Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si:1]([O:18][CH2:19][CH2:20][C@@H:21]([CH3:46])[C@H:22]([N:28]([CH3:45])[C:29](=[O:44])[C@@H:30]([N:32]([CH3:43])[C:33](=[O:42])[O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH3:31])[C:23]1[O:24]C=CC=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH2:47].C(Cl)(Cl)(Cl)Cl.CC#N>CC#N.O>[CH2:35]([O:34][C:33]([N:32]([CH3:43])[C@@H:30]([CH3:31])[C:29]([N:28]([C@@H:22]([C@H:21]([CH3:46])[CH2:20][CH2:19][O:18][Si:1]([C:14]([CH3:17])([CH3:15])[CH3:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:23]([OH:24])=[O:47])[CH3:45])=[O:44])=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: C[C@H](CCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)[C@@H](c1ccco1)N(C)C(=O)[C@H](C)N(C)C(=O)OCc1ccccc1
Reactant: O
Solvent: CC#N
Solvent: ClC(Cl)(Cl)Cl
Product: C[C@H](CCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)[C@@H](C(=O)O)N(C)C(=O)[C@H](C)N(C)C(=O)OCc1ccccc1
Reaction time: 0.25 h

Procedure:
To a stirred mixture of NalO4 (485.0 mg, 2.30 mmol, 6.0 equiv) in H2O/CCl4/CH3CN (3/2/3, 10.4 mL) was added RuCl3 (26.6 mg, 0.13 mmol, 0.34 equiv) and the mixture was stirred vigorously for 15 minutes. To the mixture was then added a solution of 2.18.1g (242.0 mg, 0.38 mmol) in CH3CN (3 mL). After stirring for 15 minutes, the reaction mixture was diluted with water and extracted with EtOAc. The combined organic layer was washed with saturated aqueous NaHSO3 solution, brine, dried over Na2SO4, and concentrated to give product 2.18.1h (242.0 mg) which was used for the next step without further purification. MS m/z (M+1) 619.4.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([OH:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1)#[CH:2].CS(O[CH2:28][CH2:29][O:30][CH3:31])(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([O:20][CH2:28][CH2:29][O:30][CH3:31])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1)#[CH:2]
Reactant: COCCOS(C)(=O)=O
Reactant: C#Cc1cccc(Nc2ncnc3cc(OC)c(O)cc23)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: C#Cc1cccc(Nc2ncnc3cc(OC)c(OCCOC)cc23)c1
Temperature: 25 °C
Yield: 42.9 %

Procedure:
A solution of 4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-ol (2.9 g, 0.01 mol), 2-methoxyethyl methane sulfonate (4.6 g, 0.03 mol, 3 equiv), and cesium carbonate (9.9 g, 0.03 mol, 3 equiv) in DMF (100 ml) was heated to 60° C. for 12 hours. The reaction mixture was cooled to room temperature and poured into cold water, the solid was filtrated and dried to give 1.5 g product. MS (ESI) m/z: 350 (M+1).
Reaction SMILES: [Cl:1][C:2]1[C:7]2[CH:8]=[CH:9][N+:10]([O-])([C:11]3[C:16]([Cl:17])=[CH:15][C:14]([C:18]([F:21])([F:20])[F:19])=[CH:13][N:12]=3)[C:6]=2[CH:5]=[CH:4][N:3]=1.C(=O)(O)[O-].[Na+].P(Cl)(Cl)([Cl:30])=O>>[Cl:17][C:16]1[C:11]([N:10]2[C:6]3[CH:5]=[C:4]([Cl:30])[N:3]=[C:2]([Cl:1])[C:7]=3[CH:8]=[CH:9]2)=[N:12][CH:13]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:15]=1
Reactant: [O-][N+]1(c2ncc(C(F)(F)F)cc2Cl)C=Cc2c1ccnc2Cl
Reactant: O=P(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: FC(F)(F)c1cnc(-n2ccc3c(Cl)nc(Cl)cc32)c(Cl)c1
Temperature: 25 °C

Procedure:
4 -chloro-1-(3-chloro-5-trifluoromethylpyridin-2-yl) pyrrolo[3,2-c]pyridine N-oxide (Compound 4, 1.2 g, 3.4 mmol) was heated in phosphorus oxychloride (20 ml) under reflux for 18 hours. The mixture was cooled to room temperature, poured into ice-water, and the mixture made neutral by addition of solid sodium bicarbonate. The resulting mixture was extracted with dichloromethane, and the organic extracts combined, dried over magnesium sulfate, filtered and the filtrate evaporated in vacuo. The residue was further purified by flash column chromatography on silica gel to give 1-(3-chloro-5-trifluoromethylpyridin-2-yl)-4,6-dichloropyrrolo[3,2-c]pyridine (0.24 g) as a colorless oil.
Reaction SMILES: BrC1C=C(Cl)C=CC=1O.C(O[CH:13](OCC)[CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=1[Br:23])C>>[Cl:22][C:19]1[CH:18]=[C:17]([Br:23])[C:16]2[O:15][CH:14]=[CH:13][C:21]=2[CH:20]=1
Reactant: CCOC(COc1ccc(Cl)cc1Br)OCC
Agent: Oc1ccc(Cl)cc1Br
Product: Clc1cc(Br)c2occc2c1

Procedure:
Beginning with 25 gm (120.5 mMol) 2-bromo-4-chlorophenol, 41.16 gm crude 2-(2-bromo-4-chlorophenoxy)acetaldehyde diethyl acetal was prepared essentially as described in Preparation IV. A sample of this crude material was subjected to silica gel chromatography to provide an analytical sample.
Reaction SMILES: Cl[C:2]1[C:7]2[CH2:8][O:9][C:10](=[C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[C:17](F)[CH:18]=4)[NH:13][C:12]3=[O:21])[C:6]=2[CH:5]=[CH:4][N:3]=1.[CH:22]([O-])=O.[NH4+]>C(O)C.[Pd]>[C:10]1(=[C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([CH3:22])[CH:18]=3)[NH:13][C:12]2=[O:21])[C:6]2[CH:5]=[CH:4][N:3]=[CH:2][C:7]=2[CH2:8][O:9]1
Reactant: O=C1Nc2ccc(F)cc2C1=C1OCc2c1ccnc2Cl
Reactant: O=C[O-]
Agent: [Pd]
Agent: [NH4+]
Solvent: CCO
Product: Cc1ccc2c(c1)C(=C1OCc3cnccc31)C(=O)N2
Temperature: 25 °C
Reaction time: 24 h
Yield: 44.5 %

Procedure:
A solution of 3-(4-chloro-3H-furo[3,4-c]pyridin-1-ylidene)-5-fluoro-1,3-dihydro-indol-2-one (50 mg, 0.17 mmol) is dissolved in ethanol (10 mL) and treated with 5% Pd/C (50 mg), ammonium formate (500 mg, 7.93 mmol) The reaction mixture is stirred at room temperature for 24 h. The reaction mixture is evaporated and the residue is loaded onto silica gel and purified by chromatography (silica gel). The product containing fractions are concentrated to give the title compound as a yellow solid (20 mg, 45%).
Reaction SMILES: CCCCCC.C([Li])CCC.[CH2:12]([O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1Br)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[Br:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=[O:33])=[CH:30][CH:29]=1.[Cl-].[NH4+]>C1COCC1>[CH2:12]([O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH:32]([C:31]1[CH:34]=[CH:35][C:28]([Br:27])=[CH:29][CH:30]=1)[OH:33])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Brc1ccccc1OCc1ccccc1
Reactant: O=Cc1ccc(Br)cc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: OC(c1ccc(Br)cc1)c1ccccc1OCc1ccccc1
Reaction time: 0.25 h
Yield: 82.8 %

Procedure:
In a nitrogen stream, an n-butyllithium hexane solution (1.59 M, 11.57 mL) was added dropwise to a solution of 1-benzyloxy-2-bromobenzene (4.4 g, 16.72 mmol) in THF (168 mL) at −78° C. and the mixture solution was stirred at the same temperature for 15 minutes. To this solution, a solution of 4-bromobenzaldehyde (2.47 g, 13.34 mmol) in THF (50 mL) was added dropwise at −78° C. The reaction mixture was stirred at the same temperature for 30 minutes and at 0° C. for 30 minutes, and then a saturated ammonium chloride aqueous solution was added thereto and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and dried (anhydrous magnesium sulfate), and then the solvent was distilled under reduced pressure. The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:10)] to obtain the title compound (4.08 g, 83%) as a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH2:12]([O:14][C:15](=[O:29])[CH:16]([C:21](=O)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:17][C:18](=O)[CH3:19])[CH3:13].CC1C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:12]([O:14][C:15]([C:16]1[CH:17]=[C:18]([CH3:19])[N:1]([C:2]2[CH:11]=[CH:10][CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[CH:3]=2)[C:21]=1[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:29])[CH3:13]
Reactant: COC(=O)c1cccc(N)c1
Reactant: CCOC(=O)C(CC(C)=O)C(=O)c1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCO
Product: CCOC(=O)c1cc(C)n(-c2cccc(C(=O)OC)c2)c1-c1ccccc1

Procedure:
Methyl 3-aminobenzoate (10 mmol, 1.4 g), 2-benzoyl-4-oxo-pentanoic acid ethyl ester (10 mmol, 2.5 g), and tosic acid (0.1 g) were combined in ethanol, then heated under reflux. The named product was purified over silica gel and crystallized upon standing, 1H-NMR (CDCl3, ppm) 1.15 t (3H), 2.08 s (3H), 3.88 s (3H), 4.05 q (2H), 6.56 s (1H), 7.15-7.33 bm (7H), 7.79-7.97 bm (2H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:13][C:12](=[O:14])[CH2:11][C:10](=O)[CH2:9]1.Cl.[NH2:17][CH2:18][C:19]#[C:20][CH3:21].O1CCCC1>C(N(CC)CC)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:9][C:10]2[N:17]=[CH:18][CH:19]=[C:20]([CH3:21])[C:11]=2[C:12](=[O:14])[CH2:13]1
Reactant: O=C1CC(=O)CC(c2ccccc2F)C1
Reactant: CC#CCN
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: Cc1ccnc2c1C(=O)CC(c1ccccc1F)C2
Temperature: 25 °C
Reaction time: 1 h
Yield: 28.9 %

Procedure:
To a mixture of 5-(2-fluorophenyl)cyclohexane-1,3-dione (0.98 g), 1-amino-2-butyne hydrochloride (0.5 g), molecular sieves 4A (2 g) and tetrahydrofuran (20 ml) was added triethylamine (0.48 g), and the mixture was stirred at room temperature for 1 hour, refluxed for 12 hours and cooled. Insoluble materials were filtered off. Under reduced pressure, the solvent was evaporated, and the residue was stirred for 6 hours at 220° C. and cooled, to which were added ethyl acetate and sodium hydrogen carbonate solution. The organic layer was washed with water and saturated brine, dried with magnesium sulfate and concentrated under reduced pressure, and the residue was purified with silica gel column chromatography (EtOAc/hexane) to give oil of 7-(2-fluorophenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one (0.35 g).
Reaction SMILES: NCC[N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])[CH2:6][CH2:5]1.N1C=CC=CC=1.BrCCC(Cl)=O>ClCCl>[CH3:17][O:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[N:7]1[CH2:8][CH2:9][NH:4][CH2:5][CH2:6]1
Reactant: COc1ccccc1N1CCN(CCN)CC1
Agent: O=C(Cl)CCBr
Solvent: ClCCl
Solvent: c1ccncc1
Product: COc1ccccc1N1CCNCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 107.4 %

Procedure:
To a chilled solution (0° C.) of 4-[(2-amino)ethyl]-1-(2-methoxyphenyl)piperazine (10.46 mmol) in 40 mL of dichloromethane were added pyridine (12.55 mmol) and a solution of 3-bromopropionyl chloride (11.51 mmol) in 10 mL of dichloromethane. After addition, the reaction mixture was warmed to room temperature, and stirred for 1 hour. The reaction mixture was quenched with saturated sodium carbonate, extracted with dichloromethane. The organic phase was washed with brine, water, and dried over magnesium sulfate Filtration and evaporation of the solvents gave a residue that was purified by flash chromatography using 3-5% of methanol and 0.5% of ammonium hydroxide in ethyl acetate to give 4-[2-(3′-bromo)propionamido)ethyl]-1-(2-methoxyphenyl)piperazine (2.16 g, 56%).
Reaction SMILES: Cl.Cl.[NH2:3][C:4]1[CH:5]=[C:6]([CH:15]=[CH:16][CH:17]=1)[O:7][C:8]1[CH:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=1.[F:18][C:19]([F:30])([F:29])[C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=1)[C:23](Cl)=[O:24]>CN(C)C(=O)C>[NH2:14][C:11]1[N:12]=[CH:13][C:8]([O:7][C:6]2[CH:5]=[C:4]([NH:3][C:23](=[O:24])[C:22]3[CH:26]=[CH:27][CH:28]=[C:20]([C:19]([F:18])([F:29])[F:30])[CH:21]=3)[CH:17]=[CH:16][CH:15]=2)=[CH:9][CH:10]=1
Reactant: O=C(Cl)c1cccc(C(F)(F)F)c1
Reactant: Nc1cccc(Oc2ccc(N)nc2)c1
Agent: Cl
Solvent: CC(=O)N(C)C
Product: Nc1ccc(Oc2cccc(NC(=O)c3cccc(C(F)(F)F)c3)c2)cn1
Temperature: 25 °C
Reaction time: 6 h
Yield: 83.3 %

Procedure:
To a solution of 5-(3-aminophenoxy)pyridine-2-amine dihydrochloride (3.5 g, 12.7 mmol) in N,N-dimethylacetamide (30 mL) was added 3-(trifluoromethyl)benzoylchloride (2.80 g, 13.4 mmol), and the mixture was stirred at room temperature for 6 hr. The reaction mixture was concentrated under reduced pressure, 5% aqueous sodium hydrogen carbonate solution (100 mL) was added to the residue, and the mixture was extracted with ethyl acetate (200 mL). The organic layer was washed with water (100 mL) and saturated brine (100 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. Ethyl acetate (30 mL)/hexane (20 mL) was added to the obtained residue, and the obtained precipitate was collected by filtration and air-dried to give the title compound (3.95 g, 83%) as a colorless powder.
Reaction SMILES: Cl.[CH3:2][C:3]1([CH3:21])[C:7]([CH3:9])([CH3:8])[O:6][B:5]([C:10]2[CH:11]=[N:12][N:13]([CH:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[CH:14]=2)[O:4]1.[C:22](Cl)(=[O:24])[CH3:23].CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:2][C:3]1([CH3:21])[C:7]([CH3:8])([CH3:9])[O:6][B:5]([C:10]2[CH:11]=[N:12][N:13]([CH:15]3[CH2:20][CH2:19][N:18]([C:22](=[O:24])[CH3:23])[CH2:17][CH2:16]3)[CH:14]=2)[O:4]1
Reactant: CC1(C)OB(c2cnn(C3CCNCC3)c2)OC1(C)C
Reactant: CC(=O)Cl
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(=O)N1CCC(n2cc(B3OC(C)(C)C(C)(C)O3)cn2)CC1
Temperature: 25 °C
Yield: 99.3 %

Procedure:
A solution of 4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine hydrochloride (3.66 g, 11.7 mmol) in DMF (109.8 mL) was charged with acetyl chloride (0.91 mL, 12.84 mmol) and DIPEA (5.08 mL, 29.17 mmol) at 0° C. and left to warm up to RT in an ice bath overnight. The crude product was concentrated in vacuo to a solid and purified by flash chromatography (0 to 5% MeOH:EtOAc) to afford 3.71 g (99%) of the title compound. 1H NMR (400 MHz, DMSO-d6): δ 7.97 (s, 1H), 7.59 (s, 1H), 4.38-4.48 (m, 2H), 3.85-3.94 (m, 1H), 3.13-3.22 (m, 1H), 2.69 (td, J=12.8, 2.7 Hz, 1H), 2.03 (s, 3H), 1.81-2.02 (m, 3H), 1.72 (qd, J=12.1, 4.6 Hz, 1H), 1.24 (s, 12H).
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][CH3:10])[C:4]=1[NH:11][C:12]([NH:14][C:15](=[NH:18])[NH:16][CH3:17])=[O:13])[CH3:2].[CH3:19]N(C(OC)OC)C.[ClH:27].CO>CC#N>[ClH:27].[CH2:9]([C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([CH2:1][CH3:2])[C:4]=1[N:11]1[CH:17]=[N:16][C:15]([NH:18][CH3:19])=[N:14][C:12]1=[O:13])[CH3:10]
Reactant: CCc1cccc(CC)c1NC(=O)NC(=N)NC
Reactant: COC(OC)N(C)C
Agent: Cl
Solvent: CO
Solvent: CC#N
Product: CCc1cccc(CC)c1-n1cnc(NC)nc1=O
Yield: 47 %

Procedure:
To a suspension of 22.8 g (80.0 mmol) of 1-(2,6-diethylphenyl)-3-methylamidinourea in CH3CN (100 ml) were added 19.1 g (160.0 mmol) of DMF-DMA and the reaction mixture was heated at reflux for 3 hours. The CH3CN was removed under reduced pressure and the residue partitioned between CHCl3 and H2O. The layers were separated and the aqueous layer extracted with CHCl3 (1×100 ml), dried (MgSO4) and concentrated under reduced pressure to give an off-white solid, which by NMR confirmed the desired free base. The solution was dissolved in H2OH and acidified with HCl/MeOH and the MeOH removed under reduced pressure to give an off-white solid which was crystallized from CH3CN to give after vacuum drying the weekend (105° C., house vacuum) 16.7 g (71%) of crude product. The material was recrystallized from CH3CN (a hot filtration was necessary to remove some undissolved solid) to give 11.0 g (47%) of desired product as a white crystalline solid:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1C1(N)CCCCC1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH:20]([C:22]1[CH:32]=[CH:31][C:25]([O:26][CH2:27][C:28]([OH:30])=[O:29])=[CH:24][CH:23]=1)=O.OOS([O-])=O.[K+]>CN(C=O)C.O>[CH2:8]([O:7][C:5]([C:4]1[CH:10]=[CH:11][C:12]2[N:1]([CH:2]3[CH2:3][CH2:4][CH2:10][CH2:11][CH2:12]3)[C:20]([C:22]3[CH:32]=[CH:31][C:25]([O:26][CH2:27][C:28]([OH:30])=[O:29])=[CH:24][CH:23]=3)=[N:1][C:2]=2[CH:3]=1)=[O:6])[CH3:9]
Reactant: CCOC(=O)c1ccc(C2(N)CCCCC2)c(N)c1
Reactant: O=Cc1ccc(OCC(=O)O)cc1
Agent: O=S([O-])OO
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc2c(c1)nc(-c1ccc(OCC(=O)O)cc1)n2C1CCCCC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 65 %

Procedure:
Following the procedure of example 1, ethyl 3-amino-4-(aminocyclohexyl)benzoate (1.077 g, 4.1 mmol) and 4-formylphenoxyacetic acid (0.748 g, 4.15 mmol) were dissolved in a mixture of DMF (8 mL) and water (0.5 mL). Oxone® (0.7 equivalent, 2.87 mmol, 1.764 g) was added and the mixture stirred for 30 min at room temperature (HPLC: complete). Water was added to precipitate the product, which was collected by filtration, washed with water and dried (1.130 g, 65% yield, brown solid).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.[O:12]=[S:13]1(=[O:30])[CH2:18][CH2:17][N:16]2[CH2:19][CH2:20][CH2:21][C@@H:22]([C:23]3[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=3)[C:15]2=[N:14]1.N1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC#N.C(O[Cu]OC(=O)C)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][CH:8]=1)[O:29][C:26]1[CH:25]=[CH:24][C:23]([C@H:22]2[C:15]3=[N:14][S:13](=[O:30])(=[O:12])[CH2:18][CH2:17][N:16]3[CH2:19][CH2:20][CH2:21]2)=[CH:28][CH:27]=1
Reactant: COc1cccc(B(O)O)c1
Reactant: O=S1(=O)CCN2CCC[C@@H](c3ccc(O)cc3)C2=N1
Agent: CC(=O)O[Cu]OC(C)=O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Solvent: c1ccncc1
Product: COc1cccc(Oc2ccc([C@@H]3CCCN4CCS(=O)(=O)N=C34)cc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 11.6 %

Procedure:
A mixture of (3-methoxyphenyl)boronic acid (813 mg), 4-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenol (500 mg), pyridine (3.60 mL), cesium carbonate (581 mg), diacetoxycopper (648 mg), and powdered 4A MS (5.00 g) in MeCN (18 mL) was stirred at room temperature overnight. The mixture was added with NH silica gel, concentrated in vacuo, and purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc) then recrystallized from EtOAc to give the title compound (80.0 mg) as a white solid.
Reaction SMILES: [CH3:1][C:2]1[N:6]([CH2:7][O:8][CH2:9][CH2:10][Si:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[N:4][CH:3]=1.[Li]CCCC.C([C:22]([O:24][CH2:25][CH3:26])=[O:23])#N>C1COCC1.CCOC(C)=O>[CH2:25]([O:24][C:22]([C:5]1[N:6]([CH2:7][O:8][CH2:9][CH2:10][Si:11]([CH3:13])([CH3:12])[CH3:14])[C:2]([CH3:1])=[CH:3][N:4]=1)=[O:23])[CH3:26]
Reactant: CCOC(=O)C#N
Reactant: Cc1cncn1COCC[Si](C)(C)C
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCOC(=O)c1ncc(C)n1COCC[Si](C)(C)C
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 38 %

Procedure:
To a solution of 5-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole (as prepared in the previous step, 0.320 g, 1.50 mmol) in 5 mL of THF at −78° C. was added n-BuLi (0.80 mL, 2 M in cyclohexane) and the mixture was allowed to attain RT and stirred for 30 min. The mixture was cooled to −78° C. and ethyl cyanoformate (0.160 g, 1.65 mmol) was added and the mixture allowed to stir for 10 h at RT. The reaction was diluted with 15 mL of EtOAc and washed with NaHCO3 (2×15 mL) and brine (15 mL). The title compound was eluted from a 20-g SPE with 50% EtOAc/hexanes to give 0.160 g (38%) of a light brown oil: Mass spectrum (ESI, m/z): Calcd. for C13H24N2O3Si, 285.2 (M+H). found 284.9.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH3:11])[N:5]=[C:4]([NH:12][CH2:13][CH2:14][CH3:15])[N:3]=1.Cl.[CH2:17]([O:20][NH2:21])[CH:18]=[CH2:19].[OH-].[Na+]>O1CCOCC1.O>[CH2:17]([O:20][NH:21][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH3:11])[N:5]=[C:4]([NH:12][CH2:13][CH2:14][CH3:15])[N:3]=1)[CH:18]=[CH2:19]
Reactant: CCCNc1nc(Cl)nc(NCCC)n1
Reactant: C=CCON
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: C=CCONc1nc(NCCC)nc(NCCC)n1
Temperature: 60 °C
Yield: 88.4 %

Procedure:
A mixture of 2-chloro-N-(4,6-bis-(n-propylamino)-[1,3,5]triazine (XXXIV) (2.00 g, 8.71 mmol), O-allyl-hydroxylamine hydrochloride (1.91 g, 17.42 mmol) and NaOH (0.70 g, 17.42 mmol) in 1,4-dioxane (25 mL) and water (5 mL) was heated at 60° C. for 4 h. The volatiles were removed under reduced pressure. Saturated NaHCO3 solution (100 mL) was added to the residue and the mixture was extracted with EtOAc (3×25 mL). The combined organic extracts were washed with water (50 mL), brine (50 mL) and dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was purified by flash column chromatography using gradient elution from CH2Cl2/EtOH (99:1) to CH2Cl2/EtOH (95:5) to yield O-allyl-N-(4,6-bis-propylamino-[1,3,5]triazin-2-yl)-hydroxylamine (XLIII, 2.05 g, 88% yield). ESI-MS (m/z) 267 [M+H]+.
Reaction SMILES: Cl[C:2]1[S:3][C:4]2[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[CH3:14][CH:15]([NH2:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN1CCCC1=O.O>[N+:11]([C:10]1[C:4]2[S:3][C:2]([NH:22][CH:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:14])=[N:6][C:5]=2[CH:7]=[CH:8][CH:9]=1)([O-:13])=[O:12]
Reactant: O=[N+]([O-])c1cccc2nc(Cl)sc12
Reactant: CC(N)c1ccccc1
Solvent: CN1CCCC1=O
Solvent: O
Product: CC(Nc1nc2cccc([N+](=O)[O-])c2s1)c1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 73.5 %

Procedure:
To 0.160 g (0.75 mmol) of 2-chloro-7-nitro-1,3-benzothiazole in 2 mL of 1-methyl-2-pyrrolidinone (NMP) was added 0.29 μL (2.2 mmol) of racemic α-methylbenzylamine. The reaction was stirred at room temperature for 18 h, diluted with water and extracted with dichloromethane. The organic layer was concentrated in vacuo and purified by flash chromatography eluting with a 25% ethyl acetate/hexanes mixture to give 0.165 g (74%) of the title compound as a light yellow solid which was used without further analysis in the subsequent step.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[CH:14]=[C:13]([C:16]([O:18]C)=[O:17])[NH:12][C:11]=3[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[OH-].[Na+].C1COCC1>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[C:15]3[CH:14]=[C:13]([C:16]([OH:18])=[O:17])[NH:12][C:11]=3[CH2:10][CH2:9]2)=[CH:6][CH:7]=1
Reactant: COC(=O)c1cc2c([nH]1)CCC2c1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)c1cc2c([nH]1)CCC2c1ccc(Cl)cc1
Yield: 48 %

Procedure:
The title compound was synthesized from methyl 4-(4-chlorophenyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.0492 g, 0.18 mmol) and sodium hydroxide (0.45 mL, 10M, 25 equiv), according to General Procedure 7. A 1:4 mixture of THF and methanol (5 mL) was used. The resulting product was purified by preparative HPLC using the Chromeleon purification system. A 0.1% formic acid/1% acetonitrile mixture in water (aqueous phase) and methanol (no modifier added—organic phase) using a 50 mm Dynamax HPLC C-18 column at 28 mL/min (initial gradient of 40% methanol and increasing to 100% over 7 minutes) afforded the title compound (22.6 mg, 48%) with purity by HPLC of 93.6% (UV) and 100% (ELSD). LCMS m/e 260 (M−H). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.23-7.28 (m, 2H), 7.15-7.19 (m, 2H), 6.52 (s, 1H), 4.18 (t, J=7.17 Hz, 1H), 2.70-2.97 (m, 3H), 2.20 (dddd, J=12.75, 8.60, 6.53, 6.41 Hz, 1H).
Reaction SMILES: [CH2:1]=[CH:2][C:3](=[CH2:5])[CH3:4].Cl[CH:7]([CH3:10])[C:8]#[N:9]>>[CH2:1]=[CH:2][C:3](=[CH2:4])[CH3:5].[C:8](#[N:9])[CH:7]=[CH2:10]
Reactant: CC(Cl)C#N
Solvent: C=CC(=C)C
Product: C=CC#N
Temperature: 80 °C
Reaction time: 114 h

Procedure:
Then, were added thereto 68.2 parts of isoprene and 1.79 parts of 2-chloropropionitrile as an organic halide, and stirred under heating at 80° C. to conduct a polymerization reaction. After 114 hours, the glass reaction vessel was cooled in a dry ice-methanol bath, and the volatiles were distilled off under reduced pressure to give a random (isoprene/acrylonitrile) copolymer. The conversion rate of isoprene was 84% and the conversion rate of acrylonitrile was 76%. The analysis results of the random (isoprene/acrylonitrile) polymer obtained are shown in Table 5. The polymer was confirmed to have a chlorine atom at the terminal of the polymer chain.