Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:14]2[C:5](=[CH:6][C:7]3[C:12](C=2)=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1.[CH2:15]([C:17]([CH3:19])=O)[CH3:16]>>[CH:15]([C:17]1[CH:19]=[CH:1][C:14]2[C:8]3[C:7](=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH2:6][C:5]=2[C:4]=1[CH:3]=[CH2:2])=[CH2:16]
Reactant: CCC(C)=O
Reactant: c1ccc2cc3ccccc3cc2c1
Product: C=Cc1ccc2c(c1C=C)Cc1ccccc1-2

Procedure:
A suspension of 2,7-Bis(diethylphosphonatomethyl)-9,9-dipropylfluorene (4) (2.15 g, 4.0 mmol), 3,4,5-trimethoxybenzaldehyde (5) (1.76 g, 9.0 mmol), and potassium hydroxide (0.75 g, 13 mmol) in THF (20 mL) and DMSO (1 mL) was heated at 70° C. for 4 hours. The suspension was diluted with Ethanol (50 mL) and the solvent removed under vacuum. The product was purified by refluxing in Methanol followed by filtration. After drying, (II-1) was obtained as a pale yellow powder (1.90 g, 76%). The UV/VIS spectrum of (II-1) in methyl ethyl ketone (MEK) has two maxima at 380 nm and at 399 nm with a molar extinction coefficient of 89724 Mol−1 cm−1 and 72301 Mol−1 cm−1 respectively. Under UV irradiation in MEK, (II-1) shows a strong blue fluorescence with fluorescence peaks at 417 nm and 439 nm. The fluorescence quantum yield of (II-1) relative to the anthracene standard is 0.65 (in MEK solvent, not degassed). The 1H-NMR data in CDCl3 are summarized in table 1; in the table s means singlet, d means doublet, dd means double doublet, m means multiplet and J means the coupling constant.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]2[CH2:12][N:11]([CH3:13])[CH2:10]2)=[C:4]([N+:14]([O-:16])=[O:15])[CH:3]=1.[F:17][C:18]1[CH:19]=[CH:20][C:21]2=[C:22]([CH:43]=1)[O:23][CH2:24][C:25]1[C:41]([F:42])=[CH:40][CH:39]=[CH:38][C:26]=1/[C:27]/2=[CH:28]\B1OC(C)(C)C(C)(C)O1.O1CCCC1.C[O-].[Na+]>CO.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:17][C:18]1[CH:19]=[CH:20][C:21]2=[C:22]([CH:43]=1)[O:23][CH2:24][C:25]1[C:41]([F:42])=[CH:40][CH:39]=[CH:38][C:26]=1/[C:27]/2=[CH:28]\[C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]2[CH2:12][N:11]([CH3:13])[CH2:10]2)=[C:4]([N+:14]([O-:16])=[O:15])[CH:3]=1
Reactant: CN1CC(Nc2ccc(Br)cc2[N+](=O)[O-])C1
Reactant: CC1(C)OB(/C=C2/c3ccc(F)cc3OCc3c(F)cccc32)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CO
Product: CN1CC(Nc2ccc(/C=C3/c4ccc(F)cc4OCc4c(F)cccc43)cc2[N+](=O)[O-])C1
Yield: 118.3 %

Procedure:
Purge with nitrogen for five min a mixture of (4-bromo-2-nitro-phenyl)-(1-methyl-azetidin-3-yl)-amine (709 μmol, 203 mg), (E)-3,7-difluoro-11-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-ylmethylene)-6,11-dihydro-dibenzo[b,e]oxepine (723 μmol, 268 mg) in methanol (1.0 mL)/tetrahydrofuran (3.0 mL) (1:3 solvent ratio) in a sealed tube. Add sodium methoxide (1.42 mmol, 77 mg), tetrakis(triphenylphosphine)palladium (35 μmol, 41 mg) and heat at 70° C. overnight. Dilute with ethyl acetate, wash with 10% sodium bicarbonate twice, dry over anhydrous sodium sulfate, filter, and concentrate in vacuo to obtain 377 mg of an orange oil residue. Purify on a 12 g silica gel column eluting with 5% methanol in dichloromethane to obtain the title compound (199 mg, 62%). LC-MS m/z 450.0 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12](Cl)=[C:11]1[C:6]([CH:7]=[CH:8][C:9]([O:17][CH3:18])=[CH:10]1)=[N:5]2.[NH2:19][CH2:20][CH2:21][CH2:22][CH2:23][N:24]([CH2:28][CH3:29])[C:25](=[O:27])[CH3:26]>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12]([NH:19][CH2:20][CH2:21][CH2:22][CH2:23][N:24]([CH2:28][CH3:29])[C:25](=[O:27])[CH3:26])=[C:11]1[C:6]([CH:7]=[CH:8][C:9]([O:17][CH3:18])=[CH:10]1)=[N:5]2
Reactant: CCN(CCCCN)C(C)=O
Reactant: COc1ccc2nc3cc(Cl)ccc3c(Cl)c2c1
Product: CCN(CCCCNc1c2ccc(Cl)cc2nc2ccc(OC)cc12)C(C)=O

Procedure:
Following the general procedure of Example 1, and making non-critical variations but using 6,9-dichloro-2-methoxyacridine and N-(4-aminobutyl)-N-ethylacetamide (Step 1), the title compound was obtained; MS (Found M+1=400).
Reaction SMILES: [OH:1][N:2]=[C:3](Cl)[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][CH:5]=1.[C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)#[CH:12].N>>[C:13]1([C:11]2[O:1][N:2]=[C:3]([C:4]3[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=3)[CH:12]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: ON=C(Cl)c1cccnc1
Reactant: C#Cc1ccccc1
Agent: N
Product: c1ccc(-c2cc(-c3cccnc3)no2)cc1

Procedure:
The titled compound was prepared according to Method CB using the product of Example 1A (78 mg, 0.5 mmol) and 1-ethynyl-benzene (Aldrich, 52 mg, 0.5 mmol). 1H NMR (300 MHz, MeOH-d4) δ 7.37 (s, 1H), 7.46-7.68 (m, 4H), 7.85-8.00 (m, 2H), 8.37 (dt, J=7.9, 2.0 Hz, 1H), 8.66 (dd, J=4.9, 1.5 Hz, 1H), 9.10 (d, J=2.4 Hz, 1H) ppm; MS (DCI/NH3) m/z 223 (M+H)+.
Reaction SMILES: I[CH2:2][C:3]1[S:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[N:5][C:4]=1[CH3:18].[CH3:19][O:20][C:21](=[O:33])[CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][OH:31])=[CH:26][C:25]=1[CH3:32].[H-].[Na+]>CN(C=O)C>[CH3:19][O:20][C:21](=[O:33])[CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][O:31][CH2:2][C:3]2[S:7][C:6]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=3)=[N:5][C:4]=2[CH3:18])=[CH:26][C:25]=1[CH3:32]
Reactant: COC(=O)CCc1ccc(CO)cc1C
Reactant: Cc1nc(-c2ccc(C(F)(F)F)cc2)sc1CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)CCc1ccc(COCc2sc(-c3ccc(C(F)(F)F)cc3)nc2C)cc1C
Temperature: 25 °C
Reaction time: 3 h
Yield: 15.3 %

Procedure:
To a solution of 5-Iodomethyl-4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole (0.14 g, 0.37 mmol) and 3-(4-Hydroxymethyl-2-methyl-phenyl)-propionic acid methyl ester (0.064 g, 0.31 mmol) in DMF (1 mL) is added sodium hydride (60% dispersion, 0.036 g, 1.50 mmol). The mixture is stirred at RT for 3 h. The reaction is quenched with water, and the mixture is extracted with EtOAc. The organics are dried with MgSO4 and concentrated. The crude material is purified by flash chromatography to yield the title compound (0.022 g, 16%).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:25]=[CH:24][C:7]([CH2:8][N:9]([C:16]2[CH:21]=[CH:20][C:19]([S:22][CH3:23])=[CH:18][CH:17]=2)[CH2:10][C:11]2[CH:15]=[CH:14][S:13][CH:12]=2)=[CH:6][CH:5]=1)[CH3:2].OOS([O-])=O.[K+].[OH2:32].C[OH:34]>>[CH2:1]([O:3][C:4]1[CH:25]=[CH:24][C:7]([CH2:8][N:9]([C:16]2[CH:17]=[CH:18][C:19]([S:22]([CH3:23])(=[O:34])=[O:32])=[CH:20][CH:21]=2)[CH2:10][C:11]2[CH:15]=[CH:14][S:13][CH:12]=2)=[CH:6][CH:5]=1)[CH3:2]
Reactant: O
Reactant: CO
Reactant: CCOc1ccc(CN(Cc2ccsc2)c2ccc(SC)cc2)cc1
Agent: O=S([O-])OO
Agent: [K+]
Product: CCOc1ccc(CN(Cc2ccsc2)c2ccc(S(C)(=O)=O)cc2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 92 %

Procedure:
To 241 mg (0.652 mmol) of (4-Ethoxy-benzyl)-(4-methylsulfanyl-phenyl)-thiophen-3-ylmethyl-amine dissolved in 6 mL methanol was added 800 mg (1.3 mmol) OXONE™ followed by 600 μL water. The mixture was stirred at room temperature for 2 h, then partitioned between EtOAc and water, adding 1 N NaOH until the aqueous phase was neutral. The organic layer was then dried over MgSO4 and concentrated. (4-Ethoxy-benzyl)-(4-methanesulfonyl-phenyl)-thiophen-3-ylmethyl-amine was obtained in 92% yield (240 mg) and appeared pure by 1H NMR.
Reaction SMILES: [Cl:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([C:8]2[CH:9]=[CH:10][CH:11]=[C:12]3[C:16]=2[NH:15]C=[C:13]3[CH2:17][CH2:18][C:19]([OH:21])=[O:20])=[O:7])=[CH:4][CH:3]=1.[O:24]=[O+][O-].[I-].[K+].[C:29](OCC)(=O)[CH3:30]>C(O)C>[NH2:15][C:16]1[C:8]([C:6](=[O:7])[C:5]2[CH:22]=[CH:23][C:2]([Cl:1])=[CH:3][CH:4]=2)=[CH:9][CH:10]=[CH:11][C:12]=1[C:13](=[O:24])[CH2:17][CH2:18][C:19]([O:21][CH2:29][CH3:30])=[O:20]
Reactant: CCOC(C)=O
Reactant: O=C(O)CCc1c[nH]c2c(C(=O)c3ccc(Cl)cc3)cccc12
Reactant: O=[O+][O-]
Agent: [I-]
Agent: [K+]
Solvent: CCO
Product: CCOC(=O)CCC(=O)c1cccc(C(=O)c2ccc(Cl)cc2)c1N
Reaction time: 18 h
Yield: 26 %

Procedure:
A solution of 13.1 g (0.04 mole) of 7-(4-chlorobenzoyl)-1-H-indole-3-propanoic acid in 450 ml of ethyl acetate and 150 ml of absolute ethanol was treated with ozone until ozone was present above the solution. The solution was then stirred with an aqueous solution of potassium iodide, followed by a wash with aqueous sodium thiosulfate. The organic fraction was concentrated and the residue was dissolved in 250 ml of 190 proof ethanol. The solution was heated to reflux, 150 ml of 6N hydrochloric acid was added, and heating was continued for 18 hr. The mixture was diluted with 400 ml of water and a gummy solid separated. The gum was partitioned between dilute sodium hydroxide solution and methylene chloride. The basic aqueous fraction contained only a small amount of acidic material upon acidification, so it was discarded. The methylene chloride layer was dried over anhydrous sodium sulfate and passed through a column of silica gel. The yellow-colored eluant was concentrated and the crystalline residue was recrystallized from cyclohexane to give 3.5 g (26%) of bright yellow powder, m.p. 112°-115° C.
Reaction SMILES: [CH3:1][C:2]1[CH:20]=[CH:19][C:5]2[NH:6][C:7](=O)[C:8]3[C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=4[S:11][C:9]=3[S:10][C:4]=2[CH:3]=1.P(Cl)(Cl)(Cl)=O.[CH3:26][N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1>>[CH3:1][C:2]1[CH:20]=[CH:19][C:5]2[N:6]=[C:7]([N:30]3[CH2:31][CH2:32][N:27]([CH3:26])[CH2:28][CH2:29]3)[C:8]3[C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=4[S:11][C:9]=3[S:10][C:4]=2[CH:3]=1
Reactant: CN1CCNCC1
Reactant: Cc1ccc2c(c1)Sc1sc3ccccc3c1C(=O)N2
Solvent: O=P(Cl)(Cl)Cl
Product: Cc1ccc2c(c1)Sc1sc3ccccc3c1C(N1CCN(C)CC1)=N2

Procedure:
In the same manner as in Example 80 and using 8-methyl-[1]benzothieno[2,3-b][1,5]benzothiazepin-12(11H)-one, phosphorus oxychloride, N,N-dimethylanilne, 1-methylpiperazine, 8-methyl-12-(4-methylpiperazin-1-yl)-[1]benzothieno[2,3-b][1,5]benzothiazepine is obtained.
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[C:3]1[CH:4]=[C:5]([S:9](Cl)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.[NH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]1[CH2:21][C:22]([OH:24])=[O:23].Cl>O1CCOCC1.[OH-].[Na+]>[F:1][C:2]([F:14])([F:13])[C:3]1[CH:4]=[C:5]([S:9]([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]2[CH2:21][C:22]([OH:24])=[O:23])(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1
Reactant: O=S(=O)(Cl)c1cccc(C(F)(F)F)c1
Reactant: O=C(O)CC1CCCCN1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: O=C(O)CC1CCCCN1S(=O)(=O)c1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 4.5 h

Procedure:
A solution of 3-trifluoromethylbenzenesulfonic acid chloride (2.70 g, 11 mmol) in 1,4-dioxane (10 ml) was added slowly, in the course of 1 h, to a solution of 2-(piperidin-2-yl)acetic acid (1.43 g, 10 mmol) in 1,4-dioxane (5 ml) and 1 N sodium hydroxide solution (22 ml). The mixture was then stirred for 4.5 h at room temperature, then acidified with 1 N hydrochloric acid and subsequently extracted with DCM (3×60 ml). The combined organic phases were dried over sodium sulfate and concentrated in vacuo.
Reaction SMILES: [OH-].[K+].O.[CH3:4][C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[CH:8]=O.[CH:13](=[O:16])[CH2:14][CH3:15]>C(O)CO>[CH3:15]/[C:14](=[CH:8]\[C:7]1[CH:10]=[CH:11][CH:12]=[C:5]([CH3:4])[CH:6]=1)/[CH:13]=[O:16]
Reactant: CCC=O
Reactant: Cc1cccc(C=O)c1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: OCCO
Product: C/C(C=O)=C\c1cccc(C)c1
Temperature: 40 °C
Yield: 69.7 %

Procedure:
A solution of potassium hydroxide (24 g, 0.36 mol, 0.6 eq, with a purity of 85%) in ethylene glycol (120 g) and water (12 g) was charged into a 500 mL three-necked round-bottom flask equipped with a reflux condenser and a mechanical stirrer. 3-methyl benzaldehyde (70 g, 0.59 mol) was added dropwise. The stirred reaction mixture was heated at 38-42° C. and propionaldehyde (41 g, 0.71 mol, 1.2 eq) was dosed in over 3.25 h. After a further hour at 40° C., the reaction mixture was cooled to ambient temperature and the two layers separated. The organic layer thus obtained was washed with water (2×100 mL), dried over magnesium sulphate and concentrated. The resulting crude product was distilled via a Vigreux column (1.0 mBar, 87-92° C.), to give (2E)-2-methyl-3-(3-methylphenyl)acrylaldehyde (65.9 g, gc purity>95%; yield 70%).
Reaction SMILES: B([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([N:13]([C:20]1[O:24][N:23]=[C:22]([CH3:25])[C:21]=1[CH3:26])[CH2:14][O:15][CH2:16][CH2:17][O:18][CH3:19])(=[O:12])=[O:11])(O)O.C([O-])([O-])=O.[Na+].[Na+].[C:33]1([CH3:39])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CCO>[CH3:25][C:22]1[C:21]([CH3:26])=[C:20]([N:13]([CH2:14][O:15][CH2:16][CH2:17][O:18][CH3:19])[S:10]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:14]2[N:13]([S:10]([C:5]3[CH:4]=[CH:9][CH:8]=[CH:7][CH:6]=3)(=[O:11])=[O:12])[C:38]3[C:33]([CH:39]=2)=[CH:34][CH:35]=[CH:36][CH:37]=3)(=[O:12])=[O:11])[O:24][N:23]=1
Reactant: COCCOCN(c1onc(C)c1C)S(=O)(=O)c1ccccc1B(O)O
Reactant: Cc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Product: COCCOCN(c1onc(C)c1C)S(=O)(=O)c1ccccc1-c1cc2ccccc2n1S(=O)(=O)c1ccccc1
Temperature: 85 °C
Yield: 19 %

Procedure:
Tetrakis(triphenylphosphine)palladium(0) (230 mg; 10 mol %) was added to a degassed solution of the title product of Step (A) (766 mg; 2 mmol) and the title product of Step (B) (900 mg; 2.34 mmol) in 10 ml of toluene and 8.5 ml of EtOH under argon. After adding 7 ml of 2M Na2CO3, the heterogeneous mixture was heated to 85° C. for 5 hrs with vigorous stirring. At this time, an additional amount of the title product of Step (B) (100 mg; 0.26 mmol) was added and the mixture was heated an additional 2 hrs. After cooling to room temperature, the reaction mixture was partitioned between ethyl acetate (75 ml) and water (50 ml). The organic layer was washed with brine (50 ml), dried (MgSO4), and concentrated to afford a yellow residue which was chromatographed on a 5×20 cm silica gel column, using 4 L EtOAc:Hexanes, 3:7, 2 L EtOAc:hexanes, 4:6 and 1 L EtOAc:Hexanes, 1:1 as the mobile phase. The pure fractions were concentrated to afford 222 mg (19%) of the title product of this step as a light yellow foam.
Reaction SMILES: C([NH:8][C@@H:9]([CH2:35][C@H:36]1[CH2:41][CH2:40][CH2:39][O:38][CH2:37]1)[CH2:10][NH:11][C:12]([N:14]1[CH2:19][CH2:18][CH2:17][C@@H:16]([C@H:20]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=2)[O:21][CH2:22][CH2:23][NH:24][C:25](=[O:27])[O-:26])[CH2:15]1)=[O:13])(OC(C)(C)C)=O.C(Cl)Cl.[C:45]([OH:51])([C:47]([F:50])([F:49])[F:48])=[O:46]>>[OH:51][C:45]([C:47]([F:50])([F:49])[F:48])=[O:46].[NH2:8][C@@H:9]([CH2:35][C@H:36]1[CH2:41][CH2:40][CH2:39][O:38][CH2:37]1)[CH2:10][NH:11][C:12]([N:14]1[CH2:19][CH2:18][CH2:17][C@@H:16]([C@H:20]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=2)[O:21][CH2:22][CH2:23][NH:24][C:25](=[O:26])[OH:27])[CH2:15]1)=[O:13]
Reactant: CC(C)(C)OC(=O)N[C@H](CNC(=O)N1CCC[C@@H]([C@@H](OCCNC(=O)[O-])c2cccc(Cl)c2)C1)C[C@H]1CCCOC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N[C@H](CNC(=O)N1CCC[C@@H]([C@@H](OCCNC(=O)O)c2cccc(Cl)c2)C1)C[C@H]1CCCOC1
Reaction time: 0.5 h
Yield: 54 %

Procedure:
The 2-((R)—((R)-1-((S)-2-(Boc-amino)-3-((R)-tetrahydro-2H-pyran-3-yl)propylcarbamoyl)piperidin-3-yl)(3-chlorophenyl)methoxy)ethylcarbamate (5 mg, 0.008 mmol) was dissolved in DCM/TFA (3/1 mL). The solution was stirred for 30 min and concentrated. The crude mixture was purified on preparative HPLC to afford 2-((R)—((R)-1-((S)-2-amino-3-((R)-tetrahydro-2H-pyran-3-yl)propylcarbamoyl)piperidin-3-yl)(3-chlorophenyl)methoxy)ethylcarbamate TFA salt 2.8 mg, yield 54%. 1H NMR (CD3OD) δ 7.36-7.32 (m, 3H), 7.23 (d, J=7.6 Hz, 1H), 4.20 (br d, J=13.6 Hz, 1H), 4.04 (d, J=8.8 Hz, 1H), 3.89-3.78 (m, 3H), 3.64 (s, 3H), 3.48-3.42 (m, 2H), 3.37 (m, 1H), 3.28-3.24 (m, 5H), 3.15 (dd, J=10.8, 9.2 Hz, 1H), 2.92 (m, 2H), 1.97 (m, 1H), 1.78 (m, 2H), 1.68-1.54 (m, 4H), 1.45-1.07 (m, 5H). MS ESI+ve m/z 511 (M+H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([NH2:16])[CH2:11][C:10]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:9]2)=[CH:4][CH:3]=1.C(OC(N1[C:26](=[O:27])[C:25]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]2[C:23]1=[O:32])=O)C.C(N(CC)CC)C>C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([N:16]3[C:26](=[O:27])[C:25]4[C:24](=[CH:31][CH:30]=[CH:29][CH:28]=4)[C:23]3=[O:32])[CH2:11][C:10]3([O:12][CH2:13][CH2:14][O:15]3)[CH2:9]2)=[CH:4][CH:3]=1
Reactant: NC1(c2ccc(Br)cc2)CC2(C1)OCCO2
Reactant: CCOC(=O)N1C(=O)c2ccccc2C1=O
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: O=C1c2ccccc2C(=O)N1C1(c2ccc(Br)cc2)CC2(C1)OCCO2
Temperature: 70 °C

Procedure:
To a solution of Compound [XXXV] (6.03 g, 21.2 mmol, 1.0 eq.) in CHCl3 (100 mL, anhydrous) was added N-ethoxycarbonylphthalimide (5.12 g, 23.3 mmol, 1.1 eq.) and triethylamine (11.8 mL, 84.9 mmol, 4.0 eq.). The mixture was then heated to 70° C. for 24 hours. The reaction was then cooled and concentrated. Methanol was added to the residue, and the mixture concentrated, then methanol was added again, and the resulting solid collected by filtration to provide Compound [XXXVI] as a light tan solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.30-3.39 (m, 2H) 3.44-3.53 (m, 2H) 3.89 (s, 4H) 7.42-7.49 (m, 2H) 7.50-7.58 (m, 2H) 7.69 (dd, J=5.34, 3.10 Hz, 2H) 7.78 (dd, J=5.54, 3.00 Hz, 2H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][NH:7][CH:8]=1)([O-:3])=[O:2].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:16][CH2:17][OH:18]>CC#N.C(Cl)Cl>[N+:1]([C:4]1[CH:5]=[N:6][N:7]([CH2:16][CH2:17][OH:18])[CH:8]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cn[nH]c1
Reactant: OCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: ClCCl
Solvent: CC#N
Product: O=[N+]([O-])c1cnn(CCO)c1
Temperature: 80 °C

Procedure:
To a solution of 4-nitro-1H-pyrazole (6.09 g, 52.20 mmol) in MeCN (80 mL), Cs2CO3 (18.71 g, 57.42 mmol) and 2-bromoethanol (4.59 mL, 62.64 mmol) was added. The resulting mixture was refluxed (80° C.) for 3.5 h, then the reaction mixture was allowed to reach rt. The mixture was diluted with DCM, filtered, the filter cake was washed with DCM and the filtrate was concentrated in vacuo. The residue was partitionned between water and EtOAc, the org. layer was separated and the aq. layer was extracted with EtOAc (1×). The combined org. layers were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. Purification was performed by FC (EtOAc/hept 7:3 to EtOAc/MeOH 9:1) to obtain 2-(4-nitro-1H-pyrazol-1-yl)ethanol as a white solid. LC-MS conditions A: tR=0.44 min, [M+H]+=no ionization.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:7][CH:6]1Cl)(=[O:3])[CH3:2].C(O[C@@H]1O[C@H](COC(=O)C)[C@@H](OC(=O)C)[C@H]1OC(=O)C)(=O)C.[C:42]([C:45]1[N+:49]([CH2:50][C:51]2[CH:56]=[CH:55][C:54]([N+:57]([O-:59])=[O:58])=[CH:53][CH:52]=2)=[CH:48][NH:47][C:46]=1[O-:60])(=[O:44])[NH2:43]>>[N+:57]([C:54]1[CH:53]=[CH:52][C:51]([CH2:50][N:49]2[C:45]([C:42]([NH2:43])=[O:44])=[C:46]([O:60][C@@H:6]3[O:7][C@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[C@@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@H:5]3[O:4][C:1](=[O:3])[CH3:2])[N:47]=[CH:48]2)=[CH:56][CH:55]=1)([O-:59])=[O:58]
Reactant: CC(=O)OC[C@H]1OC(Cl)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: NC(=O)c1c([O-])[nH]c[n+]1Cc1ccc([N+](=O)[O-])cc1
Agent: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Product: CC(=O)OC[C@H]1O[C@@H](Oc2ncn(Cc3ccc([N+](=O)[O-])cc3)c2C(N)=O)[C@H](OC(C)=O)[C@@H]1OC(C)=O

Procedure:
Following a procedure similar to that of Example 1 but using 2,3,5-tri-O-acetyl-D-ribofuranosyl chloride prepared from 2.50 g of 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose and 1.022 g of 5-carbamoyl-1-(4-nitrobenzyl)imidazolium-4-olate there was obtained 0.986 g of 1-(4-nitrobenzyl)-4-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)oxy-1H-imidazole-5-carboxamide which was recrystallized from ethanol. m.p. 155.5°-156.5° C.
Reaction SMILES: Cl.[NH2:2][C:3]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([C:12]([O:14][CH3:15])=[O:13])[NH:5][C:4]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[CH:22](=O)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>CO>[CH:22](=[N:2][C:3]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([C:12]([O:14][CH3:15])=[O:13])[NH:5][C:4]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=Cc1ccccc1
Reactant: COC(=O)c1[nH]c(-c2ccccc2)c(N)c1C(=O)OC
Agent: Cl
Solvent: CO
Product: COC(=O)c1[nH]c(-c2ccccc2)c(N=Cc2ccccc2)c1C(=O)OC

Procedure:
From the compound of Example 41 and benzaldehyde, yeild, 78% m.p. 218°-20° C. (from methanol).
Reaction SMILES: C(OC(=O)C)(=O)C.[CH:8]([OH:10])=O.[NH2:11][C:12]1[CH:13]=[C:14]([C:18](=[O:20])[CH3:19])[CH:15]=[CH:16][CH:17]=1.C(N(C(C)C)CC)(C)C>ClCCl>[C:18]([C:14]1[CH:13]=[C:12]([NH:11][CH:8]=[O:10])[CH:17]=[CH:16][CH:15]=1)(=[O:20])[CH3:19]
Reactant: CC(=O)c1cccc(N)c1
Reactant: O=CO
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CC(=O)OC(C)=O
Product: CC(=O)c1cccc(NC=O)c1
Temperature: 50 °C

Procedure:
A 25 ml portion of acetic anhydride was cooled at 0° C. in an ice bath. A 12.5 ml portion of formic acid was added, the mixture was heated at 50° C. for 15 minutes then cooled to 0° C., giving 9.69 g of crude mixed formicacetic anhydride. This anhydride was reacted with 13.52 g of m-aminoacetophenone, 14.21 g of diisopropylethylamine and 800 ml of dichloromethane as described in Example 1, giving 13.27 g of N-(3-acetylphenyl)formamide, mp 100°-102° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=O.[NH:11]1[CH2:17][C:15](=[O:16])[NH:14][C:12]1=[O:13].C(CN)O>O>[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=[C:17]1[NH:11][C:12](=[O:13])[NH:14][C:15]1=[O:16]
Reactant: O=C1CNC(=O)N1
Reactant: O=Cc1ccc(O)c(O)c1
Solvent: O
Solvent: NCCO
Product: O=C1NC(=O)C(=Cc2ccc(O)c(O)c2)N1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 3,4-dihydroxybenzaldehyde (2.072 g.) and hydantoin (1.50 g.) in water (15 ml) was heated to 70° to give a clear solution. To this was added monoethanolamine (1.38 g.) and the magnetically stirred mixture was heated (90°-92°, bath temperature) for 4 hours. Within 10 minutes crystallization occurred. The product was allowed to cool to room temperature and was stored overnight. After immersing in an ice-bath, the mixture was acidified with ECl, refrigerated 5 hours, filtered, washed with cold (-10°) 1:1 methanol-water and dried. The title compound was obtained as a pale brown solid: 2.776 g, m.p. 300°-310°. (Trituration with hot absolute ethanol gave a pale brown solid in ca 65% recovery, m.p. 320° decomp.)
Reaction SMILES: [CH3:1][C:2]([O:10][Si:11]([CH3:14])([CH3:13])[CH3:12])([CH2:6][CH2:7][O:8][CH3:9])[CH2:3][C:4]#[CH:5].N(C(C)(C)C#N)=NC(C)(C)C#N.[CH2:27]([SnH:31]([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:32][CH2:33][CH2:34][CH3:35])[CH2:28][CH2:29][CH3:30]>>[CH2:36]([Sn:31]([CH2:27][CH2:28][CH2:29][CH3:30])([CH2:32][CH2:33][CH2:34][CH3:35])/[CH:5]=[CH:4]/[CH2:3][C:2]([CH3:1])([O:10][Si:11]([CH3:14])([CH3:12])[CH3:13])[CH2:6][CH2:7][O:8][CH3:9])[CH2:37][CH2:38][CH3:39]
Reactant: CCCC[SnH](CCCC)CCCC
Reactant: C#CCC(C)(CCOC)O[Si](C)(C)C
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Product: CCCC[Sn](/C=C/CC(C)(CCOC)O[Si](C)(C)C)(CCCC)CCCC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a stirred solution of 15 g. (0.069 moles) of 4-methyl-4-trimethylsilyloxy-7-oxa-1-octyne and 75 mg. of azobisisobutyronitrile is added dropwise, under nitrogen atmosphere, 21.1 g. (0.073 moles) of tri-n-butyltin hydride. The solution is stirred at 130°-135° C. for 11/2 hours, then cooled to ambient temperature. Distillation provides 29 g. (86%) of product as a colorless oil; b.p. 165°-167° C. (0.25 mm.).