Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].[O:5]=[C:6]1[C:11]2[CH:12]=[CH:13]O[C:10]=2[CH2:9][CH2:8][CH2:7]1.C(OC(C)C)(C)C>C(O)C>[O:5]=[C:6]1[CH2:7][CH2:8][CH2:9][C:10]2[N:4]([CH2:3][CH2:1][OH:2])[CH:13]=[CH:12][C:11]1=2
Reactant: NCCO
Reactant: O=C1CCCc2occc21
Solvent: CCO
Solvent: CC(C)OC(C)C
Product: O=C1CCCc2c1ccn2CCO
Temperature: 130 °C
Yield: 83.8 %

Procedure:
80 g of ethanolamine were added to a solution of 136 g of 4-oxo-4,5,6,7-tetrahydrobenzofuran in 250 cm3 of ethanol. The solution was heated at 130° C. for 6 hours. After allowing the reaction mixture to return to room temperature with stirring, the mixture was poured over a mixture of 800 cm3 of isopropyl ether and 200 cm3 of petroleum ether. A product crystallized with stirring, and then it was drained, washed with petroleum ether and dried under vacuum over phosphorus pentoxide. 160 g of the expected product was recovered, which product was recrystallized from 240 cm3 of isopropanol. 150 g of the expected product was obtained whose melting point ranged from 96° to 97° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[C@H:13]([S:22][CH3:23])[CH2:14][CH2:15][C@H:16]([C:18]([O:20]C)=[O:19])[CH2:17][C:11]=3[O:10][N:9]=2)=[CH:4][CH:3]=1.[OH-].[Na+].O>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[C@H:13]([S:22][CH3:23])[CH2:14][CH2:15][C@H:16]([C:18]([OH:20])=[O:19])[CH2:17][C:11]=3[O:10][N:9]=2)=[CH:4][CH:3]=1
Reactant: COC(=O)[C@H]1CC[C@@H](SC)c2c(-c3ccc(Cl)cc3)noc2C1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CS[C@@H]1CC[C@H](C(=O)O)Cc2onc(-c3ccc(Cl)cc3)c21
Temperature: 25 °C
Reaction time: 1 h
Yield: 63.6 %

Procedure:
0.024 g (0.068 mmol) of methyl cis-3-(4-chlorophenyl)-5,6,7,8-tetrahydro-4-methylthio-4H-cyclohept[d]isoxazole-7-carboxylate was stirred in 5 ml of dioxane and 2 ml of 1N aqueous sodium hydroxide solution were added. The mixture was stirred at room temperature for 1 hour. Water was then added and the solution was partially evaporated. The aqueous solution was acidified with 1N hydrochloric acid and the precipitate was collected, washed with water and dried to give 0.0146 g of cis-3-(4-chlorophenyl)-5,6,7,8-tetrahydro-4-methylthio-4H-cyclohept[d]isoxazole7-carboxylic acid of melting point 241°-242° C.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][N:7]1[C:19]2[C:18]3[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=3[N:12]=[C:11]([NH2:20])[C:10]=2[N:9]=[C:8]1[CH2:21][CH2:22][O:23][CH3:24].CCN(CC)CC.[C:32](Cl)(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.CCOCC>C(Cl)Cl.CO>[NH2:20][C:11]1[C:10]2[N:9]=[C:8]([CH2:21][CH2:22][O:23][CH3:24])[N:7]([CH2:6][CH2:5][O:4][CH2:3][CH2:2][NH:1][C:32](=[O:39])[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:19]=2[C:18]2[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=2[N:12]=1
Reactant: COCCc1nc2c(N)nc3c(c2n1CCOCCN)CCCC3
Reactant: O=C(Cl)c1ccccc1
Solvent: CCOCC
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COCCc1nc2c(N)nc3c(c2n1CCOCCNC(=O)c1ccccc1)CCCC3
Temperature: 0 °C
Yield: 36.3 %

Procedure:
1-[2-(2-Aminoethoxy)ethyl]-2-(2-methoxyethyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine (1.00 g, 3.00 mmol) was dissolved in 30 mL of anhydrous CH2Cl2 and cooled to 0° C. under N2. To the stirred solution were added Et3N (0.84 mL, 6.00 mmol) and benzoyl chloride (348 μL, 3.00 mmol) and the reaction was allowed to warm to room temperature overnight. The reaction mixture was then quenched by addition of saturated NaHCO3 solution (30 mL). The organic layer was separated and washed with H2O and brine, dried over Na2SO4 and concentrated under reduced pressure to give a yellow oil. The oil was dissolved in a minimum amount of hot MeOH and then treated with Et2O (50 mL) which caused a white percipitate to form. The solid was isolated by filtration and dried under vacuum to give 476 mg of N-(2-{2-[4-amino-2-(2-methoxyethyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl]ethoxy}ethyl)benzamide as a white powder. m.p. 141-143° C.;
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@H:13]([CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[O:12][C@@H:11]([N:23]2[C:33]3[N:32]=[CH:31][N:30]=[C:27]([O:28][CH3:29])[C:26]=3[N:25]=[CH:24]2)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1(OC2C3N=CN(C=3N=CN=2)[C@@H]2O[C@H](CO[Si](C(C)(C)C)(C)C)[C@@H](O[Si](C(C)(C)C)(C)C)C2)C2C=CC=C[C:37]=2N=N1.C([O-])([O-])=O.[Cs+].[Cs+]>CCO>[Si:1]([O:8][C@@H:9]1[C@@H:13]([CH2:14][O:15][Si:16]([C:19]([CH3:20])([CH3:21])[CH3:22])([CH3:18])[CH3:17])[O:12][C@@H:11]([N:23]2[C:33]3[N:32]=[CH:31][N:30]=[C:27]([O:28][CH2:29][CH3:37])[C:26]=3[N:25]=[CH:24]2)[CH2:10]1)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OC[C@H]1O[C@@H](n2cnc3c(On4nnc5ccccc54)ncnc32)C[C@@H]1O[Si](C)(C)C(C)(C)C
Reactant: COc1ncnc2c1ncn2[C@H]1C[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCO
Product: CCOc1ncnc2c1ncn2[C@H]1C[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O1
Yield: 95 %

Procedure:
As described for the synthesis of 3′,5′-bis-O-(tert-butyldimethylsilyl)-O6-methyl-2′-deoxyinosine, the ethyl derivative was prepared by a reaction between O6-(benzotriazol-1-yl)-3′,5′-bis-O-(tert-butyldimethylsilyl)-2′-deoxyinosine (26) (59.8 mg, 0.100 mmol) and EtOH (1 mL) in the presence of Cs2CO3 (65.2 mg, 0.200 mmol) over 1 h. Chromatographic purification (SiO2, elution with 20% EtOAc in hexanes) afforded 48.2 mg (95% yield) of the title compound as a clear gum. Rf (20% EtOAc in hexanes)=0.16. 1H NMR (500 MHz, CDCl3): δ 8.50 (s, 1H, Ar—H), 8.26 (s, 1H, Ar—H), 6.50 (t, 1H, H-1′, J=6.4), 4.65 (q, 2H, OCH2, J=7.0), 4.61 (m, 1H, H-3′), 4.01 (q, 1H, H-4′, J=3.4), 3.87 (dd, 1H, H-5′, J=11.2, 3.9), 3.77 (dd, 1H, H-5′, J=11.2, 2.9), 2.61 (quint, 1H, H-2′, J=6.3), 2.44 (ddd, 1H, H-2′, J=12.9, 6.1, 3.9), 1.50 (t, 3H, CH3, J=7.3), 0.91 (s, 18H, tert-Bu), 0.09, 0.08 (2 s, 12H, SiCH3). 13C NMR (126 MHz, CDCl3): δ 160.8, 152.0, 151.5, 140.5, 121.9, 87.9, 84.4, 71.8, 63.1, 62.7, 41.5, 26.0, 25.7, 18.4, 18.0, 14.5, −4.7, −4.8, −5.4, −5.5. FAB HRMS calcd for C24H45N4O4Si2 (M++H) 509.2979. found 509.2953.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[C:10]([N:12]1[CH:17]=[CH:16][C:15]2[N:18]([C:21]3[CH:26]=[N:25][CH:24]=[CH:23][N:22]=3)[N:19]=[N:20][C:14]=2[CH:13]1[CH3:27])=[O:11].C([SiH](CC)CC)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[C:10]([N:12]1[CH2:17][CH2:16][C:15]2[N:18]([C:21]3[CH:26]=[N:25][CH:24]=[CH:23][N:22]=3)[N:19]=[N:20][C:14]=2[CH:13]1[CH3:27])=[O:11]
Reactant: CC1c2nnn(-c3cnccn3)c2C=CN1C(=O)c1ccc(F)c(Cl)c1Cl
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC1c2nnn(-c3cnccn3)c2CCN1C(=O)c1ccc(F)c(Cl)c1Cl
Temperature: 80 °C
Yield: 39.8 %

Procedure:
To a solution of the product of Example 140, Step 1 (350 mg, 0.864 mmol) in TFA (2 mL) was added triethylsilane (0.35 mL, 2.16 mmol). The reaction was sealed and heated at 80° C. for 2 h. The reaction was diluted with CH2Cl2 and the organic portion washed with NaHCO3. The organic portion was then dried over Na2SO4, concentrated and purified by chromatography on silica gel eluted with heptane/EtOAc to afford the title compound (140 mg, 40%) MS (ESI) mass calcd. C17H13Cl2FN6O 406.1. m/z found, 407.0 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:19][C:20]2[C:21]3[N:28]([CH2:29][C:30]([O:32]CC)=[O:31])[CH:27]=[CH:26][C:22]=3[N:23]=[CH:24][N:25]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=1.Cl>O1CCCC1.C(O)C.[OH-].[Na+]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:19][C:20]2[C:21]3[N:28]([CH2:29][C:30]([OH:32])=[O:31])[CH:27]=[CH:26][C:22]=3[N:23]=[CH:24][N:25]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:16])([F:18])[F:17])[CH:10]=1
Reactant: CCOC(=O)Cn1ccc2ncnc(Nc3ccc(Oc4cccc(C(F)(F)F)c4)c(Cl)c3)c21
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: O=C(O)Cn1ccc2ncnc(Nc3ccc(Oc4cccc(C(F)(F)F)c4)c(Cl)c3)c21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 81.4 %

Procedure:
Ethyl [4-({3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]acetate (221.2 mg) was dissolved in a mixed solvent of tetrahydrofuran (1.5 mL)/ethanol (1.5 mL), 1N aqueous sodium hydroxide solution (0.6 mL) was added, and the mixture was stirred at room temperature for 30 min. The reaction mixture was adjusted to pH 2-3 with 1N hydrochloric acid and extracted with a mixed solvent of ethyl acetate/tetrahydrofuran=1/1. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was collected by filtration and dried to give the title compound (169.8 mg) as a yellow powder.
Reaction SMILES: [CH3:1][N:2]([CH3:27])[C:3]([C:5]1[CH:25]=[CH:24][C:8]([O:9][C:10]2[C:15]3[CH2:16][C:17]([CH3:20])([CH3:19])[O:18][C:14]=3[CH:13]=[C:12]([C:21](O)=[O:22])[CH:11]=2)=[CH:7][C:6]=1[F:26])=[O:4].[NH2:28][C:29]1[CH:33]=[CH:32][O:31][N:30]=1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[O:31]1[CH:32]=[CH:33][C:29]([NH:28][C:21]([C:12]2[CH:11]=[C:10]([O:9][C:8]3[CH:24]=[CH:25][C:5]([C:3](=[O:4])[N:2]([CH3:27])[CH3:1])=[C:6]([F:26])[CH:7]=3)[C:15]3[CH2:16][C:17]([CH3:19])([CH3:20])[O:18][C:14]=3[CH:13]=2)=[O:22])=[N:30]1
Reactant: CN(C)C(=O)c1ccc(Oc2cc(C(=O)O)cc3c2CC(C)(C)O3)cc1F
Reactant: Nc1ccon1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CN(C)C(=O)c1ccc(Oc2cc(C(=O)Nc3ccon3)cc3c2CC(C)(C)O3)cc1F
Temperature: 50 °C
Reaction time: 8 h
Yield: 3.6 %

Procedure:
To a solution of 4-(4-dimethylcarbamoyl-3-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (143a) (80 mg, 0.21 mmol), 3-aminoisoxazole (36 mg, 0.429 mmol) and triethylamine (0.0597 mL, 0.4294 mmol) in 2 mL of DMF was added HATU (163 mg, 0.429 mmol). The mixture was stirred at 50° C. overnight, and purified by reverse phase column chromatography to give a white solid (3.3 mg, 4% yield). 1H NMR (400 MHz, CDCl3) δ 9.23 (s, 1 H) 7.39 (t, J=8.08 Hz, 1 H) 7.27 (s, 1 H) 7.20 (d, J=1.77 Hz, 1 H) 7.13 (d, J=4.55 Hz, 2 H) 6.82 (dd, J=8.59, 2.27 Hz, 1 H) 6.71 (dd, J=10.61, 2.27 Hz, 1 H) 3.16 (s, 3 H) 3.00 (s, 3 H) 2.92 (s, 2 H) 1.51 (s, 6 H); LCMS for C23H22FN3O5 m/z 440.20 (M+H+).
Reaction SMILES: [NH2:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[I:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=1)[C:21](Cl)=[O:22].C(Cl)(Cl)Cl>C1COCC1>[I:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=1)[C:21]([NH:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][N:3]=1)=[O:22]
Reactant: O=C(Cl)c1cccc(I)c1
Reactant: COc1cccnc1N
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: COc1cccnc1NC(=O)c1cccc(I)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 26.9 %

Procedure:
2-Amino-3-methoxypyridine (1.50 g) was dissolved in THF (20 mL), and at 0° C., triethylamine (3.37 mL) and 3-iodobenzoyl chloride (3.23 g) were added thereto and stirred at room temperature for 30 minutes. Triethylamine (3.37 mL) and 3-iodobenzoyl chloride (3.23 g) were further added and stirred at room temperature for 18 hours. Chloroform was added to the reaction liquid, then washed with aqueous saturated sodium hydrogencarbonate solution, and dried with sodium sulfate. The drying agent was removed through filtration, and the solvent was evaporated off under reduced pressure. The residue was suspended in ethyl acetate (about 50 mL) added thereto, then the solid was collected through filtration as a colorless solid (5.96 g). Methanol (50 mL) and aqueous 2 M sodium hydrogencarbonate solution (3.42 mL) were added to the obtained solid (2.00 g), and stirred at room temperature for 18 hours. Methanol was evaporated off under reduced pressure, then ethyl acetate was added to the residue, washed with water and saturated brine in that order, and dried with sodium sulfate. The drying agent was removed through filtration, and the solvent was evaporated off under reduced pressure. The residue was purified through silica gel column chromatography (ethyl acetate/hexane=from 0% to 100%, gradient) to give the entitled compound (1.15 g, 80%) as an orange oil.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[N:12]1.[C:20]([NH2:24])(=[O:23])[CH:21]=[CH2:22]>N1C=CC=CC=1.CO.C(=O)(O)[O-].[Na+]>[N:11]1([CH2:10][C:2]2[N:1]([CH2:22][CH2:21][C:20]([NH2:24])=[O:23])[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[N:12]1
Reactant: c1ccc2[nH]c(Cn3nnc4ccccc43)nc2c1
Reactant: C=CC(N)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: c1ccncc1
Product: NC(=O)CCn1c(Cn2nnc3ccccc32)nc2ccccc21
Yield: 33.3 %

Procedure:
1-(1H-Benzimidazol-2-ylmethyl)-1H-benzotriazole (300 mg, 1.20 mmol) and acrylamide (86 mg, 1.20 mmol) were dissolved in pyridine (5 mL). Triton B (40% by weight in methanol, 0.010 mL, 0.024 mmol) was added at room temperature. The temperature was slowly raised to reflux. The reaction mixture was stirred at reflux overnight under nitrogen. The solvent was stripped under reduced pressure. The residue was taken up in aqueous saturated sodium bicarbonate solution and extracted with EtOAc (4×100 mL). The combined organic extracts were dried over magnesium sulfate, filtered and evaporated. The residue was purified by chromatography (EtOAc/MeOH 12:1 to 4:1) to give 128 mg (33%) of the title compound as a white solid.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[N:9]=[C:10]=[S:11].[OH:12][CH2:13][CH2:14][CH2:15][NH2:16]>C1C=CC=CC=1>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([NH:16][CH2:15][CH2:14][CH2:13][OH:12])=[S:11]
Reactant: NCCCO
Reactant: Cc1ccc(N=C=S)c(C)c1
Solvent: c1ccccc1
Product: Cc1ccc(NC(=S)NCCCO)c(C)c1
Reaction time: 16 h

Procedure:
A solution of 2,4-dimethylphenylisothiocyanate in about 70 ml. of benzene was added dropwise to an agitated solution of 3-hydroxypropylamine (3.8 grams) in about 80 ml. of benzene. The resulting reaction mixture was maintained, with stirring, at ambient temperatures for about 16 hours. Following such period, the benzene in the reaction mixture was removed in vacuo and the residual oil triturated with ethyl ether and the desired product crystallized therefrom and washed again with ethyl ether. As a result of such operations, the desired N-(2,4-dimethylphenyl)-N'-(3-hydroxypropyl)-thiourea product was obtained as a white solid having a melting point of 90° - 93°C.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[CH:7]=[C:6]([N+:13]([O-:15])=[O:14])[C:5]=1[CH3:16])([O-])=O>C(O)(=O)C.O.[Fe]>[NH2:1][C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[CH:7]=[C:6]([N+:13]([O-:15])=[O:14])[C:5]=1[CH3:16]
Reactant: Cc1c([N+](=O)[O-])cc([N+](=O)[O-])cc1[N+](=O)[O-]
Agent: [Fe]
Solvent: O
Solvent: CC(=O)O
Product: Cc1c(N)cc([N+](=O)[O-])cc1[N+](=O)[O-]
Yield: 43.8 %

Procedure:
1.0 gram of 2,4,6-trinitrotoluene was dissolved in 22 ml of glacial acetic acid. With vigorous stirring, 0.82 g of iron powder (400 mesh) was added in small portions over two hours. The red reaction suspension was diluted to 50 ml with water giving a bright yellow precipitate. Filtration gave 0.38 grams of 2-amino-4,6-dinitrotoluene of sufficient spectral and chromatographic purity for use in the subsequent synthesis without recrystallization.
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH:5]=[CH:6]1)[CH2:3][CH:2]2[C:8]([OH:10])=[O:9].S(Cl)(Cl)=O.[CH3:15][C:16](O)([CH2:18][CH2:19][Si:20]([Si:29]([CH3:32])([CH3:31])[CH3:30])([Si:25]([CH3:28])([CH3:27])[CH3:26])[Si:21]([CH3:24])([CH3:23])[CH3:22])[CH3:17].C(N(CC)CC)C>O.O1CCCC1>[CH:1]12[CH2:7][CH:4]([CH:5]=[CH:6]1)[CH2:3][CH:2]2[C:8]([O:10][C:16]([CH3:17])([CH2:18][CH2:19][Si:20]([Si:29]([CH3:32])([CH3:31])[CH3:30])([Si:21]([CH3:24])([CH3:23])[CH3:22])[Si:25]([CH3:28])([CH3:27])[CH3:26])[CH3:15])=[O:9]
Reactant: O=C(O)C1CC2C=CC1C2
Reactant: CC(C)(O)CC[Si]([Si](C)(C)C)([Si](C)(C)C)[Si](C)(C)C
Solvent: C1CCOC1
Solvent: O
Solvent: O=S(Cl)Cl
Product: CC(C)(CC[Si]([Si](C)(C)C)([Si](C)(C)C)[Si](C)(C)C)OC(=O)C1CC2C=CC1C2
Temperature: 50 °C
Yield: 71.7 %

Procedure:
An oven-dried reaction flask equipped for magnetic stirring and fitted with a reflux condenser was flushed with nitrogen and charged with of bicyclo[2.2.1]hept-5-ene-2-carboxylic acid (55.3 g, 0.4 mol) and thionyl chloride (190.0 g, 1.6 mol). The mixture was heated at 50° C. for 2 hours. Excess thionyl chloride was evaporated under reduced pressure, of tetrahydrofuran (20 mL) was added to the concentrate, and volatiles were again separated under reduced pressure. To the amber concentrate, of tetrahydrofuran (200 mL), 2,6,6-Trimethyl-5,5-bis(trimethylsilyl)-5,6-disilaheptan-2-ol (33.5 g, 0.1 mol), and triethylamine (41.0 g, 0.4 mol) were added, and the reaction mixture was heated at 50° C. for 24 hours. The reaction mixture was poured into water (200 mL), the organic phase was separated, and the aqueous phase was extracted three 50 mL portions of diethyl ether. The combined organic phases were washed with one 50 mL portion of saturated aqueous sodium chloride and dried over magnesium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (90:10 hexanes:diethyl ether, Rf=0.47 and 0.58), affording the title compound (32.6 g, 72%) as a clear, colorless oil. The 1H, 13C, and 29Si NMR spectra of the product were consistent with the structure of the title compound as an approximately 55:45 mixture of the endo and exo isomers.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3](B(O)O)=[CH:2]1.Br[C:10]1[S:18][C:17]2[C:12](=[N:13][CH:14]=[CH:15][C:16]=2[NH:19][C:20]2[CH:21]=[C:22]3[C:26](=[CH:27][CH:28]=2)[NH:25][C:24]([CH3:29])=[CH:23]3)[CH:11]=1>>[O:1]1[CH:5]=[CH:4][C:3]([C:10]2[S:18][C:17]3[C:12](=[N:13][CH:14]=[CH:15][C:16]=3[NH:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][C:24]([CH3:29])=[CH:23]4)[CH:11]=2)=[CH:2]1
Reactant: OB(O)c1ccoc1
Reactant: Cc1cc2cc(Nc3ccnc4cc(Br)sc34)ccc2[nH]1
Product: Cc1cc2cc(Nc3ccnc4cc(-c5ccoc5)sc34)ccc2[nH]1

Procedure:
The title compound was prepared from 3-furanboronic acid and (2-bromo-thieno[3,2-b]pyridin-7-yl)-(2-methyl-1H-indol-5-yl)-amine by the procedure analogous to Example 2 above. 1H NMR (400 MHz, CD3OD) δ8.02 (d, 1H), 7.91 (s, 1H), 7.53 (m, 1H), 7.35 (s, 1H), 7.31 (d, 1H), 7.27 (d, 1H), 6.94 (dd, 1H), 6.77 (m, 1H), 6.54 (d, 1H), 6.10 (s, 1H), 2.40 (s, 3H), RP18-HPLC RT: 5.39 minutes; API MS: 346 (M+1).
Reaction SMILES: [C:1]([CH:3]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1)#[N:2].[Br:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21]Br)=[C:17]([I:23])[CH:16]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Br:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:3]2([C:1]#[N:2])[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]2)=[C:17]([I:23])[CH:16]=1
Reactant: BrCc1ccc(Br)cc1I
Reactant: CC(C)(C)OC(=O)N1CC(C#N)C1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CC(C#N)(Cc2ccc(Br)cc2I)C1
Temperature: 25 °C
Yield: 75.3 %

Procedure:
To a solution of tert-butyl 3-cyanoazetidine-1-carboxylate (2.1774 g, 11.95 mmol) and 4-bromo-1-(bromomethyl)-2-iodobenzene (5.0227 g, 13.36 mmol) in THF (30 mL) was added LiHMDS (1.0 M in THF, 15 mL, 15 mmol) at −78° C. The mixture was allowed to slowly warm to room temperature over 20 h. The reaction mixture was then quenched with saturated NH4Cl, extracted with EtOAc, and dried over Na2SO4. After the solvent was evaporated under reduced pressure, the residue was purified by chromatography on silica gel eluted with hexanes/ethyl acetate to afford 4.2959 g (75%) of tert-butyl 3-(4-bromo-2-iodobenzyl)-3-cyanoazetidine-1-carboxylate as foam. LC-MS tR=2.17 min in 3 min chromatography, m/z 477, 479 (MH+), 462, 464 (MH+-15), 421, 423 (MH+-56).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]=2)=[CH:4][CH:3]=1>CO.[Pd]>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CC=C(c2ccc(N)nc2)CC1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(N)nc2)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 32 %

Procedure:
A suspension of tert-butyl 6-amino-5′,6′-dihydro-[3,4′-bipyridine]-1′(2′H)-carboxylate (560 mg, 2.03 mmol), 5% Pd/C (1082 mg, 0.5 mmol) in methanol (30 mL) was purged with nitrogen for 2 min. The reaction mixture was stirred under hydrogen at ambient temperature for 16 h. The reaction mixture was diluted with dichloromethane (50 mL) and was filtered through Celite pad. The filtrate was concentrated and the residue was purified by flash column chromatography on silica gel (ISCO) eluting with 0-90% ethyl acetate in heptane to give tert-butyl 4-(6-aminopyridin-3-yl)piperidine-1-carboxylate (180 mg, 31.9%) as yellow color solid. LCMS (m/z): 278 (MH+), 0.57 min.
Reaction SMILES: Cl[C:2]1[C:3](O)=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12](=[O:16])[C:11]1[C:10](O)=[CH:9][CH:8]=[C:7](O)[C:6]=1[C:5]2=[O:19].NC1C=CC=CC=1>>[CH:7]1[C:6]2[C:5](=[O:19])[C:4]3[C:13](=[CH:14][CH:15]=[CH:2][CH:3]=3)[C:12](=[O:16])[C:11]=2[CH:10]=[CH:9][CH:8]=1
Reactant: O=C1c2ccc(Cl)c(O)c2C(=O)c2c(O)ccc(O)c21
Agent: *CC*
Agent: O=C(O)c1ccc(C(=O)O)cc1
Solvent: Nc1ccccc1
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
Blue anthraquinone dyestuffs are prepared from the reaction of 6-chloro-1,4,5-trihydroxyanthraquinone with an appropriate aniline reactant. The resultant blue dyestuffs are 6-anilino-1,4,5-trihydroxyanthraquinones which produce excellent blue dyeings on polyester fabrics, particularly polyethylene terephthalate.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([N:19]3[C@@H:24]([CH3:25])[CH2:23][O:22][CH2:21][C@H:20]3[CH3:26])=[O:18])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:27]([O:30][CH2:31][C:32]1[C:33]([N:47]2[CH2:58][CH2:57][N:56]3[C:49](=[CH:50][C:51]4[CH2:52][C:53]([CH3:60])([CH3:59])[CH2:54][C:55]=43)[C:48]2=[O:61])=[N:34][CH:35]=[CH:36][C:37]=1B1OC(C)(C)C(C)(C)O1)(=[O:29])[CH3:28].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C(#N)C>[C:27]([O:30][CH2:31][C:32]1[C:33]([N:47]2[CH2:58][CH2:57][N:56]3[C:49](=[CH:50][C:51]4[CH2:52][C:53]([CH3:60])([CH3:59])[CH2:54][C:55]=43)[C:48]2=[O:61])=[N:34][CH:35]=[CH:36][C:37]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([N:19]3[C@@H:24]([CH3:25])[CH2:23][O:22][CH2:21][C@H:20]3[CH3:26])=[O:18])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1)(=[O:29])[CH3:28]
Reactant: CC(=O)OCc1c(B2OC(C)(C)C(C)(C)O2)ccnc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O
Reactant: C[C@@H]1COC[C@H](C)N1C(=O)c1ccc(Nc2cc(Cl)nn(C)c2=O)nc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC(=O)[O-]
Solvent: CC#N
Solvent: O
Product: CC(=O)OCc1c(-c2cc(Nc3ccc(C(=O)N4[C@H](C)COC[C@@H]4C)cn3)c(=O)n(C)n2)ccnc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O
Temperature: 100 °C

Procedure:
A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 321a (140 mg, 0.37 mmol), (2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate 199e (355 mg, 0.74 mmol), K3PO4 (157 mg, 0.74 mmol), sodium acetate (61 mg, 0.74 mmol), 1,1′-bis(diphenylphosphino) ferrocenedichloropalladium(II) (36 mg, 0.040 mmol), acetonitrile (10 mL), and water (0.2 mL). The system was subjected to three cycles of vacuum/nitrogen flush and heated at 100° C. under N2 protection for 1.5 h. Analysis of reaction mixture by LCMS showed complete conversion to the desired product. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between dichloromethane (30 mL) and water (30 mL). The aqueous layer was separated and extracted with dichloromethane (3×20 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The dark residue was purified by gel-silica column chromatograpthe by eluting with 60:1 dichloromethane/methanol to afford 320b (105 mg, 41%) as a black solid. MS-ESI: [M+H]+ 695.3