Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:17]=[C:16]([C:18](O)=[O:19])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl.[OH:22][C:23]1[C:32]([O:33][CH3:34])=[CH:31][CH:30]=[C:29]2[C:24]=1[CH2:25][CH2:26][NH:27][CH2:28]2>>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:17]=[C:16]([C:18]([N:27]3[CH2:26][CH2:25][C:24]4[C:29](=[CH:30][CH:31]=[C:32]([O:33][CH3:34])[C:23]=4[OH:22])[CH2:28]3)=[O:19])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc2c(c1O)CCNC2
Reactant: O=C(O)c1nc(-c2cccc(F)c2)nc2ccccc12
Agent: Cl
Product: COc1ccc2c(c1O)CCN(C(=O)c1nc(-c3cccc(F)c3)nc3ccccc13)C2
Yield: 24 %

Procedure:
Reaction of 2-(3-fluorophenyl)quinazoline-4-carboxylic acid with 5-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride gave compound 42 (24% yield) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 2.63 and 2.90 (2t, 2H), 3.50 and 4.04 (2t, 2H), 3.74 and 3.80 (2s, 3H), 4.40 and 4.92 (2s, 2H), 6.32 and 6.77 (2d, 1H), 6.71 and 6.91 (2d, 1H), 7.44-7.46 (m, 1H), 7.61-7.82 (m, 2H), 7.89-8.00 (2d, 1H), 8.08-8.26 (m, 3H), 8.31-8.41 (m, 1H); 8.68-8.72 (2s, 1H); MS (ESI) m/z 430 ([M+H]+).
Reaction SMILES: [NH:1]1[C:10](=[S:11])[C:9]2[NH:8][CH:7]=[N:6][C:5]=2[N:4]=[C:2]1[NH2:3].[CH2:12](Br)[C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:14].[C:22](=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[NH2:3][C:2]1[N:4]=[C:5]2[C:9]([NH:8][CH:7]=[N:6]2)=[C:10]([S:11][CH2:22][CH2:12][C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:14])[N:1]=1
Reactant: O=C(CBr)c1ccccc1
Reactant: Nc1nc2nc[nH]c2c(=S)[nH]1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Nc1nc(SCCC(=O)c2ccccc2)c2[nH]cnc2n1
Temperature: 25 °C
Reaction time: 20 h
Yield: 68.8 %

Procedure:
A mixture of thioguanine (8.36 g), phenacyl bromide (9.95 g) and potassium carbonate (7.60 g) in N,N-dimethylformamide (100 cm3) was stirred at ambient temperature for 20 hours. The reaction mixture was filtered and the filtrate evaporated to give a cream solid. Recrystallisation from boiling methanol (100 cm3) gave 10.3 g (72.2%) of the title compound m.p. 204°-205° C.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[S-:11][C:12]#[N:13].[NH4+].[CH3:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][C:22]=1[N:23]1[CH:27]=[CH:26][CH:25]=[CH:24]1)[NH2:19]>CC(C)=O>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:13][C:12]([NH:19][C:18]1[CH:20]=[CH:21][C:22]([N:23]2[CH:27]=[CH:26][CH:25]=[CH:24]2)=[C:16]([CH3:15])[CH:17]=1)=[S:11])=[O:5]
Reactant: O=C(Cl)c1ccccc1Cl
Reactant: Cc1cc(N)ccc1-n1cccc1
Reactant: N#C[S-]
Agent: [NH4+]
Solvent: CC(C)=O
Product: Cc1cc(NC(=S)NC(=O)c2ccccc2Cl)ccc1-n1cccc1
Yield: 95.4 %

Procedure:
In a manner similar to Douglas and Dains, J. Am. Chem. Soc., 56, 719 (1934), the reaction of 3.1 g (0.017 mole) of 2-chlorobenzoyl chloride with 1.3 g (0.017 mole) of ammonium thiocyanate and 3.0 g (0.017 mole) of 3-methyl-4-(1H-pyrrol-1-yl)aniline (compound of Example 2) in 100 ml of acetone produced 6.0 g of 2-chloro-N-[[[3-methyl-4-(1H-pyrrol-1-yl)phenyl]amino]thioxomethyl]benzamide (mp 134°-136° C.).
Reaction SMILES: [F:1][C:2]1[C:7]([CH:8]2[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:15][Si](C=[N+]=[N-])(C)C.O>C(Cl)Cl>[F:1][C:2]1[C:7]([CH:8]2[CH2:15][CH2:9][CH2:10][C:11](=[O:14])[CH2:12][CH2:13]2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: O=C1CCC(c2cccnc2F)CC1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: O
Solvent: ClCCl
Product: O=C1CCCC(c2cccnc2F)CC1

Procedure:
To a solution of boron trifluoride-diethyl etherate (0.64 g, 4.50 mmol) and 4-(2-fluoropyridin-3-yl)cyclohexanone (0.79 g, 4.09 mmol) in DCM (8 mL) at −25° C. under argon was added (trimethylsilyl)diazomethane (2.25 mL, 5.18 mmol, 2.0 M in hexanes). The reaction was stirred for 2 h at that temperature, water was added, and the mixture was extracted with DCM (2×). The combined organic extracts were washed with 10:1 saturated ammonium chloride/ammonium hydroxide mixture (1×), water (1×), saturated aqueous sodium chloride (1×), and dried over anhydrous magnesium sulfate. The mixture was filtered and the filtrate concentrated in vacuo. The resulting oil was purified by silica gel chromatography to give 4-(2-fluoropyridin-3-yl)cycloheptanone. MS (ESI, pos. ion) m/z: 208.1 (M+1).
Reaction SMILES: C[O:2][C:3](=[O:31])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:30])[CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]34[CH2:29][CH:24]5[CH2:25][CH:26]([CH2:28][CH:22]([CH2:23]5)[CH2:21]3)[CH2:27]4)=[CH:16][CH:15]=2)=[CH:6][CH:5]=1.Cl>O1CCOCC1.O>[C:20]12([C:17]3[CH:18]=[CH:19][C:14]([O:13][CH2:12][C:11]([NH:10][C:7]4[CH:6]=[CH:5][C:4]([C:3]([OH:31])=[O:2])=[CH:9][CH:8]=4)=[O:30])=[CH:15][CH:16]=3)[CH2:27][CH:26]3[CH2:28][CH:22]([CH2:23][CH:24]([CH2:25]3)[CH2:29]1)[CH2:21]2
Reactant: COC(=O)c1ccc(NC(=O)COc2ccc(C34CC5CC(CC(C5)C3)C4)cc2)cc1
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Product: O=C(COc1ccc(C23CC4CC(CC(C4)C2)C3)cc1)Nc1ccc(C(=O)O)cc1
Yield: 62.7 %

Procedure:
A solution of 4-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-benzoic acid methyl ester (79.1 mg, 0.16 mmol) in 1,4-dioxane/H2O (3:1, 8 ml) was treated with LiOHH2O (15.9 mg, 0.38 mmol) at room temperature until the reaction was complete, as judged by TLC. The reaction mixture was then acidified with 10% HCl to PH 2, and then partitioned between ethyl acetate and brine. The organic phase was washed with water, dried (MgSO4 anh), and concentrated. The residue was purified by silica gel flash column chromatography (n-Hexane:EtoAc:MeOH=6:3:1) to give 4-[2-(4-Adamantan-1-yl-phenoxy)acetylamino]-benzoic acid as a white solid (40.7 mg, 53.1% yield).
Reaction SMILES: [NH2:1]/[C:2](/[CH3:7])=[CH:3]\[C:4]([O-:6])=[O:5].[C:8]([O:14][CH2:15][CH2:16][C:17]#[N:18])(=[O:13])[CH2:9][C:10]([CH3:12])=O.[N+:19]([C:22]1[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=1[CH:24]=O)([O-:21])=[O:20]>C(O)(C)C>[C:17]([CH2:16][CH2:15][O:14][C:8]([C:9]1[CH:24]([C:23]2[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=2[N+:19]([O-:21])=[O:20])[C:3]([C:4]([OH:6])=[O:5])=[C:2]([CH3:7])[NH:1][C:10]=1[CH3:12])=[O:13])#[N:18]
Reactant: O=Cc1ccccc1[N+](=O)[O-]
Reactant: CC(=O)CC(=O)OCCC#N
Reactant: C/C(N)=C/C(=O)[O-]
Solvent: CC(C)O
Product: CC1=C(C(=O)O)C(c2ccccc2[N+](=O)[O-])C(C(=O)OCCC#N)=C(C)N1
Yield: 86.8 %

Procedure:
10.2 g of 3-nitratopropyl 3-aminocrotonate, 7.8 g of 2-cyanoethyl acetoacetate and 7.7 g of 2-nitrobenzaldehyde in 77 ml of isopropyl alcohol were heated at reflux for 8 hours, and the isopropyl alcohol was evaporated under reduced pressure. The residue was applied to a silica gel column chromatography (eluent: dichloromethane) and recrystallized from a mixture of dichloromethane and diethyl ether to give 16.2 g of 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-(2-cyanoethyl) ester 5-(3-nitratopropyl) ester.
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[C:2]1=[O:11])[CH2:8]2.S(=O)(=O)(O)O.[C-:17]#[N:18].[Na+].CCOCC>CO>[C:17]([C:2]1([OH:11])[CH:3]2[CH2:9][CH:7]3[CH2:6][CH:5]([CH2:10][CH:1]1[CH2:8]3)[CH2:4]2)#[N:18]
Reactant: O=C1C2CC3CC(C2)CC1C3
Reactant: [C-]#N
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CCOCC
Solvent: CO
Product: N#CC1(O)C2CC3CC(C2)CC1C3
Temperature: 25 °C
Yield: 80.9 %

Procedure:
To a well stirred solution of 2-adamantanone (45.0 grams, 0.3 mol) in 200 ml methanol were added 50 ml concentrated sulfuric acid at a rate that caused the solution to reflux. Then a saturated aqueous solution of sodium cyanide (88.2 grams, 0.6 mol) was added, and the mixture was first refluxed for 1 hour and then stirred at room temperature for 3 additional hours. Ether was added, and the organic solution was decanted from the precipitated salts. The ether solution was washed with an aqueous solution of sodium chloride and water and then dried and evaporated to leave 43.0 grams (81%) of compound 4 as a beige crystalline solid, melting point >240° C. (decomposition).
Reaction SMILES: [CH2:1]([N:8]([CH2:18][C:19]1(O)[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]1)[CH2:9][CH:10]([OH:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>Br>[CH2:1]([N:8]1[CH2:18][C:19]2([CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[O:17][CH:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCC(O)(CN(Cc2ccccc2)CC(O)c2ccccc2)CC1
Agent: Br
Product: c1ccc(CN2CC(c3ccccc3)OC3(CCNCC3)C2)cc1
Temperature: 55 °C
Reaction time: 10 h
Yield: 97 %

Procedure:
To tert-butyl 4-[[benzyl-(2-hydroxy-2-phenyl-ethyl)amino]methyl]-4-hydroxy-piperidine-1-carboxylate (6.2 g, 14.07 mmol) was added HBr (60 mL of 48% w/w,) and the reaction mixture was stirred at 55° C. for 10 hours. The reaction mixture was evaporated in vacuo, basified the aqueous with 50% aq. NaOH to pH13, then extracted with DCM (3×75 mL). The combined organics were dried over MgSO4, filtered and concentrated in vacuo to give 4-benzyl-2-phenyl-1-oxa-4,9-diazaspiro[5.5]undecane (4.4 g, 97%) as a yellow oil, which was used directly without further purification. ESI-MS m/z calc. 322.2. Found 323.7 (M+1)+; Retention time: 1.72 minutes (3 min run).
Reaction SMILES: [CH3:1][I:2].[CH2:3]([O:10][C:11]1[C:12]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[N:13][S:14][N:15]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>CC(C)=O>[I-:2].[CH2:3]([O:10][C:11]1[C:12]([C:16]2[CH2:17][N:18]([CH3:1])[CH:19]=[CH:20][CH:21]=2)=[N:13][S:14][N:15]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: CI
Reactant: c1ccc(COc2nsnc2-c2cccnc2)cc1
Solvent: CC(C)=O
Product: CN1C=CC=C(c2nsnc2OCc2ccccc2)C1
Product: [I-]
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of methyl iodide (0.5 ml, 7.5 mmol) and 3-(4-benzyloxy-1,2,5-thiadiazol-3-yl)pyridine (673 mg, 2.5 mmol) in acetone (5 ml) was stirred at room temperature for 18 h. The title compound precipitated from the solution and was collected by filtration to yield 0.75 g (73%).
Reaction SMILES: [C:1]1([C:7]2[O:8][C:9]3[C:14]([C:15](=[O:17])[CH:16]=2)=[CH:13][CH:12]=[CH:11][C:10]=3[CH:18]=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:20]/[C:21](/[CH3:27])=[CH:22]\[C:23]([O:25][CH3:26])=[O:24].[N+:28]([CH2:31][C:32](=O)[CH3:33])([O-:30])=[O:29]>CCO>[CH3:27][C:21]1[NH:20][C:32]([CH3:33])=[C:31]([N+:28]([O-:30])=[O:29])[CH:18]([C:10]2[CH:11]=[CH:12][CH:13]=[C:14]3[C:9]=2[O:8][C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:16][C:15]3=[O:17])[C:22]=1[C:23]([O:25][CH3:26])=[O:24]
Reactant: COC(=O)/C=C(/C)N
Reactant: O=Cc1cccc2c(=O)cc(-c3ccccc3)oc12
Reactant: CC(=O)C[N+](=O)[O-]
Solvent: CCO
Product: COC(=O)C1=C(C)NC(C)=C([N+](=O)[O-])C1c1cccc2c(=O)cc(-c3ccccc3)oc12

Procedure:
10 mmol each of 2-phenyl-4-oxo-4H-chromen-8-aldehyde, methyl 3-aminocrotonate and nitroacetone are boiled under reflux in 20 ml of absolute EtOH for 3 hours, the mixture is concentrated and the residue is crystallized from methanol.
Reaction SMILES: [Si:1]([O:8][C@@H:9]([CH:19]1[CH2:21][N@@:20]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:10][O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH:29]1[CH:33]=[CH:32][N:31]=[CH:30]1.[CH2:34]([P:38]([CH2:43][CH2:44][CH2:45][CH3:46])[CH2:39][CH2:40][CH2:41][CH3:42])[CH2:35][CH2:36][CH3:37].[H-].[Na+]>C1(C)C=CC=CC=1>[Si:1]([O:8][C@H:9]([CH2:10][O:11][Si:12]([C:15]([CH3:16])([CH3:18])[CH3:17])([CH3:13])[CH3:14])[C@@H:19]([NH:20][C:22](=[O:23])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])[CH2:21][N:29]1[CH:33]=[CH:32][N:31]=[CH:30]1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2].[CH2:43]([P:38](=[O:8])([CH2:34][CH2:35][CH2:36][CH3:37])[CH2:39][CH2:40][CH2:41][CH3:42])[CH2:44][CH2:45][CH3:46]
Reactant: c1c[nH]cn1
Reactant: CCCCP(CCCC)CCCC
Reactant: CC(C)(C)OC(=O)N1CC1[C@@H](CO[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N[C@@H](Cn1ccnc1)[C@@H](CO[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C
Product: CCCCP(=O)(CCCC)CCCC
Reaction time: 3 h

Procedure:
A solution of (5)-tert-butyl 2-((S)-1,2-bis(tert-butyldimethylsilyloxy)ethyl)aziridine-1-carboxylate (0.740 g, 1.7 mmol) and 1H-imidazole (0.35 g, 5.1 mmol) in 3 mL toluen was thoroughly degassed and treated with tributylphosphine (0.42 ml, 1.7 mmol). The reaction mixture was heated to reflux and allowed to stir for 3 hours. NaH (60% dispersion in mineral oil) (0.069 g, 2.9 mmol) was added and the reaction mixture was allowed to stir at 110° C. overnight. The reaction mixture was quenched with saturated NH4Cl solution and diluted with EtOAc. The reaction mixture was washed with water then brine. The organics were dried over MgSO4 and concentrated in vacuo. Purification of the crude residue by column chromatography gave tert-butyl (2S,3S)-3,4-bis(tert-butyldimethylsilyloxy)-1-(1H-imidazol-1-yl)butan-2-ylcarbamate with tributylphosphine oxide as the major impurity. This material was used without further purification.
Reaction SMILES: [C:1]1([CH3:9])[CH:6]=[C:5]([CH3:7])[CH:4]=[C:3]([CH3:8])[CH:2]=1.[Cl-:10].[Na+].S(=O)(=O)(O)O.I([O-])(=O)(=O)=O.[Na+]>C(#N)C.O>[Cl:10][C:2]1[C:3]([CH3:8])=[CH:4][C:5]([CH3:7])=[CH:6][C:1]=1[CH3:9]
Reactant: Cc1cc(C)cc(C)c1
Reactant: [Cl-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: O
Solvent: CC#N
Product: Cc1cc(C)c(Cl)c(C)c1
Temperature: 80 °C
Yield: 40 %

Procedure:
Mesitylene (1 mmol) was treated with sodium chloride (1.2 mmol) in acetonitrile: water (2:1, 6 ml). 20% Sulfuric acid (5 ml) and sodium periodate (20 mol %) was added to the reaction mixture. The mixture was heated at 80° C. under inert atmosphere for 6 h. The product was purified by column chromatography to give chloromesitylene (40%).
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:9]([CH2:10]O)=[CH:8][N:7]=[CH:6]2)[CH2:3][CH2:2]1.S(Cl)([Cl:14])=O>>[ClH:14].[Cl:14][CH2:10][C:9]1[N:5]([CH2:4][CH:1]2[CH2:3][CH2:2]2)[CH:6]=[N:7][CH:8]=1
Reactant: OCc1cncn1CC1CC1
Reactant: O=S(Cl)Cl
Product: Cl
Product: ClCc1cncn1CC1CC1
Temperature: 90 °C

Procedure:
To 1-cyclopropylmethyl-5-hydroxymethylimidazole (4.5 g) was added thionyl chloride (30 ml) by portions at 0° C., and the mixture was heated for 30 minutes under nitrogen atmosphere at 90° C. The mixture was allowed to be at room temperature. The solvent was distilled off under reduced pressure and the obtained residue was dissolved in methanol, and the solvent was distilled off again under reduced pressure. The obtained solid was recrystallized from ethyl acetate, to give 5-chloromethyl-1-cyclopropylmethylimidazole hydrochloride (4.5 g) as colorless crystals.
Reaction SMILES: [Cl:1][CH2:2][C:3]([CH2:5][O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].[C:13]1([P:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(OCC)C>C(Cl)(Cl)Cl>[Cl-:1].[O:4]=[C:3]([CH2:5][O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH2:2][P+:19]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: O=C(CCl)COc1ccccc1
Solvent: CCOCC
Solvent: ClC(Cl)Cl
Product: O=C(COc1ccccc1)C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: [Cl-]
Yield: 62.9 %

Procedure:
A solution of 1-chloro-3-phenoxyacetone (6.8 g.) and triphenylphosphine (12 g.) in chloroform (16 ml.) was saturated with nitrogen and heated at reflux under nitrogen overnight. An excess of dry diethyl ether was added, and then the solvents were decanted from the gum that separated. The remaining solvent was removed in vacuo to give crude 2-oxo-3-phenoxypropyltriphenylphosphonium chloride (10.35 g.). This was stirred vigorously with a solution of sodium carbonate (18 g.) in water (180 ml.) for 24 hours. The solution was extracted with diethyl ether and the ethereal extracts dried over sodium sulphate. The solvent was removed by evaporation to give phenoxyacetylmethylenetriphenylphosphorane (5.3 g.), a sticky solid.
Reaction SMILES: [F:1][CH:2]([F:19])[N:3]1[C:7](=[O:8])[N:6]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([O:16][CH3:17])[CH:10]=2)[N:5]=[C:4]1[CH3:18].S(Cl)([Cl:23])(=O)=O>C(Cl)(Cl)Cl.C(Cl)Cl>[Cl:23][C:14]1[CH:13]=[C:12]([CH3:15])[C:11]([O:16][CH3:17])=[CH:10][C:9]=1[N:6]1[C:7](=[O:8])[N:3]([CH:2]([F:1])[F:19])[C:4]([CH3:18])=[N:5]1
Reactant: COc1cc(-n2nc(C)n(C(F)F)c2=O)ccc1C
Reactant: O=S(=O)(Cl)Cl
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: COc1cc(-n2nc(C)n(C(F)F)c2=O)c(Cl)cc1C
Yield: 97 %

Procedure:
A solution of 15.0 g (0.056 mole) of 4-difluoromethyl-4,5-dihydro-1-(4-methyl-3-methoxyphenyl)-3-methyl-1,2,4-triazol-5(1H)-one and 7.5 g (0.056 mole) of sulfuryl chloride in 100 mL of chloroform was stirred at room temperature for two hours. The reaction mixture was concentrated under reduced pressure to leave a residue. This residue was dissolved in methylene chloride and washed with an aqueous 10% sodium hydroxide solution. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to yield 16.5 g of 1-(2-chloro-4-methyl-5-methoxyphenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one as a solid.
Reaction SMILES: [H-].[Na+:2].CO.[O:5]1[CH2:11][CH:10]([OH:12])[CH2:9][O:8][C:7]2=[CH:13][S:14][CH:15]=[C:6]12.[CH2:16]1[S:20](=[O:22])(=[O:21])[O:19][CH2:18][CH2:17]1>C1(C)C=CC=CC=1.CC(C)=O>[O:12]1[CH:10]([CH2:11][O:5][CH2:18][CH2:17][CH2:16][S:20]([O-:22])(=[O:21])=[O:19])[CH2:9][O:8][C:7]2=[CH:13][S:14][CH:15]=[C:6]12.[Na+:2]
Reactant: OC1COc2cscc2OC1
Reactant: O=S1(=O)CCCO1
Agent: [H-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: CO
Solvent: Cc1ccccc1
Product: O=S(=O)([O-])CCCOCC1COc2cscc2O1
Temperature: 40 °C
Reaction time: 1 h
Yield: 83 %

Procedure:
The monomer was formed as follows. Initially, 5.86 grams of pure NaH and 240 milliliters of toluene were added to three necks of a round bottom flask equipped with a stirrer, thermometer, and condenser placed in a heating mantle. The mixture was kept under argon. A solution of 40 grams 2,3-dihydro-thieno[3,4-b][1,4]dioxin-2-yl)-methanol (EDOT MeOH) and 3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepin-3-ol (ProDOT-OH) (ratio 80:20) in 400 ml toluene were added drop wise for 15 minutes. The mixture was stirred at 40° C. for 1 hour. A solution of 28.4 grams of propane sultone in 240 milliliters toluene was added drop wise during 15 minutes. The resulting mixture was heated at reflux for an additional 2 hours. The solution was cooled to ambient temperature and 3.6 liters of acetone was added quickly. The precipitated product was filtered through a fine porosity frit and then dried under vacuum at ambient temperature for 6 days. 61 grams of sodium 3-(2,3-dihydrothieno[3,4-b][1,4]dioxin-2-ylmethoxy)-propane-1-sulfonate (EDOTSNa) was obtained (83% yield).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=[O:15])[CH2:10][CH2:9]2)=[C:4]([N+:17]([O-])=O)[CH:3]=1.[Sn](Cl)[Cl:21].O>C(OCC)(=O)C>[ClH:21].[NH2:17][C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=1[N:8]1[CH2:9][CH2:10][CH:11]([C:14]([OH:16])=[O:15])[CH2:12][CH2:13]1
Reactant: Cl[Sn]Cl
Reactant: O=C(O)C1CCN(c2ccc(F)cc2[N+](=O)[O-])CC1
Solvent: O
Solvent: CCOC(C)=O
Product: Cl
Product: Nc1cc(F)ccc1N1CCC(C(=O)O)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
The solution of 804 mg of 1-(4-fluoro-2-nitrophenyl)piperidine-4-carboxylic acid in 40 ml of ethyl acetate was admixed with 3.8 g of tin(II) chloride and stirred at RT for 2 hours. 50 ml of water were then added and the mixture was filtered through a clarifying layer. The ethyl acetate phase was removed, dried over sodium sulfate and concentrated by rotary evaporator, leaving a semisolid residue which was subjected directly to further reaction.
Reaction SMILES: [OH:1][N:2]1[C:6]2[CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=[CH:10][C:5]=2[N:4]=[N:3]1.[C:14]1([S:20](Cl)(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O.C(OCC)(=O)C>[OH-].[Na+]>[C:14]1([S:20]([O:1][N:2]2[C:6]3[CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=[CH:10][C:5]=3[N:4]=[N:3]2)(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=[N+]([O-])c1ccc2nnn(O)c2c1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Product: O=[N+]([O-])c1ccc2nnn(OS(=O)(=O)c3ccccc3)c2c1
Temperature: 25 °C
Yield: 53.6 %

Procedure:
In 1 N aqueous sodium hydroxide (45 ml) is dissolved 1-hydroxy-6-nitro-1,2,3-benzotriazole (7.2 g). To the solution is added dropwise benzenesulfonyl chloride (7.0 g) with stirring at room temperature and further are added thereto water (50 ml) and ethyl acetate (100 ml) and the mixture is stirred for 1 hour. The ethyl acetate layer is separated, dried over magnesium sulfate-charcoal, filtered and concentrated until it becomes about 30 ml. n-Hexane (50 ml) is thereto added and the mixture is allowed to stand. The precipitated crystals are separated by filtration and dried to give faint yellow prisms of 1-benzenesulfonyloxy-6-nitro-1,2,3-benzotriazole (6.8 g), melting point: 122°-124° C. The product is recrystallized from ethyl acetate-n-hexane to give a pure product: melting point: 124° C.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([CH2:11][CH3:12])=[CH:5][C:6]=1[C:7]([O:9]C)=O.ClC(Cl)(O[C:17](=O)[O:18][C:19](Cl)(Cl)Cl)Cl.C(N(CC)CC)C.[CH3:32][O:33][C:34]1[CH:39]=[C:38]([O:40]C)[N:37]=[C:36]([NH2:42])[N:35]=1>C(Cl)Cl>[CH3:32][O:33][C:34]1[CH:39]=[C:17]([O:18][CH3:19])[N:42]=[C:36]([N:37]2[C:7](=[O:9])[C:6]3[CH:5]=[C:4]([CH2:11][CH3:12])[S:3][C:2]=3[NH:1][C:38]2=[O:40])[N:35]=1
Reactant: CCc1cc(C(=O)OC)c(N)s1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc(OC)nc(N)n1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCc1cc2c(=O)n(-c3nc(OC)cc(OC)n3)c(=O)[nH]c2s1
Temperature: 25 °C
Reaction time: 2 h
Yield: 228.2 %

Procedure:
To a solution (40 mL) of methyl 2-amino-5-ethylthiophene-3-carboxylate (0.5 g) in methylene chloride were added triphosgene (0.35 g) and triethylamine (0.6 mL), and the mixture was stirred at room temperature for 2 hr. To the reaction mixture was added 4,6-dimethoxypyrimidin-2-amine (1 g), and the mixture was further stirred at room temperature for 1 hr. The reaction mixture was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in methanol (40 mL), sodium methoxide (1 g) was added, and the mixture was stirred at 60° C. for 2 hr. The reaction mixture was neutralized with hydrochloric acid (10% methanol solution), insoluble material was filtered off, and the solvent was evaporated under reduced pressure. The precipitated solid was collected by filtration to give the title compound as a colorless solid (0.9 g, 100%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:11])[CH3:10])[CH:5]=[N:6][CH:7]=1.C([Sn](CCCC)(CCCC)[C:17]([O:19][CH2:20][CH3:21])=[CH2:18])CCC>CN(C=O)C.[F-].[K+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:20]([O:19][C:17]([C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:11])[CH3:10])[CH:5]=[N:6][CH:7]=1)=[CH2:18])[CH3:21]
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Reactant: CC(=O)Nc1cncc(Br)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [F-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=C(OCC)c1cncc(NC(C)=O)c1
Temperature: 80 °C
Reaction time: 24 h

Procedure:
To a solution of N-(5-bromopyridin-3-yl)acetamide (2.7 mmol) and Pd(PPh3)2Cl2 (0.13 mmol) in DMF (5 mL) under an atmosphere of nitrogen was added tributyl(1-ethoxyvinyl)stannane (2.97 mmol). The reaction was allowed to stir at 80° C. until for approximately 24 hrs. The reaction mixture was allowed to cool to rt and then diluted with aq KF solution (10 mL) and allowed to stir for 30 min. A thick white precipitate formed and was filtered. The filter cake was washed with water and Et2O. The filtrate was diluted with water and extracted with Et2O. The organic solutions were combined, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to give N-[5-(1-ethoxyvinyl)pyridin-3-yl]acetamide in quantitative yield. LCMS: (FA) ES+ 205.2.