Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH2:7][O:8][C:9]2[CH:10]=[CH:11][C:12]([C:20](=[O:23])[CH2:21][Cl:22])=[C:13]3[C:18]=2[NH:17][C:16](=[O:19])[CH:15]=[CH:14]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1>C1(C)C=CC=CC=1.C1COCC1>[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[CH:11][C:12]([C@@H:20]([OH:23])[CH2:21][Cl:22])=[C:13]3[C:18]=2[NH:17][C:16](=[O:19])[CH:15]=[CH:14]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(CCl)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Agent: CB1OC(c2ccccc2)(c2ccccc2)[C@H]2CCCN12
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: O=c1ccc2c([C@@H](O)CCl)ccc(OCc3ccccc3)c2[nH]1
Temperature: 1 °C

Procedure:
A dry 3 L, 4-necked flask equipped with a mechanical stirrer, thermometer, addition funnel and refluxing condenser is charged with 50 g 8-(phenylmethoxy)-5-(α-chloroacetyl)-(1H)-quinolin-2-one and 600 mL dry THF under N2. Then 15 mL of a 1 molar solution of (R)-tetrahydro-1-methyl-3,3-diphenyl-(1H,3H)-pyrrolo[1,2-c][1,3,2]-oxazaborole in toluene is added. The mixture is cooled to an internal temperature of 0-2° C. and while maintaining an internal temperature of 0-2° C., 153 mL of a 1 molar solution of BH3 in THF is added over 1-2 hours. The reaction is stirred for another hour at an internal temperature of 0-2° C. and then quenched by addition of 65 mL methanol. The resulting solution is warmed to 25° C. and concentrated to a volume of 250 mL (50° C./200 mbar). To this concentrate is added a mixture of 713 mL water and 37 g HCl 37%. During the addition 8-(phenylmethoxy)-5-((R)-2-chloro-1-hydroxy-ethyl)-(1-H)-quinolin-2-one precipitates as a nearly colourless precipitation. The resulting suspension is stirred for 30 minutes at 25° C., filtrated and washed with 220 mL water in several portions. Drying in a vacuum drier at 50° C. for 12 hours results in 47.41 g of 8-(phenylmethoxy)-5-((R)-2-chloro-1-hydroxy-ethyl)-(1H)-quinolin-2-one as a slightly yellowish powder.
Reaction SMILES: [F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:11]3=[CH:12][N:13]=[C:14]([C:16]([OH:18])=O)[CH:15]=[C:10]3[CH:9]=[CH:8]2)=[CH:4][CH:3]=1.Cl.[CH3:22][NH:23][OH:24]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:11]3=[CH:12][N:13]=[C:14]([C:16]([N:23]([OH:24])[CH3:22])=[O:18])[CH:15]=[C:10]3[CH:9]=[CH:8]2)=[CH:19][CH:20]=1
Reactant: O=C(O)c1cc2ccn(Cc3ccc(F)cc3)c2cn1
Reactant: CNO
Agent: Cl
Product: CN(O)C(=O)c1cc2ccn(Cc3ccc(F)cc3)c2cn1

Procedure:
The title compound was prepared by coupling of 1-(4-fluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid with N-methyl hydroxylamine hydrochloride in a manner similar to step (c) of example 1. 1H NMR (DMSO-d6) δ: 12.00 (br s, 1H), 8.91 (s, 1H), 8.03 (s, 1H), 7.91 (d, 1H, J=2.8 Hz), 7.38 (dd, 2H, J=5.7 Hz, J=8.5 Hz), 7.12 (d, 2H, J=8.5 Hz), 6.71 (d, 1H, J=3.0 Hz), 5.59 (s, 2H), 3.33 (s, 3H). LCMS (API-ES, M+H+): 301.1. HRMS calcd for C16H15FN3O2 (M+H) 300.1148, found 300.1138. HPLC: 100% purity
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:10])[CH:9]=1)[CH:5]=O.C1C(/C=N/O)=CC=[N+:15](C[N+]2C=CC(/C=N/O)=CC=2)C=1.[Br-].[Br-].B>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:10])[CH:9]=1)[CH2:5][NH2:15]
Reactant: O/N=C/c1cc[n+](C[n+]2ccc(/C=N/O)cc2)cc1
Reactant: O=Cc1cc(Cl)cc(Cl)c1
Agent: B
Agent: [Br-]
Solvent: C1CCOC1
Product: NCc1cc(Cl)cc(Cl)c1
Yield: 69.6 %

Procedure:
The reaction of 3,5-dichlorobenzaldehyde methoxime, (17.4 g, 85.7 mmole) and 0.98M borane in tetrahydrofuran (86 ml) substantially as described in 1B above produced 10.5 g (70%) of the title compound as a light yellow oil.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([CH2:12][C:13]([O:15][C:16]2[CH:21]=[CH:20][C:19](C(CC(C)(C)C)(C)C)=[CH:18][CH:17]=2)=[O:14])=[C:7]([CH3:30])[C:6]=1[OH:31])([CH3:4])([CH3:3])[CH3:2].C(C1C=CC(O)=CC=1)(CC(C)(C)C)(C)C.C1(O)C=CC=CC=1>>[C:1]([C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([CH2:12][C:13]([O:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:14])=[C:7]([CH3:30])[C:6]=1[OH:31])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1cc(C(C)(C)C)c(O)c(C)c1CC(=O)Oc1ccc(C(C)(C)CC(C)(C)C)cc1
Agent: CC(C)(C)CC(C)(C)c1ccc(O)cc1
Solvent: Oc1ccccc1
Product: Cc1cc(C(C)(C)C)c(O)c(C)c1CC(=O)Oc1ccccc1

Procedure:
p-tert.-Octylphenyl 4-tert.-butyl-2,6-dimethyl-3-hydroxyphenylacetate is made in analogous manner by substitutin p-tert.-octylphenol for phenol in the above procedure.
Reaction SMILES: [Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=[O:2].[K+].[K+].C(N[C:16]1[CH:25]=[C:24]([NH:26][C:27](=[O:29])[CH3:28])[C:23]([O:30]C(=O)C)=[C:22]2[C:17]=1[CH:18]=[CH:19][C:20]([CH3:34])=[N:21]2)(=O)C>C(O)(=O)C.O>[C:27]([NH:26][C:24]1[C:23](=[O:30])[C:22]2[N:21]=[C:20]([CH3:34])[CH:19]=[CH:18][C:17]=2[C:16](=[O:2])[CH:25]=1)(=[O:29])[CH3:28]
Reactant: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Reactant: CC(=O)Nc1cc(NC(C)=O)c2ccc(C)nc2c1OC(C)=O
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: CC(=O)NC1=CC(=O)c2ccc(C)nc2C1=O
Temperature: 25 °C
Reaction time: 22 h
Yield: 56 %

Procedure:
This compound was prepared by the oxidation of the corresponding acylamido with potassium dichromate in glacial acetic acid. Into a 1000 ml Erlenmeyer flask, 240 ml of glacial acetic acid, and 5,7-diacetamido-2-methyl-8-acetoxyquinoline (31) (prepared as described in Example 31) (6.3 g, 2.0 mmol) were added. To the resulting suspension, a solution of potassium dichromate (17.64 g) in 200 ml of water was added. This black solution was magnetically stirred at room temperature for 20-24 hours. The solution was then poured into 900 ml of water and extracted with dichloromethane (5×200 ml). The organic extracts were washed with a solution of 5% sodium carbonate in a saturated salt solution (3×300 ml). The organic layer was dried overnight with anhydrous magnesium sulfate. The magnesium sulfate was filtered off, and the solvent was evaporated to leave an orange/yellow solid. The solid 7-acetamino-2-methylquinoline-5,8-dione (27) was dried overnight under vacuum. 2.6 g of product was obtained for a yield of 56%.
Reaction SMILES: [CH3:1][C:2]1[C:10]2[C:9](=[O:11])[NH:8][CH:7]=[N:6][C:5]=2[S:4][CH:3]=1.[Cl:12][S:13](O)(=[O:15])=[O:14].S(Cl)(Cl)=O>>[CH3:1][C:2]1[C:10]2[C:9](=[O:11])[NH:8][CH:7]=[N:6][C:5]=2[S:4][C:3]=1[S:13]([Cl:12])(=[O:15])=[O:14]
Reactant: O=S(=O)(O)Cl
Reactant: Cc1csc2nc[nH]c(=O)c12
Solvent: O=S(Cl)Cl
Product: Cc1c(S(=O)(=O)Cl)sc2nc[nH]c(=O)c12
Reaction time: 0.17 h

Procedure:
5-Methylthieno[2,3-d]pyrimidin-4(3H)-one (2 g, 12 mmol) was added portionwise into chlorosulfonic acid (8.0 mL, 120 mmol) maintaining the internal temperature below 0° C. After addition the reaction was stirred for 10 minutes, thionyl chloride (4.4 mL, 60 mmol) added drop wise, the mixture stirred for 0.5 hours at ambient temperature and then at reflux for 2 hours. The solution was poured onto crushed ice, the precipitated solid collected by filtration, washed with ice-water, and dried under vacuum to give cream solid. (1.1 g, 34%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[O:5][CH2:6][CH:7]1[O:11][C:10](=[O:12])[N:9]([CH2:13][CH2:14][CH2:15][C:16](OCC)=[O:17])[CH2:8]1.[BH4-].[Na+].O1CCCC1>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[O:5][CH2:6][CH:7]1[O:11][C:10](=[O:12])[N:9]([CH2:13][CH2:14][CH2:15][CH2:16][OH:17])[CH2:8]1
Reactant: CCOC(=O)CCCN1CC(COc2cccc(Cl)c2)OC1=O
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: O=C1OC(COc2cccc(Cl)c2)CN1CCCCO
Yield: 100.5 %

Procedure:
A procedure similar to that described in Preparation 5 was repeated, except that 1.43 g of ethyl 4-[5-(3-chlorophenoxymethyl)-2-oxooxazolidin-3-yl]butyrate (prepared as described in Preparation 116), 183 mg of sodium borohydride, 20 ml of anhydrous tetrahydrofuran and 135 mg of anhydrous methanol were used, to give 1.26 g of the title compound having an Rf value of 0.31 (on silica gel thin layer chromatography, using ethyl acetate as the developing solvent).
Reaction SMILES: OC1CCCCC1=O.[CH:9](S)([SH:11])[CH3:10].[C:13]1(C)[CH:18]=[CH:17][C:16]([S:19](O)(=O)=O)=[CH:15][CH:14]=1>>[S:19]1[C:16]2[CH2:17][CH2:18][CH2:13][CH2:14][C:15]=2[S:11][CH2:9][CH2:10]1
Reactant: CC(S)S
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C1CCCCC1O
Product: C1CCC2=C(C1)SCCS2
Yield: 75.1 %

Procedure:
The method of Example 4 was used, using 2-hydroxycyclohexanone (10 g), ethane dithiol (8.3 g) and p-toluenesulphonic acid to give 5,6,7,8-tetrahydro-1,4-benzodithian as a brownish oil (not distilled), yield 75.1%. NMR (CDCl3) 3.14 δ, 1.5-2.3 δ (two overlapping complex multiplets).
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([NH:10][C:11](=[O:26])[C:12]2[CH:17]=[CH:16][C:15]([CH2:18][N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)=[CH:14][CH:13]=2)[CH:6]=[CH:7][C:8]=1[CH3:9])=O.ClCCl.[NH2:30][C:31]1[CH:32]=[C:33]2[CH:39]=[C:38]([C:40]([O:42][CH3:43])=[O:41])[NH:37][C:34]2=[N:35][CH:36]=1.C(O[BH3-])(=O)C.[Na+]>C(O)(=O)C>[CH3:25][N:22]1[CH2:21][CH2:20][N:19]([CH2:18][C:15]2[CH:14]=[CH:13][C:12]([C:11]([NH:10][C:5]3[CH:6]=[CH:7][C:8]([CH3:9])=[C:3]([CH:4]=3)[CH2:1][NH:30][C:31]3[CH:32]=[C:33]4[CH:39]=[C:38]([C:40]([O:42][CH3:43])=[O:41])[NH:37][C:34]4=[N:35][CH:36]=3)=[O:26])=[CH:17][CH:16]=2)[CH2:24][CH2:23]1
Reactant: Cc1ccc(NC(=O)c2ccc(CN3CCN(C)CC3)cc2)cc1C=O
Reactant: COC(=O)c1cc2cc(N)cnc2[nH]1
Agent: [BH3-]OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: COC(=O)c1cc2cc(NCc3cc(NC(=O)c4ccc(CN5CCN(C)CC5)cc4)ccc3C)cnc2[nH]1
Temperature: 25 °C
Reaction time: 24 h
Yield: 10.1 %

Procedure:
A reactor is charged with 120 mg (0.34 mmol) of the solid obtained in step 2, 15 ml of anhydrous dichloromethane, 78 mg (0.41 mmol) of methyl 5-amino-1H-pyrrolo[2,3-b]pyridine-2-carboxylate, 216 mg (1.02 mmol) of sodium acetoxyborohydride and a catalytic amount of acetic acid. The mixture is stirred at room temperature for 24 hours. The solvent is then evaporated under reduced pressure and the residue is taken off in 100 ml of water. The aqueous phase is extracted by 3*30 ml ethyl acetate. The aqueous phases are combined, dried on sodium sulphate and then evaporated under reduced pressure. The raw product obtained is purified by preparative HPLC and 18 mg of a solid is obtained (10%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:5]=[C:6]([Br:8])[CH:7]=1.[CH3:13][O:14][C:15]1[C:20](B(O)O)=[CH:19][CH:18]=[CH:17][N:16]=1.C([O-])([O-])=O.[Na+].[Na+]>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.CO.C(Cl)Cl>[Br:8][C:6]1[CH:7]=[C:2]([C:20]2[C:15]([O:14][CH3:13])=[N:16][CH:17]=[CH:18][CH:19]=2)[CH:3]=[C:4]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:5]=1
Reactant: CC(C)(C)c1cc(Br)cc(Br)c1
Reactant: COc1ncccc1B(O)O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: COc1ncccc1-c1cc(Br)cc(C(C)(C)C)c1
Yield: 57.9 %

Procedure:
step 1—A sealed tube containing 3,5-dibromo-tert-butylbenzene (1.00 g, 3.425 mmol, CASRN 129316-09-2), 37 (522 mg, 3.413 mmol), Pd(PPh3)4 (194 mg, 0.168 mmol) and Na2CO3 (942 mg, 8.888 mmol) and a mixture of MeOH/DCM (8/2 10 mL) was irradiated in a microwave synthesizer at 100° C. for 10 min. The organic volatiles were removed under reduced pressure. The residue was partitioned between EtOAc and water. The organic layer was washed with brine, dried (Na2SO4), filtered and concentrated. The crude residue was purified by SiO2 chromatography eluting with a EtOAc/hexane gradient (0 to 2% EtOAc) to afford 0.633 g (58%) of 3-(3-bromo-5-tert-butyl-phenyl)-2-methoxy-pyridine (122) as a colorless oil.
Reaction SMILES: [C:1]1([C:7]2[NH:8][C:9](=[O:24])[N:10]([S:12]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[NH:20][CH2:19][CH2:18]4)(=[O:14])=[O:13])[CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:25]([N:27]=[C:28]=[O:29])[CH3:26]>C1(C)C=CC=CC=1>[C:1]1([C:7]2[NH:8][C:9](=[O:24])[N:10]([S:12]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[N:20]([C:28](=[O:29])[NH:27][CH2:25][CH3:26])[CH2:19][CH2:18]4)(=[O:14])=[O:13])[CH:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCN=C=O
Reactant: O=c1[nH]c(-c2ccccc2)cn1S(=O)(=O)c1ccc2c(c1)CCN2
Solvent: Cc1ccccc1
Product: CCNC(=O)N1CCc2cc(S(=O)(=O)n3cc(-c4ccccc4)[nH]c3=O)ccc21
Temperature: 80 °C
Reaction time: 8 h
Yield: 94.5 %

Procedure:
4-Phenyl-1-(indoline-5-sulfonyl)-2-imidazolone (100 mg, 0.29 mmol) prepared in Preparation 3 was dissolved in 10 ml of toluene, and ethylisocyanate (35 μl, 0.435 mmol) was added thereto. The reaction mixture was stirred for 8 hours at 80° C. The solvent was evaporated therefrom under reduced pressure. The residue was dissolved in 30 ml of dichloromethane, washed twice with brine, dried over anhydrous magnesium sulfate, concentrated to an oily state, and then purified by silica gel column chromatography (eluent:dichloromethane/methanol=15/1, v/v) to obtain 113 mg of the title compound.
Reaction SMILES: [F:1][C:2]([F:9])([F:8])[C:3]([O:5]CC)=O.C[O-].[Na+].[Cl:13][C:14]1[C:23]([Cl:24])=[C:22]2[C:17]([C:18](=[O:25])[CH2:19][CH2:20][S:21]2)=[CH:16][CH:15]=1.Cl>CCOCC>[Cl:13][C:14]1[C:23]([Cl:24])=[C:22]2[C:17]([C:18](=[O:25])[CH:19]([C:3](=[O:5])[C:2]([F:1])([F:8])[F:9])[CH2:20][S:21]2)=[CH:16][CH:15]=1
Reactant: O=C1CCSc2c1ccc(Cl)c2Cl
Reactant: CCOC(=O)C(F)(F)F
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCOCC
Product: O=C1c2ccc(Cl)c(Cl)c2SCC1C(=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 19.4 h

Procedure:
Ethyl trifluoroacetate (0.29 g, 2.0 mmol) was placed in a round bottom flask, and dissolved in ether (12 mL). To the stirred solution was added sodium methoxide (25%) (0.84 g, 3.9 mmol), followed by 7,8-dichlorothiochroman-4-one from Step 2 (0.42 g, 1.8 mmol). The reaction was stirred at room temperature overnight (19.4 hours) and treated with 3N hydrochloric acid. The organic layer was collected, washed with brine, dried over MgSO4, and concentrated in vacuo to give a brown oily solid which was used without purification in the next step.
Reaction SMILES: COC([CH:5]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH:15]=[CH:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:6]1=[O:22])=O.S(=O)(=O)(O)O>[OH-].[Na+].C(O)C.C1COCC1>[C:6]1(=[O:22])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH:14]=[CH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:5]1
Reactant: COC(=O)C1CCCCCCC=CCCCCCCCC1=O
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: O=C1CCCCCCCC=CCCCCCCC1
Temperature: 80 °C
Yield: 94.5 %

Procedure:
2-Methoxycarbonyl-9-cycloheptadecenone (92 mg, 0.30 mmol) was dissolved in a mixed solvent of 5% aqueous NaOH/ethanol/THF (2.5:5.0:2.5, vol./vol./vol.) and the solution was refluxed at 80° C. for 5 hours. After cooling to 0° C., the reaction solution was rendered slightly acidic using 10% sulfuric acid aqueous solution and the whole was further refluxed for 10 minutes. After the evaporation of the solvent under reduced pressure, the residue was extracted with ether. The organic layer was washed with saturated sodium hydrogen carbonate aqueous solution, water, and saturated brine, and then dried over anhydrous sodium sulfate. After the evaporation of the solvent under reduced pressure, the crude product was purified by silica gel chromatography (hexane/ethyl acetate=40/1) to obtain the aimed product (71 mg, 95%)
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:5][N:4]=[C:3]1[CH:13]=O.[N:15]1[C:24]2[CH:23]([NH:25][CH2:26][CH2:27][CH2:28][CH2:29][NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:22][CH2:21][CH2:20][C:19]=2[CH:18]=[CH:17][CH:16]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.CC(O)=O>[CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:5][N:4]=[C:3]1[CH2:13][N:25]([CH:23]1[C:24]2[N:15]=[CH:16][CH:17]=[CH:18][C:19]=2[CH2:20][CH2:21][CH2:22]1)[CH2:26][CH2:27][CH2:28][CH2:29][NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34]
Reactant: CC(C)(C)OC(=O)NCCCCNC1CCCc2cccnc21
Reactant: Cn1c(C=O)nnc1-c1ccccc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Solvent: CC(=O)O
Product: Cn1c(CN(CCCCNC(=O)OC(C)(C)C)C2CCCc3cccnc32)nnc1-c1ccccc1
Temperature: 65 °C
Reaction time: 18 h

Procedure:
To a solution of 4-methyl-5-phenyl-4H-1,2,4-triazole-3-carbaldehyde, 36, (0.41 g, 2.20 mmol) in 1,2-dichloroethane (4 mL) was added tert-butyl 4-(5,6,7,8-tetrahydroquinolin-8-ylamino)butylcarbamate, 3, (0.76 g, 2.40 mmol), sodium triacetoxyborohydride (0.84 g, 3.95 mmol), and AcOH (10 drops). The reaction mixture was heated to 65° C. and stirred for 18 h. The reaction mixture was cooled to room temperature and poured into saturated aqueous NaHCO3 (15 mL) and extracted with ethyl acetate (2×10 mL). The combined organic phases were washed with brine then dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by silica gel chromatography (0-5% methanol/dichloromethane) to yield 37: 1H NMR (400 MHz, CDCl3) δ 8.40, (d, J=5.2 Hz, 1H), 7.60-7.57 (m, 2H), 7.48-7.44, (m, 3H), 7.31, (d, J=7.2 Hz, 1H), 7.0, (dd, J=8.0, 5.2 Hz, 1H), 5.01, (bs, 1H), 4.20-3.92, (m, 3H), 3.20-2.60, (m, 6H), 2.20-1.85, (m, 4H), 1.75-1.30 (m, 13H); ESI+ MS: m/z (rel intensity) 491 (100, M+H). Step g: Preparation of N-(4-aminobutyl)-N-((4-methyl-5-phenyl-4H-1,2,4-triazol-3-yl)methyl)-5,6,7,8-tetrahydroquinolin-8-amine tetrahydrochloride (BQ). Through a methanol (2 mL) solution of 37 (0.16 g, 0.32 mmol) was bubbled HCl(g) generated by the addition of sulfuric acid to dry NaCl. Upon total conversion of the reaction as monitored by LC-MS, the reaction mixture was concentrated in vacuo to yield BQ: ESI+ MS: m/z (rel intensity) 391 (100, M+H).
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10](F)[C:11]=2[F:13])[C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4]1)[CH3:2].[CH3:20][CH:21]1[CH2:26][NH:25][CH2:24][CH2:23][NH:22]1>N1C=CC=CC=1>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10]([N:25]3[CH2:24][CH2:23][NH:22][CH:21]([CH3:20])[CH2:26]3)[C:11]=2[F:13])[C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4]1)[CH3:2]
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(F)c(F)c(F)c21
Reactant: CC1CNCCN1
Solvent: c1ccncc1
Product: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCNC(C)C3)c(F)c21
Yield: 27.8 %

Procedure:
A mixture of 1.00 g of 1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 1.10 g of 2-methylpiperazine and 10 ml of pyridine was heated for 15 minutes under reflux. The reaction mixture was evaporated and methanol was added to the residue. The precipitate was filtered and recrystallized from ethanol to give 0.36 g of the title compound as colorless needles, M.p. 239°-240.5° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][O:9][C:10]([O:12][CH:13]([CH2:18][O:19][CH2:20][CH3:21])[CH2:14][O:15][CH2:16][CH3:17])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:22][S:23]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[S:32](Cl)(=[O:34])=[O:33])(=[O:25])=[O:24]>>[C:1]([O:5][C:6]([N:8]([O:9][C:10]([O:12][CH:13]([CH2:14][O:15][CH2:16][CH3:17])[CH2:18][O:19][CH2:20][CH3:21])=[O:11])[S:32]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[S:23]([CH3:22])(=[O:25])=[O:24])(=[O:34])=[O:33])=[O:7])([CH3:3])([CH3:2])[CH3:4]
Reactant: CCOCC(COCC)OC(=O)ONC(=O)OC(C)(C)C
Reactant: CS(=O)(=O)c1ccccc1S(=O)(=O)Cl
Product: CCOCC(COCC)OC(=O)ON(C(=O)OC(C)(C)C)S(=O)(=O)c1ccccc1S(C)(=O)=O

Procedure:
1-({[(tert-Butoxy)carbonyl]({[(1,3-diethoxypropan-2-yl)oxy]carbonyl}oxy)-amino}sulfonyl)-2-methanesulfonylbenzene (102) is prepared from 2-{[({[(tert-butoxy)carbonyl]amino}oxy)carbonyl]oxy}-1,3-diethoxypropane and 2-methylsulfonyl benzene sulfonyl chloride according to Scheme 11. (2.3 g, 47%), 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.39 (2H, ddd, 12.2, 7.5, 1.5 Hz), 7.84 (2H, m), 5.06 (1H, quin, 5.1 Hz), 3.68 (4H, t, 4.9 Hz), 3.48-3.61 (4H, m), 1.43 (9H, s), 1.27 (3H, t, 7.2 Hz), 1.19 (3H, t, 6.9 Hz).
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([S:12]([OH:15])(=[O:14])=[O:13])=[CH:7][CH:6]=[CH:5][C:4]=2[C:3]=1[S:16]([OH:19])(=[O:18])=[O:17].[OH-].[Na+:21].[N+:22]([C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=1)[C:28](Cl)=[O:29])([O-:24])=[O:23].Cl>O>[Na+:21].[Na+:21].[N+:22]([C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=1)[C:28]([NH:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([S:12]([O-:15])(=[O:14])=[O:13])=[CH:7][CH:6]=[CH:5][C:4]=2[C:3]=1[S:16]([O-:19])(=[O:18])=[O:17])=[O:29])([O-:24])=[O:23]
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1
Reactant: Nc1ccc2c(S(=O)(=O)O)cccc2c1S(=O)(=O)O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(Nc1ccc2c(S(=O)(=O)[O-])cccc2c1S(=O)(=O)[O-])c1cccc([N+](=O)[O-])c1
Reaction time: 0.25 h

Procedure:
A 48.5 g portion of 2-amino-1,5-naphthalenedisulfonic acid is suspended in 80 ml of water and 160 ml of 1N sodium hydroxide is added, then 60.0 g of m-nitrobenzoyl chloride is added all at once. The mixture is shaken for about 15 minutes and another 160 ml of 1N sodium hydroxide is added with shaking for 1/2 hour. The latter addition of sodium hydroxide and shaking is repeated two more times, then 100 ml of water is added and the mixture is acidified with 17 ml of concentrated hydrochloric acid. The resulting mixture is then copiously extracted with ether with the addition of 700 ml of water during the ether extraction. The ether is removed by vacuum siphoning and the aqueous solution is filtered. The filtrate is then concentrated in vacuo at 55°-60° C. until formation of crystals. The material is then allowed to stand 48 hours at room temperature and the solid residue of fine feathery needles is broken up and is filtered. The residue is washed with two 100 ml portions of saturated saline solution and then is slurried with two 200 ml portions of 90% ethyl alcohol followed by 200 ml of absolute ethyl alcohol and two 300 ml portions of ether. The product is then dried at 120° C. overnight to give 52.8 g of product. A 27.8 g portion of this material is dissolved in 110 ml of boiling water. The solution is then cooled to room temperature and the crystallized final product is filtered and is washed with a small amount of cold water then is dried at 120° C. overnight.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH3:14])[NH:11][C@H:10]([CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:16][C:17]([CH:19]=[CH2:20])=[O:18]>C(Cl)(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH3:14])[N:11]([CH2:20][CH2:19][C:17](=[O:18])[CH3:16])[C@H:10]([CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: C=CC(C)=O
Reactant: C[C@@H]1CN(C(=O)OC(C)(C)C)C[C@H](C)N1
Solvent: ClC(Cl)Cl
Product: CC(=O)CCN1[C@H](C)CN(C(=O)OC(C)(C)C)C[C@@H]1C

Procedure:
Cis-3,5-dimethylpiperazine-1-carboxylic acid tert-butyl ester (3.00 g; prepared according to the method E. Jon Jacobson et. al.: J. Med. Chemistry. 1999, Vol. 42, 1123-144) in 47 mL chloroform was treated with methylvinylketone (1.7 mL) at room temperature and heated at reflux for two days. The reaction was then concentrated, diluted with THF and heated at reflux for 1 day before purifying by column chromatography (0 to 10% MeOH/DCM) to afford 0.865 g of the title compound as a clear, colorless oil. 1H NMR (CDCl3, 300 MHz) δ ppm 1.08 (d, 2H, J=6.07 Hz), 1.47 (s, 9H), 2.17 (s, 3H), 2.52 (m, 6H), 3.10 (m, 2H), 2.86 (bs, 2H); 13C NMR (CDCl3, 75 MHz) 17.6 (2C), 28.62 (5C), 30.8, 37.34, 42.46, 53.57 (4C), 79.85, 154.49, 208.29.