Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][S:12]([NH2:15])(=[O:14])=[O:13])[CH:5]=[CH:6][C:7]=1[N+:8]([O-])=O.CCO.CC(O)=O>[Pd].C1COCC1>[NH2:8][C:7]1[CH:6]=[CH:5][C:4]([CH2:11][S:12]([NH2:15])(=[O:13])=[O:14])=[CH:3][C:2]=1[CH3:1]
Reactant: Cc1cc(CS(N)(=O)=O)ccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: Cc1cc(CS(N)(=O)=O)ccc1N
Reaction time: 3 h

Procedure:
The sulfonamide 14 (31.7 g, 138 mmol) was dissolved into boiling EtOH (600 ml) containing some AcOH (80 ml). To this solution was added 10% Pd/C (1.4 g) and this mixture was stirred under hydrogen (40 psi) for 3 h. THF (50 ml) was then added and this mixture heated to dissolve the precipitated product. This solution was filtered through celite and concentrated. The resulting solid was triturated with ether:hexane 1:1 (200 ml) to yield 27.28 g (99%) of pure 15.
Reaction SMILES: [Cl:1][C:2]1[C:8]([CH:9]([O:11][CH3:12])[CH3:10])=[CH:7][C:5]([NH2:6])=[C:4]([F:13])[CH:3]=1.[C:14]1(=O)[O:19][C:17](=[O:18])[CH:16]2[CH2:20][CH2:21][CH:22]=[CH:23][CH:15]12.C(O)(=O)C>C(OCC)C>[Cl:1][C:2]1[C:8]([CH:9]([O:11][CH3:12])[CH3:10])=[CH:7][C:5]([N:6]2[C:17](=[O:18])[C:16]3[CH2:20][CH2:21][CH2:22][CH2:23][C:15]=3[C:14]2=[O:19])=[C:4]([F:13])[CH:3]=1
Reactant: O=C1OC(=O)C2CCC=CC12
Reactant: COC(C)c1cc(N)c(F)cc1Cl
Solvent: CC(=O)O
Solvent: CCOCC
Product: COC(C)c1cc(N2C(=O)C3=C(CCCC3)C2=O)c(F)cc1Cl
Yield: 40.8 %

Procedure:
A mixture of 0.58 g (0.0029 mole) of 4-chloro-2-fluoro-5-(1-methoxyethyl)aniline, 0.82 g (0.0054 mole) of tetrahydrophthalic anhydride, and 15 ml of acetic acid was refluxed overnight. The acetic acid was then evaporated under reduced pressure, leaving a residue which was dissolved in diethyl ether. This solution was washed successively with water and an aqueous solution of sodium bicarbonate. The solution was dried, filtered, and the solvent was evaporated under reduced pressure leaving a residue. This residue was passed through a silica gel column, eluting with ethyl acetate/heptane (1/4). Appropriate fractions were combined, and the solvent was evaporated under reduced pressure, yielding 0.4 g of N-[4-chloro-2-fluoro-5-(1-methoxyethyl)phenyl]-3,4,5,6-tetrahydrophthalimide as a solid, m.p. 141°-44° C. The nmr and ir spectra were consistent with the proposed structure.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].Cl[CH2:17][C:18]([CH3:20])=[CH2:19].C(N(CC)CC)C>C(#N)C>[CH3:19][C:18](=[CH2:17])[CH2:20][N:13]1[CH2:14][CH2:15][N:10]([C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=2)[CH2:11][CH2:12]1
Reactant: O=[N+]([O-])c1ccc(N2CCNCC2)cc1
Reactant: C=C(C)CCl
Solvent: CC#N
Solvent: CCN(CC)CC
Product: C=C(C)CN1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Yield: 80.2 %

Procedure:
To a solution of 1-(4-nitrophenyl)-piperazine (prepared as described in Reference Example 29; 13 g, 63 mmol) in acetonitrile (150 mL) were added, successively, 3-chloro-2-methyl-propene (6.82 g, 75.4 mmol) and triethylamine (17.6 mL, 126 mmol). The mixture was heated at reflux for 8 hours then the solvent was evaporated under reduced pressure to give a residue which was partitioned between water (150 mL) and ethyl acetate (2×100 mL). The combined organic layers were washed twice with water then dried over sodium sulfate. Filtration and concentration afforded 1-(2-methyl-allyl)-4-(4-nitrophenyl)-piperazine (13.2 g, 79%) as a yellow solid.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([NH2:17])=[N:13][CH:14]=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl[CH2:19][CH2:20][S:21](Cl)(=[O:23])=[O:22].O>CN(C)C(=O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]3=[N:17][S:21](=[O:23])(=[O:22])[CH2:20][CH2:19][N:13]3[CH:14]=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(-c2cccnc2N)cc1
Reactant: O=S(=O)(Cl)CCCl
Solvent: O
Solvent: CC(=O)N(C)C
Product: CC(C)(C)c1ccc(C2=CC=CN3CCS(=O)(=O)N=C23)cc1
Temperature: 60 °C
Reaction time: 3 h
Yield: 87 %

Procedure:
A solution of 3-(4-tert-butylphenyl)pyridin-2-amine (301 mg) in N,N-dimethylacetoamide (4 mL) was added dropwise to 2-chloroethanesulfonyl chloride (437 mg) and additional N,N-dimethylacetoamide (1 mL) was used to complete the addition of above solution. After being stirred at 60° C. for 3 hr, the mixture was cooled to room temperature. Water (10 mL) was added dropwise to the reaction mixture and the whole was stirred at room temperature for 0.5 hr. The precipitate was collected by filtration, washed with water (10 mL) and diisopropyl ether (3 mL), and dried in vacuo at 60° C. to give the title compound (366 mg) as an off-white powder.
Reaction SMILES: [O:1]=[O+][O-].[CH2:4]([CH:8]1[CH2:16][C:15]2[C:10](=[CH:11][C:12]([O:17][CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:13][CH:14]=2)[C:9]1=[O:23])[CH:5]=CC>ClCCl.CO>[O:1]=[CH:5][CH2:4][CH:8]1[CH2:16][C:15]2[C:10](=[CH:11][C:12]([O:17][CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:13][CH:14]=2)[C:9]1=[O:23]
Reactant: O=[O+][O-]
Reactant: CC=CCC1Cc2ccc(OC3CCCC3)cc2C1=O
Solvent: CO
Solvent: ClCCl
Product: O=CCC1Cc2ccc(OC3CCCC3)cc2C1=O
Reaction time: 1 h
Yield: 73 %

Procedure:
An ozone stream (1.5 g ozone/hour) was conducted for 60 minutes while stirring through a solution, cooled to -70°, of 8.1 g of (RS)-2-(2-buten-1-yl)-6-cyclopentoxy-1-indanone in 150 ml of anhydrous dichloromethane and 30 ml of anhydrous methanol. Subsequently, the solution was flushed with oxygen for 5 minutes and with argon for 10 minutes. After the addition of 3.29 ml of dimethyl sulfide, the mixture was stirred at room temperature for 21 hours. The reaction mixture was evaporated in a vacuum. The residue was treated with 75 ml of dichoromethane and, after the addition of 12.5 ml of water and 12.5 ml of trifluoroacetic acid, stirred at room temperature for 5 hours. The mixture was subsequently poured into 150 ml of water and neutralized by the spatula-wise addition of sodium hydrogen carbonate while stirring. An additional 50 ml of water were added. The phases were separated and the aqueous phase was extracted twice with 150 ml of dichloromethane each time. The combined organic phases were dried over magnesium sulfate and concentrated in a vacuum. 5.63 g (73%) of (RS)-2-(2-oxoethyl)-6-cyclopentoxy-1-indanone were obtained as an orange oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([N+:16]([O-])=O)[CH:6]=[CH:7][C:8]=1[N:9]([CH2:13][CH2:14][Cl:15])[CH2:10][CH2:11][Cl:12]>CO.O1CCCC1.[Pd]>[ClH:12].[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:8]=1[N:9]([CH2:10][CH2:11][Cl:12])[CH2:13][CH2:14][Cl:15])[NH2:16]
Reactant: COc1cc([N+](=O)[O-])ccc1N(CCCl)CCCl
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: COc1cc(N)ccc1N(CCCl)CCCl
Product: Cl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
In a reactor, 144 mg (0.49 mmol) of 3-methoxy-4-[N,N-bis(2-chloroethyl)amino]nitrobenzene were dissolved in a mixed solvent of 10 ml of methanol and 2 me of tetrahydrofuran, followed by the addition of 150 mg of 10% Pd/C under a nitrogen gas atmosphere. The reactor was purged with hydrogen gas, followed by stirring at room temperature for one hour. After completion of the reaction, the reactor was purged with nitrogen gas, followed by stirring for 30 minutes. The 10% Pd/C was then filtered off. To the thus-obtained methanol solution, 200 μl of a solution of 4N hydrochloric acid/dioxane were added, whereby 3-methoxy-4-[N,N-bis(2-chloroethyl)amino]aniline hydrochloride were obtained. The hydrochloride was provided for use in the next reaction. In 5 ml of DMF, 200 mg (0.7 mmol) of 1H-2-(1-methyl-4-nitropyrrol-2-yl)benzimidazole-5-carboxylic acid and the 3-methoxy-4-[N,N-bis(2-chloroethyl)amino]aniline hydrochloride were dissolved, followed by cooling to 0° C. To the resulting solution, 102 μl (0.74 mmol) of triethylamine and then 112 μl (0.74 mmol) of DECP were added under a nitrogen gas atmosphere, followed by stirring for 20 minutes as was. The reaction mixture was stirred at room temperature for further one hour and was then allowed to stand overnight. The solvent was distilled out under reduced pressure. The residue so obtained was purified by chromatography on a silica gel column (ethyl acetate/n-hexane=1/1), whereby 80 mg of yellow powder were obtained (yield: 31%).
Reaction SMILES: [Cl-].[CH3:2][O:3]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C([Li])CCC.[CH:29]([C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[NH:33][C:32]=1[C:40](OCC)=O)=[O:30].[O:45]1[CH2:49][CH2:48]CC1>C(OCC)(=O)C>[CH3:48][CH2:49][O:45][C:29]([C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[NH:33][C:32]=1[CH2:40][CH:2]=[O:3])=[O:30]
Reactant: C1CCOC1
Reactant: CCOC(=O)c1[nH]c2ccccc2c1C=O
Reactant: COC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Product: CCOC(=O)c1c(CC=O)[nH]c2ccccc12
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 48 %

Procedure:
A suspension of 11.95 g (34.9 mmol) of methoxymethyltriphenylphosphonium chloride in 200 ml of anhydrous tetrahydrofuran was cooled to 0° C. under N2 atmosphere and treated dropwise with 14.3 ml (35.8 mmol) of n-butyllithium. The resulting solution was stirred for 15 min, treated with 3.70 g (17 mmol) of the resultant compound of Example 97, and stirred at ambient temperature for 3 h. After concentration of the solvent in vacuo, and the residue was taken up in ethyl acetate, washed sequentially with water and saturated brine, dried over MgSO4, and concentrated. The crude mixture of vinyl ethers was partially purified by silica gel chromatography using 6:1 hexane:ethyl acetate. The mixture (2.98 g, 71%) was subsequently treated with 20 ml of 1M HCl and 40 ml of tetrahydrofuran and heated at reflux for 6 h. After cooling, the solution was partitioned between ether and saturated aqueous NaHCO3, dried over MgSO4, and concentrated. Purification by silica gel chromatography using 4:1 hexane:ethyl acetate gave 1.35 g (48%) of the desired compound which was recrystallized from ethyl acetate/hexane. 1H NMR (CDCl3) δ 1.42 (t,J=7 Hz,3H), 4.17 (d,J=2 Hz,2H), 4.42 (q,J=7 Hz,2H), 7.19 (ddd,J=8,7,1 Hz,1H), 7.37 (ddd,J=8,7,1 Hz), 7.43 (br d,J=8 Hz,1H), 7.61 (br d,J=8 Hz,1H), 8.94 (br s,1H), 9.73 (t,J=2 Hz,1H). Mass spectrum: (M+H)+ =232.
Reaction SMILES: [C:1]([CH2:3][C:4](Cl)=[O:5])#[N:2].[CH3:7][NH:8][CH2:9][CH2:10][CH2:11][Si:12]([O:17][CH3:18])([O:15][CH3:16])[O:13][CH3:14].N1C=CC=CC=1>C(OCC)C>[CH3:7][N:8]([CH2:9][CH2:10][CH2:11][Si:12]([O:15][CH3:16])([O:17][CH3:18])[O:13][CH3:14])[C:4](=[O:5])[CH2:3][C:1]#[N:2]
Reactant: CNCCC[Si](OC)(OC)OC
Reactant: N#CCC(=O)Cl
Solvent: CCOCC
Solvent: c1ccncc1
Product: CO[Si](CCCN(C)C(=O)CC#N)(OC)OC
Temperature: 25 °C
Yield: 77.6 %

Procedure:
To a 1 L reactor equipped with a thermometer, a condenser and a loading glass were added 200 mL of diethylether and 11 g of cyanoacetylchloride, followed by stirring at room temperature in the presence of nitrogen. To the reactor were slowly added 20 g of N-methylaminopropyl trimethoxysilane (0.104 mol) and 11 g of pyridine (0.14 mol) in 100 mL of diethylether by using the loading glass. The reaction mixture was stirred for 2 hours at room temperature and then the precipitated pyridine salt was eliminated. After removing the solvent and non-reactants, the reaction mixture was distilled under reduced pressure to give 21 g of N-methyl-N-(3-trimethoxysilylpropyl)cyanoacetamide (formula 3). The yield was 75%.
Reaction SMILES: [C:1]([CH:5]1[CH2:10][CH:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][CH2:7][C:6]1=[O:17])([CH3:4])([CH3:3])[CH3:2].C(C1CCCC([Cl:28])C1=O)(C)(C)C>>[C:1]([CH:5]1[CH2:10][CH:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][CH:7]([Cl:28])[C:6]1=[O:17])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)C1CC(c2ccccc2)CCC1=O
Reactant: CC(C)(C)C1CCCC(Cl)C1=O
Product: CC(C)(C)C1CC(c2ccccc2)CC(Cl)C1=O

Procedure:
The chlorination of 2-tert-butyl-4-phenyl-cyclohexanone takes place in a manner similar to that described above for the preparation of 2-tert-butyl-6-chloro-cyclohexanone. The title compound is reacted as a crude product without further characterization.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:17][NH:18][O:19][CH3:20].C(N(CC)CC)C.Cl>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[C:14](=[O:16])[N:18]([O:19][CH3:20])[CH3:17])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CNOC
Reactant: CC(C)(C)OC(=O)N1CCCCC1C(=O)O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CON(C)C(=O)C1CCCCN1C(=O)OC(C)(C)C
Yield: 77.6 %

Procedure:
To (RS)-1-(tert-butyloxycarbonyl)-2-piperidine carboxylic acid (2.64 g, 11.5 mmol) in dichloromethane (10 ml) was added sequentially N,O-dimethyl hydroxylamine (1.34 g, 13.7 mmol), triethylamine (6 ml, 43.0 mmol) and Py.Bop (6.60 g, 12.7 mmol). The resultant mixture was stirred at ambient temperature for 6 h, then diluted with dichloromethane (170 ml) and poured into 1M HCl (22 ml). The organic phase was separated and washed with saturated aqueous sodium hydrogen carbonate (3×25 ml) and brine (25 ml) then evaporated in vacuo. The resultant colourless oil was chromatographed on silica gel eluting with 20% ethyl acetate in hexane to give the title compound (2.43 g, 77%) as a colourless oil.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Cl[C:15]1[CH:16]=[C:17]([CH:23]=[CH:24][N:25]=1)[C:18]([O:20][CH2:21][CH3:22])=[O:19]>>[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6]([C:15]2[CH:16]=[C:17]([CH:23]=[CH:24][N:25]=2)[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:5][CH:4]=1
Reactant: CCOC(=O)c1ccnc(Cl)c1
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Product: CCOC(=O)c1ccnc(-c2ccc(C(F)(F)F)cc2)c1

Procedure:
4-Trifluoromethylphenylboronic acid (255 mg) and ethyl 2-chloroisonicotinate (200 mg) were reacted in the same manner as in Preparation Example 1 to obtain the title compound.
Reaction SMILES: [CH:1]1([C:6]2[C:10]([N+:11]([O-:13])=[O:12])=[C:9]([C:14]([O:16]CC)=O)[O:8][N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH3:19]>>[CH:1]1([C:6]2[C:10]([N+:11]([O-:13])=[O:12])=[C:9]([C:14]([NH2:19])=[O:16])[O:8][N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: N
Reactant: CCOC(=O)c1onc(C2CCCC2)c1[N+](=O)[O-]
Product: NC(=O)c1onc(C2CCCC2)c1[N+](=O)[O-]
Yield: 62 %

Procedure:
51.59 g (203 mmol) of ethyl 3-cyclopentyl-4-nitro-isoxazole-5-carboxylate (example IV) are stirred, at room temperature for 3 hours, in 600 ml of a 2M solution of ammonia. The solvent is removed in vacuo and the residue is triturated with cyclohexane and dried in vacuo. 31.17 g (62%) of colorless solid are obtained.
Reaction SMILES: [C:1]1([N:7]2[C:13]3[CH:14]=[CH:15][C:16]([C:18]4[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][CH3:30])=[CH:20][CH:19]=4)=[CH:17][C:12]=3[CH:11]=[C:10]([C:31](O)=[O:32])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)([Cl:36])=O.[CH3:38][N:39]([CH:41]=O)[CH3:40]>>[ClH:36].[C:1]1([N:7]2[C:13]3[CH:14]=[CH:15][C:16]([C:18]4[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][CH3:30])=[CH:20][CH:19]=4)=[CH:17][C:12]=3[CH:11]=[C:10]([C:31]([NH:7][C:1]3[CH:6]=[CH:5][C:4]([CH2:41][N:39]([CH3:38])[CH:40]4[CH2:26][CH2:25][O:24][CH2:21][CH2:20]4)=[CH:3][CH:2]=3)=[O:32])[CH2:9][CH2:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCN3c2ccccc2)cc1
Reactant: CN(C)C=O
Reactant: O=S(Cl)Cl
Product: CCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN(C)C4CCOCC4)cc2)CCN3c2ccccc2)cc1
Product: Cl
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
In DMF (6 ml) was dissolved 1-phenyl-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.2 g). Under ice-cooling, to the mixture was added thionyl chloride (0.08 ml). The mixture was stirred at room temperature for 30 minutes. The solvent was evaporated under reduced pressure. In THF (20 ml) was suspended the residue, the suspension was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.12 g) and triethylamine (0.31 ml) in THF (5 ml), under ice-cooling. The mixture was stirred at room temperature overnight under nitrogen atmosphere. The solvent was evaporated under reduced pressure. Water was added to the mixture, the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate. The solvent was evaporated, the residue was purified with silica gel column chromatography (ethyl acetate/methanol/triethylamine), which was dissolved in ethyl acetate-ethanol, 4N hydrochloric acid-ethyl acetate was added to the solution, and the solvent was evaporated to give 1-phenyl-7-[4-(2-propoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide hydrochloride (Compound 38) (0.17 g) as yellow crystals.
Reaction SMILES: [Si:1]([O:18][CH2:19][CH:20]([CH2:24][CH2:25][CH2:26][Br:27])[CH2:21][CH2:22][Br:23])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(C(O[SiH](C1C=CC=CC=1)C1C=CC=CC=1)[C@@H](CCCO)CCO)(C)(C)C.BrN1C(=O)CCC1=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>>[Si:1]([O:18][CH2:19][C@@H:20]([CH2:24][CH2:25][CH2:26][Br:27])[CH2:21][CH2:22][Br:23])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](OCC(CCBr)CCCBr)(c1ccccc1)c1ccccc1
Agent: CC(C)(C)C(O[SiH](c1ccccc1)c1ccccc1)[C@H](CCO)CCCO
Agent: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CC(C)(C)[Si](OC[C@H](CCBr)CCCBr)(c1ccccc1)c1ccccc1
Yield: 75 %

Procedure:
Following the same procedure described for the preparation of racemic dibromide, 3-(tert-butyldiphenylsilyloxymethyl)-1,6-dibromohexane, (S)-(-)-3-(tertbutyldiphenylsilyloxymethyl)-1,6-hexanediol (4.85 g, 12.53 mmol) was reacted with N-bromosuccinimide (5.35 g, 30.1 mmol) and triphenylphosphine (7.87 g, 30.1 mmol) CH2Cl2 (150 mL) at 0° C. to afford compound (S)-(-)-3-(tert-butyldiphenylsilyloxymethyl)-1,6-dibromohexane 4.81 (75%) as a clear, colorless oil which was homogenous by TLC (Rf =0.8, 10% EtOAc in hexanes. Both the TLC properties and 1H spectra of this compound were identical in all respects with racemic isomer. MS.
Reaction SMILES: [N-]1C=CN=C1.[CH:6]1([N:9]2[C:18]3[C:13](=[CH:14][C:15]([F:33])=[C:16]([N:20]4[CH2:24][CH2:23][CH:22]([NH:25]C(OC(C)(C)C)=O)[CH2:21]4)[C:17]=3[Cl:19])[C:12](=[O:34])[C:11]([C:35]([OH:37])=O)=[CH:10]2)[CH2:8][CH2:7]1.[C:38](#[N:42])[CH2:39][C:40]#[N:41]>>[ClH:19].[CH:6]1([N:9]2[C:18]3[C:13](=[CH:14][C:15]([F:33])=[C:16]([N:20]4[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21]4)[C:17]=3[Cl:19])[C:12](=[O:34])[C:11]([C:35](=[O:37])[CH:39]([C:38]#[N:42])[C:40]#[N:41])=[CH:10]2)[CH2:7][CH2:8]1
Reactant: CC(C)(C)OC(=O)NC1CCN(c2c(F)cc3c(=O)c(C(=O)O)cn(C4CC4)c3c2Cl)C1
Reactant: N#CCC#N
Agent: c1c[n-]cn1
Product: Cl
Product: N#CC(C#N)C(=O)c1cn(C2CC2)c2c(Cl)c(N3CCC(N)C3)c(F)cc2c1=O
Yield: 116.5 %

Procedure:
5.2 g of 1-cyclopropyl-6-fluoro-8-chloro-7-(3-t-butoxycarbonylaminopyrrolidin-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid imidazolide and 3.30 g of malononitrile as starting materials were subjected to the same process as described in Example 39 to obtain 2.56 g of the object compound
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][C:5]2[NH:6][C:7]3[C:12]([C:13]=2[CH:14]=1)=[CH:11][CH:10]=[CH:9][CH:8]=3.[CH3:15]OC(OC)N(C)C.N1(C2CCCCCCC2)CCCCCCN1>CN(C)C=O>[CH3:1][C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:15])[C:7]3[C:12]([C:13]=2[CH:14]=1)=[CH:11][CH:10]=[CH:9][CH:8]=3
Reactant: COC(OC)N(C)C
Reactant: Cc1cc2c(cn1)[nH]c1ccccc12
Agent: C1CCCC(N2CCCCCCN2)CCC1
Solvent: CN(C)C=O
Product: Cc1cc2c3ccccc3n(C)c2cn1

Procedure:
0.182 g of 3-methyl-β-carboline (example 5), 0.5 ml of N,N-dimethylformamide-dimethylacetal (90%) and 0.02 g of diazabicyclooctane (Dabco) are stirred in 30 ml of absolute N,N-dimethylformamide for 15 hours at 110° C. The solvent is distilled off under vacuum and the residue is chromatographed on silica gel. (Methylene chloride/ethanol: 9+1). 0.095 g of 3,9-dimethyl-β-carboline with a 134° C. melting point (decomposition) is obtained.
Reaction SMILES: [CH:1]1([C:4](=[O:30])/[CH:5]=[C:6](/[NH:9][C:10]2[CH:11]=[CH:12][C:13]([CH3:29])=[C:14]([C:16]3[C:17](=[O:28])[N:18]([CH3:27])[C:19]4[C:24]([CH:25]=3)=[CH:23][N:22]=[C:21]([CH3:26])[CH:20]=4)[CH:15]=2)\SC)[CH2:3][CH2:2]1.Cl.[NH2:32]O>CN(C=O)C>[CH:1]1([C:4]2[O:30][N:32]=[C:6]([NH:9][C:10]3[CH:11]=[CH:12][C:13]([CH3:29])=[C:14]([C:16]4[C:17](=[O:28])[N:18]([CH3:27])[C:19]5[C:24]([CH:25]=4)=[CH:23][N:22]=[C:21]([CH3:26])[CH:20]=5)[CH:15]=3)[CH:5]=2)[CH2:3][CH2:2]1
Reactant: NO
Reactant: CS/C(=C\C(=O)C1CC1)Nc1ccc(C)c(-c2cc3cnc(C)cc3n(C)c2=O)c1
Agent: Cl
Solvent: CN(C)C=O
Product: Cc1cc2c(cn1)cc(-c1cc(Nc3cc(C4CC4)on3)ccc1C)c(=O)n2C
Temperature: 100 °C

Procedure:
To the above crude mixture of (Z)-3-(5-(3-cyclopropyl-1-(methylthio)-3-oxoprop-1-enylamino)-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one 31 were added hydroxylamine hydrochloride (174 mg, 2.4 mmol) and DMF (2 mL). The resulting mixture was heated at 100° C. for 30 min. The mixture was purified by preparative LC/MS to give 3-(5-(5-cyclopropylisoxazol-3-ylamino)-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one (D4). 1H NMR (400 MHz, d6-DMSO) δ 9.21 (s, 1H), 9.13 (s, 1H), 8.10 (s, 1H), 7.96 (s, 1H), 7.39 (d, J=2.4 Hz, 1H), 7.29 (dd, J=2.4, 8.4 Hz, 1H), 7.19 (d, J=8.4 Hz, 1H), 5.83 (s, 1H), 3.72 (s, 3H), 2.79 (s, 3H), 2.07 (s, 3H), 2.05 (m, 1H), 1.01 (m, 2H), 0.84 (m, 2H). MS m/z 387.2 (M+1).
Reaction SMILES: [CH3:1][N:2]([CH3:30])[CH2:3][CH2:4][CH2:5][N:6]([C:21]1[C:26]([N+:27]([O-])=O)=[CH:25][CH:24]=[CH:23][N:22]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=O.C>C(O)(=O)C.C(O)(C)C.[Fe]>[CH3:1][N:2]([CH3:30])[CH2:3][CH2:4][CH2:5][N:6]1[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:27][C:26]2[CH:25]=[CH:24][CH:23]=[N:22][C:21]1=2
Reactant: CN(C)CCCN(c1ccccc1C(=O)c1ccccc1)c1ncccc1[N+](=O)[O-]
Agent: [Fe]
Solvent: CC(=O)O
Solvent: CC(C)O
Product: CN(C)CCCN1c2ccccc2C(c2ccccc2)=Nc2cccnc21
Reaction time: 1 h

Procedure:
To a stirred solution of 3.3 g of crude [2-[[3-(dimethylamino)propyl](3-nitro-2-pyridinyl)amino]phenyl]phenylmethanone obtained in Example 8(c) in 20 ml of acetic acid at 65° C. was added portionwise 6.6 g of iron powder. The reaction was exothermic at the beginning, the temperature rising to 90° C. Thereafter the temperature was controlled at 85° C. for 1 hr. The mixture was filtered through celite and washed with acetic acid and methanol. The filtrate and washes were combined and evaporated and the residue was dissolved in methanol. The solution was filtered to remove insoluble iron acetate. The filtrate was evaporated and the residue dissolved in water/methylene chloride and made basic with sodium hydroxide and potassium carbonate. The mixture was mixed with celite and filtered through celite. The aqueous layer of the filtrate was extracted twice with methylene chloride which had been used to wash the cake. The combined methylene chloride solution was washed once with NaCl solution, dried and treated with charcoal, filtered and evaporated to give a black foam weighing 1.63 g (46%). The foam was dissolved in isopropyl alcohol. The solution was treated with charcoal and the mixture was filtered into a solution of 0.7 g fumaric acid in isopropyl alcohol. This solution was again treated with charcoal and filtered. Chemical ionization mass spectral analysis and thin-layer chromatography confirmed the presence of the title compound.