes, and water was added thereto to stop the reaction. The solvent was removed under reduced pressure, and the residue was acidified by 1N aqueous hydrochloric acid solution and extracted with ethyl acetate. The organic layer was washed with water and aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, concentrated under reduced pressure and subjected to column chromatography(eluent: ethyl acetate/hexane=2/1, v/v) to give 1.35 g(6.0 mmol; Yield 30%) of the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([C:8]2[CH:22]=[CH:21][C:11]([O:12][C:13]([CH3:20])([CH3:19])[C:14]([O:16][CH2:17]Cl)=[O:15])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.[I-:25].[Na+]>CC(C)=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([C:8]2[CH:22]=[CH:21][C:11]([O:12][C:13]([CH3:20])([CH3:19])[C:14]([O:16][CH2:17][I:25])=[O:15])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1
Reactant: [I-]
Reactant: CC(C)(Oc1ccc(C(=O)c2ccc(Cl)cc2)cc1)C(=O)OCCl
Agent: [Na+]
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: CC(C)(Oc1ccc(C(=O)c2ccc(Cl)cc2)cc1)C(=O)OCI
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
Chloromethyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoate 1 (3.0 g, 8.2 mmol) was dissolved in acetone (50 mL) at room temperature. Sodium iodide (2.4 g, 16.3 mmol, 2 eq) was added and the clear solution was stirred 10 min at room temperature, then heated to 50° C. for 6 hr. The mixture was cooled to room temperature, diluted with ethyl acetate (200 mL) and filtered. The filtrate was washed with water (3×10 mL) and brine then dried over sodium sulfate. The drying agent was filtered off and the solution was concentrated by rotary evaporation to leave iodomethyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoate 2 as a thick, yellow oil (3.7 g, 99% yield) that was used directly in the next reaction without further purification. 1H-NMR (CDCl3) δ 7.74 (d, 2 H), 7.71 (d, 2 H), 7.45 (d, 2 H), 6.85 (d, 2 H), 5.97, (s, 2 H), 1.67 (s, 6 H) ppm.
Reaction SMILES: CC(P(C(C)(C)C)C1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:10][CH:9]=[CH:8][CH:7]=1)(C)C.C(N(CC)CC)C.[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]#[C:37][P:38](=[O:43])([OH:42])[O:39][CH2:40][CH3:41])=[CH:32][CH:31]=1.C(C1C=CC=CC=1)CCC#C>[Au].ClC(Cl)C>[Cl:29][C:30]1[CH:31]=[CH:32][C:33]([C:36]#[C:37][P:38](=[O:42])([O:43][C:8]([CH2:9][CH2:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH2:7])[O:39][CH2:40][CH3:41])=[CH:34][CH:35]=1
Reactant: CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C
Reactant: CCOP(=O)(O)C#Cc1ccc(Cl)cc1
Agent: [Au]
Agent: C#CCCCc1ccccc1
Solvent: CC(Cl)Cl
Solvent: CCN(CC)CC
Product: C=C(CCCc1ccccc1)OP(=O)(C#Cc1ccc(Cl)cc1)OCC
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 44 %

Procedure:
A gold (Ag(I)) catalyst {[Au(JohnPhos)NCCH3]+SbF6—} [JohnPhos:(2-biphenyl)di-tert-butylphosphine] (11.3 mg, 0.015 mmol) and triethylamine (Et3N) (3.0 mg, 0.03 mmol) were put into a reaction container, and dichloroethane (0.4 mL) was put thereinto. After stirring at room temperature for 5 minutes, ethyl hydrogen (4-chlorophenyl)ethynylphosphonate (73.4 mg, 0.3 mmol) diluted with 0.5 mL of dichloroethane was added thereto, and finally, pent-4-ynylbenzene (86.5 mg, 0.6 mmol) was put thereinto. Then, when all of the starting materials disappeared in the TLC, the reaction was allowed to be completed. After the solvent was removed under low atmospheric pressure, the product was separated by chromatography to obtain ethyl 5-phenylpent-1-en-2-yl 2-(4-chlorophenyl)ethynylphosphonate (51.2 mg, 44%) which is a title compound.
Reaction SMILES: [O-][CH2:2]C.[Na+].C(O)C.CI.[C:10]([NH:15][C:16]([NH2:18])=[S:17])([O:12][CH2:13][CH3:14])=[O:11]>CCOCC>[CH3:2][S:17][C:16](=[NH:18])[NH:15][C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: CCOC(=O)NC(N)=S
Reactant: CC[O-]
Agent: [Na+]
Solvent: CI
Solvent: CCO
Solvent: CCOCC
Product: CCOC(=O)NC(=N)SC
Temperature: 21 °C
Reaction time: 1 h

Procedure:
To a solution of sodium ethoxide in ethanol (made by addition of sodium (0.155 g, 6.7 mmol) to dry ethanol(15 ml)) was added methyl iodide (1.47 ml, 23.6 mmol) followed by N-carbethoxythiourea (1.0 g, 6.7 mmol). The resulting solution was stirred at 21° C. under nitrogen for 1 hr. This was then treated with ether (32 ml) and the resultant precipitate filtered off. The filtrate was evaporated to a clear syrup, which crystallised at 0-4° C. to give the title compound as a white solid (0.815 g).
Reaction SMILES: [N:1]1([CH2:6]/[CH:7]=[CH:8]/[C:9]2[CH:29]=[CH:28][C:12]([C:13]([NH:15][C@@H:16]([CH2:24][CH2:25][S:26][CH3:27])[C:17]([O:19]C(C)(C)C)=[O:18])=[O:14])=[C:11]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[CH:10]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.C(O)(C(F)(F)F)=O>ClCCl>[N:1]1([CH2:6]/[CH:7]=[CH:8]/[C:9]2[CH:29]=[CH:28][C:12]([C:13]([NH:15][C@@H:16]([CH2:24][CH2:25][S:26][CH3:27])[C:17]([OH:19])=[O:18])=[O:14])=[C:11]([C:30]3[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=3)[CH:10]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: CSCC[C@H](NC(=O)c1ccc(/C=C/Cn2ccnc2)cc1-c1ccc(F)cc1)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CSCC[C@H](NC(=O)c1ccc(/C=C/Cn2ccnc2)cc1-c1ccc(F)cc1)C(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 40 %

Procedure:
A solution of tert-butyl (2S)-2-{4-[(E)-3-(imidazol-1-yl)prop-1-en-1-yl]-2-(4-fluorophenyl)benzamido}-4-methylsulfanylbutyrate (0.2 g; 0.4 mmol) in dichloromethane (2 ml) was treated at 0° C. with TFA (2 ml). The mixture was allowed to warm to ambient temperature and stirred for 1 hour. After evaporation of the solvent, the residue was taken up with distilled water (5 ml); the pH was adjusted to 6 with NH4OH and the solution was purified on reverse phase silica eluting with methanol/ammonium carbonate buffer (2 g/l; pH 7) (40/60) to give the title compound after freeze-drying. Yield: 40%
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].[C:9]1([C:15]2[O:16][C:17](=O)[CH2:18][N:19]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.O>C(O)(=O)C>[C:15]([NH:19][CH2:18][C:17]1[S:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[N:1]=1)(=[O:16])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: O=C1CN=C(c2ccccc2)O1
Reactant: Nc1ccccc1S
Solvent: CC(=O)O
Solvent: O
Product: O=C(NCc1nc2ccccc2s1)c1ccccc1
Temperature: 40 °C
Reaction time: 1 h

Procedure:
2-Aminothiophenol (1.2 ml) is added to a solution of 2-phenyl-4,5-dihydro-1,3-oxazol-5-one (1.8 g) in acetic acid (14 ml), and the mixture is stirred for one hour while heating it at 40° C. Water is added to the reaction mixture, and the resulting precipitate is filtered off to give 2-(benzoylaminomethyl)benzothiazole (0.75 g) as crystals.
Reaction SMILES: [CH3:1][Si:2]([CH3:29])([CH3:28])[C:3]1[CH:4]=[C:5]([CH:21]=[C:22]([Si:24]([CH3:27])([CH3:26])[CH3:25])[CH:23]=1)[C:6]([NH:8][C:9]1[CH:19]=[CH:18][C:12]([CH:13]=[CH:14][C:15]([OH:17])=[O:16])=[C:11]([F:20])[CH:10]=1)=[O:7].[H][H]>O1CCCC1.CO.[C].[Pd]>[CH3:27][Si:24]([CH3:25])([CH3:26])[C:22]1[CH:21]=[C:5]([CH:4]=[C:3]([Si:2]([CH3:29])([CH3:28])[CH3:1])[CH:23]=1)[C:6]([NH:8][C:9]1[CH:19]=[CH:18][C:12]([CH2:13][CH2:14][C:15]([OH:17])=[O:16])=[C:11]([F:20])[CH:10]=1)=[O:7]
Reactant: [H][H]
Reactant: C[Si](C)(C)c1cc(C(=O)Nc2ccc(C=CC(=O)O)c(F)c2)cc([Si](C)(C)C)c1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: C[Si](C)(C)c1cc(C(=O)Nc2ccc(CCC(=O)O)c(F)c2)cc([Si](C)(C)C)c1
Yield: 75.9 %

Procedure:
Compound 2 (160 mg) was dissolved in a mixed solution of tetrahydrofuran (0.59 ml) and methanol (0.59 ml). Palladium carbon (4.4 mg) was added thereto, and the mixture was stirred in a hydrogen atmosphere for 4.5 hours. After the reaction was over, the reaction mixture was filtered through Celite. The filtrate was condensed and recrystallized with dichloromethane and n-hexane to obtain Compound 7 (122 mg, 76%) as a white solid.
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]([O:20][CH2:21][CH2:22]Br)([C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:13])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:24]1(=[O:34])[NH:28][C:27](=[O:29])[C:26]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:25]12.[K]>CN(C=O)C>[C:24]1(=[O:34])[N:28]([CH2:2][CH2:3][O:4][C:5]([O:20][CH2:21][CH2:22][N:28]2[C:27](=[O:29])[C:26]3=[CH:30][CH:31]=[CH:32][CH:33]=[C:25]3[C:24]2=[O:34])([C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:13])[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:27](=[O:29])[C:26]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:25]12
Reactant: O=C1NC(=O)c2ccccc21
Reactant: O=C(c1ccccc1)C(OCCBr)(OCCBr)c1ccccc1
Agent: [K]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCOC(OCCN1C(=O)c2ccccc2C1=O)(C(=O)c1ccccc1)c1ccccc1
Temperature: 0 °C
Yield: 96.4 %

Procedure:
Benzil-di(β-bromoethyl)ketal (8.84 g) and 7.4 g of potassium phthalimide were dissolved in 50 ml of DMF, and reacted at 50° to 60° C. for 6 hours. When the reaction mixture was poured into 100 ml of ice water, white crystals formed. The crystals were collected by filtration, well washed with water, and dried to give 11 g of benzil-di(β-phthalimidoethyl)ketal in a yield of 96%. Recrystallization from a mixture of ethanol and chloroform afforded crystals having a melting point of 132° to 134° C. The product is referred to as initiator 2.