Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH3:2][N:3]([CH3:14])[CH2:4][CH2:5][C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:7].C(=O)([O-])[O-].[K+].[K+].[BH4-].[Na+]>CO.O>[CH3:14][N:3]([CH3:2])[CH2:4][CH2:5][CH:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[OH:7]
Reactant: CN(C)CCC(=O)c1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [BH4-]
Solvent: CO
Solvent: O
Product: CN(C)CCC(O)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 65.4 %

Procedure:
To a solution of 313.7 g of 3-dimethylaminopropiophenone hydrochloride in 750 ml of methanol and 375 ml of water was added a saturated solution of potassium carbonate until the pH of the solution was 10. The solution was cooled to 0° C. by means of an external ice bath at which time 27.8 g of sodium borohydride were added in portions over a 4-hour period. The ice bath was removed and the reaction mixture stirred at room temperature overnight. The methanol was removed in vacuo and the resulting solution diluted with water and extracted four times with diethyl ether. The combined ether extracts were washed once with water, once with a saturated sodium chloride solution, dried over sodium sulfate, and concentrated in vacuo to provide an oil. The oil was taken up in 300 ml of hexanes and chilled overnight. The resulting crystals were recovered by filtration providing 172 g of desired subtitle intermediate as a white crystalline solid, m.p.=45°-46° C.
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([Cl:11])[C:3]=1[CH2:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH:22]=O)=[O:14].C([O-])([O-])=O.[Na+].[Na+]>CO>[Cl:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([Cl:11])[C:3]=1[C:12]1[C:13](=[O:14])[NH:15][C:16]2[C:17]([CH:22]=1)=[CH:18][CH:19]=[CH:20][CH:21]=2
Reactant: O=Cc1ccccc1NC(=O)Cc1c(Cl)ccc([N+](=O)[O-])c1Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Product: O=c1[nH]c2ccccc2cc1-c1c(Cl)ccc([N+](=O)[O-])c1Cl
Yield: 43.2 %

Procedure:
A solution of 2-(2,6-dichloro-3-nitro-phenyl)-N-(2-formyl-phenyl)-acetamide (0.7 g, 1.99 mmol) and Na2CO3 (1.0 g) in MeOH (150 mL) is heated for 30 minutes at 70° C. After filtration of the reaction mixture, the solvent is removed by concentration to give crude product. The crude product is purified by flash silica gel column, eluting with CH2Cl2 (100%) gradient to CH2Cl2/MeOH (2N NH3) (97/3%), resulting in the titled intermediate as a solid (0.288 g, 41.3%).
Reaction SMILES: [OH:1][C:2]1[C:6]([CH3:13])([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[S:5][C:4](=[O:14])[CH:3]=1.S(OC)(O[CH3:19])(=O)=O>>[CH3:19][O:1][C:2]1[C:6]([CH3:13])([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[S:5][C:4](=[O:14])[CH:3]=1
Reactant: CCCCCCC1(C)SC(=O)C=C1O
Reactant: COS(=O)(=O)OC
Product: CCCCCCC1(C)SC(=O)C=C1OC
Yield: 57.6 %

Procedure:
From 33 (40.3 mg, 0.19 mmol) and dimethyl sulfate (35 μL, 0.37 mmol) following general procedure H was obtained 36 (25 mg, 58%) after flash chromatography (15% EtOAc/Hexanes). 1H NMR (300 MHz, CDCl3) δ 0.86 (t, J=6.7 Hz, 3H), 1.08-1.13 (m, 1H), 1.24 (s, 6H), 1.35-1.39 (m, 1H), 1.61 (s, 3H), 1.75-1.82 (m, 2H), 3.81 (s, 3H), 5.30 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 14.0, 22.5, 25.1, 26.4, 29.2, 31.5, 38.9, 59.4, 59.4, 101.3, 187.3, 193.8.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[CH:6][C:5]2[N:8]=[N:9][N:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=3)[C:4]=2[CH:3]=1>C(O)(=O)C.[Rh]>[CH3:1][CH:2]1[NH:7][CH2:6][C:5]2[N:8]=[N:9][N:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=3)[C:4]=2[CH2:3]1
Reactant: Cc1cc2c(cn1)nnn2-c1ccccn1
Agent: [Rh]
Solvent: CC(=O)O
Product: CC1Cc2c(nnn2-c2ccccn2)CN1

Procedure:
A solution of 6-methyl-1-(pyridin-2-yl)-1H-[1,2,3]triazolo[4,5-c]pyridine (530 mg, 1.932 mmol) in acetic acid (100 mL) was passed through a Rh/C cartridge using an HCube® hydrogenation apparatus at 90 bar, 90° C. and 1 mL/min. The acetic acid was concentrated and to the residue was added 1N NaOH until pH 12 was obtained. The water layer was extracted with 20% IPA/CH2Cl2 three times. The organic layers were combined, dried over anhydrous MgSO4, filtered and concentrated to a light brown solid (243 mg, 58%). MS (ESI) mass calcd. C11H13N5, 215.12. m/z found, 216.1 [M+H]+. 1H NMR (600 MHz, MeOD) δ 8.57 (ddd, J=4.9, 1.8, 0.9 Hz, 1H), 8.11-8.03 (m, 2H), 7.47 (ddd, J=7.2, 4.9, 1.2 Hz, 1H), 4.13-3.97 (m, 2H), 3.35-3.40 (m, 1H), 3.09-3.02 (m, 1H), 2.86-2.79 (m, 1H), 1.34 (d, J=6.4 Hz, 3H).
Reaction SMILES: C[O-].[Na+].Cl.[N:5]1[CH:10]=[CH:9][C:8]([CH2:11]Cl)=[CH:7][CH:6]=1.[SH:13][CH2:14][C:15]([O:17][CH3:18])=[O:16]>CO>[N:5]1[CH:10]=[CH:9][C:8]([CH2:11][S:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])=[CH:7][CH:6]=1
Reactant: ClCc1ccncc1
Reactant: COC(=O)CS
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: COC(=O)CSCc1ccncc1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
Sodium methoxide (2.16 g., 40 mmoles) is dissolved in 24 ml. of methanol, stirring under nitrogen, and the solution cooled in an ice bath. 4-Picolyl chloride hydrochloride (3.38 g., 20 mmoles), finely divided and suspended in approximately 20 ml. of methanol, is added dropwise over approximately 15 minutes. A solution of methyl 2-mercaptoacetate (2.12 g., 20 mmoles) in 4 ml. of methanol is then added over approximately 5 minutes. The reaction mixture is warmed slowly and left to stir under nitrogen for 14 hours at room temperature. The reaction is filtered with diatomaceous earth. Solids are repulped with an additional 75 ml. of methanol. The methanol filtrates are combined and concentrated to yield title product.
Reaction SMILES: [C:1]1([CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:15](Cl)(=[O:17])[CH3:16]>>[C:15]([C:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:8])(=[O:17])[CH3:16]
Reactant: CC(c1ccccc1)c1ccccc1
Reactant: CC(=O)Cl
Product: CC(=O)C(C)(c1ccccc1)c1ccccc1

Procedure:
For example, vinylnaphthalene may be obtained by reacting formylnaphthalene with a Grignard reagent such as methyl magnesium iodide and then dehydrating the reaction product. Vinylphenylphenylethane may be obtained by reacting diphenylethane with acetyl chloride in the presence of a Friedel-Craft catalyst to produce acetylphenylphenylethane, reducing the thus produced product with sodium boron hydride and then dehydrating the thus reduced product. Isopropenylphenylphenylethane may be obtained by reacting formylphenylphenylethane with a Grignard reagent such as methyl magnesium iodide and then dehydrating the reaction product. 1,2-diphenylethylene may be obtained by reacting benzaldehyde with benzyl magnesium bromide and then dehydrating the reaction product; 1,2-diphenylpropene may likewise be obtained.
Reaction SMILES: [C@H:1]12[CH2:6][C@H:5]1[CH2:4][NH:3][C@@H:2]2[CH2:7][NH:8][C:9]([C:11]1[N:18]2[C:14]([S:15][CH:16]=[CH:17]2)=[N:13][C:12]=1[CH3:19])=[O:10].[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[S:31][C:30]([CH3:32])=[N:29][C:28]=2[C:33](O)=[O:34])=[CH:23][CH:22]=1>>[F:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[S:31][C:30]([CH3:32])=[N:29][C:28]=2[C:33]([N:3]2[CH2:4][C@H:5]3[C@H:1]([CH2:6]3)[C@H:2]2[CH2:7][NH:8][C:9]([C:11]2[N:18]3[C:14]([S:15][CH:16]=[CH:17]3)=[N:13][C:12]=2[CH3:19])=[O:10])=[O:34])=[CH:25][CH:26]=1
Reactant: Cc1nc2sccn2c1C(=O)NC[C@H]1NC[C@@H]2C[C@@H]21
Reactant: Cc1nc(C(=O)O)c(-c2ccc(F)cc2)s1
Product: Cc1nc(C(=O)N2C[C@@H]3C[C@@H]3[C@H]2CNC(=O)c2c(C)nc3sccn23)c(-c2ccc(F)cc2)s1

Procedure:
prepared by reaction of 6-Methyl-imidazo[2,1-b]thiazole-5-carboxylic acid [(1S,2S,5R)-1-(3-aza-bicyclo[3.1.0]hex-2-yl)methyl]-amide with 5-(4-Fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid.
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:8]=2[O:19][C:20](=[O:26])[NH:21][S:22](Cl)(=[O:24])=[O:23])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:27]([C:30]1[CH:36]=[CH:35][CH:34]=[C:33]([CH:37]([CH3:39])[CH3:38])[C:31]=1[NH2:32])([CH3:29])[CH3:28].C(N(CC)CC)C>O1CCCC1>[C:1]1([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:8]=2[O:19][C:20](=[O:26])[NH:21][S:22]([NH:32][C:31]2[C:33]([CH:37]([CH3:38])[CH3:39])=[CH:34][CH:35]=[CH:36][C:30]=2[CH:27]([CH3:29])[CH3:28])(=[O:24])=[O:23])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(NS(=O)(=O)Cl)Oc1c(-c2ccccc2)cccc1-c1ccccc1
Reactant: CC(C)c1cccc(C(C)C)c1N
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)c1cccc(C(C)C)c1NS(=O)(=O)NC(=O)Oc1c(-c2ccccc2)cccc1-c1ccccc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of [1,1':3', 1"-terphenyl]-2'-yl(chlorosulfonyl)carbamate (5.0 g, 12.9 mmol) in 75 mL tetrahydrofuran was added dropwise to a solution of 2,6-diisopropyl aniline (2.29 g, 12.9 mmol) and triethylamine (1.3 g, 12.9 mmol) in 100 mL tetrahydrofuran at -15° C. under an atmosphere of nitrogen. The resulting mixture was warmed to room temperature and stirred for 16 hours. Concentrated in vacuo and partitioned the residue between water and ethyl acetate. Dried the organic layer over MgSO4 and evaporated to give an off-white solid. Chromatography on silica gel gave the title compound, mp 166°-168° C.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[NH2:12][C:13]1[C:14](=[O:22])[NH:15][C:16]([CH2:19][CH2:20][CH3:21])=[CH:17][CH:18]=1>O1CCOCC1.[OH-].[Na+].O.C(=O)([O-])[O-].[Na+].[Na+]>[CH2:5]([O:4][C:2]([NH:12][C:13]1[C:14](=[O:22])[NH:15][C:16]([CH2:19][CH2:20][CH3:21])=[CH:17][CH:18]=1)=[O:3])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CCCc1ccc(N)c(=O)[nH]1
Agent: O=C([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: CCCc1ccc(NC(=O)OCc2ccccc2)c(=O)[nH]1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Benzyl chloroformate (1.8 ml, 12.6 mmol) was added to a solution of 3-amino-6-propyl-2-pyridinone (1.63 g, 10.8 mmol) in a mixture of dioxane (25 ml) and 1N NaOH at 0° C. Within minutes a white precipitate formed. The reaction mixture was stirred at the same temperature for 1 h then at room temperature for 1 h. The reaction mixture was diluted with water and extracted with ethyl acetate then methylene chloride. Each extract was washed with brine then combined and dried over magnesium sulfate. Removal of the solvents in vacuo gave a yellow semi-solid which was a mixture of starting material and product. This was redissolved in a mixture of dioxane (24 ml) and 10% aqueous sodium carbonate (12 ml) and cooled to 0° C. Benzyl chloroformate (1.5 ml, 10.5 mmol) was once again added and after stirring for 0.5 h, the reaction mixture was allowed to stir at room temperature for 3 h. After dilution with water, the precipitate was filtered off and washed thoroughly, first with water and then with ether. Drying gave the title compound as a white powder: 1H NMR (CDCl3) d 0.96 (t, J=7.3 Hz, 3 H), 1.68 (m, 2 H), 2.52 (t, J=7.5 Hz, 2 H), 5.22 (s, 2 H), 6.07 (d, J=7.5 Hz, 1 H), 7.34-7.43 (m, 4 H), 7.68 (s, 1 H), 8.05 (br d, J=5.3 Hz, 1 H).
Reaction SMILES: [C:1]([C:3]1([C:6]([OH:8])=O)[CH2:5][CH2:4]1)#[N:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:33][C:34]([F:57])([F:56])[C:35]1[CH:40]=[CH:39][C:38]([CH:41]2[CH2:46][NH:45][CH2:44][CH:43]([NH:47][C:48](=[O:55])[C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[CH2:42]2)=[CH:37][CH:36]=1>CN(C)C1C=CN=CC=1.CN(C=O)C>[C:1]([C:3]1([C:6]([N:45]2[CH2:46][CH:41]([C:38]3[CH:37]=[CH:36][C:35]([C:34]([F:57])([F:56])[F:33])=[CH:40][CH:39]=3)[CH2:42][CH:43]([NH:47][C:48]([C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=3)=[O:55])[CH2:44]2)=[O:8])[CH2:5][CH2:4]1)#[N:2]
Reactant: N#CC1(C(=O)O)CC1
Reactant: O=C(NC1CNCC(c2ccc(C(F)(F)F)cc2)C1)c1ccccc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: CN(C)c1ccncc1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: N#CC1(C(=O)N2CC(NC(=O)c3ccccc3)CC(c3ccc(C(F)(F)F)cc3)C2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
31 mg (0.28 mmol) of 1-cyanocyclopropanecarboxylic acid together with 131 mg (0.34 mmol) of HATU and 56 mg (0.46 mmol) of 4-dimethylaminopyridine were initially charged in 2 ml of DMF, and 80 mg (0.23 mmol) of N-{5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}benzamide were added. The reaction mixture was stirred overnight at RT and then purified by preparative HPLC (Reprosil C18, water/acetonitrile gradient). Yield: 73 mg (72% of theory)
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:11]=2)[C:6](=[C:18](OCC)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:5]1=[O:28])(=O)C.[NH2:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]([CH3:41])[S:37]([CH3:40])(=[O:39])=[O:38])=[CH:32][CH:31]=1>>[CH3:41][N:36]([S:37]([CH3:40])(=[O:39])=[O:38])[C:33]1[CH:32]=[CH:31][C:30]([NH:29]/[C:18](=[C:6]2\[C:5](=[O:28])[NH:4][C:12]3[C:7]\2=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:11]=3)/[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:35][CH:34]=1
Reactant: CCOC(=O)c1ccc2c(c1)N(C(C)=O)C(=O)C2=C(OCC)c1ccccc1
Reactant: CN(c1ccc(N)cc1)S(C)(=O)=O
Product: CCOC(=O)c1ccc2c(c1)NC(=O)/C2=C(\Nc1ccc(N(C)S(C)(=O)=O)cc1)c1ccccc1

Procedure:
Prepared from 1-acetyl-3-(1-ethoxy-1-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and N-(4-aminophenyl)-N-methyl-methanesulphonamide Rf value: 0.8 (aluminium oxide, ethyl acetate) C26H25N3O5S
Reaction SMILES: [F:1][C:2]1[CH:35]=[CH:34][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]3[C:16]([C:27]4[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=4)=[C:17]([CH2:22][C:23]([O:25][CH3:26])=[O:24])[N:18]([CH3:21])[C:19](=[O:20])[C:8]2=3)=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CC1(C)[C@]23C4(ON4S(=O)(=[O:54])C2)C[C@H]1CC3.Cl>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]3[C:16]([C:27]4[CH:28]=[CH:29][C:30]([CH3:33])=[CH:31][CH:32]=4)=[C:17]([CH:22]([OH:54])[C:23]([O:25][CH3:26])=[O:24])[N:18]([CH3:21])[C:19](=[O:20])[C:8]2=3)=[CH:34][CH:35]=1
Reactant: COC(=O)Cc1c(-c2ccc(C)cc2)c2c3ccccc3n(Cc3ccc(F)cc3)c2c(=O)n1C
Reactant: CC1(C)[C@@H]2CC[C@@]13CS(=O)(=O)N1OC13C2
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)C(O)c1c(-c2ccc(C)cc2)c2c3ccccc3n(Cc3ccc(F)cc3)c2c(=O)n1C
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 90.6 %

Procedure:
A −78° C. solution of methyl 2-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)acetate (45 mg, 0.096 mmol) in Tetrahydrofuran (THF) (1 mL) was treated with LiHMDS (0.207 mL, 0.207 mmol) and then stirred at −78° C. for 20 minutes. A solution of (1R)-(−)-(10-Camphorsulfonyl)oxaziridine (71.1 mg, 0.310 mmol) in Tetrahydrofuran (THF) (1 mL) was added and the mixture was then warmed to 0° C. for 20 minutes. The mixture was treated with HCl (1M) until pH<2 and then extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel (0-100% ethyl acetate/hexanes) to afford methyl 2-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)-2-hydroxyacetate (42 mg, 0.087 mmol, 90% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.30-7.45 (m, 5H) 7.16-7.26 (m, 2H) 6.89-7.02 (m, 3H) 6.54-6.63 (m, 1H) 6.29-6.37 (m, 1H) 6.13-6.24 (m, 1H) 6.01-6.11 (m, 1H) 5.34-5.42 (m, 1H) 3.81 (s, 3H) 3.70 (s, 3H) 2.51 (s, 3H); LCMS (m/z) ES+=485 (M+1).
Reaction SMILES: [OH-].[Na+].[NH2:3][CH:4]([C:7]([OH:9])=[O:8])[CH2:5][SH:6].[CH2:10](Br)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>C(O)C>[CH2:21]([S:6][CH2:5][CH:4]([NH2:3])[C:7]([OH:9])=[O:8])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH3:10]
Reactant: NC(CS)C(=O)O
Reactant: CCCCCCCCCCCCBr
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCCCCCCCCCCSCC(N)C(=O)O

Procedure:
16.5 g. (0.42 mole) solid sodium hydroxide are dissolved in 1600 ml. ethanol, mixed with a solution of 25 g. (0.21 mole) D,L-cysteine in 150 ml. ethanol and, after the dropwise addition of 60 ml. (0.25 mole) dodecyl bromide, stirred for 24 hours at ambient temperature. The precipitate is then filtered off with suction, washed with ethanol and dissolved in water. After acidification with 4N hydrochloric acid, the precipitate is filtered off after 2 hours at 5° C. Yield 48.2 g. (81% of theory); m.p. 215°-218° C. (decomp.).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][N:5]([CH3:16])[C:6]=1[C:7]1[CH:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[S:10][CH:11]=1.[CH:17]1(B(O)O)[CH2:19][CH2:18]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1>[CH:17]1([C:2]2[CH:3]=[N:4][N:5]([CH3:16])[C:6]=2[C:7]2[CH:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[S:10][CH:11]=2)[CH2:19][CH2:18]1
Reactant: COC(=O)c1cc(-c2c(Br)cnn2C)cs1
Reactant: OB(O)C1CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1CCOC1
Product: COC(=O)c1cc(-c2c(C3CC3)cnn2C)cs1
Temperature: 70 °C
Yield: 95.2 %

Procedure:
To a 20 mL sealed tube reactor was added methyl 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (505 mg, 1.68 mmol), cyclopropylboronic acid (447 mg, 5.20 mmol), Cesium Carbonate (1.90 g, 5.84 mmol) and PdCl2(dppf)-CH2Cl2Adduct (43.6 mg, 0.05 mmol) in Tetrahydrofuran (THF) (8.5 mL). The reaction was heated to 70° C. for 1.5 hours, cooled and partitioned between CHCl3 and H2O. The organic layer was dried with Na2SO4, adsorbed onto silica and purified via column chromatography (20-40% EtOAc/Hexane) affording the title compound (0.42 g, 1.60 mmol, 95%): LC-MS (ES) m/z=251 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[S:3][C@H:4]2[O:10][C@H:9]([CH2:11][OH:12])[C@@H:8]([OH:13])[C@H:7]([OH:14])[C@H:5]2[N:6]=1.[N:15]([CH2:18][CH3:19])=[C:16]=[O:17]>CN(C)C=O>[OH:13][CH:8]1[C@@H:9]([CH2:11][OH:12])[O:10][C@H:4]2[C@H:5]([N:6]=[C:2]([NH:1][C:16]([NH:15][CH2:18][CH3:19])=[O:17])[S:3]2)[C@H:7]1[OH:14]
Reactant: CCN=C=O
Reactant: NC1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2S1
Solvent: CN(C)C=O
Product: CCNC(=O)NC1=N[C@H]2[C@H](O[C@H](CO)C(O)[C@@H]2O)S1
Reaction time: 0.17 h
Yield: 15.3 %

Procedure:
A solution of (3aR,5R,6S,7R,7aR)-2-amino-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol (100 mg, 0.45 mmol) in N,N-dimethylformamide (10 mL) was treated with isocyanatoethane (32 mg, 0.45 mmol) for 1 hour at room temperature. The reaction mixture was condensed to give a residue, which was purified by Prep-HPLC with the following conditions [(Prep-HPLC): Column, 19*150 mm; mobile phase, water with 0.03% NH3H2O and CH3CN (10% CH3CN up to 45% in 10 min); Detector, 220 nm] to give the title compound as a white solid (20 mg, 15%). (ES, m/z)[M+H]+291.9; 1H NMR (300 MHz, D2O) δ6.51-6.52 (d, J=6.3 Hz, 1H), 4.60-4.65 (m, 1H), 3.96-4.02 (t, J=9.0 Hz, 1H), 3.67-3.78 (m, 3H), 3.43-3.49 (t, J=9.6 Hz, 1H), 3.08-3.18 (m, 2H), 0.98-1.02 (t, J=7.2 Hz, 3H).
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=O)[C:7]([C:12]#[N:13])=[CH:8][NH:9]2)=[CH:4][C:3]=1[O:15][CH3:16].P(Cl)(Cl)([Cl:19])=O>>[Cl:19][C:6]1[C:5]2[C:10](=[CH:11][C:2]([F:1])=[C:3]([O:15][CH3:16])[CH:4]=2)[N:9]=[CH:8][C:7]=1[C:12]#[N:13]
Reactant: O=P(Cl)(Cl)Cl
Reactant: COc1cc2c(=O)c(C#N)c[nH]c2cc1F
Product: COc1cc2c(Cl)c(C#N)cnc2cc1F
Yield: 58.1 %

Procedure:
A mixture of 7-fluoro-6-methoxy-4-oxo-1,4-dihydro-3-quinolinecarbonitrile (1.0 g, 4.59 mmol) and 14 g of phosphorous oxychloride is heated at reflux for 30 minutes then concentrated in vacuo. The residue is partitioned between aqueous sodium bicarbonate and ethyl acetate. The organic layer is dried over magnesium sulfate, filtered and concentrated on to silica gel. Purification by flash column chromatography eluting with a gradient of 1:5 ethyl acetate:hexane to 1:1 ethyl acetate:hexane, provides 631 mg of 4-chloro-7-fluoro-6-methoxy-3-quinolinecarbonitrile, mp 160-162° C.
Reaction SMILES: N1([CH:7]([N:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)N2CCCCC2)CCCCC1.[CH3:20][O:21][P:22]([NH:26][CH:27]1[C:34](=[O:35])[N:33]2[CH:28]1[S:29][CH2:30][C:31]([CH3:49])=[C:32]2[C:36]([O:38][CH2:39][C:40]1[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=1)=[O:37])([O:24][CH3:25])=[O:23]>C(OCC)(=O)C>[CH3:20][O:21][P:22]([NH:26][CH:27]1[C:34](=[O:35])[N:33]2[CH:28]1[S:29][CH2:30][C:31]([CH:49]=[CH:7][N:14]1[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]1)=[C:32]2[C:36]([O:38][CH2:39][C:40]1[CH:41]=[CH:42][C:43]([N+:46]([O-:48])=[O:47])=[CH:44][CH:45]=1)=[O:37])([O:24][CH3:25])=[O:23]
Reactant: COP(=O)(NC1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(C)CSC12)OC
Reactant: C1CCN(C(N2CCCCC2)N2CCCCC2)CC1
Solvent: CCOC(C)=O
Product: COP(=O)(NC1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(C=CN3CCCCC3)CSC12)OC
Temperature: 45 °C
Reaction time: 18 h
Yield: 18.4 %

Procedure:
Tripiperidinomethane (1.06 g) is added to a solution of 7-dimethoxyphosphorylamino-3-methyl-2-(4-nitrobenzyloxycarbonyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (0.9 g) in ethyl acetate (40 cc) at 45° C., and the reaction mixture is stirred for 18 hours at 45° C. and diluted with ethyl acetate (20 cc). The organic solution is washed with distilled water (3×20 cc) and then with a saturated solution of sodium chloride (2×15 cc), dried over magnesium sulphate and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. The residue obtained is recrystallised from ethyl acetate (5 cc), and 7-dimethoxyphosphorylamino-2-(4-nitrobenzyloxycarbonyl)-8-oxo-3-(2-piperidinovinyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene (E isomer) (0.2 g) is obtained in the form of an orange-yellow crystalline powder, m.p.=220°-221° C.
Reaction SMILES: OC1C=C(C=CC=1)C1C(=O)C2C(=C(C)C(O)=CC=2)OC=1.[C:21]([O:24][C:25](=[O:27])[CH3:26])(=O)[CH3:22].C(OC1C=[CH:52][C:35]([C:36]2[C:45](=[O:46])[C:44]3[C:39](=[C:40]([CH3:51])[C:41]([O:47][C:48](=[O:50])[CH3:49])=[CH:42][CH:43]=3)[O:38][CH:37]=2)=[CH:34][CH:33]=1)(=O)C>N1C=CC=CC=1>[C:25]([O:24][C:21]1[CH:52]=[C:35]([CH:34]=[CH:33][CH:22]=1)[C:36]1[C:45](=[O:46])[C:44]2[C:39](=[C:40]([CH3:51])[C:41]([O:47][C:48](=[O:50])[CH3:49])=[CH:42][CH:43]=2)[O:38][CH:37]=1)(=[O:27])[CH3:26]
Reactant: CC(=O)OC(C)=O
Reactant: CC(=O)Oc1ccc(-c2coc3c(C)c(OC(C)=O)ccc3c2=O)cc1
Agent: Cc1c(O)ccc2c(=O)c(-c3cccc(O)c3)coc12
Solvent: c1ccncc1
Product: CC(=O)Oc1cccc(-c2coc3c(C)c(OC(C)=O)ccc3c2=O)c1

Procedure:
3′,7-Diacetoxy-8-methylisoflavone was prepared from 3′,7-dihydroxy-8-methylisoflavone (1.3 g, 4.8 mmol), acetic anhydride (8 ml) and pyridine (1.5 ml) as described for 4′,7-diacetoxy-8-methylisoflavone. Yield: (1.2 g, 70%) m.p. 112° C. 1H NMR (CDCl3): δ 2.31 (s, 3H, CH3), 2.32, 2.39 (each s, 3H, OCOCH3), 7.13 (m, 2H, ArH), 7.37-7.45 (m, 3H, ArH), 8.1 (s, 1H, H2), 8.18 (d, 1H, J 8.7 Hz, H5). Mass spectrum: m/z 352 (M, 6%); 310 (35); 268 (100); 267 (60).
Reaction SMILES: Cl.[Cl:2][CH2:3][CH2:4][CH:5]1[CH2:11][N:10]([CH3:12])[C:9](=[O:13])[C:8]2[CH:14]=[CH:15][CH:16]=[N:17][C:7]=2[O:6]1.S(Cl)([Cl:21])(=O)=O>CN(C)C=O>[Cl:21][C:15]1[CH:16]=[N:17][C:7]2[O:6][CH:5]([CH2:4][CH2:3][Cl:2])[CH2:11][N:10]([CH3:12])[C:9](=[O:13])[C:8]=2[CH:14]=1
Reactant: CN1CC(CCCl)Oc2ncccc2C1=O
Reactant: O=S(=O)(Cl)Cl
Agent: Cl
Solvent: CN(C)C=O
Product: CN1CC(CCCl)Oc2ncc(Cl)cc2C1=O
Yield: 6.4 %

Procedure:
A sample of 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepin-5-(4H)-one hydrochloride (10 g, 136 mole) was dissolved in dimethylformamide (150 ml) and heated to reflux. Sulfuryl chloride (20 g, 0.148 mole) was then added dropwise over a period of 40-50 minutes. The reaction was allowed to stir at reflux for 30 minutes following the addition of SO2CL2. After cooling, the contents of the flask were partitioned between water (150 ml) and benzene (150 ml). The benzene layer was saved and the water layer extracted with an additional amount of benzene (2×50 ml). The benzene extracts were combined and washed with dilute aqueous potassium hydroxide (2×50 ml) followed by dilute aqueous hydrochloric acid (2×50 ml). The benzene layer was dried over sodium sulfate and concentrated by rotary evaporation (~70° C., water aspirator) yielding 2.61 g of crude material. The crude material was recrystallized from isopropyl ether giving 1.25 g (12.6%) of off-white crystals, m.p. 78°-79° C.