Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[Na+].[F:3][C:4]1[C:9]([F:10])=[CH:8][C:7]([F:11])=[CH:6][C:5]=1[C:12]#[C:13][CH2:14][N:15]1[CH2:20][CH2:19][C@@H:18]([CH2:21][CH2:22][CH:23]([NH2:36])[C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([O:34][CH3:35])[CH:32]=3)[N:27]=[CH:26][CH:25]=2)[C@@H:17]([C:37]([O:39]C)=[O:38])[CH2:16]1>O1CCOCC1.C(OC(C)C)(C)C>[F:3][C:4]1[C:9]([F:10])=[CH:8][C:7]([F:11])=[CH:6][C:5]=1[C:12]#[C:13][CH2:14][N:15]1[CH2:20][CH2:19][C@@H:18]([CH2:21][CH2:22][CH:23]([NH2:36])[C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([O:34][CH3:35])[CH:32]=3)[N:27]=[CH:26][CH:25]=2)[C@@H:17]([C:37]([OH:39])=[O:38])[CH2:16]1
Reactant: COC(=O)[C@H]1CN(CC#Cc2cc(F)cc(F)c2F)CC[C@H]1CCC(N)c1ccnc2ccc(OC)cc12
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CC(C)OC(C)C
Product: COc1ccc2nccc(C(N)CC[C@@H]3CCN(CC#Cc4cc(F)cc(F)c4F)C[C@@H]3C(=O)O)c2c1
Reaction time: 16 h
Yield: 34.7 %

Procedure:
1.37 cm3 of 5N aqueous sodium hydroxide solution are added with stirring, at a temperature in the region of 20° C., to a solution of 0.9 g of methyl (3R,4R)-1-[3-(2,3,5-trifluorophenyl)prop 2-ynyl]-4-[3-(R,S)-amino-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate in 9 cm3 of dioxane and then the combined mixture is brought to a temperature in the region of 60° C. for 16 hours. The mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ; mass 40 g), elution being carried out with a dichloromethane/methanol (90/10 by volume) mixture, a dichloromethane/methanol (80/20 by volume) mixture, a dichloromethane/methanol (60/40 by volume) mixture and a dichloromethane/methanol/triethylamine (74/25/1 by volume) mixture, with 100-cm3 fractions being collected Fractions 16 to 29 (which contain the purified product) are combined and then concentrated to dryness under the above conditions. The residue obtained is taken up in 30 cm3 of isopropyl ether, filtered off, washed 2 times with 20 cm3 of diethyl ether and then purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ; diameter 2.3 cm; mass 25 g), elution being carried out with a dichloromethane/methanol (95/05 by volume) mixture. Fractions 4 to 7 are combined and then concentrated to dryness under the above conditions. The solid obtained is taken up in 25 cm3 of isopropyl ether, filtered off, washed 3 times with 10 cm3 of pentane and dried to afford 0.304 g of (3R,4R)-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]-4-[3-(R,S)-amino-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylic acid.
Reaction SMILES: [C:1]([C:9]1[S:13][C:12]2[CH:14]=[CH:15][CH:16]=[C:17]([CH3:18])[C:11]=2[C:10]=1[OH:19])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C.[NH4+:24].C(OC(C)C)(C)C.C(OCC)(=O)C>>[NH2:24]/[C:1](/[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[C:9]1\[C:10](=[O:19])[C:11]2[C:17]([CH3:18])=[CH:16][CH:15]=[CH:14][C:12]=2[S:13]\1
Reactant: [NH4+]
Reactant: Cc1cccc2sc(C(=O)c3ccccc3)c(O)c12
Agent: CC(=O)[O-]
Solvent: CC(C)OC(C)C
Solvent: CCOC(C)=O
Product: Cc1cccc2c1C(=O)/C(=C(\N)c1ccccc1)S2
Yield: 50 %

Procedure:
Prepared as in Example 31 from 2-benzoyl-4-methyl-benzo[b]thiophen-3-ol and ammonium acetate with a yield of 50% of theory. M.p. 198°-200° C. (diisopropyl ether/ethyl acetate 2:1).
Reaction SMILES: [O:1]([C@H:9]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH2:10][C@@H:11]([OH:17])[CH2:12][C:13]([O:15][CH3:16])=[O:14])[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3].[CH2:35](Br)[C:36]#[CH:37]>>[O:1]([C@H:9]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH2:10][C@@H:11]([OH:17])[C@@H:12]([CH2:37][C:36]#[CH:35])[C:13]([O:15][CH3:16])=[O:14])[Si:2]([C:5]([CH3:6])([CH3:7])[CH3:8])([CH3:4])[CH3:3]
Reactant: C#CCBr
Reactant: CCCCCCCCCCCCCCCCC[C@H](C[C@@H](O)CC(=O)OC)O[Si](C)(C)C(C)(C)C
Product: C#CC[C@@H](C(=O)OC)[C@H](O)C[C@@H](CCCCCCCCCCCCCCCCC)O[Si](C)(C)C(C)(C)C

Procedure:
Analogously to Examples Cb) and c), methyl (3R,5R)-5-(t-butyldimethylsiloxy)-3-hydroxydocosanoate (Example lb) was reacted with propargyl bromide to give methyl (2R,3R,5R)-5-(t-butyldimethylsiloxy)-3-hydroxy-2-(2-propynyl)docosanoate, IR (cm-1): 3310, 2120, 1740, 1255, the latter was saponified to give (2R,3R,5R)-5-(t-butyldimethylsiloxy)-3-hydroxy-2-(2-propinyl)-docosanoic acid, IR (cm-1): 3315, 2120, 1715, 1255, and this acid was cyclized to give (3R,4R)-4-[(R)-2-(t-butyldimethylsiloxy)nonadecyl]-3-(2-propynyl)-2-oxetanone, IR (cm-1): 3315, 2130, 1830, 1255.
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:9](O)(=O)[CH2:10][CH2:11][CH2:12][CH3:13]>C(Cl)Cl>[CH2:10]([C:9]1[NH:1][C:2]2=[N:3][CH:4]=[CH:5][CH:6]=[C:7]2[N:8]=1)[CH2:11][CH2:12][CH3:13]
Reactant: Nc1cccnc1N
Reactant: CCCCC(=O)O
Solvent: ClCCl
Product: CCCCc1nc2cccnc2[nH]1
Yield: 60.4 %

Procedure:
10 g (91.6 mmol) of 2,3-diaminopyridine and 27.4 g of valeric acid are stirred at 170° C. for 18 h. After completion of the reaction, the mixture is diluted with 100 ml of CH2Cl2, washed with saturated NaHCO3 solution, water and saturated NaCl solution, dried over Na2SO4 and concentrated. Chromatography on SiO2 using EA/Hep 20:1 yields 9.7 g of the title compound.
Reaction SMILES: [N:1]1[C:11]2[NH:10][C:9]3[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=3[C:7](=[O:16])[NH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:20][C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH3:29])=[O:22].O>CC(N(C)C)=O>[O:22]=[C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH3:29])[CH2:20][N:6]1[C:7](=[O:16])[C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[NH:10][C:11]2[N:1]=[CH:2][CH:3]=[CH:4][C:5]1=2
Reactant: Cc1ccccc1C(=O)CBr
Reactant: O=C1Nc2cccnc2Nc2ccccc21
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: Cc1ccccc1C(=O)CN1C(=O)c2ccccc2Nc2ncccc21
Temperature: 0 °C

Procedure:
5H-benzo[e]pyrido[3,2-b][1,4]diazepin-6(11H)-one (1.0 g, 1 eq.) was suspended in dimethylacetamide (DMA) (30 mL). The reaction was cooled to 0° C. and sodium hydride (60% in mineral oil) (380 mg, 2.0 eq.) was added. The reaction was warmed to room temperature and stirred until gas evolution ceased. The reaction was cooled to 0° C. and 2-bromo-1-(o-tolyl)ethanone (1.2 g, 1.2 eq.) was added. The reaction was stirred at 50° C. overnight. The reaction was poured onto 80 mL water and extracted with dichloromethane (2×100 mL). The organic extracts were combined, washed with water (2×100 mL), brine (2×100 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product, 5-(2-oxo-2-(o-tolyl)ethyl)-5H-benzo[e]pyrido[3,2-b][1,4]diazepin-6(11H)-one (0.65 g) was used without purification. LCMS: 344 [M+H].
Reaction SMILES: C1CCN2C(=NCCC2)CC1.[CH3:12][O:13][C:14]1[CH:23]=[CH:22][C:17](/[CH:18]=[CH:19]/[CH:20]=[O:21])=[CH:16][CH:15]=1.[N:24]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:25]>ClCCl>[OH:25][N:24]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20](=[O:21])/[CH:19]=[CH:18]/[C:17]1[CH:22]=[CH:23][C:14]([O:13][CH3:12])=[CH:15][CH:16]=1
Reactant: O=Nc1ccccc1
Reactant: COc1ccc(/C=C/C=O)cc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: ClCCl
Product: COc1ccc(/C=C/C(=O)N(O)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
DBU (7.5 mg, 0.05 mmol) was added under argon to a solution of (E)-4-methoxycinnamaldehyde (162 mg, 1 mmol), nitrosobenzene (107 mg, 1 mmol) and catalyst (18.2 mg, 0.05 mmol) in dichloromethane (5 mL). The reaction mixture was stirred at room temperature for 10 min. The solvent was removed under vacuum, and the residue was purified by flash silica gel column chromatography using hexane and ethyl acetate as the eluents.
Reaction SMILES: [C:1]([C:4]1[N:5]([N:9]2C(=O)C3C(=CC=CC=3)C2=O)[CH:6]=[CH:7][CH:8]=1)(=[O:3])[CH3:2].CN.O>CN(C)C=O>[NH2:9][N:5]1[CH:6]=[CH:7][CH:8]=[C:4]1[C:1](=[O:3])[CH3:2]
Reactant: CC(=O)c1cccn1N1C(=O)c2ccccc2C1=O
Agent: CN
Solvent: O
Solvent: CN(C)C=O
Product: CC(=O)c1cccn1N
Reaction time: 2.5 h
Yield: 93.2 %

Procedure:
To a suspension of 2-(2-acetyl-1H-pyrrol-1-yl)-1H-isoindole-1,3(2H)dione (8.53 g) in dimethylformamide (25 ml) was added 33 ml of 40% methylamine solution. After 2.5 hours, the reaction mixture was poured into water (300 ml) and was extracted 4 times with EtOAc. The combined organics were washed once with water and brine, dried (MgSO4), filtered and concentrated to give the crude product. Purification via flash column chromatography (silica gel, 30% EtOAc/hexane) afforded 3.88 g of the product as an oil.
Reaction SMILES: Br[CH2:2][C:3]1[C:21]([O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])=[CH:20][C:19]([O:30][CH3:31])=[CH:18][C:4]=1[C:5]([O:7]CC1C=CC([N+]([O-])=O)=CC=1)=[O:6].[CH3:32][O:33][C:34](=[O:53])[C@H:35]([CH2:51][SH:52])[NH:36][C:37](=[O:50])[C@@H:38]([C@H:47]([CH3:49])O)[NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41]>>[Si:23]([O:22][C:21]1[C:3]2[CH2:2][S:52][CH2:51][C@@H:35]([C:34]([O:33][CH3:32])=[O:53])[NH:36][C:37](=[O:50])[C@H:38]([NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C@@H:47]([CH3:49])[O:7][C:5](=[O:6])[C:4]=2[CH:18]=[C:19]([O:30][CH3:31])[CH:20]=1)([C:26]([CH3:29])([CH3:27])[CH3:28])([CH3:25])[CH3:24]
Reactant: COc1cc(O[Si](C)(C)C(C)(C)C)c(CBr)c(C(=O)OCc2ccc([N+](=O)[O-])cc2)c1
Reactant: COC(=O)[C@H](CS)NC(=O)[C@H](NC(=O)OC(C)(C)C)[C@H](C)O
Product: COC(=O)[C@@H]1CSCc2c(O[Si](C)(C)C(C)(C)C)cc(OC)cc2C(=O)O[C@H](C)[C@@H](NC(=O)OC(C)(C)C)C(=O)N1

Procedure:
p-Nitrobenzyl 2-bromomethyl-3-(tert-butyldimethylsilyloxy)-5-methoxybenzoate was reacted with N-[N-(tert-butoxycarbonyl)-D-threonyl]-L-cysteine methyl ester in an analogous manner to the procedure described in Example 1 (f), and the product was subjected in-an analogous manner to a sequence of procedures described in Example 13 (f) and in Example 21 to yield tert-butyl (4R, 7R, 8R)-14-(tert-butyldimethylsilyloxy)-1,3,4,5,6, 7,8,10-octahydro-12-methoxy-4-methoxycarbonyl-8-methyl-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-7-carbamate as white crystals. This material was treated with ammonium fluoride in methanol in an analogous manner to the procedure described in Example 13 to yield, after crystallization from methanol/diethylether/hexane, tert-butyl (4R, 7R, 8R)-1,3,4,5,6,7,8,10-octahydro- 14-hydroxy-12-methoxy-4-methoxycarbonyl-8-methyl-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-7-carbamate as a white solid.
Reaction SMILES: Cl[CH:2]([C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:16])=O)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[NH2:17][C:18]([C:20]1[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:29])[CH3:28])[CH:21]=1)=[S:19]>C(O)(C)C>[C:27]([NH:26][C:22]1[CH:21]=[C:20]([C:18]2[S:19][C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[C:8]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[Cl:16])[N:17]=2)[CH:25]=[CH:24][N:23]=1)(=[O:29])[CH3:28]
Reactant: CC(=O)Nc1cc(C(N)=S)ccn1
Reactant: CCOC(=O)C(Cl)C(=O)c1ccccc1Cl
Solvent: CC(C)O
Product: CCOC(=O)c1sc(-c2ccnc(NC(C)=O)c2)nc1-c1ccccc1Cl
Temperature: 94 °C
Reaction time: 23 h
Yield: 21.4 %

Procedure:
To a stirred solution of crude ethyl 2-chloro-3-(2-chlorophenyl)-3-oxopropanoate (1.390 g, 5.320 mmol) in absolute isopropyl alcohol (50.00 mL) was added N-[4-(aminocarbonothioyl)pyridin-2-yl]acetamide (1.140 g, 5.860 mmol) and the resulting solution was fitted with a condenser and stirred for 23 h at 94° C. The mixture was cooled to ambient temperature and half the solvent was removed in vacuo. Diethyl ether (30.0 mL) was added to allow the formation of the thioamide by-product. The by-product was separated by filtration and the solvent was removed in vacuo. The residue was purified by column chromatography (SiO2, elution with 0-100% EtOAc in hexanes) to provide 0.457 g of product as a yellow oil (21% 2 steps). LC/MS (AA) ES+ 402. NMR (400 MHz, d1 CDCl3) δ: 8.77 (br s, 1H), 8.37-8.35 (m, 1H), 7.71-7.70 (m, 1H), 7.50-7.46 (m, 2H), 7.41-7.46 (m, 3H), 4.24 (q, J=7.2 Hz, 2H), 2.24 (s, 3H), 1.26 (t, J=7.2 Hz, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=1.F[C:15]1[C:20]([C:21]2[N:26]=[C:25]([CH3:27])[N:24]=[C:23]([NH2:28])[N:22]=2)=[CH:19][C:18]([CH:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)=[CH:17][N:16]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Cl>CN(C=O)C.O>[NH2:28][C:23]1[N:24]=[C:25]([CH3:27])[N:26]=[C:21]([C:20]2[C:15]([NH:1][C:2]3[CH:3]=[C:4]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=3)=[N:16][CH:17]=[C:18]([CH:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[CH:19]=2)[N:22]=1
Reactant: Cc1nc(N)nc(-c2cc(C3CCOCC3)cnc2F)n1
Reactant: CS(=O)(=O)Nc1cc(N)cnc1Cl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1nc(N)nc(-c2cc(C3CCOCC3)cnc2Nc2cnc(Cl)c(NS(C)(=O)=O)c2)n1
Reaction time: 1.5 h

Procedure:
To a solution of N-(5-amino-2-chloropyridin-3-yl)methanesulfonamide (60 mg, 0.271 mmol) and 4-(2-fluoro-5-(tetrahydro-2H-pyran-4-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (55 mg, 0.190 mmol) in anhydrous DMF (1 mL) cooled in an ice bath was added solid NaHMDS (210 mg, 1.088 mmol) under nitrogen. The resulting orange mixture was stirred with cooling. After 1.5 h, HCl (5N, 0.25 mL, 1.25 mmol) was added to the mixture. The resulting mixture was diluted with water (5 mL) and acidified with HCl, 5N) to about pH 5. The resulting slurry was filtered and washed with water (3×3 mL). The solid was washed with EtOAc to afford the product as a brown solid. The mother liquid was chromatographed on silica gel (0-5% MeOH in EtOAc) to give additional product. The combined product was about mg (32%). m/z (ESI, positive ion): 491.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.60-1.82 (m, 4H) 2.46 (s, 3H) 2.84 (t, J=11.35 Hz, 1H) 3.12 (s, 3H) 3.46 (t, J=10.76 Hz, 2H) 3.97 (d, J=12.13 Hz, 2H) 7.78 (br. s., 1H) 7.92 (br. s., 1H) 8.33 (s, 1H) 8.64 (d, J=3.33Hz, 2H) 8.72 (s, 1H) 9.64 (br. s., 1H) 12.17 (s, 1H).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([SH:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].[H-].[Na+].CS(O[CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1)(=O)=O>O1CCCC1>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10][CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1
Reactant: O=[N+]([O-])c1ccc(S)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(Sc2ccc([N+](=O)[O-])cc2)CC1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 72.3 %

Procedure:
4-Nitrobenzenethiol (5.93 mmol, 1.15 g), and sodium hydride (8.12 mmol, 0.325 g) were combined in tetrahydrofuran and stirred at 0° C. for 30 minutes. tert-Butyl 4-(methyl-sulfonyloxy)piperidine-1-carboxylate (8.89 mmol, 2.484 g) was added and the reaction mixture heated at 60° C. overnight. The reaction mixture was concentrated under vacuum and residue dissolved in dichloromethane and washed with water. The organic layer was separated, dried and concentrated under vacuum. The residue was purified by silica column chromatography (eluent: dichloromethane) to afford the title compound (1.45 g). MS (ESI) m/z 339.5 [M+H]+
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[CH:20][C:19]([CH:22]=O)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:5].[NH2:24][CH2:25][C:26]([CH3:30])([CH3:29])[CH2:27][OH:28].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([CH2:22][NH:24][CH2:25][C:26]([CH3:30])([CH3:29])[CH2:27][OH:28])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:5]
Reactant: O=Cc1ccc(Cl)c(C(=O)NCC23CC4CC(CC(C4)C2)C3)c1
Reactant: CC(C)(CN)CO
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: CC(C)(CO)CNCc1ccc(Cl)c(C(=O)NCC23CC4CC(CC(C4)C2)C3)c1
Yield: 18.5 %

Procedure:
Prepared according to the method described in Example 2 from 2-chloro-5-formyl-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (0.150 g, Example 1b), 3-amino-2,2-dimethylpropanol (0.093 g) and sodium triacetoxyborohydride (0.134 g) in 1,2-dichloroethane (6 ml). After work-up, the resiude was purified by NPHPLC eluting with a gradient of 0-10% ethanol in dichloromethane to give the title compound as a white powder (0.035 g).
Reaction SMILES: [C:1]([C:9]1[CH:14]=[C:13]([CH:15]=[CH2:16])[CH:12]=[CH:11][C:10]=1[NH:17]C(=O)C(F)(F)F)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+]>CO.O>[NH2:17][C:10]1[CH:11]=[CH:12][C:13]([CH:15]=[CH2:16])=[CH:14][C:9]=1[C:1]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:8]
Reactant: C=Cc1ccc(NC(=O)C(F)(F)F)c(C(=O)c2ccccc2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: C=Cc1ccc(N)c(C(=O)c2ccccc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 89.6 %

Procedure:
N-(2-Benzoyl-4-vinylphenyl)-2,2,2-trifluoroacetamide (b) (0.32 g, 1.0 mmol) was dissolved in a mixture of methanol (38 mL) and water (2.3 mL) and potassium carbonate (0.7 g, 5 mmol) was added. After stirring overnight at room temperature, the mixture was concentrated. Water (20 mL) was added to the residue and the mixture was extracted with chloroform (3×50 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated. The residue was purified by flash chromatography on silica gel [hexanes:ethyl acetate (9:1)] to produce 2-amino-5-vinylbenzophenone (c) (0.2 g, 90%). 1H NMR (300 MHz, CDCl3) δ 7.70-7.60 (m, 2H), 7.60-7.40 (m, 5H), 6.72 (d, J=10 Hz, 1H), 6.65 (dd, J=11, 19.6 Hz, 1H), 6.16 (s, br, 2H), 5.56 (d, J=19.6 Hz, 1H), 5.03 (d, J=11 Hz,1H). MS: 224.2 (M+H).
Reaction SMILES: [NH:1]([C:5]1[NH:6][C:7]2[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=2[N:9]=1)[C:2]([NH2:4])=[NH:3].[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:21](=O)[CH:22]=[CH:23]N(C)C)=[CH:17][N:16]=1>CC(O)C>[N:9]1[C:8]2[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=2[NH:6][C:5]=1[NH:1][C:2]1[N:4]=[C:21]([C:18]2[CH:19]=[CH:20][C:15]([Cl:14])=[N:16][CH:17]=2)[CH:22]=[CH:23][N:3]=1
Reactant: N=C(N)Nc1nc2ccccc2[nH]1
Reactant: CN(C)C=CC(=O)c1ccc(Cl)nc1
Solvent: CC(C)O
Product: Clc1ccc(-c2ccnc(Nc3nc4ccccc4[nH]3)n2)cn1
Temperature: 25 °C
Yield: 13.4 %

Procedure:
A solution of 2-guanidinobenzimidazole (0.83 g, 4.75 mmol) and 1-(2-chloropyrid-5-yl)-3-dimethylamino-2-propen-1-one (1.00 g, 4.75 mmol) in propan-2-ol (10 ml) was refluxed for 18 h. The solid which formed on cooling to room temperature was collected and washed with cold propan-2-ol to afford the title compound (205 mg) as a white solid m.p. 308-311°. δH (d6DMSO) 7.06 (2H, m), 7.45 (2H, m), 7.69 (1H, d, J 5.3 Hz), 7.74 (1H, d, J 8.4 Hz), 8.59 (1H, dd, J 2.5, 8.4 Hz), 8.75 (1H, d, J 5.2 Hz), 9.21 (1H, d, J 1.9 Hz) and 11.30 (1H, br s).
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11](O)=O.C(Cl)(=O)C(Cl)=O.S(N)([NH2:23])(=O)=O.[OH-].[Na+]>ClCCl.CN(C=O)C>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]#[N:23]
Reactant: NS(N)(=O)=O
Reactant: O=C(O)CCc1cccc(F)c1F
Agent: O=C(Cl)C(=O)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: N#CCCc1cccc(F)c1F
Temperature: 25 °C
Reaction time: 2 h
Yield: 100.4 %

Procedure:
To a solution of 3-(2,3-difluorophenyl)-propionic acid (A1) (6.83 g, 36 mmol) in anhydrous dichloromethane (50 ml) containing a few drops of DMF was added oxalyl chloride (6.4 ml, 73 mmol) at 0° C. under argon. The solution was stirred at ambient temperature for 2 h and the solvent removed in vacuo. The residue was dissolved in sulfolane (30 ml) and added to sulfamide (4.23 g, 44 mmol) and the mixture heated at 120° C. for 3 h. The brown solution was cooled, poured into 2M sodium hydroxide solution (300 ml) and extracted with ether. The combined extracts were washed with water, dried (MgSO4) and evaporated to give the title compound as a brown oil (6.04 g, 98%). 1H-NMR (CDCl3) δ 2.68 (2H, t), 3.04 (2H, t), 7.01-7.15 (3H, m).
Reaction SMILES: [CH:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1)=O.[C:12](#[N:15])[CH:13]=C.CN1CCOCC1>CC1C=CC(C)=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:7]([C:6]1[CH:10]=[CH:11][C:3]([CH:1]=[CH:13][C:12]#[N:15])=[CH:4][CH:5]=1)=[O:8]
Reactant: O=Cc1ccc(C(=O)Cl)cc1
Reactant: C=CC#N
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CN1CCOCC1
Solvent: Cc1ccc(C)cc1
Product: N#CC=Cc1ccc(C=O)cc1
Yield: 8.4 %

Procedure:
3.91 mg (1.6×10-5 mols) of palladium acetate, 6.74 g (40 millimols) of 4-formylbenzoyl chloride, 2.63 ml (40 millimols) of acrylonitrile and 4.41 ml (40 millimols) of N-methylmorpholine, in 80 ml of p-xylene, are stirred for 5 hours. Working up as described in the preceding examples affords 0.53 g (8% of theory) of 4-formylcinnamonitrile.
Reaction SMILES: [CH2:1]([OH:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]#[CH:15].[CH3:17][C:18]([Si:21](Cl)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([CH3:20])[CH3:19]>>[C:18]([Si:21]([O:16][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]#[CH:15])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)([CH3:20])([CH3:17])[CH3:19]
Reactant: C#CCCCCCCCCCCCCCO
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Product: C#CCCCCCCCCCCCCCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Yield: 91.9 %

Procedure:
Silylation of pentadec-14-yn-1-ol (8.80 g, 39.28 mmol) using TBDPSCl (12.92 g, 47.14 mmol) as described above gave tert-butyl(pentadec-14-ynyloxy)diphenylsilane (16.7 g, 87%) as a colorless oil. TLC: 6% EtOAc/hexanes, Rf≈0.6; 1H NMR (CDCl3, 300 MHz) δ 7.65-7.68 (m, 4H), 7.34-7.42 (m, 6H), 3.65 (t, J=7.3 Hz, 2H), 2.15-2.21 (m, 2H), 1.94 (t, J=1.9 Hz, 1H), 1.20-1.60 (m, 22H), 1.04 (s, 9H).
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:13]=[N:12][CH:11]=[N:10]2)=[CH:5][CH:4]=1)=[CH2:2].[Li]CCCC.[CH3:19][S:20]SC>C1COCC1>[CH3:19][S:20][C:13]1[N:9]([C:6]2[CH:5]=[CH:4][C:3]([CH:1]=[CH2:2])=[CH:8][CH:7]=2)[N:10]=[CH:11][N:12]=1
Reactant: CSSC
Reactant: C=Cc1ccc(-n2cncn2)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C=Cc1ccc(-n2ncnc2SC)cc1
Reaction time: 0.5 h

Procedure:
To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]-triazole (1 g, 5.8 mmol) in 50 mL of THF, was added n-BuLi (0.41 g, 6.4 mmol) at −78° C. and stirred for 30 min. To this dimethyldisulfide in THF (0.6 g, 6.43 mmol) was added and the resultant reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was quenched with a saturated aqueous NH4Cl solution and extracted with EtOAc (3×25 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO2, 100-200 mesh, 40% EtOAc in Pet ether) to afford the title compound as an off white solid (0.6 g, 48%): mp 68-70° C.; 1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.05 (m, 4H), 6.75 (dd, J=16.4, 10.7 Hz, 1H), 5.81 (d, J=16.4 Hz, 1H), 5.35 (d, J=10.7 Hz, 1H), 2.73 (s, 3H); ESIMS m/z 218.09 ([M+H]+).
Reaction SMILES: [C:1]([O:4][C:5]1[C:6]([O:22][CH3:23])=[CH:7][C:8]2[NH:9][C:10]3[C:15]([S:16][C:17]=2[C:18]=1[Br:19])=[CH:14][C:13]([O:20][CH3:21])=[CH:12][CH:11]=3)(=[O:3])[CH3:2].ClC1C=C(C=CC=1)C(OO)=[O:29]>ClCCl.CO>[C:1]([O:4][C:5]1[C:6]([O:22][CH3:23])=[CH:7][C:8]2[NH:9][C:10]3[C:15]([S:16](=[O:29])[C:17]=2[C:18]=1[Br:19])=[CH:14][C:13]([O:20][CH3:21])=[CH:12][CH:11]=3)(=[O:3])[CH3:2]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COc1ccc2c(c1)Sc1c(cc(OC)c(OC(C)=O)c1Br)N2
Solvent: CO
Solvent: ClCCl
Product: COc1ccc2c(c1)S(=O)c1c(cc(OC)c(OC(C)=O)c1Br)N2
Reaction time: 1 h
Yield: 74 %

Procedure:
To a solution of 3-acetoxy-4-bromo-2,7-dimethoxy-10H-phenothiazine (10.0 g) in dichloromethane (125 ml) and methanol (125 ml) there was added at room temperature 85% m-chloro peroxybenzoic acid (4.36 g). The mixture was stirred for one hour and the solid was filtered and washed with ether. This crude product was stirred at room temperature in dichloromethane (50 ml) overnight and filtered again to afford pure title product (7.7 g). m.p.: 243°-247° C. (dec).