Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O: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])=[CH:16][CH:15]=2)[C:10](=[O:12])[CH3:11])=[CH:5][CH:4]=1.[N:35]1[CH:40]=[CH:39][C:38]([CH3:41])=[C:37]([CH3:42])[CH:36]=1>C(#N)C>[Br-:1].[C:10]([N:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O: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])=[CH:16][CH:15]=1)[C:6]1[CH:7]=[CH:8][C:3]([CH2:2][N+:35]2[CH:40]=[CH:39][C:38]([CH3:41])=[C:37]([CH3:42])[CH:36]=2)=[CH:4][CH:5]=1)(=[O:12])[CH3:11]
Reactant: Cc1ccncc1C
Reactant: CCCCCCCCCCCCCCOc1ccc(CN(C(C)=O)c2ccc(CBr)cc2)cc1
Solvent: CC#N
Product: CCCCCCCCCCCCCCOc1ccc(CN(C(C)=O)c2ccc(C[n+]3ccc(C)c(C)c3)cc2)cc1
Product: [Br-]
Yield: 72.1 %

Procedure:
A mixture of 1.5 g of N-[4-(bromomethyl)phenyl]-N-[[4-(tetradecyloxy)phenyl]methyl]acetamide and 908.82 mg of 3,4-lutidine in 25 ml of acetonitrile is refluxed for 5 hours. The solvent is evaporated, the residue stirred with ether and the solid collected by centrifugation. The solid is washed with ether and vacuum dried to give 1.3 g of the desired product as a gummy solid, m.p. 124°-127° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]2[CH2:14][CH3:15])=[C:4]([CH2:16][O:17][CH3:18])[CH:3]=1.C([Li])CCC.[C:24](=[O:26])=[O:25].[ClH:27]>C1COCC1>[ClH:27].[CH2:14]([CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13][N:8]1[C:5]1[CH:6]=[CH:7][C:2]([C:24]([OH:26])=[O:25])=[CH:3][C:4]=1[CH2:16][O:17][CH3:18])[CH3:15]
Reactant: CCC1CCCCN1c1ccc(Br)cc1COC
Reactant: O=C=O
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCC1CCCCN1c1ccc(C(=O)O)cc1COC
Reaction time: 1 h
Yield: 70 %

Procedure:
To a solution of 1-[4-bromo-2-(methoxymethyl)phenyl]-2-ethylpiperidine (1.42 g, 4.55 mmol) in anhydrous THF was added n-butyl lithium (2.4 mL, 6.82 mmol) in drops at −78° C. After 1 hour at −78° C., the reaction mixture was poured onto crushed dry-ice (100 g). Once the excess carbon dioxide was escaped, the reaction mixture was acidified with 2N HCl. The precipitate was filtered off and dried to afford the title compound as a solid (1.0 g, 70%). HPLC (Method A), Rt: 2.5 min (purity: 97.7%). LC/MS, M+(ESI): 278.0. 1H NMR (CD3OD, 400 MHz) δ 8.20 (1H, d), 8.07 (1H, s), 7.92 (1H, d), 5.05 (2H, m), 3.89 (1H, bs), 3.69 (4H, m), 2.39 (1H, d), 2.02-2.14 (2H, m), 1.72-1.95 (3H, m), 1.46 (2H, m), 0.88 (3H, t).
Reaction SMILES: Cl.[NH2:2][OH:3].C(=O)(O)[O-].[Na+].[NH:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:18]#[N:19])[CH:16]=2)[CH:11]=[CH:10]1>CCO>[OH:3][NH:2][C:18]([C:15]1[CH:16]=[C:17]2[C:12]([CH:11]=[CH:10][NH:9]2)=[CH:13][CH:14]=1)=[NH:19]
Reactant: N#Cc1ccc2cc[nH]c2c1
Reactant: NO
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: N=C(NO)c1ccc2cc[nH]c2c1
Reaction time: 36 h
Yield: 106.5 %

Procedure:
Hydroxylamine hydrochloride (4.7 g) and sodium bicarbonate (8.6 g) were added to a solution of 1H-indole-6-carbonitrile (4.8 g) in EtOH (70 mL) successively. The reaction mixture was heated to reflux and stirred for 36 hours. The inorganic percipitate was filtered off. The solid was washed with EtOH (30 mL). The filtrate was concentrated to afford N-hydroxy-1H-indole-6-carboximidamide (D100) (6.3 g) as a yellow solid. No purification was attempted. MS (ES): C9H9N3O requires 175; found 176.2 (M+H+).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[C:4]([NH2:11])=[CH:3][CH:2]=1.[H-].[Na+].[C:14]1([S:20](Cl)(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1>[N:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[C:4]([NH:11][S:20]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:22])=[O:21])=[CH:3][CH:2]=1
Reactant: Nc1ccnc2cccnc12
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=S(=O)(Nc1ccnc2cccnc12)c1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 25.6 %

Procedure:
[1,5]Naphthyridin-4-ylamine (Intermediate 486) (60 mg, 0.41 mmol) was added to a suspension of NaH (60% in mineral oil; 25 mg, 0.53 mmol) in THF (2 ml) at 0° C. followed by a solution of benzenesulfonyl chloride (95 mg, 0.53 mmol) in THF (1 ml). The mixture was stirred at room temperature for 12 h. After completion, the reaction was quenched with water (5 ml) and the aqueous phase was extracted with EtOAc (30 ml). The organic phase was washed with brine, dried (Na2SO4) and concentrated in vacuo. The crude residue was purified by column chromatography with DCM/MeOH (98:2) as the eluent to give the title compound (30 mg, 30%).
Reaction SMILES: [CH2:1]([O:5][CH:6]([P:15](=[O:22])([O:19][CH2:20][CH3:21])[O:16][CH2:17][CH3:18])[P:7](=[O:14])([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10])[CH2:2][CH2:3][CH3:4].CC(C)([O-])C.[K+].[CH2:29](Br)[CH2:30][CH2:31][CH3:32]>C(O)(C)(C)C.C(OCC)(=O)C>[CH2:1]([O:5][C:6]([P:15](=[O:22])([O:19][CH2:20][CH3:21])[O:16][CH2:17][CH3:18])([P:7](=[O:14])([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10])[CH2:29][CH2:30][CH2:31][CH3:32])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCBr
Reactant: CCCCOC(P(=O)(OCC)OCC)P(=O)(OCC)OCC
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC(C)(C)O
Product: CCCCOC(CCCC)(P(=O)(OCC)OCC)P(=O)(OCC)OCC
Reaction time: 0.5 h

Procedure:
Tetraethyl (n-butoxymethylene)-bisphosphonate (1.2 g) was added to a stirred solution of potassium tert-butoxide (0.37 g) in tert-butanol (5 ml). After 30 minutes at room temperature, butyl bromide (0.36 ml) was added, and the mixture was refluxed for 8 hours. After cooling, the mixture was diluted with ethyl acetate and washed with water. The organic phase was dried and evaporated to give an oil which was purified by chromatography to yield the title compound.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:12]=[CH:11][C:10]=1/[CH:23]=[C:24](\[C:29]#[N:30])/[C:25]([O:27]C)=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Li+]>O1CCCC1>[OH2:8].[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:12]=[CH:11][C:10]=1/[CH:23]=[C:24](\[C:29]#[N:30])/[C:25]([OH:27])=[O:26])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)/C(C#N)=C/c1ccc(OCc2ccccc2)cc1OCc1ccccc1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: N#C/C(=C\c1ccc(OCc2ccccc2)cc1OCc1ccccc1)C(=O)O
Product: O
Temperature: 25 °C
Reaction time: 2 h
Yield: 14.9 %

Procedure:
A solution of methyl (E)-3-(2,4-dibenzyloxyphenyl)-2-cyanoacrylate (400 mg) in tetrahydrofuran (20 mL) containing 0.5 N aqueous lithium hydroxide solution (4 mL) is stirred at ambient temperature for 2 hours. The reaction is concentrated under reduced pressure and the residue taken up in water. This solution is acidified to pH 1 and extracted with diethyl ether. The organic layer is dried over magnesium sulphate, filtered and concentrated under reduced pressure to leave (E)-3-(2,4-dibenzyloxyphenyl)-2-cyanoacrylic acid hydrate as a yellow solid (30 mg). [Elemental analysis:- C, 71.43; H, 5.25; N, 3.47%; Calculated for C24H19NO4.H2O:- C, 71.40; H, 4.81; N, 3.72%].
Reaction SMILES: COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:10])=CC=1.[CH3:23][O:24][CH:25]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[O:36]/[N:37]=[C:38](\[CH3:46])/[C:39]1[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=1)[C:26]([NH:28][CH3:29])=O.O>C1(C)C=CC=CC=1>[CH3:23][O:24][CH:25]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[O:36]/[N:37]=[C:38](\[CH3:46])/[C:39]1[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=1)[C:26]([NH:28][CH3:29])=[S:10]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CNC(=O)C(OC)c1ccccc1O/N=C(\C)c1ccc(Cl)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CNC(=S)C(OC)c1ccccc1O/N=C(\C)c1ccc(Cl)cc1
Temperature: 80 °C
Yield: 137.8 %

Procedure:
Lawesson's reagent (40 mg, 0.1 mmol) was added to a solution of (E)-α-methoxy-N-methyl-2-(α-methyl-4-chlorobenzylideneaminooxy)phenylacetamide (73 mg, 0.2 mmol) in toluene (3 ml), and the mixture was heated at 80° C. for 1.5 hours with stirring. The mixture was cooled to room temperature. Water was added, and the mixture was extracted with ether and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=4/1) to give the desired compound (E)-α-methoxy-N-methyl-2-(α-methyl-4-chlorobenzylideneaminooxy)phenylthioacetamide (50 mg, 66%) as an oil.
Reaction SMILES: [C:1]([NH:3][C:4](SC)=[N:5][CH3:6])#[N:2].C(N(CC)CC)C.[O:16]1[CH:20]=[CH:19][CH:18]=[C:17]1[CH2:21][S:22][CH2:23][CH2:24][NH2:25]>CN(C)C=O.CO.[N+]([O-])([O-])=O.[Ag+]>[C:1]([NH:3][C:4]([NH:25][CH2:24][CH2:23][S:22][CH2:21][C:17]1[O:16][CH:20]=[CH:19][CH:18]=1)=[N:5][CH3:6])#[N:2]
Reactant: CN=C(NC#N)SC
Reactant: NCCSCc1ccco1
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Solvent: CN(C)C=O
Solvent: CO
Solvent: CCN(CC)CC
Product: CN=C(NC#N)NCCSCc1ccco1
Yield: 34.7 %

Procedure:
A solution of silver nitrate (8.25 g) in dimethylformamide (50 ml) was added dropwise to a solution of N-cyano-N'-methylcarbamimidothioic acid, methyl ester (6.1 g), triethylamine (4.8 g) and 2-[[[2-furanyl]methyl]thio]ethanamine (7.8 g) in methanol (150 ml). After 42 hr at 50° the mixture was filtered and the filtrate evaporated. The residue was partitioned between ethyl acetate and water. The organic layers were dried and evaporated to give an oil which yielded crystalline N-cyano-N'-[2-[[[2-furanyl]methyl]thio]ethyl]-N"-methylguanidine (3.9 g) m.p. 78°-82°.
Reaction SMILES: S(=O)(=O)(O)O.C[C:7]1([OH:14])[CH2:12][CH:11]2[CH2:13][CH:8]1[CH2:9][CH2:10]2.[C:15]([OH:18])(=O)[CH3:16].[C:19](=O)([O-])[O-].[Na+].[Na+]>O>[C:15]([O:14][CH:7]1[CH2:12][CH:11]2[CH2:13][C:8]1([CH3:19])[CH2:9][CH2:10]2)(=[O:18])[CH3:16]
Reactant: O=C([O-])[O-]
Reactant: CC(=O)O
Reactant: CC1(O)CC2CCC1C2
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: CC(=O)OC1CC2CCC1(C)C2
Temperature: 60 °C
Reaction time: 3 h

Procedure:
1 ml of 75% sulfuric acid was added to 240.0 g (1.9M) of the alcohol (II) obtained in 1--1) above and 500 ml of glacial acetic acid and the resulting mixture was stirred at 60° C. for three hours. After cooling, the reaction mixture was diluted with 3 l of water and then neutralized with sodium carbonate.
Reaction SMILES: [F:1][C:2]1[CH:8]=[C:7](I)[CH:6]=[CH:5][C:3]=1[NH2:4].[C:10]([Cu])#[N:11].CCOC(C)=O.Cl>CN(C=O)C>[NH2:4][C:3]1[CH:5]=[CH:6][C:7]([C:10]#[N:11])=[CH:8][C:2]=1[F:1]
Reactant: N#C[Cu]
Reactant: Nc1ccc(I)cc1F
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: N#Cc1ccc(N)c(F)c1
Yield: 99.1 %

Procedure:
A mixture of 2-fluoro-4-iodoaniline (10.0 g, 42.2 mmol) and CuCN (7.56 g, 84.4 mmol) in DMF (40 mL) was heated at reflux for 5 h. After being cooled down, EtOAc and 1N HCl were added. The mixture was filtered through celite. The organic phase was separated, washed sequentially with 1N HCl and brine. It was then dried over MgSO4, concentrated in vacuo to give a brown solid (5.69 g), which was pure enough for the next step. MS 137.1 (M+H).
Reaction SMILES: [CH2:1]([O:5][C:6]1[C:7]([F:13])=[C:8]([F:12])[CH:9]=[CH:10][CH:11]=1)[CH2:2][CH2:3][CH3:4].C([Li])(CC)C.[O:19]1[C:23]2([CH2:28][CH2:27][CH:26]([CH:29]3[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]3)[CH2:25][CH2:24]2)[O:22][CH2:21][CH2:20]1.[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[O:19]1[C:23]2([CH2:24][CH2:25][CH:26]([CH:29]3[CH2:34][CH2:33][C:32]([C:9]4[CH:10]=[CH:11][C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])=[C:7]([F:13])[C:8]=4[F:12])([OH:35])[CH2:31][CH2:30]3)[CH2:27][CH2:28]2)[O:22][CH2:21][CH2:20]1
Reactant: O=C1CCC(C2CCC3(CC2)OCCO3)CC1
Reactant: CCCCOc1cccc(F)c1F
Agent: [Cl-]
Agent: [Li]C(C)CC
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCCOc1ccc(C2(O)CCC(C3CCC4(CC3)OCCO4)CC2)c(F)c1F
Reaction time: 2 h
Yield: 99.6 %

Procedure:
3-Butoxy-1,2-difluorobenzene (7) (10.0 g) and THF (200 ml) were added to a reaction vessel under an atmosphere of nitrogen, and cooled to −74° C. sec-Butyllithium (1.00 M, in n-hexane and cyclohexane solution; 64.0 ml) was added dropwise in the temperature range of −74° C. to −70° C., and the stirring was continued for another 2 hours. Successively, 4-(1,4-dioxaspiro[4.5]decan-8-yl)-cyclohexanone (21) (12.8 g) in THF (50 ml) solution was added dropwise in the temperature range of −75° C. to −70° C., while the mixture was allowed to come to 25° C. The reaction mixture was poured into a 3%-aqueous solution of ammonium chloride (100 ml) and ethyl acetate (100 ml) in a vessel and mixed with them. The mixture was then allowed to stand until it had separated into two phases of organic and aqueous phases, and the extraction into an organic phase was carried out. The resulting organic phase was separated, and washed successively with water, a saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure to leave 4-(1,4-dioxaspiro[4.5]decan-8-yl)-1-(4-butoxy-2,3-difluorophenyl)-cyclohexanol (22) (22.7 g). The resulting compound (22) was a pale yellow oil.
Reaction SMILES: [CH3:1][C:2]([NH2:7])([CH3:6])[CH2:3][CH2:4][NH2:5].[CH3:8][C:9]([CH3:13])(O)[C:10]#N.[OH2:14]>>[CH3:8][C:9]1([CH3:13])[NH:5][CH:4]=[CH:3][C:2]([CH3:6])([CH3:1])[NH:7][C:10]1=[O:14]
Reactant: CC(C)(O)C#N
Reactant: CC(C)(N)CCN
Reactant: O
Product: CC1(C)C=CNC(C)(C)C(=O)N1

Procedure:
In a manner analogous to that described in Example 3C hereinabove, 3-methyl-1,3-diaminobutane, water and acetone cyanohydrin are reacted, and the reaction product recovered. When dissolved and recrystallized from acetone it is identified as 3,3,7,7-tetramethyl-1,4-diazepin-2-one. Other primary amines may be used for other substituents.
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][CH:4]([O:10][C:11]2[CH:17]=[CH:16][C:14]([NH2:15])=[CH:13][CH:12]=2)[CH2:3]1.[N:19]([O-])=O.[Na+].O.O.[Sn](Cl)[Cl:26]>O.Cl>[ClH:26].[CH3:9][C:6]1([CH3:8])[CH2:7][C:2]([CH3:18])([CH3:1])[CH2:3][CH:4]([O:10][C:11]2[CH:12]=[CH:13][C:14]([NH:15][NH2:19])=[CH:16][CH:17]=2)[CH2:5]1
Reactant: CC1(C)CC(Oc2ccc(N)cc2)CC(C)(C)C1
Reactant: O=N[O-]
Reactant: Cl[Sn]Cl
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CC1(C)CC(Oc2ccc(NN)cc2)CC(C)(C)C1
Temperature: -10 °C
Reaction time: 0.75 h

Procedure:
A stirred mixture, cooled to −10° C., of 3.7 g of 4-(3,3,5,5-tetramethylcyclohexyloxy)aniline, 7.5 ml of water and 15.5 ml of conc. HCl is mixed dropwise with a solution of 1.13 g of sodium nitrite in 7.5 ml of water, and the mixture is stirred at −10° C. for 45 min and subsequently added dropwise to a suspension of 9.3 g of tin dichloride dihydrate in 7 ml of conc. HCl. The precipitate is filtered off with suction, washed with water, suspended under nitrogen in 200 ml of water and decomposed at 10-15° C. using 100 ml of 30% strength aqueous sodium hydroxide solution. The precipitate that is then formed is filtered off with suction, washed with water, taken up in 200 ml of ether and dried with sodium sulfate. The product is precipitated using ethereal HCl, filtered off with suction and dried under reduced pressure.
Reaction SMILES: [CH2:1]([Mg]Br)[CH3:2].[C:5]1([CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:12]=[O:13])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH2:20]1[CH2:24][O:23][CH2:22][CH2:21]1>>[C:14]1([CH:11]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:12](=[O:13])[C:12]#[C:11][CH2:14][CH:2]2[CH2:1][CH2:21][C:20]3[C:10](=[CH:5][CH:6]=[CH:7][C:24]=3[O:23][CH3:22])[CH2:9]2)[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CC[Mg]Br
Reactant: O=CC(c1ccccc1)c1ccccc1
Reactant: C1CCOC1
Product: COc1cccc2c1CCC(CC#CC(=O)C(c1ccccc1)c1ccccc1)C2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a mixture of ethylmagnesium bromide (5.7 ml; 3.0M/L in ether solution) and THF (40 ml) was added dropwise a solution of the compound prepared in reference example 30 (3.0 g) in THF (20 ml) over a 10 min period. The mixture was stirred for 2 h at room temperature. To the mixture was added a solution of diphenylacetaldehyde (2.94 g) in THF (10 ml). The mixture was stirred for 2 h. After quenched by addition of ammonium chloride, the mixture was extracted with ether. The extract was washed with water and a saturated aqueous solution of sodium chloride, successively, dried over anhydrous magnesium sulfate, and evaporated. To a solution of the residue in ether (50 ml) was added manganese (IV) oxide (2.7 g) at room temperature. The mixture was stirred for 2 h. The mixture was filtrated, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=7:1) to give the title compound (2.41 g) having the following physical data.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[C:11](Cl)(=[O:15])[C:12](Cl)=[O:13].C(Cl)Cl.[CH3:20][O-:21].[Na+].CO>C(OCC)C>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=[O:15])[C:12]([O:21][CH3:20])=[O:13])=[CH:7][NH:8]2)=[CH:4][CH:3]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: Cc1ccc2cc[nH]c2c1
Reactant: C[O-]
Agent: [Na+]
Solvent: CCOCC
Solvent: ClCCl
Solvent: CO
Product: COC(=O)C(=O)c1c[nH]c2cc(C)ccc12
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 54 %

Procedure:
To a solution of 6-methylindole (1.00 g, 7.62 mmol) in diethyl ether (10 mL) at 4° C. was added a 2.0 M solution of oxalyl chloride in methylene chloride (4.0 mL, 8.0 mmol). The resulting solution was allowed to warm to room temperature. After 90 min, the solution was cooled to −78° C. To this solution was added 25% (w/w) solution of sodium methoxide in methanol (3.65 mL, 16.0 mmol). The resulting solution was allowed to warm to room temperature. After 1 h, the solution was filtered to give the title compound (894 mg, 54%) as a beige solid.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]([OH:12])[CH:9]=[C:8]2[C:3]=1[C:4](CCC)=[CH:5][C:6](=[O:13])[O:7]2.[C:17](Cl)(=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19].N1[CH:29]=[CH:28][CH:27]=CC=1>C1COCC1>[C:17]([O:1][C:2]1[CH:11]=[C:10]([O:12][C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])[CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([CH2:29][CH2:28][CH3:27])[C:6](=[O:13])[O:7]2)(=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19]
Reactant: CC(C)(C)C(=O)Cl
Reactant: c1ccncc1
Reactant: CCCc1cc(=O)oc2cc(O)cc(O)c12
Solvent: C1CCOC1
Product: CCCc1cc2c(OC(=O)C(C)(C)C)cc(OC(=O)C(C)(C)C)cc2oc1=O
Temperature: 25 °C
Reaction time: 24 h
Yield: 98 %

Procedure:
To a solution of 5,7-dihydroxy-4-propylcoumarin (2) (1.10 g, 5 mmol) in pyridine (12 mL) and THF (6 mL ) was added pivaloyl chloride (0.673 mL, 5.5 mmol) and the reaction mixture was allowed to stir at room temperature for 24 h. TLC revealed formation of a new less polar spot and unreacted starting material. In an effort to drive the reaction to completion, pivaloyl chloride (0.50 mL) was added and the reaction continued to stir at room temperature for another 72 h. The pyridinium hydrochloride was removed by filtration and washed a few times with ethyl acetate. The organic solutions were combined and washed, successively, with 1 M HCl (2×25 mL), water (25 mL), aqueous saturated sodium bicarbonate (25 mL). After being dried over sodium sulfate and concentrated under vacuum, the crude product was purified by silica gel chromatography (2:1 hexane/ethyl acetate) to obtain 8b as a white solid (1.90 g, 98% yield). mp 110-112° C.; Rf=0.49 (4:1 hexane/ethyl acetate); 1H-NMR (CDCl3),: 1.03 (3H, t, J=7.8 Hz), 1.36 (9H, s), 1.41 (9H, s), 1.69 (2H, sextet, J=7.4 Hz), 2.81 (2H, t,j=7.8 Hz), 6.22 (1H, s), 6.60 (1H, d, J=2.4 Hz), 7.03 (1H, d, J=2.1 Hz); 13C-NMR (CDCl3) : 13.5, 20.7, 26.4, 26.8, 26.9, 36.4, 39.2, 39.4, 108.6, 111.5, 113.4, 114.2, 149.4, 152.7, 154.9, 155.4, 159.9, 177.1; IR (film): 3090, 2971, 2941, 2876, 1757, 1615, 1481, 1422, 1273 cm−1; MS m/e 389 (M+1); Anal. Calcd. for C22H28O6: C, 68.02; H, 7.26. Found: C, 67.77; H, 7.18.
Reaction SMILES: [CH2:1]([N:3]([CH2:9][CH3:10])[C:4](=O)[C@H:5](Cl)[CH3:6])[CH3:2].[K].[S:12]1C=CC=C1CC(O)=O.[CH2:21]([OH:23])[CH3:22]>ClCCl>[CH2:1]([N:3]([CH2:9][CH3:10])[C:4](=[S:12])[C@H:5]([C:21](=[O:23])[CH3:22])[CH3:6])[CH3:2]
Reactant: O=C(O)Cc1cccs1
Reactant: CCO
Reactant: CCN(CC)C(=O)[C@@H](C)Cl
Agent: [K]
Solvent: ClCCl
Product: CCN(CC)C(=S)[C@@H](C)C(C)=O
Temperature: 55 °C

Procedure:
(R)-N,N-Diethyl-2-chloropropionamide (20 g) dissolved in ethanol (30 cc) is added to a suspension of the potassium salt of thiolacetic acid (16 g) in ethanol (70 cc). The reaction mixture is then heated for 2 hours at a temperature in the vicinity of 55° C. and then concentrated to dryness under reduced pressure (130 Pa) at a temperature in the vicinity of 60° C. The residue obtained is crushed in dichloromethane (300 cc) and then washed with distilled water (200 cc). The organic phase is decanted, dried over sodium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at a temperature in the vicinity of 30° C. The residue obtained is distilled under reduced pressure (17 Pa). (S)-N,N-Diethyl-2-acetylthiopropionamide (22 g) in the form of a slightly yellow oil [b.p.17Pa =105°-107° C.; [α]D20 =-169° (c=10; CHCl3)] is thereby obtained.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([Cl:12])[C:5]2[S:10][C:9](=[O:11])[NH:8][C:6]=2[N:7]=1.C(O[CH:17]1[O:29][C@H:28]([CH2:30][O:31][C:32](=[O:34])[CH3:33])[C@@H:23]([O:24][C:25](=[O:27])[CH3:26])[C@H:18]1[O:19][C:20](=[O:22])[CH3:21])(=O)C.[N+](C1C=CC(OP([O-])(OC2C=CC([N+]([O-])=O)=CC=2)=O)=CC=1)([O-])=O>CCOC(C)=O>[Cl:1][C:2]1[N:3]=[C:4]([Cl:12])[C:5]2[S:10][C:9](=[O:11])[N:8]([C@@H:17]3[O:29][C@H:28]([CH2:30][O:31][C:32](=[O:34])[CH3:33])[C@@H:23]([O:24][C:25](=[O:27])[CH3:26])[C@H:18]3[O:19][C:20](=[O:22])[CH3:21])[C:6]=2[N:7]=1
Reactant: O=c1[nH]c2nc(Cl)nc(Cl)c2s1
Reactant: CC(=O)OC[C@H]1OC(OC(C)=O)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: O=[N+]([O-])c1ccc(OP(=O)([O-])Oc2ccc([N+](=O)[O-])cc2)cc1
Solvent: CCOC(C)=O
Product: CC(=O)OC[C@H]1O[C@@H](n2c(=O)sc3c(Cl)nc(Cl)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 170 °C

Procedure:
A finely powdered mixture of 24 (3.7 g, 16 mmol), 1,2,3,5-tetra-O-acetyl-D-ribofuranose (5.3 g, 16 mmol) and bis-(p-nitrophenyl)phosphate (20 mg) was heated at 170° C. for 10 min under reduced pressure. After cooling to room temperature the brown solid mass was dissolved in EtOAc (500 mL) and washed with saturated aqueous sodium bicarbonate (3×300 mL). The dried (Na2SO4) organic layer was evaporated to yield a syrup which was purified by silica gel column chromatography (4×40 cm) using toluene-EtOAc (5:1). The resulting syrup was crystallized from ethanol to give a colorless powder: yield 6.4 g, 80%: mp 125°-126° C.: 1H NMR (DMSO-d6) δ 1.99, 2.06, 2.08 (3s, 9H, acetyl), 6.07 (d, J=3.40 Hz, 1H, C1,H), and other sugar protons. Anal. Calcd. for C16H15Cl2N3O8S: C, 40.01: H, 3.15: C1, 14.76: N, 8.75: S, 6.68. Found: C, 40.20: H, 3 31: C1, 14.79: N, 8.61: S, 6 66.
Reaction SMILES: [Cl:1][C:2]1[C:10]2[O:9][C:8]([CH3:12])([CH3:11])[CH2:7][C:6]=2[C:5]([CH3:13])=[C:4]([CH3:14])[CH:3]=1.[CH3:15][O:16]C(Cl)Cl>ClCCl>[Cl:1][C:2]1[C:10]2[O:9][C:8]([CH3:11])([CH3:12])[CH2:7][C:6]=2[C:5]([CH3:13])=[C:4]([CH3:14])[C:3]=1[CH:15]=[O:16]
Reactant: Cc1cc(Cl)c2c(c1C)CC(C)(C)O2
Reactant: COC(Cl)Cl
Solvent: ClCCl
Product: Cc1c(C)c2c(c(Cl)c1C=O)OC(C)(C)C2
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To a solution of 20 g of the 7-chloro-2,3-dihydro-2,2,4,5-tetramethylbenzofuran in 200 ml of absolute dichloromethane was added 27.3 ml of titanium chloride(IV) and 18.75 ml of α,α-dichloromethyl methyl ether at 0° C. With stirring at room temperature for 45 minutes and refluxing for 15 minutes, the reaction mixture was quenched with 200 ml of ice-water and stirred for 30 minutes and the aqueous layer was extracted with dichloromethane. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford a crude product. Final purification was carried by silica-gel column chromatography to afford 14 g of 7-chloro-2,3-dihydro-2,2,4,5-tetramethylbenzofuran-6-carboxaldehyde.