Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N1C=CC=CC=1.[CH3:7][Si:8]([CH3:19])([CH3:18])[C:9]1[O:13][CH:12]=[C:11]([CH2:14][CH2:15][CH2:16][OH:17])[CH:10]=1.[C:20](Cl)(=[O:32])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]>O1CCCC1.CCOCC>[C:20]([O:17][CH2:16][CH2:15][CH2:14][C:11]1[CH:10]=[C:9]([Si:8]([CH3:7])([CH3:18])[CH3:19])[O:13][CH:12]=1)(=[O:32])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]
Reactant: CCCCCCCCCCCC(=O)Cl
Reactant: C[Si](C)(C)c1cc(CCCO)co1
Solvent: c1ccncc1
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCCCCCCCCCCC(=O)OCCCc1coc([Si](C)(C)C)c1
Reaction time: 14 h

Procedure:
Pyridine (0.06 ml, 0.72 mmol) was added to a mixture of 3-(5-trimethylsilyl-3-furyl)propan-1-ol (from above) and lauroyl chloride (0.17 ml, 0.72 mmol) in tetrahydrofuran (4 ml) at room temperature. After 14 hours, the mixture was diluted with ether (10 ml) and washed successively with water, copper (II) sulphate and brine. Evaporation of the dried (magnesium sulphate) organic layers gave an oil, which was purified by preparative TLC (20×20 cm, 500u silica plate; developed with 10% ethyl ether/petroleum ether). The title ester was obtained as a colorless oil.
Reaction SMILES: [CH:1]1([CH2:7][C@@H:8]([NH:15]C(=O)OC(C)(C)C)[CH:9]([OH:14])[C:10]([NH:12][NH2:13])=[O:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1C=CC=CC=1.[Cl:29][C:30]1[CH:37]=[CH:36][C:33]([CH:34]=O)=[CH:32][CH:31]=1>C(O)C>[NH2:15][C@H:8]([CH2:7][CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)[CH:9]([OH:14])[C:10]([NH:12]/[N:13]=[CH:34]/[C:33]1[CH:36]=[CH:37][C:30]([Cl:29])=[CH:31][CH:32]=1)=[O:11]
Reactant: CC(C)(C)OC(=O)N[C@H](CC1CCCCC1)C(O)C(=O)NN
Reactant: O=Cc1ccc(Cl)cc1
Solvent: c1ccncc1
Solvent: CCO
Product: N[C@H](CC1CCCCC1)C(O)C(=O)N/N=C/c1ccc(Cl)cc1
Temperature: 85 °C
Reaction time: 16 h

Procedure:
A solution of Example 14A (0.064 g, 0.20 mmol) in ethanol (3 mL) was treated with pyridine (2 mL) and 4-chlorobenzaldehyde (0.033 mL, 0.23 mmol), heated to 85° C., stirred for 16 hours, and concentrated. The concentrate was purified by flash column chormatography on silica gel with ethyl acetate in hexanes, and the purified concntrate was treated with 4N HCl in dioxane, stirred for 4 hours, concentrated, precipitated from diethyl ether, and collected by filtration to provide the desired product.
Reaction SMILES: [C:1]([O:16][CH2:17][CH2:18][N:19]([C:38](=[O:46])[CH2:39][S:40][CH2:41][CH2:42][N:43]([CH3:45])[CH3:44])[CH2:20][CH2:21][O:22][C:23](=[O:37])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[Br:47][CH2:48][CH2:49][OH:50]>>[Br-:47].[C:23]([O:22][CH2:21][CH2:20][N:19]([CH2:18][CH2:17][O:16][C:1](=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[C:38](=[O:46])[CH2:39][S:40][CH2:41][CH2:42][N+:43]([CH2:48][CH2:49][OH:50])([CH3:44])[CH3:45])(=[O:37])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36]
Reactant: OCCBr
Reactant: CCCCCCCCCCCCCC(=O)OCCN(CCOC(=O)CCCCCCCCCCCCC)C(=O)CSCCN(C)C
Product: CCCCCCCCCCCCCC(=O)OCCN(CCOC(=O)CCCCCCCCCCCCC)C(=O)CSCC[N+](C)(C)CCO
Product: [Br-]
Temperature: 75 °C
Reaction time: 8 h
Yield: 66.6 %

Procedure:
In a sealed system, ((2-((2-(dimethylamino)ethyl)thio)acetyl)azanediyl)bis(ethane-2,1-diyl) ditetradecanoate (1.00 g, 1.49 mmol) was combined with 2-bromoethanol (687 uL, 9.69 mmol) was added. The reaction vessel was flushed with inert gas and then sealed. Reaction was heated to 75° C. and allowed to stir overnight, then cooled, and concentrated in vacuo. Purification by silica gel chromatography with DCM/MeOH gradient yielded 2-((2-(bis(2-(tetradecanoyloxy)ethyl)amino)-2-oxoethyl)thio)-N-(2-hydroxyethyl)-N,N-dimethylethanaminium bromide (HES104) (790 mg). LCMS ESI+: m/z 715.7 (M+H).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].Br[CH2:11][CH:12]=[C:13]([CH3:15])[CH3:14].[OH-].[C:17]([OH:29])(=[O:28])[CH2:18][C:19]([CH2:24][C:25]([OH:27])=[O:26])([C:21]([OH:23])=[O:22])[OH:20]>C(#N)C.[OH-].[Na+]>[C:17]([O-:29])(=[O:28])[CH2:18][C:19]([CH2:24][C:25]([O-:27])=[O:26])([C:21]([O-:23])=[O:22])[OH:20].[CH3:14][C:13]([CH3:15])=[CH:12][CH2:11][N+:6]1[CH:7]=[CH:8][CH:9]=[C:4]([C:1](=[O:3])[CH3:2])[CH:5]=1.[CH3:14][C:13]([CH3:15])=[CH:12][CH2:11][N+:6]1[CH:7]=[CH:8][CH:9]=[C:4]([C:1](=[O:3])[CH3:2])[CH:5]=1.[CH3:14][C:13]([CH3:15])=[CH:12][CH2:11][N+:6]1[CH:7]=[CH:8][CH:9]=[C:4]([C:1](=[O:3])[CH3:2])[CH:5]=1
Reactant: CC(=O)c1cccnc1
Reactant: O=C(O)CC(O)(CC(=O)O)C(=O)O
Reactant: CC(C)=CCBr
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Product: CC(=O)c1ccc[n+](CC=C(C)C)c1
Product: O=C([O-])CC(O)(CC(=O)[O-])C(=O)[O-]

Procedure:
3-Acetylpyridine is reacted with 1-bromo-3-methyl-2-butene in acetonitrile; the halide intermediate is converted to the hydroxide in methanolic sodium hydroxide, and then reacted with citric acid.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[C:19]([O:30][CH2:31][CH2:32][CH2:33][OH:34])[N:18]=[C:17]([N:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1.[CH:63](O)=[O:64].Cl>CN(C)C=O.C(Cl)Cl.O>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[C:19]([O:30][CH2:31][CH2:32][CH2:33][OH:34])[N:18]=[C:17]([N:35]3[CH2:36][CH2:37][N:38]([CH:63]=[O:64])[CH2:39][CH2:40]3)[N:16]=2)(=[O:13])=[O:12])=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(N2CCNCC2)nc1OCCCO
Reactant: O=CO
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Solvent: ClCCl
Product: COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(N2CCN(C=O)CC2)nc1OCCCO
Temperature: 25 °C
Reaction time: 8 h
Yield: 23.8 %

Procedure:
4-t-Butyl-N-[6-(3-hydroxypropyloxy)-5-(2-methoxyphenoxy)-2-piperazinyl-4-pyrimidinyl]-benzenesulfonamide (80 mg; 0.14 mmol), WSC·HCl (61.6 mg; 0.28 mmol), N-hydroxybenzotriazole (75.6 mg; 0.56 mmol), and formic acid (6.5 mg; 0.15 mmol) were dissolved in dimethylformamide-methylene chloride (1:1, 1 ml). The mixture was stirred overnight at room temperature. The reaction mixture was poured into water, made acidic with hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, and evaporated. The residue was purified by silica gel column chromatography (chloroform:methanol=15:1), to thereby obtain 20 mg (yield: 23.8%) of the title compound as a pale yellow oil.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][C@@H:13]2[O:18][C:17]3[C:19]([CH2:26][CH:27]=[CH2:28])=[C:20]([N+:23]([O-:25])=[O:24])[CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1>C1C=CC=CC=1.CC#N.CC#N.Cl[Pd]Cl>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[O:18][C:17]3[C:19]([CH:26]=[CH:27][CH3:28])=[C:20]([N+:23]([O-:25])=[O:24])[CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=[O:9])=[O:10])=[CH:4][CH:3]=1
Reactant: C=CCc1c([N+](=O)[O-])ccc2c1O[C@@H](COS(=O)(=O)c1ccc(C)cc1)CO2
Agent: Cl[Pd]Cl
Solvent: CC#N
Solvent: c1ccccc1
Product: CC=Cc1c([N+](=O)[O-])ccc2c1OC(COS(=O)(=O)c1ccc(C)cc1)CO2
Yield: 74 %

Procedure:
To a solution of 10.0 g (24.0 mmole) of (R)-[8-allyl-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate in 700 mL of benzene was added 1.03 g of bis(acetonitrile)dichloropalladium (II) and the mixture was refluxed under nitrogen for 48 hours. The catalyst was then removed by filtration and the filtrate concentrated in vacuum to a brown oil. Column chromatography on silica gel with methylene chloride as eluent gave 7.2 g of the title compound as a mixture of E and Z isomers. A sample of {(2R)-7-nitro-8[(E)-1-propenyl]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate was obtained as a yellow solid (m.p. 105-106° C.) by evaporation of a pure E isomer-containing fraction.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]2[C:18]3[CH:17]=[CH:16][C:15]([O:19][CH2:20][C@@H:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:14][C:13]=3[O:12][CH2:11][C:8]2=[CH:9][N:10]=1)(=[O:3])[CH3:2].C1C(=O)N([Cl:41])C(=O)C1>C(#N)C>[C:1]([NH:4][C:5]1[CH:6]=[C:7]2[C:18]3[CH:17]=[C:16]([Cl:41])[C:15]([O:19][CH2:20][C@@H:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])[CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:14][C:13]=3[O:12][CH2:11][C:8]2=[CH:9][N:10]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1cc2c(cn1)COc1cc(OC[C@H](CC(C)C)NC(=O)OC(C)(C)C)ccc1-2
Reactant: O=C1CCC(=O)N1Cl
Solvent: CC#N
Product: CC(=O)Nc1cc2c(cn1)COc1cc(OC[C@H](CC(C)C)NC(=O)OC(C)(C)C)c(Cl)cc1-2
Temperature: 25 °C
Yield: 79.1 %

Procedure:
The stirred solution of (S)-tert-butyl (1-((2-acetamido-5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (100 mg, 0.220 mmol) (prepared as described in Example 18, Part H) and NCS (29.3 mg, 0.220 mmol) in acetonitrile (15 mL) was heated to 80° C. for 12 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The residue was partitioned between water (25 mL) and DCM (25 mL). The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to afford (S)-tert-butyl (1-((2-acetamido-9-chloro-5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (120 mg, 0.174 mmol, 79% yield) as an off-white solid. The product was used as is for the next step without purification. LCMS (ESI) m/e 490.2 [(M+H)+, calcd for C25H33ClN3O5 490.2]; LC/MS retention time (Method D): tR=1.98 min.
Reaction SMILES: [Mg].Br[C:3]1[CH:4]=[CH:5][C:6]2[CH:10]=[CH:9][S:8][C:7]=2[CH:11]=1.[CH3:12][Si:13]([CH3:30])([CH3:29])[CH2:14][CH2:15][O:16][CH2:17][N:18]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[N:20]=[C:19]1[CH:27]=[O:28].Cl>O1CCCC1>[S:8]1[CH:9]=[CH:10][C:6]2[CH:5]=[CH:4][C:3]([CH:27]([C:19]3[N:18]([CH2:17][O:16][CH2:15][CH2:14][Si:13]([CH3:29])([CH3:30])[CH3:12])[C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=4[N:20]=3)[OH:28])=[CH:11][C:7]1=2
Reactant: C[Si](C)(C)CCOCn1c(C=O)nc2ccccc21
Reactant: Brc1ccc2ccsc2c1
Agent: Cl
Agent: [Mg]
Solvent: C1CCOC1
Product: C[Si](C)(C)CCOCn1c(C(O)c2ccc3ccsc3c2)nc2ccccc21
Reaction time: 12 h

Procedure:
To a suspension of magnesium (86 mg) in tetrahydrofuran is added a solution of 6-bromobenzo[b]thiophene (which can be prepared according to WO2006/107784) (500 mg) in tetrahydrofuran. After reflux for 3 h, a solution of 1-(2-trimethylsilylethoxymethyl)-1H-benzimidazole-2-carbaldehyde (which can be prepared according to US2003/220341 or US6476041 for example) (635 mg) in tetrahydrofuran is added to the Grignard reagent at room temperature. After stirring for 12 h, the reaction mixture is treated with diluted hydrochloric acid and the organic phase is dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol from 100/0 to 90/10) to afford benzo[b]thiophen-6-yl[1-(2-trimethylsilylethoxymethyl)-1H-benzimidazol-2-yl]methanol.
Reaction SMILES: ClCCN(CCCl)C(Cl)=O.[Cl:11][CH2:12][CH2:13][N:14]([C:18]([N:20]=[C:21]=[S:22])=[O:19])[CH2:15][CH2:16][Cl:17].[CH3:23][O:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][C:34]=1[O:35][CH3:36])[N:31]=[CH:30][CH:29]=[C:28]2[O:37][C:38]1[CH:44]=[CH:43][C:41]([NH2:42])=[CH:40][CH:39]=1.C1(C)C=CC=CC=1>C(O)C>[Cl:17][CH2:16][CH2:15][N:14]([C:18]([N:20]=[C:21]=[S:22])=[O:19])[CH2:13][CH2:12][Cl:11].[CH3:23][O:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][C:34]=1[O:35][CH3:36])[N:31]=[CH:30][CH:29]=[C:28]2[O:37][C:38]1[CH:39]=[CH:40][C:41]([NH:42][C:21]([NH:20][C:18]([N:14]([CH2:13][CH2:12][Cl:11])[CH2:15][CH2:16][Cl:17])=[O:19])=[S:22])=[CH:43][CH:44]=1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Agent: O=C(Cl)N(CCCl)CCCl
Agent: O=C(N=C=S)N(CCCl)CCCl
Solvent: Cc1ccccc1
Solvent: CCO
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)N(CCCl)CCCl)cc3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 55 %

Procedure:
[Di(2-chloroethyl)amino]methanoyl isothiocyanate was prepared using commercially available N,N-di(2-chloroethyl)carbamic chloride (80 mg) as a starting compound according to the description of the literature. [Di(2-chloroethyl)amino]methanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (48 mg, yield 55%).
Reaction SMILES: [C:1]1([N:7]2[C:12](=[O:13])[C:11]3[S:14][CH:15]=[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:10]=3[N:9]=[CH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.NC1C(C2C=C[C:32]([O:35]C)=CC=2)=CSC=1C(OC)=O.[CH:41](OCC)(OCC)[O:42]CC.COC1C=CC(N)=CC=1>C(O)(=O)C>[CH3:32][O:35][C:4]1[CH:5]=[CH:6][C:1]([N:7]2[C:12](=[O:13])[C:11]3[S:14][CH:15]=[C:16]([C:17]4[CH:18]=[CH:19][C:20]([O:42][CH3:41])=[CH:21][CH:22]=4)[C:10]=3[N:9]=[CH:8]2)=[CH:2][CH:3]=1
Reactant: COC(=O)c1scc(-c2ccc(OC)cc2)c1N
Reactant: CCOC(OCC)OCC
Reactant: O=c1c2scc(-c3ccccc3)c2ncn1-c1ccccc1
Solvent: COc1ccc(N)cc1
Solvent: CC(=O)O
Product: COc1ccc(-c2csc3c(=O)n(-c4ccc(OC)cc4)cnc23)cc1
Yield: 87.5 %

Procedure:
In the same manner as the synthesis of Compound 1, methyl 3-amino-4-(4-methoxyphenyl)thiophene-2-carboxylate (80 mg, 0.3 mmol), triethyl orthoformate (0.66 ml), p-anisidine (70.2 mg, 0.57 mmol), and acetic acid (0.08 ml) were used to give 95.7 mg (0.26 mmol, 87.5% yield) of the title compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:41])[NH:7][CH2:8][CH2:9][CH2:10][N:11]([CH:21]([C:24]1[N:29](CC2C=CC=CC=2)[C:28](=[O:37])[C:27]2=[CH:38][CH:39]=[CH:40][N:26]2[N:25]=1)[CH2:22][CH3:23])[C:12](=[O:20])[C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1)([CH3:4])([CH3:3])[CH3:2].ClC1C=CC(C(Cl)=O)=CC=1.[H][H]>C(O)C.[OH-].[OH-].[Pd+2]>[C:1]([O:5][C:6](=[O:41])[NH:7][CH2:8][CH2:9][CH2:10][N:11]([C:12](=[O:20])[C:13]1[CH:14]=[CH:15][C:16]([CH3:19])=[CH:17][CH:18]=1)[CH:21]([C:24]1[NH:29][C:28](=[O:37])[C:27]2=[CH:38][CH:39]=[CH:40][N:26]2[N:25]=1)[CH2:22][CH3:23])([CH3:3])([CH3:2])[CH3:4]
Reactant: CCC(c1nn2cccc2c(=O)n1Cc1ccccc1)N(CCCNC(=O)OC(C)(C)C)C(=O)c1ccc(C)cc1
Reactant: [H][H]
Agent: [Pd+2]
Agent: O=C(Cl)c1ccc(Cl)cc1
Agent: [OH-]
Solvent: CCO
Product: CCC(c1nn2cccc2c(=O)[nH]1)N(CCCNC(=O)OC(C)(C)C)C(=O)c1ccc(C)cc1
Yield: 65 %

Procedure:
A mixture of {3-[[1-(3-benzyl-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)-propyl]-(4-methylbenzoyl)-amino]-propyl}-carbamic acid tert-butyl ester (115 mg, 0.21 mmol, prepared using an identical synthetic sequence to that outlined for Example 12 A–F, except substituting p-toluoyl chloride for 4-chlorobenzoyl chloride in F) and Pd(OH)2 (20 wt. % Pd on carbon, 66 mg) in ethanol (6 mL) was stirred at 50° C., under 60 psi of hydrogen, for 22 h. The catalyst was filtered off and the residue was purified by preparative HPLC (YMC S10 ODS, 30×500 mm, 30 minute gradient from 62–90% aqueous methanol with 0.1% TFA). The appropriate fractions were combined, neutralized with saturated aqueous sodium bicarbonate, and then concentrated in vacuo to remove the methanol. The mixture was extracted with ethyl acetate (3×10 mL). The combined organic layers were washed once each with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to yield the title compound (63 mg, 65%): 1H NMR (CDCl3) δ 10.52 (s, 1H), 7.37–7.35 (m, 3H), 7.27–7.23 (m, 2H), 7.07 (m, 1H), 6.54 (m, 1H), 4.60 (m, 1H), 4.21 (m, 1H), 3.40 (m, 2H), 2.89 (m, 2H), 2.40 (s, 3H), 2.29 (m, 2H), 1.64 (m, 2H), 1.37 (s, 9H), 1.08 (t, 3H, J=7.15 Hz); MS (ESI+) 468.21 (M++H).
Reaction SMILES: [C:1]1([S:7]([CH2:10][C:11]2[CH:20]=[CH:19][C:18](Br)=[CH:17][C:12]=2[C:13]([O:15][CH3:16])=[O:14])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:22][C:23]1[O:24][C:25](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:27]=1>>[C:1]1([S:7]([CH2:10][C:11]2[CH:20]=[CH:19][C:18]([C:27]3[CH:26]=[CH:25][O:24][C:23]=3[CH3:22])=[CH:17][C:12]=2[C:13]([O:15][CH3:16])=[O:14])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)c1cc(Br)ccc1CS(=O)(=O)c1ccccc1
Reactant: Cc1ccc(B2OC(C)(C)C(C)(C)O2)o1
Product: COC(=O)c1cc(-c2ccoc2C)ccc1CS(=O)(=O)c1ccccc1

Procedure:
Prepared by proceeding in a similar manner to Example 36, starting from methyl 2-(benzenesulphonylmethyl)-5-bromobenzoate (Intermediate 63) and 2-methylfuran-5-boronic acid pinacol ester.
Reaction SMILES: [Cl:1][CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[NH:12][C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1)=[O:4].CC1C=CC(NC2C(N)=CC=CC=2)=CC=1.[NH2:35][C:36]1[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=1>C(Cl)(Cl)Cl>[ClH:1].[CH3:19][C:16]1[CH:17]=[CH:18][C:13]([NH:12][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[NH:5][C:3](=[O:4])[CH2:2][NH:35][C:36]2[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=2)=[CH:14][CH:15]=1
Reactant: Nc1ccncc1
Reactant: Cc1ccc(Nc2ccccc2NC(=O)CCl)cc1
Agent: Cc1ccc(Nc2ccccc2N)cc1
Solvent: ClC(Cl)Cl
Product: Cc1ccc(Nc2ccccc2NC(=O)CNc2ccncc2)cc1
Product: Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-Chloro-N-[2-[(4-methylphenyl)amino]phenyl]acetamide which had been synthesized from N-(4-methylphenyl)-1,2-benzenediamine by substantially the same manner as described in Reference Example 1 and 4-aminopyridine were dissolved in chloroform and the solution was left on standing under stirring at room temperature overnight, whereby the reaction was completed. The resulting precipitates were collected by filtration and recrystallized from ethanol to give N-[2-[(4-methylphenyl)amino]phenyl]-2-[(4-pyridinyl)amino]-acetamide hydrochloride.
Reaction SMILES: [C@H:1]([NH:5][C:6]1[C:7](=[O:20])[NH:8][C:9]2[C:14]([N:15]=1)=[CH:13][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][CH:10]=2)([CH2:3][CH3:4])[CH3:2].N1C=CC=CC=1.[O:27](S(C(F)(F)F)(=O)=O)[S:28]([C:31]([F:34])([F:33])[F:32])(=O)=[O:29]>ClCCl>[C@H:1]([NH:5][C:6]1[C:7]([O:20][S:28]([C:31]([F:34])([F:33])[F:32])(=[O:29])=[O:27])=[N:8][C:9]2[C:14]([N:15]=1)=[CH:13][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][CH:10]=2)([CH2:3][CH3:4])[CH3:2]
Reactant: CC[C@@H](C)Nc1nc2cc(C(=O)OC)ccc2[nH]c1=O
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC[C@@H](C)Nc1nc2cc(C(=O)OC)ccc2nc1OS(=O)(=O)C(F)(F)F
Temperature: 0 °C

Procedure:
To a solution of (R)-methyl 3-(sec-butylamino)-2-oxo-1,2-dihydroquinoxaline-6-carboxylate (300 mg, 1.10 mmol) in dichloromethane (40 mL) was added pyridine (344 mg, 4.36 mmol) and then Tf2O (615 mg, 2.18 mmol) was added dropwise with stirring at 0° C. The resulting solution was stirred for 2 h at room temperature and then washed with water (3×50 mL), dried over anhydrous sodium sulfate and concentrated in vacuo to afford (R)-methyl 3-(sec-butylamino)-2-(trifluoromethylsulfonyloxy)quinoxaline-6-carboxylate as red oil (400 mg, crude).
Reaction SMILES: [C:1]([O:5][C:6](=[O:35])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:27][CH:26]=2)[C:15](=[O:24])[NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][CH:18]=2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].C=O.[C:38]([BH3-])#N.[Na+].CCOC(C)=O>CC(O)=O>[C:1]([O:5][C:6](=[O:35])[C:7]1[CH:12]=[CH:11][C:10]([N:13]([CH:14]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:27][CH:26]=2)[C:15](=[O:24])[NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][CH:18]=2)[CH3:38])=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: [BH3-]C#N
Reactant: CC(C)(C)OC(=O)c1ccc(NC(C(=O)Nc2ccc(I)cc2)c2ccc(C(C)(C)C)cc2)cc1
Agent: C=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CN(c1ccc(C(=O)OC(C)(C)C)cc1)C(C(=O)Nc1ccc(I)cc1)c1ccc(C(C)(C)C)cc1
Temperature: 25 °C
Yield: 105.5 %

Procedure:
4-{[(4-tert-Butyl-phenyl)-(4-iodo-phenylcarbamoyl)-methyl]-amino}-benzoic acid tert-butyl ester (110 mg, 0.19 mmol) was dissolved in 2 mL of HOAc. paraformaldehyde (51 mg, 0.57 mmol) and sodium cyano-borohydride (36 mg, 0.57 mmol) were then added and heated to 40 C for 1 h. Cooled to RT, EtOAc (20 mL) was added and extracted water (20 mL). The organic layer was washed again with water (20 mL), dried over sodium sulfate, filtered and the organic layer was removed under reduced pressure to give a white solid (120 mg, 100%). 1H NMR showed the compound to be very clean and sufficient for the following step. LCMS (M+1=599.4)
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[OH:5][CH:6]1[CH2:10][CH:9]([OH:11])[CH:8]=C1>N1C=CC=CC=1>[CH3:2][C:1]([O-:3])=[O:5].[CH3:8][C:9]([CH2:10][C:6]([OH:3])=[O:5])=[O:11]
Reactant: CC(=O)Cl
Reactant: OC1C=CC(O)C1
Solvent: c1ccncc1
Product: CC(=O)CC(=O)O
Product: CC(=O)[O-]
Reaction time: 5 h

Procedure:
Forty-eight milligrams (0.6 mmol) of acetic acid chloride was added to a mixture of 111 milligrams (1.1 mmols) of 3,5-dihydroxycyclopent-1-ene and 0.5 milliliter of pyridine with stirring over a period of 5 hours. The aftertreatment was carried out as in Example 1, and 62 milligrams of a crude product was obtained. When calculations were made from the results of the chromatographic analysis, the yields of the monoacetate and diacetate were 22% and 7%, respectively.
Reaction SMILES: [C:1]1([CH2:10][C:11]#[N:12])[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]#[N:9])[CH:2]=1.N[CH:14]([CH2:17][CH3:18])[CH2:15][OH:16]>CC1C=CC=CC=1C.O.O.O.O.[N+]([O-])([O-])=O.[Cd+2].[N+]([O-])([O-])=O>[CH2:17]([CH:14]1[CH2:15][O:16][C:11]([CH2:10][C:1]2[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]3[O:16][CH2:15][CH:14]([CH2:17][CH3:18])[N:9]=3)[CH:2]=2)=[N:12]1)[CH3:18]
Reactant: CCC(N)CO
Reactant: N#CCc1cccc(CC#N)c1
Agent: O=[N+]([O-])[O-]
Agent: [Cd+2]
Solvent: O
Solvent: Cc1ccccc1C
Product: CCC1COC(Cc2cccc(CC3=NC(CC)CO3)c2)=N1
Temperature: 130 °C
Reaction time: 72 h
Yield: 66.4 %

Procedure:
In a one liter four-necked round-bottom flask equipped with a condenser, N2 inlet/outlet, magnetic stirrer, and thermometer, was charged with 52.65 g of 1,3-phenylene-diacetonitrile (0.337 mol, Aldrich), 78.13 g of 2-amino-1-butanol (0.876 mol, Aldrich), and 3.38 g of cadmium nitrate tetrahydrate (0.011 mol, Aldrich) in 300 mL of o-xylene. The mixture was heated to 130° C. and the reaction was run for 72 hours. The cooled mixture was washed with de-ionized water (2×200 mL). The organic layer was dried over sodium sulfate and acidic alumina gel. After removal of solvent in vacuo, 67.21 g of an amber liquid resin was obtained in a yield of 67%. The viscosity of this resin at room temperature is 250 mPa.·. 1H NMR (CDCl3, 400 MHz): δ 7.11-7.19 (m, 4H), 4.20 (t, 2H), 3.91-3.97 (m, 2H), 3.77 (t, 2H), 3.52 (s, 4H), 1.53-1.61 (m, 2H), 1.40-1.47 (m, 2H), 0.86 (t, 6H).
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4](=[O:25])[C:5]([N+:22]([O-:24])=[O:23])=[C:6]([C:8]([C:20]#[N:21])([CH2:14][C:15]2[O:16][CH:17]=[CH:18][CH:19]=2)C(OCC)=O)[N:7]=1.Cl>[OH-].[Na+]>[NH2:1][C:2]1[NH:3][C:4](=[O:25])[C:5]([N+:22]([O-:24])=[O:23])=[C:6]([CH:8]([CH2:14][C:15]2[O:16][CH:17]=[CH:18][CH:19]=2)[C:20]#[N:21])[N:7]=1
Reactant: CCOC(=O)C(C#N)(Cc1ccco1)c1nc(N)[nH]c(=O)c1[N+](=O)[O-]
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: N#CC(Cc1ccco1)c1nc(N)[nH]c(=O)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.03 h
Yield: 76.2 %

Procedure:
A solution of 2-Amino-α-cyano-α-(2-furanyl-methyl)-1,6-dihydro-5-nitro-6-oxo-4-pyrimidineacetic acid, ethyl ester (5.0 g) in 1N NaOH (200 mL) is stirred at room temperature for 2 h. The reaction mixture is acidified (pH 1) by the dropwise addition of conc HCl and is stirred at room temperature for 2 min. The precipitate is collected by filtration, washed with water, and dried to give 2-Amino-α-(2-Furanylmethyl)-1,6-dihydro-5-nitro-6-oxo-4-pyrimidineacetonitrile (3.02 g 73%). ##STR21##