Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH2:2][O:3][C:4]([CH:6]1[C:10](=[O:11])[CH2:9][CH2:8][CH2:7]1)=[O:5].[C:12]1([C:14](=[CH:16][CH:17]=[CH:18][CH:19]=1)O)[OH:13].C1(C)C=CC(S(O)(=O)=O)=CC=1.C1C=CC=CC=1>O>[C:10]12([O:13][C:12]3[CH:14]=[CH:16][CH:17]=[CH:18][C:19]=3[O:11]1)[CH2:9][CH2:8][CH2:7][CH:6]2[C:4]([O:3][CH2:2][CH3:1])=[O:5]
Reactant: CCOC(=O)C1CCCC1=O
Reactant: Oc1ccccc1O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Solvent: O
Product: CCOC(=O)C1CCCC12Oc1ccccc1O2

Procedure:
A mixture of 15.7 g. of ethyl cyclopentanone-2-carboxylate, 11 g. of pyrocatechol, 0.5 g. of p-toluenesulphochloride and 0.5g. of p-toluenesulphonic acid in 100 cc. of anhydrous benzene is refluxed until the theoretical amount of water no longer distils azeotropically. The mixture is washed first with dilute NaOH and then with H2O until neutral. After drying with Na2SO4 the solvent is removed under vacuum. The residual oil is fractionated, and the desired product boils at 136°-139°C./0.3 mm.
Reaction SMILES: C1(CNCC2C=C(C3C=[C:15]4[C:19](=[C:20](C(N)=O)C=3)[NH:18][CH:17]=[C:16]4C3CCN(S(CC)(=O)=O)CC3)C=NC=2)CC1.[CH3:36][C:37]1([CH3:52])[C:41]([CH3:43])([CH3:42])[O:40][B:39]([C:44]2[CH:45]=[C:46]([CH:50]=O)[CH:47]=[N:48][CH:49]=2)[O:38]1.CC1CCCN1.[BH3-]C#N.[Na+]>>[CH3:20][CH:19]1[CH2:15][CH2:16][CH2:17][N:18]1[CH2:50][C:46]1[CH:47]=[N:48][CH:49]=[C:44]([B:39]2[O:38][C:37]([CH3:52])([CH3:36])[C:41]([CH3:43])([CH3:42])[O:40]2)[CH:45]=1
Reactant: CC1(C)OB(c2cncc(C=O)c2)OC1(C)C
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cncc(CNCC5CC5)c4)cc23)CC1
Agent: CC1CCCN1
Agent: [BH3-]C#N
Agent: [Na+]
Product: CC1CCCN1Cc1cncc(B2OC(C)(C)C(C)(C)O2)c1

Procedure:
Following the general procedure of 5-(5-{[(cyclopropylmethyl)amino]methyl}-3-pyridinyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide, 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinecarbaldehyde (30 mg, 0.129 mmol), 2-methylpyrrolidine (0.013 mL, 0.129 mmol), and NaCNBH3 (16 mg, 0.258 mmol) were reacted to give 25 mg of crude 3-[(2-methyl-1-pyrrolidinyl)methyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine. The crude 3-[(2-methyl-1-pyrrolidinyl)methyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine was then reacted with 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (30 mg, 0.0723 mmol), potassium carbonate (60 mg, 0.434 mmol), and chloro-2-(dimethylaminomethyl)-ferrocen-1-yl-(dinorbornylphosphine)palladium(II) (4.4 mg, 0.00723 mmol) to give 6 mg of the title compound (16%).
Reaction SMILES: [N+:1]([C:4]1[C:5]([C:13]([O:15][CH3:16])=[O:14])=[N:6][NH:7][C:8]=1[C:9]([O:11][CH3:12])=[O:10])([O-:3])=[O:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:36]([O:39][CH2:40][CH2:41]O)([CH3:38])[CH3:37].N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH:36]([O:39][CH2:40][CH2:41][N:7]1[C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:4]([N+:1]([O-:3])=[O:2])[C:5]([C:13]([O:15][CH3:16])=[O:14])=[N:6]1)([CH3:38])[CH3:37]
Reactant: COC(=O)c1n[nH]c(C(=O)OC)c1[N+](=O)[O-]
Reactant: CC(C)OCCO
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)c1nn(CCOC(C)C)c(C(=O)OC)c1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Dimethyl 4-nitro-1H-pyrazole-3,5-dicarboxylate (11.4 g, 50 mmol) was dissolved in tetrahydrofuran (200 mL) and the solution treated with triphenylphosphine (14.4 g, 55 mmol) and 2-isopropoxyethanol (6.36 mL, 55 mmol). The mixture was cooled on an ice bath to 0° C. and diisopropyl azodicarboxylate (10.8 mL, 55 mmol) added dropwise over 10 minutes, keeping the temperature between 20° C. and 30° C. The reaction mixture was then stirred at room temperature for 30 minutes. The reaction mixture was concentrated in vacuo and the crude product azeotroped with dichloromethane to yield the title product. 1H NMR (CDCl3, 400 MHz) δ: 1.02 (d, 6H), 3.45 (m, 1H), 3.72 (t, 2H), 3.90 (s, 3H), 3.94 (s, 3H), 4.74 (t, 2H). MS ES+ m/z 216 [MH]+
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.ClC1C=CC=CC=1.Cl[C:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[S:17][N:16]=1>C(O)CO>[N:1]1([C:15]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[S:17][N:16]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1
Reactant: Clc1nsc2ccccc12
Reactant: C1CNCCN1
Solvent: OCCO
Solvent: Clc1ccccc1
Product: c1ccc2c(N3CCNCC3)nsc2c1
Yield: 92.3 %

Procedure:
215.4 g (2.50 mol) of piperazine, 50.0 g of chlorobenzene, 100.0 g of ethylene glycol were placed in a four-neck 1000 ml flask equipped with a stirrer, a thermometer, a dropping funnel and a condenser, 169.5 g (1.00 mol) of 3-chloro-1,2-benzisothiazole was added dropwise in the melted state at about 120° C. over 1 hour while stirring, which was thereafter stirred for 2 hours to complete the reaction. After excess piperazine was removed with water, the reaction mixture was made acidic with hydrochloric acid, extracted into an aqueous layer, which was made alkaline with aqueous sodium hydroxide to obtain 202.4 g (m.p. 89-90° C.) of 3-(1-piperazinyl)-1,2-benzisothiazole as crystals. Yield from 3-chloro-1,2-benzisothiazole was 92.4%.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[N:11]([CH2:35][CH2:36][OH:37])[N:12]=[C:13]3[C:22]4[C:17](=[C:18]([O:23][CH2:24][C:25]5[C:30]([CH3:31])=[CH:29][C:28]([CH3:32])=[CH:27][C:26]=5[CH3:33])[CH:19]=[CH:20][CH:21]=4)[C:16](=[O:34])[C:15]=1[C:14]=23.ClC1C=CC2N(CCO)N=C3C4C(=CC=CC=4OCC4C(C)=CC(C)=CC=4C)C(=O)C=1C=23>>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[N:11]([CH2:35][CH2:36][O:37][S:2]([CH3:1])(=[O:4])=[O:3])[N:12]=[C:13]3[C:22]4[C:17](=[C:18]([O:23][CH2:24][C:25]5[C:30]([CH3:31])=[CH:29][C:28]([CH3:32])=[CH:27][C:26]=5[CH3:33])[CH:19]=[CH:20][CH:21]=4)[C:16](=[O:34])[C:15]=1[C:14]=23
Reactant: Cc1cc(C)c(COc2cccc3c2C(=O)c2c(Cl)ccc4c2c-3nn4CCO)c(C)c1
Reactant: CS(=O)(=O)Cl
Agent: Cc1cc(C)c(COc2cccc3c2-c2nn(CCO)c4ccc(Cl)c(c24)C3=O)c(C)c1
Product: Cc1cc(C)c(COc2cccc3c2C(=O)c2c(Cl)ccc4c2c-3nn4CCOS(C)(=O)=O)c(C)c1

Procedure:
Starting with methanesulfonyl chloride and the mixture of regioisomers of 5-chloro-2-(2-hydroxyethyl)-7-[(2,4,6-trimethylphenyl)methoxy]anthra-[1,9cd]pyrazol-6-(2H)-one II and 5-chloro-2-(2-hydroxyethyl)-10-[(2,4,6-trimethylphenyl) methoxy]anthra-[1,9-cd]pyrazol-6(2H)-one III, usiong the procedure of example 3, the title compound was prepared.
Reaction SMILES: [F:1][CH:2]([F:25])[C:3]1[CH:4]=[CH:5][C:6]([F:24])=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15]O)=[CH:11][C:10]=2[C:17]2[C:21]([CH3:23])([CH3:22])[CH2:20][CH2:19][CH:18]=2)[CH:8]=1.S(Cl)([Cl:28])=O>C(Cl)Cl.CN(C=O)C>[Cl:28][CH2:15][C:12]1[CH:13]=[CH:14][C:9]([C:7]2[CH:8]=[C:3]([CH:2]([F:25])[F:1])[CH:4]=[CH:5][C:6]=2[F:24])=[C:10]([C:17]2[C:21]([CH3:23])([CH3:22])[CH2:20][CH2:19][CH:18]=2)[CH:11]=1
Reactant: CC1(C)CCC=C1c1cc(CO)ccc1-c1cc(C(F)F)ccc1F
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC1(C)CCC=C1c1cc(CCl)ccc1-c1cc(C(F)F)ccc1F
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 98 %

Procedure:
To a solution of T26.3 (0.1666 g, 0.481 mmol) in dry DCM (3 mL) and dry DMF (0.06 mL) was added thionyl chloride (0.07 mL, 0.96 mmol) at 0° C. The resulting solution was warmed to room temperature and monitored with TLC and LCMS. After 45 minutes, the reaction was concentrated and then purified by silica gel flash chromatography (0-5% EtOAc/hexane) to afford T26 (172.1 mg, 98% yield). 1H NMR (500 MHz, CDCl3) δ ppm 7.46 (2H, m), 7.39 (1H, m), 7.33 (1H, m), 7.28 (1H, d, J=1.7 Hz), 7.17 (1H, m), 6.62 (1H, t), 5.51 (1H, td, J=2.3, 1.0 Hz), 4.64 (2H, s), 2.24 (2H, td, J=7.1, 2.4 Hz), 1.68 (2H, m), 0.85 (6H, s).
Reaction SMILES: O.NN.[C:4]([C:8]1[CH:35]=[CH:34][C:11]([CH2:12][N:13]2[C:21]3[C:16](=[CH:17][C:18]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=4)=[CH:19][CH:20]=3)[C:15]([C:29](=O)[C:30]([OH:32])=[O:31])=[CH:14]2)=[CH:10][CH:9]=1)([CH3:7])([CH3:6])[CH3:5].C[O-].[Na+]>COCCO>[C:4]([C:8]1[CH:35]=[CH:34][C:11]([CH2:12][N:13]2[C:21]3[C:16](=[CH:17][C:18]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=4)=[CH:19][CH:20]=3)[C:15]([CH2:29][C:30]([OH:32])=[O:31])=[CH:14]2)=[CH:10][CH:9]=1)([CH3:7])([CH3:5])[CH3:6]
Reactant: Cc1cccc(-c2ccc3c(c2)c(C(=O)C(=O)O)cn3Cc2ccc(C(C)(C)C)cc2)c1
Agent: C[O-]
Agent: NN
Agent: [Na+]
Solvent: COCCO
Solvent: O
Product: Cc1cccc(-c2ccc3c(c2)c(CC(=O)O)cn3Cc2ccc(C(C)(C)C)cc2)c1
Temperature: 60 °C
Reaction time: 1 h
Yield: 46.7 %

Procedure:
Hydrazine monohydrate (0.56 mL, 11.75 mmol) was added to a stirring solution of 2-[1-[4-(tert-Butyl)benzyl]-5-(3-methylphenyl)-1H-indol-3-yl]-2-oxoacetic acid (WAY-201417, 1.0 g, 2.35 mmol) in 2-methoxyethanol (10 mL). After the mixture was heated to 60° C. Sodium methoxide (1.34 g, 23.5 mmol) was added portionwise to the mixture. The reaction mixture was then slowly heated to 150° C., and concentrated. The mixture was kept stirring at 150° C. for 1 hour. The reaction mixture was cooled and poured onto ice water (100 mL). The aqueous mixture was extracted with methylene chloride and acidified with concentrated hydrocloric acid at 0° C. The organic extracts were washed with water and brine. Evaporation of the solvent and purification by flash column chromatography (5% methanol in methylene chloride) afforded an orange solid (0.452 g), m.p. 91-92° C. Mass spectrum [+ESI, (M+H)+] m/z 412. 1H NMR (400 MHz, DMSO-d6) δ 12.00 (br s, 1H), 7.75 (s, 1H), 7.51 (d, 1H, J=8.55 Hz), 7.45 (s, 1H), 7.42-7.37 (m, 3H), 7.32-7.29 (m, 3H), 7.15 (d, 2H, J=8.25 Hz), 7.19 (d, 1H, J=7.48 Hz), 5.34 (s, 2H), 3.70 (s, 2H), 2.37 (s, 3H), and 1.22 ppm (s, 9H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[CH2:4][C:5]1[CH:10]=[C:9]([OH:11])[CH:8]=[C:7]([Cl:12])[CH:6]=1.F[C:15]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][C:16]=1[CH:17]=[O:18].C(=O)([O-])[O-].[K+].[K+].Cl>O1CCOCC1.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:13])[CH2:4][C:5]1[CH:10]=[C:9]([O:11][C:15]2[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][C:16]=2[CH:17]=[O:18])[CH:8]=[C:7]([Cl:12])[CH:6]=1
Reactant: COC(=O)Cc1cc(O)cc(Cl)c1
Reactant: O=Cc1cc([N+](=O)[O-])ccc1F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COC(=O)Cc1cc(Cl)cc(Oc2ccc([N+](=O)[O-])cc2C=O)c1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
(3-Chloro-5-hydroxy-phenyl)-acetic acid methyl ester (2.9 g, 14.5 mmol), 2-fluoro-5-nitrobenzaldehyde (2.7 g, 15.9 mmol), and potassium carbonate (4.0 g, 28.9 mmol) were combined in 1,4-dioxane (20 mL) and stirred at 100° C. overnight. Once no starting material was seen by analyical LCMS and tlc, the mixture was worked up with EtOAc and 10% aqueous HCl, and the crude material was purified by silica gel chromatography to give the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7]/[C:8]/2=[C:11](/[C:17]#[N:18])\C(OCC)=O)=[CH:4][CH:3]=1.[C-:19]#[N:20].[K+]>C(O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][C:8]2([CH2:11][C:17]#[N:18])[C:19]#[N:20])=[CH:4][CH:3]=1
Reactant: CCOC(=O)/C(C#N)=C1\CCc2ccc(Cl)cc21
Reactant: [C-]#N
Agent: [K+]
Solvent: O
Solvent: CCO
Product: N#CCC1(C#N)CCc2ccc(Cl)cc21
Temperature: 65 °C
Reaction time: 16 h
Yield: 35.4 %

Procedure:
A solution of (E)-ethyl 2-cyano-2-(6-chloro-2,3-dihydro-1H-inden-1-ylidene)acetate (Prep38, 15.00 g, 0.06 mol) in ethanol (300 ml) was treated with a solution of KCN (9.75 g, 0.15 mol) in water (90 ml). The mixture was warmed to 65° C., and stirred for 16 h. The mixture was concentrated in vacuo to remove solvent. The residue was extracted with EA (100 ml×3). The organic layers were combined and washed with a saturated solution of NaHCO3, brine and dried over Na2SO4. The crude was purified by FC (P:E=10/1) to obtain the title compound (4.60 g, y=37.1%).
Reaction SMILES: B([O-])([O-])O[C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH3:11])=[C:5]([F:12])[CH:4]=1.Br[C:16]1[CH:17]=[CH:18][C:19]2[N:25]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH2:23][C:22]([C:33]([O:35][CH3:36])=[O:34])=[CH:21][C:20]=2[CH:37]=1.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:29]([O:28][C:26]([N:25]1[C:19]2[CH:18]=[CH:17][C:16]([C:3]3[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH3:11])=[C:5]([F:12])[CH:4]=3)=[CH:37][C:20]=2[CH:21]=[C:22]([C:33]([O:35][CH3:36])=[O:34])[CH2:23][CH2:24]1)=[O:27])([CH3:32])([CH3:31])[CH3:30]
Reactant: COC(=O)C1=Cc2cc(Br)ccc2N(C(=O)OC(C)(C)C)CC1
Reactant: CCOc1ccc(OB([O-])[O-])cc1F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: CCOc1ccc(-c2ccc3c(c2)C=C(C(=O)OC)CCN3C(=O)OC(C)(C)C)cc1F
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
In a mixture of water:ethanol toluene (1:1:10, v/v, 42.0 ml) were dissolved 4-ethoxy-3-fluorophenyl borate (754 mg) and methyl 7-bromo-1-(t-butoxycarbonyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate (1305 mg). To the solution was added potassium carbonate (1132 mg), and the mixture was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (158 mg), and the mixture was heated to reflux under argon atmosphere for 10 hours. The mixture was diluted with ethyl acetate, and washed with water and saturated brine, and the organic layer was dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with silica gel column chromatography (75 g, hexane:ethyl acetate=4:1) to give methyl 1-(t-butoxycarbonyl)-7-(4-ethoxy-3-fluorophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate as yellow amorphous. The obtained methyl 1-(t-butoxycarbonyl)-7-(4-ethoxy-3-fluorophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate was dissolved in ethyl acetate (80 ml). To the solution was added 1N hydrochloric acid (15 ml) at room temperature, and the mixture was stirred at 100° C. for 1 hour and neutralized with 1N sodium hydroxide and saturated sodium hydrogen carbonate solution. To the mixture was added ethyl acetate, and the separated organic layer was washed with saturated sodium hydrogen carbonate solution, water and saturated brine, and dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with silica gel column chromatography (50 g, hexane:ethyl acetate=9:1→4:1→2:1) to give methyl 7-(4-ethoxy-3-fluorophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate (1007 mg, 86%) as yellow crystals.
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH:11]3[CH2:13][CH:8]2[CH2:9][NH:10]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2-].[Na+].Br[CH2:17][CH2:18][CH2:19][Cl:20]>C1(C)C=CC=CC=1>[Cl:20][CH2:19][CH2:18][CH2:17][N:10]1[CH2:9][CH:8]2[CH2:13][CH:11]1[CH2:12][N:7]2[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: c1ccc(N2CC3CC2CN3)cc1
Reactant: ClCCCBr
Agent: [NH2-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: ClCCCN1CC2CC1CN2c1ccccc1

Procedure:
129 (1.0 g, 5.7 mmoles), 0.23 g (5.7 mmoles) of sodium amide and 20 mL of toluene are refluxed for 1 hour. After that, 0.93 g (5.7 mmoles) of 1-bromo-3-chloropropane in 10 mL of toluene are added dropwise over a period of 20 minutes and refluxed for 2 hours. After cooling, the reaction mixture is extracted with 2N HCl (2×50 mL) and the aqueous phase made alkaline with 30% sodium hydroxide and extracted with toluene (3×40 mL). Evaporation and bulb tube evaporation (boiling point at 0.05 mbar: 120°-130° C.) resulted in 0.97 g (70.4% of the theoretical yield) of 136 as a colorless oil.
Reaction SMILES: [I:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[CH:4][CH:3]=1.[CH3:10][C:11]1([OH:17])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1>ClCCl.C(O)C>[I:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:14]2[CH2:15][CH2:16][C:11]([CH3:10])([OH:17])[CH2:12][CH2:13]2)=[CH:4][CH:3]=1
Reactant: BrCc1ccc(I)cc1
Reactant: CC1(O)CCNCC1
Solvent: CCO
Solvent: ClCCl
Product: CC1(O)CCN(Cc2ccc(I)cc2)CC1

Procedure:
Prepared analogously to Example 1.1.c. from 4-iodobenzyl bromide and 4-methylpiperidin-4-ol. Yield: 0.22 g (30% of theory); C13H18INO (M=331.19); calc.: molecular ion peak (M+H)+: 332; found: molecular ion peak (M+H)+: 332; Rf value: 0.45 (silica gel, dichloromethane/ethanol (20:1)).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[CH2:14][CH2:13][C:12]([CH3:16])([CH3:15])[CH2:11][CH:10]=2)[CH:3]=1.[K+].[C:18]([C:20]1[N:21]=[C:22]([C:33]([O-])=[O:34])[N:23]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:24]=1)#[N:19].CCN(C(C)C)C(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:33]([C:22]2[N:23]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:24]=[C:20]([C:18]#[N:19])[N:21]=2)=[O:34])=[C:4]([C:9]2[CH2:14][CH2:13][C:12]([CH3:16])([CH3:15])[CH2:11][CH:10]=2)[CH:3]=1
Reactant: C[Si](C)(C)CCOCn1cc(C#N)nc1C(=O)[O-]
Reactant: CC1(C)CC=C(c2cc(Br)ccc2N)CC1
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Agent: [K+]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC1(C)CC=C(c2cc(Br)ccc2NC(=O)c2nc(C#N)cn2COCC[Si](C)(C)C)CC1
Temperature: 25 °C
Reaction time: 10 h
Yield: 85.8 %

Procedure:
To a suspension of 4-bromo-2-(4,4-dimethyl-cyclohex-1-enyl)-phenylamine (0.640 g, 2.29 mmol) (prepared in the previous step) and 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt (0.700 g, 2.30 mmol) (prepared in this example, step (d)) in DCM (12 mL) was added DIPEA (0.800 mL, 4.60 mmol) and PyBroP (1.29 g, 2.76 mmol) and the mixture allowed to stir at RT for 10 h. The mixture was diluted with DCM (50 mL) and washed with NaHCO3 (2×50 mL) and the organic layer dried over Na2SO4 and concentrated. The title compound was eluted from a 20-g SPE with 1:1 DCM/hexanes to give 1.04 g (86%) of the title compound as a white solid. Mass spectrum (ESI, m/z): Calcd. for C25H33BrN4O2Si, 529.1 (M+H), found 529.1.
Reaction SMILES: [C:1]([O:5][CH2:6][CH3:7])(=[O:4])[C:2]#[CH:3].[N+:8]([C:11]1[CH:30]=[CH:29][C:14]([CH2:15][O:16][C:17]([N:19]2[CH2:27][CH2:26][N+:25]3[C-:21](C(=O)O[N:24]=3)[CH2:20]2)=[O:18])=[CH:13][CH:12]=1)([O-:10])=[O:9]>CC1C=CC=CC=1C>[N+:8]([C:11]1[CH:12]=[CH:13][C:14]([CH2:15][O:16][C:17]([N:19]2[CH2:27][CH2:26][N:25]3[N:24]=[C:2]([C:1]([O:5][CH2:6][CH3:7])=[O:4])[CH:3]=[C:21]3[CH2:20]2)=[O:18])=[CH:29][CH:30]=1)([O-:10])=[O:9]
Reactant: O=C(OCc1ccc([N+](=O)[O-])cc1)N1CC[n+]2noc(=O)[c-]2C1
Reactant: C#CC(=O)OCC
Solvent: Cc1ccccc1C
Product: CCOC(=O)c1cc2n(n1)CCN(C(=O)OCc1ccc([N+](=O)[O-])cc1)C2

Procedure:
ethyl propiolate (cont. 99%)(8.28 g) was added to the o-xylene (348 mL) solution of 5-(4-nitrobenzyloxycarbonyl)-3-oxo-3a,4,6,7-tetrahydro-3H-2-oxa-1,5-diaza-7a-azoniainden-3a-ide (22.3 g) under a nitrogen atmosphere and refluxed for 16 h. The solution was concentrated under reduced pressure, followed by silica-gel column chromatography 3 times (n-hexane/AcOEt=2/1–1/3). The titled compound was obtained as pale yellow crystals (16.78 g, 64%). Besides, 6,7-dihydro-4H-pyrazolo[1,5-a]pyrazine-3,5-dicarboxylic acid 3-ethyl ester 5-(4-nitrobenzyl) ester was obtained as pale yellow crystals (6.18 g, 24%).
Reaction SMILES: C(O[C:4]([C:6]1[C:7]([OH:28])=[C:8]2[C:16]([Cl:17])=[C:15]([Cl:18])[N:14]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[C:22]([F:27])[CH:21]=3)[C:9]2=[C:10]([C:12]#[N:13])[N:11]=1)=[O:5])C.[NH2:29][CH2:30][C:31]([OH:33])=[O:32].C[O-].[Na+].CO>>[Cl:18][C:15]1[N:14]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[C:22]([F:27])[CH:21]=2)[C:9]2=[C:10]([C:12]#[N:13])[N:11]=[C:6]([C:4]([NH:29][CH2:30][C:31]([OH:33])=[O:32])=[O:5])[C:7]([OH:28])=[C:8]2[C:16]=1[Cl:17]
Reactant: NCC(=O)O
Reactant: CCOC(=O)c1nc(C#N)c2c(c1O)c(Cl)c(Cl)n2Cc1ccc(F)c(F)c1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: N#Cc1nc(C(=O)NCC(=O)O)c(O)c2c(Cl)c(Cl)n(Cc3ccc(F)c(F)c3)c12

Procedure:
Prepared in analogy to that of Example 1(e) from 2,3-dichloro-7-cyano-1-(3,4-difluoro-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester, glycine and NaOMe/HOMe. The title compound, ESI MS (m/z): 455 (M+H)+.
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][C:4]([N:7]=[N:8][C:9]2[CH:10]=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=2)=[CH:5][CH:6]=1.CCC(C(N)=O)(C(N)=O)C1C=CC=CC=1>>[CH:1]1[CH:2]=[CH:3][C:4]([NH:7][N:8]=[C:9]2[CH:10]=[CH:11][C:12](=[O:15])[CH:13]=[CH:14]2)=[CH:5][CH:6]=1
Reactant: Oc1ccc(N=Nc2ccccc2)cc1
Agent: CCC(C(N)=O)(C(N)=O)c1ccccc1
Product: O=C1C=CC(=NNc2ccccc2)C=C1

Procedure:
4-Phenylazophenol, [Solvent Yellow 7 (SY7)], a conventional yellow dye obtained from Aldrich Chemical Company in the amount of 10.3 mg was dissolved into a 10.01 g solution of monomers containing 66% PEA, 30.5% PEMA, and 3.3% BDDA by weight respectively giving a SY7 concentration of 0.103 wt %. After dissolving the SY7 into the monomer solution 52.3 mg of bis(4-tert-butylcyclohexylperoxy dicarbonate (Perkadox-16, AZKO Corp.) was added as the polymerization iniator (catalyst). One mm thick sheets were made by placing the SY7 monomer solution via syringe into a mold formed between two glass plates and a 1 mm Teflon gasket. The glass plates were held together with metal clips. Polymerization was effected by placing the mold into a 65° C. oven and curing for 17 hours. The temperature of the oven was raised to 100° C. and the mold heated for 3 hours to effect post-cure of the sheetstock. Approximately 1×2 cm. rectangles were cut from the sheet and the UV/visible measurements performed. The curve exhibited a strong attentuation of the short wavelengths of visible light in the 400 to 500 nm blue light region of the spectrum yielding a 50% transmission level at 473 nm. The rectangular samples were placed into individual tissue capsules and soxhlet extracted in acetone followed by drying in air then under vacuum at 50° C. Afterwards UV/visible measurements were performed again. The UV/visible transmission and absorption spectra were measured both before and after soxhlet extraction and drying. From the absorbance of the samples, at appropiate wavelengths between 400 and 500 rim, the percentage of the dye which is removed by soxhlet extraction was found to be 84%.
Reaction SMILES: [OH-:1].[Na+].O.[C:4]([S:8][CH2:9][C:10]1([CH3:17])[NH:14][C:13](=[O:15])[NH:12][C:11]1=[O:16])([CH3:7])([CH3:6])[CH3:5]>C(#N)C>[C:13]([NH:14][C@:10]([CH3:17])([C:11]([OH:1])=[O:16])[CH2:9][S:8][C:4]([CH3:7])([CH3:6])[CH3:5])(=[O:15])[NH2:12]
Reactant: [OH-]
Reactant: CC(C)(C)SCC1(C)NC(=O)NC1=O
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: CC(C)(C)SC[C@](C)(NC(N)=O)C(=O)O

Procedure:
First, sodium hydroxide and water were added to 5-tert-butylthiomethyl-5-methylhydantoin, and the resultant mixture was heated to a predetermined temperature and stirred. The reaction solution was analyzed by HPLC (column: COSMOSIL 5C18-AR (produced by Nacalai Tesque Inc.), mobile phase: acetonitrile/10 mM aqueous potassium dihydrogen phosphate solution=30/70, flow rate: 1.0 ml/min, detection wavelength: 210 nm, column temperature: 40° C.) to determine the yield of the title compound. The results are shown in Table 1.
Reaction SMILES: [N:1]([CH2:4][CH2:5][NH:6]C(=O)CCCCCCCCCCCCC)=[N+:2]=[N-:3].[CH3:22][C:23]1[C:28]([CH3:29])=[C:27]([CH3:30])[C:26]([CH3:31])=[C:25]([CH3:32])[C:24]=1[S:33](Cl)(=[O:35])=[O:34].N(CCN)=[N+]=[N-].C(N(CC)CC)C>ClCCl>[N:1]([CH2:4][CH2:5][NH:6][S:33]([C:24]1[C:23]([CH3:22])=[C:28]([CH3:29])[C:27]([CH3:30])=[C:26]([CH3:31])[C:25]=1[CH3:32])(=[O:35])=[O:34])=[N+:2]=[N-:3]
Reactant: CCCCCCCCCCCCCC(=O)NCCN=[N+]=[N-]
Reactant: Cc1c(C)c(C)c(S(=O)(=O)Cl)c(C)c1C
Agent: [N-]=[N+]=NCCN
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1c(C)c(C)c(S(=O)(=O)NCCN=[N+]=[N-])c(C)c1C
Yield: 81 %

Procedure:
As in the synthesis of N-(2-azidoethyl)tetradecanamide, 2,3,4,5,6-pentamethylbenzene-1-sulfonyl chloride (0.304 g, 1.23 mmol) was reacted with 2-azidoethanamine (0.106 g, 1.23 mmol) and triethylamine (0.249 g, 2.46 mmol) in dichloromethane (5 mL) to give N-(2-azidoethyl)-2,3,4,5,6-pentamethylbenzenesulfonamide (0.296 g, 81%). 1H NMR (300 MHz, CDCl3) δ 5.12 (t, 1H) δ 3.35 (t, 2H), δ 3.05 (q, 2H), 2.59 (s, 6H), δ 2.28 (s, 3H), 2.24 (s, 6H) ppm; 13C NMR (75 MHz, CDCl3) δ 139.9, 136.1, 135.2, 134.2, 51.1, 42.3, 19.2, 17.9, 17.3 ppm; HRMS (ESI) calcd for C13H20N4O2S (M+) 296.1307. found 296.1304.