Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](OCC)(OCC)[CH:10]([NH2:20])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:21]1([CH3:30])[CH:26]=[CH:25][CH:24]=[C:23]([N:27]=[C:28]=S)[CH:22]=1>C(Cl)(Cl)Cl>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2[N:27]([C:23]3[CH:22]=[C:21]([CH3:30])[CH:26]=[CH:25][CH:24]=3)[CH:28]=[N:20][C:10]=2[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC1(OCC)CCN(Cc2ccccc2)CC1N
Reactant: Cc1cccc(N=C=S)c1
Solvent: ClC(Cl)Cl
Product: Cc1cccc(-n2cnc3c2CCN(Cc2ccccc2)C3)c1
Temperature: 25 °C
Yield: 74.9 %

Procedure:
A solution of 1-benzyl-4,4-diethoxy-piperidin-3-ylamine 16 (600 mg, 2.2 mmol), and m-tolyl isothiocyanate (328 mg, 2.2 mmol) in 10 mL chloroform was heated at 60° C. for 2 hr. The solvent was removed in vacuo, and the residue was treated with 10 mL each of 10% hydrochloric acid and dioxane and heated at reflux for 1 h. After removal of the solvent the residue was dissolved in 50 mL ethanol followed by addition of Raney Nickel (ca. 3.0 g). The suspension was heated at reflux for 2 h then allowed to cool to room temperature. The solids were removed by filtration. The solvent was evaporated in vacuo, and the residue was diluted with 10% sodium hydroxide solution and extracted into chloroform. The organic layer was dried over potassium carbonate, filtered and concentrated to provide 500 mg of 5-benzyl-1-m-tolyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine 17a as a light brown oil, [M+H]+=304.
Reaction SMILES: Br[C:2]1[C:7]2[CH:8]([O:20][CH3:21])[O:9][C:10]3[C:15]([C:6]=2[CH:5]=[CH:4][C:3]=1[NH:22]C(=O)OCC1C=CC=CC=1)=[C:14]([O:16][CH:17]([F:19])[F:18])[CH:13]=[CH:12][CH:11]=3>[Pd].CO.C1COCC1>[F:19][CH:17]([F:18])[O:16][C:14]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:15]=1[C:6]1[CH:5]=[CH:4][C:3]([NH2:22])=[CH:2][C:7]=1[CH:8]([O:20][CH3:21])[O:9]2
Reactant: COC1Oc2cccc(OC(F)F)c2-c2ccc(NC(=O)OCc3ccccc3)c(Br)c21
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: COC1Oc2cccc(OC(F)F)c2-c2ccc(N)cc21

Procedure:
A mixture of Example 96A (82 mg, 0.16mmol) and 10% palladium on carbon (8 mg) in methanol (10 ml) and THF (10 ml) was stirred under hydrogen gas for 1.5 hour, filtered through diatomaceous earth (Celite®), and concentrated to provide the desired product. MS (ESI(+)Q1MS) m/z 294 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[CH:4]([C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=1)[CH3:5].C(=O)([O-])[O-].[K+].[K+].[CH2:20](Br)[CH:21]=[CH2:22]>CN(C)C=O.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:13])[CH:4]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:22][CH:21]=[CH2:20])=[CH:8][CH:7]=1)[CH3:5]
Reactant: COC(=O)C(C)c1ccc(O)cc1
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: C=CCOc1ccc(C(C)C(=O)OC)cc1
Temperature: 80 °C

Procedure:
A solution of the product of Example 46A (2.6 g, 12 mmol) in anhydrous dimethylformamide (20 mL) was treated with potassium carbonate (3.3 g, 24 mmol) and allyl bromide (1.2 mL, 13 mmol), and reaction heated for 16 hours at 80° C. Reaction mixture cooled and diluted with ethyl acetate. Mixture washed with water and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. Residue purified by normal phase HPLC on silica gel eluting with 3% ethyl acetate/hexane to provide the title compound.
Reaction SMILES: [F:1][CH:2]1[C:7](=O)[CH2:6][CH2:5][N:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:3]1.[CH3:19][NH2:20].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C1COCC1>[F:1][CH:2]1[CH:7]([NH:20][CH3:19])[CH2:6][CH2:5][N:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:3]1
Reactant: CN
Reactant: O=C1CCN(C(=O)OCc2ccccc2)CC1F
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClCCCl
Product: CNC1CCN(C(=O)OCc2ccccc2)CC1F
Reaction time: 2 h

Procedure:
To a solution of 9.4 g (37.5 mmol) of 2-2 in 150 mL of 1,2-dichloroethane was added 37.5 mL (74.9 mmol) of a 2M solution of methylamine in THF and 11.9 g (56.2 mmol) of Na(OAc)3BH. After stirring for 2 h, the reaction was quenched with saturated aqueous K2CO3, partitioned with EtOAc, separated, and the aqueous phase extracted 3×EtOAc. The combined organic extracts were washed with brine, dried over MgSO4, filtered, and concentrated by rotary evaporation. The residue was loaded onto a silica gel column and eluted with 80:10:10 CHCl3/EtOAc/MeOH to provide both the cis and trans isomers of 2-2a as colorless oils. Data for the trans isomer of 2-2a, first to elute (confirmed by NOE analysis): 1HNMR (600 MHz, CD2Cl2) δ 7.4-7.3 (m, 5H), 5.1 (m, 2H), 4.4-4.1 (m, 2H), 3.9 (m, 1H), 3.15-3.05 (m, 2H), 2.75 (m, 1H), 2.4 (s, 3H), 2.0 (in, 1H), 1.25 (m, 1H) ppm. Data for the cis isomer of 2-2a, second to elute (confirmed by NOE analysis): 1HNMR (600 MHz, CD2Cl2) δ 7.4-7.2 (m, 5H), 5.1 (m, 2H), 4.9-4.7 (m 1H), 4.4 (m, 1H), 4.15 (m, 1H), 3.1-2.9 (m, 2H), 2.6 (m, 1H), 2.4 (s, 3H), 1.8 (m, 1H), 1.6 (m, 1H) ppm. HRMS (ES) calc'd M+H for C14H19F1N2O2: 267.1504. Found: 267.1500.
Reaction SMILES: [C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[CH2:13]([NH:20][C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]=[C:23]([Cl:31])[C:22]=1[NH2:32])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>O1CCCC1>[CH2:13]([N:20]1[C:21]2[C:30]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[N:24]=[C:23]([Cl:31])[C:22]=2[N:32]=[C:1]1[OH:2])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Nc1c(Cl)nc2ccccc2c1NCc1ccccc1
Solvent: C1CCOC1
Product: Oc1nc2c(Cl)nc3ccccc3c2n1Cc1ccccc1
Temperature: 50 °C
Yield: 62.4 %

Procedure:
1,1′-Carbonyldiimidazole (2.9 g, 18 mmol) was added to a solution of N4-benzyl-2-chloroquinoline-3,4-diamine (5.0 g, 18 mmol) in tetrahydrofuran (THF) (50 mL), and the reaction was heated at 50° C. for three days. An analysis by liquid chromatography/mass spectrometry (LC/MS) indicated the presence of starting material, and additional 1,1′-carbonyldiimidazole (1.5 g, 9.2 mmol) was added. The reaction was stirred for several hours at 80° C., and additional 1,1′-carbonyldiimidazole (2.9 g, 18 mmol) was added. The reaction was stirred for one hour at 80° C. and overnight at 50° C. A solid was present and was isolated by filtration, washed with diethyl ether, and dried under vacuum to provide 3.48 g of 1-benzyl-4-chloro-1H-imidazo[4,5-c]quinolin-2-ol as a fluffy, white solid. Diethyl ether was added to the filtrate, and the resulting mixture was stirred for 20 minutes. A solid was present and was isolated by filtration and dried under vacuum to provide 0.95 g of 1-benzyl-4-chloro-1H-imidazo[4,5-c]quinolin-2-ol as a fluffy, beige solid.
Reaction SMILES: [F:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:3]=1[C:4]([N:6]=[C:7]=[O:8])=[O:5].[Cl:14][C:15]1[CH:21]=[CH:20][C:18]([NH2:19])=[CH:17][C:16]=1[C:22]([F:25])([F:24])[F:23]>C1(C)C=CC=CC=1>[Cl:14][C:15]1[CH:21]=[CH:20][C:18]([NH:19][C:7]([NH:6][C:4](=[O:5])[C:3]2[C:2]([F:1])=[CH:12][CH:11]=[CH:10][C:9]=2[F:13])=[O:8])=[CH:17][C:16]=1[C:22]([F:23])([F:24])[F:25]
Reactant: O=C=NC(=O)c1c(F)cccc1F
Reactant: Nc1ccc(Cl)c(C(F)(F)F)c1
Solvent: Cc1ccccc1
Product: O=C(NC(=O)c1c(F)cccc1F)Nc1ccc(Cl)c(C(F)(F)F)c1
Temperature: 40 °C
Reaction time: 1 h
Yield: 95.1 %

Procedure:
A solution of 9.2 g (0.05 mole) of 2,6-difluorobenzoylisocyanate in 50 ml of toluene was added dropwise at 40° C to a solution of 9.8 g (0.05 mole) of 4-chloro-3-trifluoromethylaniline in 100 ml of toluene. The batch was stirred for 1 hour at 40° C. The substance which separated out was filtered off after cooling the reaction mixture to 20° C, and washed with toluene and petroleum ether. After drying, 18.0 g (95% of theory) of N-(4-chloro-3-trifluoromethylphenyl)-N'-(2,6-difluorobenzoyl)-urea of melting point 220° C were obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:31]=[C:30]([O:32][CH2:33][CH:34]2[CH2:36][CH2:35]2)[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[S:6][C:7]([C:10]2[CH:14]=[C:13]([CH:15]([N:17]3C(=O)C4C(=CC=CC=4)C3=O)[CH3:16])[O:12][N:11]=2)=[CH:8][N:9]=1.O.NN>C(O)C>[Cl:1][C:2]1[CH:31]=[C:30]([O:32][CH2:33][CH:34]2[CH2:36][CH2:35]2)[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[S:6][C:7]([C:10]2[CH:14]=[C:13]([CH:15]([NH2:17])[CH3:16])[O:12][N:11]=2)=[CH:8][N:9]=1
Reactant: CC(c1cc(-c2cnc(Oc3ccc(OCC4CC4)cc3Cl)s2)no1)N1C(=O)c2ccccc2C1=O
Agent: NN
Solvent: CCO
Solvent: O
Product: CC(N)c1cc(-c2cnc(Oc3ccc(OCC4CC4)cc3Cl)s2)no1
Temperature: 60 °C
Yield: 96.8 %

Procedure:
To a solution of Example 30G (276 mg, 0.53 mmol) in ethanol (6 mL) was added hydrazine monohydrate (0.16 mL, 3.2 mmol). The reaction was heated at 60° C. for 45 minutes and filtered. The filtrate was concentrated and purified on silica gel eluting with 90:8:2 dichloromethane/methanol/concentrated ammonium hydroxide to provide 201 mg of the title compound (97%) as an amber liquid. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.29-0.38 (m, 2H) 0.53-0.65 (m, 2H) 1.12-1.23 (m, 1H) 1.34 (d, J=7.35 Hz, 3 H) 3.88 (d, J=7.35 Hz, 2H) 3.97-4.15 (m, 1H) 6.84 (s, 1H) 7.03 (dd, J=9.19, 2.94 Hz, 1H) 7.24 (d, J=2.94 Hz, 1H) 7.53 (d, J=9.19 Hz, 1H) 7.91 (s, 1H); MS (ESI) m/z 392.0 (M+H)+.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:22][N:21]4[CH:30]=[C:31]([C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)[N:32]=[C:20]4[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.Cl.CO>CO>[C:33]1([C:31]2[N:32]=[C:20]3[N:19]=[C:18]([C:15]4[CH:16]=[CH:17][C:12]([C:8]5([NH2:7])[CH2:11][CH2:10][CH2:9]5)=[CH:13][CH:14]=4)[C:23]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)=[CH:22][N:21]3[CH:30]=2)[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc4nc(-c5ccccc5)cn4cc3-c3ccccc3)cc2)CCC1
Agent: Cl
Solvent: CO
Product: NC1(c2ccc(-c3nc4nc(-c5ccccc5)cn4cc3-c3ccccc3)cc2)CCC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To the solution of 5-2 (52 mg, 0.1 mmol) in 1 mL of MeOH was added 4M HCl/MeOH (2 mL) and the mixture was stirred at room temperature for 3 h. The mixture was concentrated by evaporation and the residue was purified by prep.HPLC to give the product 5-3.
Reaction SMILES: C(OC([NH:8][C@H:9]([C:32]([OH:34])=[O:33])[CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([O:17][CH2:18][CH:19]1[C:31]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:25]2[C:20]1=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl.FC(F)(F)C([O-])=O.[CH3:52][O:53][C:54]1[CH:59]=[CH:58][C:57]([S:60](Cl)(=[O:62])=[O:61])=[CH:56][CH:55]=1>>[O:53]([C:54]1[CH:59]=[CH:58][C:57]([S:60]([NH:8][C@H:9]([C:32]([OH:34])=[O:33])[CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([O:17][CH2:18][CH:19]2[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:25]3[C:20]2=[CH:21][CH:22]=[CH:23][CH:24]=3)=[O:16])(=[O:62])=[O:61])=[CH:56][CH:55]=1)[CH3:52]
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC(C)(C)OC(=O)N[C@@H](CCCCNC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Agent: O=C([O-])C(F)(F)F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(S(=O)(=O)N[C@@H](CCCCNC(=O)OCC2c3ccccc3-c3ccccc32)C(=O)O)cc1
Yield: 65 %

Procedure:
Nα-tert-butoxycarbonyl-Nε-(9-fluorenylmethoxycarbonyl)-L-lysine was deprotected at the α position by treatment with TFA/CH2Cl2 as described in the procedure outlined in example 24 and the resulting trifluoroacetate salt was alkylated with 4-methoxybenzenesulfonyl chloride as described in example 2, affording the title compound in 65% yield.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[I:7][C:8]1[CH:13]=[CH:12][C:11]([S:14](Cl)(=[O:16])=[O:15])=[CH:10][CH:9]=1.N1C=CC=CC=1.C(Cl)Cl>>[I:7][C:8]1[CH:13]=[CH:12][C:11]([S:14]([NH:1][C:2]2[S:3][CH:4]=[CH:5][N:6]=2)(=[O:16])=[O:15])=[CH:10][CH:9]=1
Reactant: O=S(=O)(Cl)c1ccc(I)cc1
Reactant: Nc1nccs1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=S(=O)(Nc1nccs1)c1ccc(I)cc1
Reaction time: 96 h
Yield: 54.8 %

Procedure:
2-Aminothiazole (1.32 g, 0.0132 mol) was added to a solution of 4-iodobenzenesulfonyl chloride (4.00 g, 0.0132 mol) in Pyridine (10 mL, 0.1 mol) and methylene chloride (36 mL, 0.56 mol). After stirring 4 d, the reaction mixture was concentrated in vacuo. The resulting oil was taken up in 1:1 methylene chloride-methanol and stirred. A white precipitate formed. The solid was collected by filtration. 2.65 g (49%) of the product was obtained as an off-white solid.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][Br:14].[CH:15]1([Mg]Br)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.S(=O)(=O)(O)O.C(OCC)(=O)C>O1CCCC1.[Li+].[Li+].[Cl-].[Cl-].[Cl-].[Cl-].[Cu+2]>[CH:15]1([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][Br:14])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: Br[Mg]C1CCCCC1
Reactant: BrCCCCCCCCCCCCBr
Agent: [Cu+2]
Agent: O=S(=O)(O)O
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: BrCCCCCCCCCCCCC1CCCCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 40.2 %

Procedure:
To 98 g (0.30 mole) of 1,12-dibromododecane in 300 ml of anhydrous tetrahydrofuran (THF), cyclohexyl magnesium bromide (0.30 mole) in 300 ml of THF was added dropwise at 10°-15° C. over a period of 1.5 hours in the presence of 0.5 mole percent of dilithium tetrachlorocuprate (Li2CuCl4), and the mixture was stirred at room temperature overnight. To the reaction mixture 16 ml of 2N sulfuric acid was added until pH became about 2, and about 500 ml of ethyl acetate was added. The insoluble material was filtrated off, and the filtrate was washed with water, saturated aqueous solution of sodium hydrogencarbonate, and water, successively, and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and the resulting oil was subjected to distillation under reduced pressure. The distillate having a boiling point of 166°-167° C. (0.3 mm Hg) was collected, to give 40 g (40%) of the above-captioned compound.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][CH2:15][C:16]2[N:20]=[C:19]([C:21]3[O:29][C:28]4[CH:27]=[CH:26][N:25]=[C:24]([CH:30](C(C)(C)C)[O:31][SiH2]C)[C:23]=4[CH:22]=3)[O:18][N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][CH2:15][C:16]2[N:20]=[C:19]([C:21]3[O:29][C:28]4[CH:27]=[CH:26][N:25]=[C:24]([CH2:30][OH:31])[C:23]=4[CH:22]=3)[O:18][N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: C[SiH2]OC(c1nccc2oc(-c3nc(COC4CCN(C(=O)OC(C)(C)C)CC4)no3)cc12)C(C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(OCc2noc(-c3cc4c(CO)nccc4o3)n2)CC1
Reaction time: 0.17 h

Procedure:
To solution of 4-{5-[4-(tert-butylmethylsilanyloxymethyl)furo[3,2-c]pyridine-2-yl]-[1,2,4]oxadiazole-3-ylmethoxy}piperidine-1-carboxylic acid tert-butyl ester (Preparation 8, 54 mg, 99 μmol) in THF was added TBAF (0.25 mL of a 1.0M solution in THF, 250 μmol). After 10 min, the mixture was diluted with EtOAc, washed with H2O and brine, before being dried and concentrated. Purification via column chromatography afforded the title compound: RT=2.92 min; m/z (ES+)=431.1 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[C:8]([CH3:9])=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].CCN(CC)CC.[C:17](Cl)(=[O:19])[CH3:18].Cl>C(Cl)Cl>[CH3:9][C:8]1[CH:7]=[CH:6][CH:5]=[C:3]([NH:4][C:17]([CH3:18])=[O:19])[C:2]=1[CH3:1]
Reactant: Cc1cccc(N)c1C
Reactant: CC(=O)Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)Nc1cccc(C)c1C
Reaction time: 8 h
Yield: 93 %

Procedure:
To a solution of 2,3-dimethylaniline (1.1 mL, 1.00 equiv.) and Et3N (1.5 mL, 1.30 equiv.) in CH2Cl2 (15 mL) at 0° C. was added acetyl chloride (0.73 mL, 1.25 equiv.) over 30 min. The reaction mixture was allowed to stir overnight at room temp., then was treated with a 2N HCl solution (10 mL) and CH2Cl2 (25 mL). The resulting mixture was extracted with EtOAc (3×25 mL). The combined organics were washed with a 2N HCl solution (2×25 mL), water (2×25 mL), a saturated NaHCO3 solution (2×25 mL) and a saturated NaCl solution (2×25 mL), dried (Na2SO4), and concentrated under reduced pressure to give 2,3-dimethylacetanilide as a white solid (1.25 g, 93%): 1H NMR (CDCl3) δ2.05 (s, 3H), 2.15 (s, 3H), 2.25 (s, 3H), 6.95 (d, 7.5 Hz, 1H) 7.02 (app t, J=7.5 Hz, 1H), 7.35 (d, J=6.9 Hz, 1H).
Reaction SMILES: [S:1]([O-:4])([O-:3])=[O:2].[Na+].[Na+].Cl[C:8]1[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:12]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:11]([N+:24]([O-:26])=[O:25])=[C:10]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:9]=1>O.C(O)C>[CH2:17]([O:16][C:14]([C:13]1[C:8]([S:1]([OH:4])(=[O:3])=[O:2])=[N:9][C:10]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[C:11]([N+:24]([O-:26])=[O:25])[C:12]=1[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[O:15])[CH3:18]
Reactant: O=S([O-])[O-]
Reactant: CCOC(=O)c1c(Cl)nc(-c2ccccc2)c([N+](=O)[O-])c1C(=O)OCC
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CCOC(=O)c1c(S(=O)(=O)O)nc(-c2ccccc2)c([N+](=O)[O-])c1C(=O)OCC
Yield: 59.9 %

Procedure:
A solution of 0.28 g of sodium sulfite in 7 ml of water was added to a solution of 0.70 g of 2-chloro-3,4-diethoxycarbonyl-5-nitro-6-phenylpyridine in 7 ml of ethanol, and the mixture was heated under reflux for minutes. After the reaction mixture was concentrated, the concentrate was acidified with 1N HCl, followed by extraction with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over magnesium sulfate. After concentration to dryness under reduced pressure, the residue was recrystallized from chloroform/ether, to give 0.47 g of white crystals.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[Cl-].[CH3:15]O>>[CH3:15][O:7][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([NH2:1])=[C:3]([N+:11]([O-:13])=[O:12])[CH:4]=1
Reactant: Nc1ccc(C(=O)O)cc1[N+](=O)[O-]
Reactant: CO
Agent: [Cl-]
Product: COC(=O)c1ccc(N)c([N+](=O)[O-])c1
Temperature: 25 °C
Yield: 81 %

Procedure:
To a mixture of 4-amino-3-nitro-benzoic acid (10.0 g, 54.9 mmol) suspended in methanol (150 mL) was added thiony chloride (3.99 mL, 54.9 mmol). The mixture was heated to reflux overnight, then cooled to room temperature and filtered. The solid recovered by filtration was rinsed with cold methanol and dried to give 8.68 g (81%) of 4-amino-3-nitro-benzoic acid methyl ester.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[C:9]1([C:15]2([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[O:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[O:16]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(Cl)(Cl)Cl>[Br:1][C:22]1[CH:21]=[CH:20][C:18]2[O:19][C:15]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[O:16][C:17]=2[CH:23]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: c1ccc(C2(c3ccccc3)Oc3ccccc3O2)cc1
Solvent: ClC(Cl)Cl
Product: Brc1ccc2c(c1)OC(c1ccccc1)(c1ccccc1)O2

Procedure:
18.75 g of N-bromosuccinimide are added to a solution of 27.4 g of 2,2-diphenyl-1,3-benzodioxol in 80 ml of chloroform and the mixture was boiled at reflux for 20 hours. The reaction mixture was cooled and the separated succinimide was filtered off. The filtrate was washed with water, dried over sodium sulphate and the solvent was removed in a vacuum. By crystallization of the residue from ethanol, there was obtained 5-bromo-2,2-diphenyl-1,3-benzodioxol as white crystals of melting point 88-89° C.
Reaction SMILES: [CH2:1]([C:4]1[NH:5][C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[C:8]([C:13]([O:15][CH3:16])=[O:14])[CH:7]=2)[CH2:2][CH3:3].[Cl:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20]Br>>[Cl:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20][N:5]1[C:6]2[C:11](=[CH:10][CH:9]=[C:8]([C:13]([O:15][CH3:16])=[O:14])[CH:7]=2)[CH:12]=[C:4]1[CH2:1][CH2:2][CH3:3]
Reactant: Clc1ccccc1CBr
Reactant: CCCc1cc2ccc(C(=O)OC)cc2[nH]1
Product: CCCc1cc2ccc(C(=O)OC)cc2n1Cc1ccccc1Cl
Yield: 72.6 %

Procedure:
Methyl 1-(2-chlorobenzyl)-2-propylindole-6-carboxylate (400 mg) was prepared from methyl 2-propylindole-6-carboxylate (350 mg) and 2-chlorobenzyl bromide (364 mg) in a similar manner to that of Example 1.
Reaction SMILES: [N+:1]([CH:4]=[CH:5][C:6]1[C:15]2[O:14][CH2:13][CH2:12][O:11][C:10]=2[CH:9]=[CH:8][CH:7]=1)([O-])=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[O:11]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([CH2:5][CH2:4][NH2:1])[C:15]=2[O:14][CH2:13][CH2:12]1
Reactant: O=[N+]([O-])C=Cc1cccc2c1OCCO2
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: NCCc1cccc2c1OCCO2

Procedure:
In close analogy to the procedure described above, 5-(2-Nitro-vinyl)-2,3-dihydro-benzo[1,4]dioxine is reacted with lithium aluminium hydride to provide the title compound.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([I:21])=[CH:17][CH:16]=1)[C:10](OC)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].Cl.C(N(CC)CC)C.CS([Cl:36])(=O)=O.[Cl-].[Li+]>O.CN(C)C=O.O1CCCC1.CO>[Cl:36][CH2:10][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([I:21])=[CH:17][CH:16]=1
Reactant: COC(=O)[C@@H](Cc1ccc(I)cc1)NC(=O)OC(C)(C)C
Reactant: CS(=O)(=O)Cl
Agent: Cl
Agent: [BH4-]
Agent: [Cl-]
Solvent: CO
Solvent: CCN(CC)CC
Solvent: O
Product: CC(C)(C)OC(=O)N[C@@H](CCl)Cc1ccc(I)cc1
Reaction time: 17 h

Procedure:
25 ml of methanol and 25 ml of tetrahydrofuran were added to 6.2 g (18 mmol) of methyl (2R)-t-butoxycarbonylamino-3-(4-iodophenyl)propionate. 3.44 g (91 mmol) of sodium borohydride was added to the resultant mixture under cooling with ice, and they were stirred for 17 hours. The reaction liquid was slowly poured into 1 N hydrochloric acid. After the extraction with ethyl acetate, the organic layer was successively washed with water, 1 N hydrochloric acid, 1 N sodium hydroxide and saturated aqueous NaCl solution, and then dried over anhydrous magnesium sulfate. The solvent was evaporated. 50 ml of dichloromethane was added to the residue. Then, 5.02 ml (36 mmol) of triethylamine and 3.09 g (27 mmol) of methanesulfonyl chloride were added to the resultant mixture under cooling with ice, and they were stirred for 30 minutes. The temperature was elevated to room temperature, and the mixture was stirred for 15 hours. The reaction liquid was diluted with water. After the extraction with dichloromethane, the organic layer was successively washed with 1 N hydrochloric acid, 1 N sodium hydroxide and saturated aqueous NaCl solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. 40 ml of dimethylformamide and 3.85 g (91 mmol) of lithium chloride were added to the residue, and they were stirred at 50° C. for 19 hours. The reaction liquid was diluted with water. After the extraction with ethyl acetate, the organic layer was successively washed with water and saturated aqueous NaCl solution. The solvent was evaporated, and the residue was purified by the silica gel column chromatography to obtain the title compound.
Reaction SMILES: C1(C)C=CC=CC=1.[CH3:8][C:9]([NH2:17])([CH3:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[CH3:18][CH:19]([C:23]([CH3:26])([CH3:25])[CH3:24])[C:20](Cl)=[O:21]>N1C=CC=CC=1>[CH3:8][C:9]([NH:17][C:20](=[O:21])[CH:19]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH3:18])([CH3:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CC(C(=O)Cl)C(C)(C)C
Reactant: CC(C)(N)c1ccccc1
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CC(C(=O)NC(C)(C)c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 3 h
Yield: 83.8 %

Procedure:
Into a 200 ml four-necked flask, there were charged toluene (100 ml), α,α-dimethylbenzylamine (9 g) and pyridine (5.8 g), and α-methyl-tert-butylacetyl chloride (9.9 g) was dropwise added thereto while stirring at room temperature. Stirring was continuted for 3 hours. The reaction mixture was washed with water to remove pyridine hydrochloride. After the toluene layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was recrystallized from ethanol to give 13.8 g of N-(α,α-dimethylbenzyl)-α-methyl-tert-butylacetamide. M.P., 162.5°-163.5° C.