Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([NH:15][C:16](=[O:20])OCC)=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2.[C:21]1([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C1CCN2C(=NCCC2)CC1>O1CCCC1>[CH3:1][O:2][C:3]1[C:4]([NH:15][C:16]([N:30]2[CH2:31][CH2:32][N:27]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:28][CH2:29]2)=[O:20])=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2
Reactant: c1ccc(N2CCNCC2)cc1
Reactant: CCOC(=O)Nc1nc2ccc(OC)cc2nc1OC
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: COc1ccc2nc(NC(=O)N3CCN(c4ccccc4)CC3)c(OC)nc2c1
Temperature: 70 °C
Reaction time: 7 h
Yield: 91.5 %

Procedure:
Ethyl N-(3,6-dimethoxyquinoxalin-2-yl)carbamate (28 mg, 0.10 mmol) and 1-phenylpiperazine (24 mg, 0.15 mmol) were dissolved in tetrahydrofuran (2 ml) at room temperature and thereto DBU (23 mg, 0.15 mmol) was added. The resulting mixture was stirred at 70° C. for 7 hours and concentrated under the reduced pressure to remove the solvent, and purified by SiO2 column chromatography. Extraction of the residue with a n-hexane:ethyl acetate (2:1) mixture and concentration gave 36 mg of the titled compound (yield, 91%). 1H NMR (300 MHz, CDCl3): δ 3.27 (s, 4H), 3.76 (s, 4H), 3.89 (s, 3H), 4.12 (s, 3H), 6.87-6.96 (m, 3H), 7.13 (s, 2H), 7.29-7.31 (m, 2H), 7.72-7.75 (s, 1H).
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.Cl.[N:17]1([CH2:23][CH2:24][C:25]2[N:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]3=[C:27]([C:34](Cl)=[O:35])[N:26]=2)[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1>C(Cl)Cl>[CH3:1][N:2]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[C:34]([C:27]1[N:26]=[C:25]([CH2:24][CH2:23][N:17]2[CH2:18][CH2:19][O:20][CH2:21][CH2:22]2)[N:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=12)=[O:35]
Reactant: O=C(Cl)c1nc(CCN2CCOCC2)n2ccccc12
Reactant: CNc1ccccc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN(C(=O)c1nc(CCN2CCOCC2)n2ccccc12)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 64 %

Procedure:
To a solution of n-methylaniline (0.060 mL, 0.54 mmol) and triethylamine (0.16 mL, 1.14 mmol) in CH2Cl2 (10 mL) was added 3-(2-morpholin-4-yl-ethyl)-imidazo[1,5-a]pyridine-1-carbonyl chloride hydrochloride (150 mg, 0.45 mmol). The mixture was stirred at ambient temperature for 1 h then washed with sat. aq. NaHCO3 (20 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane (20 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica to yield the title compound (105 mg, 64%). 1H NMR (DMSO-d6) δ 8.23 (1H), 8.00 (1H), 7.30 (2H), 7.19 (3H), 7.05 (1H), 6.81 (1H), 3.52 (4H), 3.48 (3H), 2.95 (2H), 2.45 (2H), 2.33 (4H); m/z (M+H)=365.26.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]2[C:3]=1[C:4](=[N+:14]=[N-:15])[C:5](=[O:13])[NH:6]2.[CH2:16]([OH:19])[C:17]#[CH:18]>C(OCC)C.C(O)C>[Cl:1][C:2]1[C:3]2[C:4]3[N:14]([N:15]=[C:17]([CH2:16][OH:19])[CH:18]=3)[C:5](=[O:13])[NH:6][C:7]=2[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1
Reactant: C#CCO
Reactant: COc1ccc(Cl)c2c1NC(=O)C2=[N+]=[N-]
Solvent: CCO
Solvent: CCOCC
Product: COc1ccc(Cl)c2c1[nH]c(=O)n1nc(CO)cc21
Yield: 63.9 %

Procedure:
2.0 g (0.0089 mole) of the 4-chloro-7-methoxy-3-diazooxindole (prepared in part B) and 10.3 g of 97% propargyl alcohol are refluxed under argon for 4 hours and cooled. The reaction mixture is diluted with 200 ml of ethyl ether and stirred for ~20 minutes and cream-colored precipitates are filtered off. Yield: 2.53 g, m.p. 221°-222°; quantitative crude yield (theor.: 2.49 g). This crude product is taken up in 200 ml absolute ethanol, the clear solution filtered while hot and the filtrate concentrated down to a volume of 50 ml and cooled. The resulting precipitates are filtered off and dried in vacuo at 45° over the weekend to give 1.59 g of title compound, m.p. 230°-232°.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])=[O:10])=[CH:4][CH:3]=1.C1C(=O)N(Br)C(=[O:22])C1.O>CS(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:22])[C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])=[O:10])=[CH:4][CH:3]=1
Reactant: O=C(Cc1ccc(Cl)cc1)c1ccc(Cl)cc1Cl
Reactant: O=C1CCC(=O)N1Br
Solvent: CS(C)=O
Solvent: O
Product: O=C(C(=O)c1ccc(Cl)cc1Cl)c1ccc(Cl)cc1

Procedure:
To a solution of 100 g (0.33 mol) of 2-(4-chlorophenyl)-1-(2,4-dichlorophenyl)ethanone in 1 L of DMSO, 75 g (0.42 mol) of NBS was added and the mixture was stirred over a weekend. The reaction was poured into 8 L of water and stirred for 30 min. The yellow solid formed was filtered and dried. This solid was purified by passing through a plug of 1 Kg of silica gel using hexane and 5% EtOAc-hexane to isolate the title compound. 1H NMR: (500 MHz, CDCl3): δ 7.4–8.0 (m, 7H).
Reaction SMILES: O=[C:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]([CH:11]2[CH2:13][CH2:12]2)=[O:10])[CH2:4][CH2:3]1.Cl.[C:15]([C:17]1[CH:22]=[CH:21][C:20]([NH:23]N)=[CH:19][CH:18]=1)#[N:16]>>[C:15]([C:17]1[CH:18]=[C:19]2[C:20](=[CH:21][CH:22]=1)[NH:23][C:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]([CH:11]3[CH2:13][CH2:12]3)=[O:10])[CH2:4][C:3]2=1)#[N:16]
Reactant: N#Cc1ccc(NN)cc1
Reactant: O=C1CCC(NC(=O)C2CC2)CC1
Agent: Cl
Product: N#Cc1ccc2[nH]c3c(c2c1)CC(NC(=O)C1CC1)CC3

Procedure:
Prepare the title compound from cyclopropanecarboxylic acid(4-oxocyclohexyl)amide (51.3 g, 283 mmol) and 4-cyanophenylhydrazine hydrochloride (48.0 g, 283 mmol) by essentially following procedures as described in Preparation 3 to obtain 57.0 g (72%) of a pale yellow solid. mp: 231-233° C.; MS (ES): m/z 280 (M+1).
Reaction SMILES: [CH:1]1[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[Cl-].[Al+3].[Cl-].[Cl-].[C:18](Cl)(=[O:26])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].Cl>C(=S)=S.C(OCC)(=O)C>[C:18]([C:9]1[CH:8]=[CH:7][C:6]2[C:5]3[C:13](=[CH:1][CH:2]=[CH:3][CH:4]=3)[CH2:12][C:11]=2[CH:10]=1)(=[O:26])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: c1ccc2c(c1)Cc1ccccc1-2
Reactant: CCCCCCCC(=O)Cl
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: CCOC(C)=O
Solvent: S=C=S
Product: CCCCCCCC(=O)c1ccc2c(c1)Cc1ccccc1-2
Temperature: 0 °C
Reaction time: 0.83 h

Procedure:
To a solution of 10.00 g (60.2 mM) of fluorene in 100 ml of dry carbon disulfide, 9.40 g (70.5 mM) of anhydrous aluminum chloride was added while being cooled on an ice-common salt bath. Under cooling on the bath, 10.3 ml (60.3 mM) of octanoylchloride was gradually added dropwise to the mixture at -2.5° to 1° C., followed by stirring for 2 hours and 50 minutes without cooling on the bath. After the reaction, the reaction mixture was poured into a mixture of 150 g of ice and 50 ml of hydrochloric acid. To the resultant mixture, 100 ml of ethyl acetate was added, followed by stirring at room temperature to precipitate a crystal. The crystal was recovered by filtration and recrystallized from acetone to obtain 3.70 g of 2-octanoylfluorene. The organic layer separated from the filtrate was washed with water, dried with anhydrous sodium sulfate, and condensed into about 100 ml of the resultant solution, followed by cooling on an ice bath to precipitate a crystal. The crystal was recovered by filtration and recrystallized from acetone to obtain 4.09 g of 2-octanoylfluorene. The total amount of 2-octanoylfluorene obtained was 7.79 g (Yield: 44.3%).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][C:3]=1[O:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[F:19].[CH3:20][S:21](Cl)(=[O:23])=[O:22]>N1C=CC=CC=1>[F:19][C:13]1[CH:14]=[C:15]([F:18])[CH:16]=[CH:17][C:12]=1[O:11][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:2]=1[NH:1][S:21]([CH3:20])(=[O:23])=[O:22])[C:6]([NH2:8])=[O:7]
Reactant: CS(=O)(=O)Cl
Reactant: NC(=O)c1ccc(N)c(Oc2ccc(F)cc2F)c1
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1ccc(C(N)=O)cc1Oc1ccc(F)cc1F
Temperature: 5 °C
Reaction time: 0.5 h
Yield: 69.7 %

Procedure:
A mixture of 4-amino-3-(2,4-difluorophenoxy)benzamide (0.82 g) and methanesulfonyl chloride (0.39 g) in pyridine (5 ml) was stirred for 15 minutes at 5° C. and for 30 minutes at room temperature. Pyridine was evaporated under reduced pressure, and the residue was dissolved in ethyl acetate, washed with diluted hydrochloric acid and a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The residue (1.1 g) was subjected to column chromatography on silica gel (20 g) eluting with a mixture of toluene and ethyl acetate (1:2). The fractions containing the desired compound were combined and concentrated to give colorless crystals of 3-(2,4-difluorophenoxy)-4-(methanesulfonamido)benzamide (0.74 g).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][CH:22]=[C:23]([C:25]4[C:34]5[C:29](=[N:30][CH:31]=[CH:32][CH:33]=5)[N:28]=[C:27]([C:35]5[CH:40]=[C:39]([Cl:41])[CH:38]=[CH:37][C:36]=5[F:42])[CH:26]=4)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C>Cl.O1CCOCC1.CO>[ClH:41].[ClH:41].[Cl:41][C:39]1[CH:38]=[CH:37][C:36]([F:42])=[C:35]([C:27]2[CH:26]=[C:25]([C:23]3[CH:22]=[N:21][CH:20]=[C:19]([C:17]4[CH:16]=[N:15][N:14]([CH:11]5[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]5)[CH:18]=4)[CH:24]=3)[C:34]3[C:29](=[N:30][CH:31]=[CH:32][CH:33]=3)[N:28]=2)[CH:40]=1
Reactant: CC(C)(C)OC(=O)N1CCC(n2cc(-c3cncc(-c4cc(-c5cc(Cl)ccc5F)nc5ncccc45)c3)cn2)CC1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: Fc1ccc(Cl)cc1-c1cc(-c2cncc(-c3cnn(C4CCNCC4)c3)c2)c2cccnc2n1
Reaction time: 3 h

Procedure:
A slurry of 155 mg (0.265 mmol) 4-(4-{5-[2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl-ester in 1.5 ml 4 N HCl in dioxane was treated with 1 drop of methanol. The solution thus formed was left for 3 hours at room temperature and subsequently evaporated. The residue was treated with tert-butyl-methyl-ether and the solid was filtered off. The residue was dissolved in water and lyophilized yielding 2-(5-chloro-2-fluoro-phenyl)-4-[5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-3-yl]-[1,8]naphthyridine dihydrochloride als colourless lyophilisate; HPLC-MS: 1.65 min, [M+H] 485.
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[Br:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[OH:17].C(=O)([O-])[O-].[K+].[K+].CN(C)C(=O)C>O>[Br:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[O:17][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1
Reactant: O=Cc1ccc(F)cc1
Reactant: Oc1ccccc1Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: O=Cc1ccc(Oc2ccccc2Br)cc1
Temperature: 150 °C
Yield: 37.5 %

Procedure:
To a mixture of 4-fluorobenzaldehyde (2.5 g, 20.2 mmol), 2-bromophenol (3.5 g, 20.2 mmol) and potassium carbonate (3.35 g, 24.3 mmol) is added N,N-dimethylacetamide (20 mL) and the resulting reaction mixture is heated to 150° C. for 12 hours. Once complete, the reaction is cooled to room temperature and diluted with water prior to being extracted with ethyl acetate. The combined extracts are washed with brine and dried over sodium sulfate and concentrated. The resulting yellow oil is purified by column chromatography (5% ethyl acetate in hexanes) to afford 2.1 g of 4-(2-bromophenoxy)benzaldehyde.
Reaction SMILES: [O-:1][CH2:2][CH3:3].[Na+].C(OCC)(=O)CC(OCC)=O.[F:16][C:17]1[CH:18]=[CH:19][C:20]([O:28][CH3:29])=[C:21]([CH:23]=[CH:24][C:25](=[O:27])[CH3:26])[CH:22]=1>C(O)C>[F:16][C:17]1[CH:18]=[CH:19][C:20]([O:28][CH3:29])=[C:21]([CH:23]2[CH2:3][C:2](=[O:1])[CH2:26][C:25](=[O:27])[CH2:24]2)[CH:22]=1
Reactant: CC[O-]
Reactant: COc1ccc(F)cc1C=CC(C)=O
Agent: [Na+]
Solvent: CCOC(=O)CC(=O)OCC
Solvent: CCO
Product: COc1ccc(F)cc1C1CC(=O)CC(=O)C1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 20% sodium ethoxide in ethanol (21.4 g) was added at room temperature diethyl malonate (11.2 g) and then was added little by little 4-(5-fluoro-2-methoxyphenyl)-3-buten-2-one (13 g), and the reaction mixture was stirred at room temperature for 30 minutes, refluxed for 2 hours and cooled. The solvent was evaporated, and to the residue was added water. The aqueous layer was washed with ethyl acetate and concentrated. To the residue was added 2M sodium hydroxide (50 ml), and the mixture was refluxed for 2 hours and cooled. To the mixture was added 2.5M sulfuric acid (50 ml) for 15 minutes, and the mixture was refluxed for 15 minutes and cooled. Precipitated crystals were washed with ethyl acetate to give 5-(5-fluoro-2-methoxyphenyl)cyclohexane-1,3-dione (9.6 g) as pale yellow crystals.
Reaction SMILES: [CH3:1][N:2](S(C1C=CC(C)=CC=1)(=O)=O)[N:3]=[C:4](Cl)[C:5]1[C:10]([F:11])=[CH:9][CH:8]=[CH:7][C:6]=1[Cl:12].[Cl:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][C:26]=1[O:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38].ClC1C=CC=CC=1Cl>C(Cl)(Cl)Cl.[Fe](Cl)(Cl)Cl>[Cl:12][C:6]1[CH:7]=[CH:8][CH:9]=[C:10]([F:11])[C:5]=1[C:4]1[N:30]=[C:29]([C:28]2[CH:31]=[CH:32][C:25]([Cl:24])=[C:26]([O:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[CH:27]=2)[N:2]([CH3:1])[N:3]=1
Reactant: Cc1ccc(S(=O)(=O)N(C)N=C(Cl)c2c(F)cccc2Cl)cc1
Reactant: CCCCCOc1cc(C#N)ccc1Cl
Agent: Cl[Fe](Cl)Cl
Solvent: ClC(Cl)Cl
Solvent: Clc1ccccc1Cl
Product: CCCCCOc1cc(-c2nc(-c3c(F)cccc3Cl)nn2C)ccc1Cl
Temperature: 140 °C
Reaction time: 0.5 h
Yield: 41.8 %

Procedure:
A mixture of N-methyl-N-(p-toluenesulfonyl)-2-chloro-6-fluorobenzohydrazonoyl chloride (1.10 g), 4-chloro-3-pentyloxybenzonitrile (0.70 g), anhydrous iron (III) chloride (0.60 g) and o-dichlorobenzene (5 ml) is stirred at an oil bath temperature of 140° C. for 30 minutes. After cooling, the reaction mixture is dissolved in chloroform (100 ml), washed with dilute hydrochloric acid, dilute aqueous solution of sodium hydroxide and saline in this order, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate is purified by silica gel column chromatography using mixed solvent of hexane-ethyl acetate as eluent to give 0.50 g of desired compound.
Reaction SMILES: [N:1]([CH2:4][C@H:5]([OH:15])[CH2:6][P:7]([CH3:14])(=[O:13])[O:8][CH2:9][CH:10]([CH3:12])[CH3:11])=[N+]=[N-].[H][H]>C(O)C.[Pd]>[NH2:1][CH2:4][C@H:5]([OH:15])[CH2:6][P:7]([CH3:14])(=[O:13])[O:8][CH2:9][CH:10]([CH3:12])[CH3:11]
Reactant: CC(C)COP(C)(=O)C[C@@H](O)CN=[N+]=[N-]
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CC(C)COP(C)(=O)C[C@@H](O)CN

Procedure:
To a solution of 1.2 g of isobutyl P-[3-azido-2(S)-hydroxy-propyl]-P-methyl-phosphinate in 25 ml of ethanol are added 0.25 g of 5% palladium on charcoal. The resulting mixture is hydrogenated at 1 bar until hydrogen uptake ceases. The mixture is then filtered and the filtrate evaporated to give isobutyl P-[3-amino-2(S)-hydroxy-propyl]-P-(methyl)-phosphinate as a viscous oil, 31P-NMR spectrum: δ=+55.6 and +54.6 ppm (CDCl3), [α]D25 =+10.9 (c=0.50% in ethanol).
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8](Cl)=[O:9])=[CH:6][N:5]=[C:4]([S:11][CH3:12])[N:3]=1.[Cl:13][C:14]1[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=1[CH2:16][Mg]Cl>>[Cl:1][C:2]1[C:7]([C:8](=[O:9])[CH2:16][C:15]2[CH:19]=[CH:20][CH:21]=[CH:22][C:14]=2[Cl:13])=[CH:6][N:5]=[C:4]([S:11][CH3:12])[N:3]=1
Reactant: CSc1ncc(C(=O)Cl)c(Cl)n1
Reactant: Cl[Mg]Cc1ccccc1Cl
Product: CSc1ncc(C(=O)Cc2ccccc2Cl)c(Cl)n1
Temperature: -78 °C

Procedure:
An oven dried flask, equipped with stir bar and septa, was charged with 4-chloro-2-(methylthio)pyrimidine-5-carbonyl chloride (Aaron Chemistry, 1338 mg, 6 mmol). The flask was capped with septa, evacuated and backfilled with nitrogen (three times). The solid was dissolved in tetrahydrofuran (24.0 mL), cooled to −78° C. and kept under nitrogen. (2-Chlorobenzyl)magnesium chloride (14.40 mL, 7.20 mmol) was then slowly added. After the addition was completed, the dry ice/acetone bath was removed and the mixture was stirred at ambient temperature for 3 hours. The mixture was quenched with aqueous 1 M HCl (50 mL), extracted with ethyl acetate (3×80 mL) and the combined extracts were washed with brine, dried over magnesium sulfate (MgSO4), filtered and concentrated. The crude product obtained was purified by flash chromatography (Isco®, Redi-Sep® column, 0-30% ethyl acetate/hexane, linear gradient) to afford the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 8.72 (s, 1H), 7.47-7.36 (m, 1H), 7.36-7.21 (m, 3H), 4.41 (s, 2H), 2.61 (s, 3H); MS (ESI) m/z 313 (M+H)+.
Reaction SMILES: [CH3:1][CH2:2][C@@:3]1([OH:26])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:24](=[CH:25][C:4]1=2)[C:23]1[N:22]=[C:21]2[C:16]([CH:17]=[CH:18][CH:19]=[CH:20]2)=[CH:15][C:14]=1[CH2:13]3)=[O:11].[CH2:27](O)[CH2:28]C.OO>S(=O)(=O)(O)O>[CH3:27][CH2:28][C:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:22]=[C:23]2[C:14]=1[CH2:13][N:12]1[C:10](=[O:11])[C:5]3[CH2:6][O:7][C:8]([C@:3]([OH:26])([CH2:2][CH3:1])[C:4]=3[CH:25]=[C:24]12)=[O:9]
Reactant: CCCO
Reactant: CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2cc3ccccc3nc2-1
Agent: O=S(=O)(O)O
Agent: OO
Product: CCc1c2c(nc3ccccc13)-c1cc3c(c(=O)n1C2)COC(=O)[C@]3(O)CC
Temperature: 0 °C
Reaction time: 1 h

Procedure:
In an aqueous solution of sulfuric acid (15 ml of concentrated sulfuric acid in 30 ml of water) were dissolved camptothecin (1.00 g, 2.87 m-mol), ferrous sulfate heptahydrate (5.60 g, 20.1 m-mol) and 1-propanol (6 ml, 86.1 m-mol). To this solution was added dropwise under ice-cooling and agitation a 30% aqueous solution of hydrogen peroxide (2.1 ml, 20.1 m-mol) in small portions. After addition of the hydrogen peroxide, the agitation was continued for one hour at room temperature. The reaction was diluted with ice water (2 l) and extracted with chloroform (2.5 l). The chloroform layer was dried with anhydrous magnesium sulfate, filtered and evaporated until dryness under reduced pressure. The residue was subjected to column chromatography (chloroform) through silica gel (15 g) to effect separation and purification of the product which was then recrystallized from n-hexane-chloroform whereby 265 mg (25.3%) of the objective compound were obtained as light yellow white needle crystals. M.P. 258°-261° C.
Reaction SMILES: [Na].[C:2]([C:4]1[C:5](=[O:22])[NH:6][N:7]=[C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)#[N:3].[CH3:23][N:24]([CH3:28])[C:25](Cl)=[O:26].O>CN(C)C=O>[CH3:23][N:24]([CH3:28])[C:25]([N:6]1[C:5](=[O:22])[C:4]([C:2]#[N:3])=[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:7]1)=[O:26]
Reactant: N#Cc1c(-c2ccccc2)c(-c2ccccc2)n[nH]c1=O
Reactant: CN(C)C(=O)Cl
Agent: [Na]
Solvent: O
Solvent: CN(C)C=O
Product: CN(C)C(=O)n1nc(-c2ccccc2)c(-c2ccccc2)c(C#N)c1=O
Temperature: 110 °C

Procedure:
5.0 grams (0.016 mole) of the sodium salt of 4-cyano-5,6-diphenyl-3-(2H)-pyridazinone was reacted with 1.83 grams (0.017 mole) of dimethylcarbamyl chloride in 50 mls of dimethylformamide. This solution was heated 110° C. for 3 hours, cooled, and poured into excess water. The precipitant solid was filtered, washed with water and air dried. This solid was taken up in chloroform, dried over sodium sulfate and the solvent distilled at reduced pressure. The residual solid was recrystallized from ethyl alcohol to give 3.0 grams of a solid which melted at 231° C. The infrared spectrum showed the methyl group at 3.5μ, the nitrile band at 4.5μ, and two carbonyl bands at 5.8 and 6.0μ.
Reaction SMILES: [C:1](#[N:6])/[CH:2]=[CH:3]\[CH2:4][CH3:5].CC(=CC)C#[N:10].CC(C=C)C#N.[C:19](#[N:24])[CH2:20][CH2:21][CH2:22][CH3:23].N>C1C=CC=CC=1.C1CCCCC1>[NH2:10][CH:3]([CH2:4][CH3:5])[CH2:2][C:1]#[N:6].[C:19](#[N:24])/[CH:20]=[CH:21]\[CH2:22][CH3:23]
Reactant: CC=C(C)C#N
Reactant: CCCCC#N
Agent: C=CC(C)C#N
Agent: CC/C=C\C#N
Agent: N
Solvent: C1CCCCC1
Solvent: c1ccccc1
Product: CCC(N)CC#N

Procedure:
A mixture of approximately 70 weight percent cis-2-pentenenitrile, 14 weight percent 2-methyl-2-butenenitrile, 4 weight percent 2-methyl-3-butenenitrile, with cyclohexane, benzene, and valeronitrile making up the balance, was reacted with 29 weight percent aqueous ammonia (at 15 percent molar excess relative to cis-2-pentenenitrile) in a stirred batch reactor at about 90° to 100° C., at an autogeneous pressure of about 60 to 118 psig, for approximately ten hours Vacuum distillation of the crude reaction mixture to remove low boiling impurities and water resulted in 91% selectivity to 3-aminopentanenitrile at 97% conversion of the starting cis-2-pentenenitrile
Reaction SMILES: [Br:1][C:2]1[CH:24]=[CH:23][C:5]2[C:6]([NH:16][CH:17]([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[N:7][C:8]3[C:9](I)=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(NC(C)C)(C)C.[CH:48]1([C:51]#[CH:52])[CH2:50][CH2:49]1>[Cu]I.C(OCC)(=O)C>[Br:1][C:2]1[CH:24]=[CH:23][C:5]2[C:6]([NH:16][CH:17]([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[N:7][C:8]3[C:9]([C:52]#[C:51][CH:48]4[CH2:50][CH2:49]4)=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1
Reactant: C#CC1CC1
Reactant: CC(Nc1nc2c(I)c[nH]c(=O)c2c2cc(Br)ccc12)C(C)(C)C
Agent: [Cu]I
Agent: c1coc(P(c2ccco2)c2ccco2)c1
Solvent: CCOC(C)=O
Solvent: CC(C)NC(C)C
Product: CC(Nc1nc2c(C#CC3CC3)c[nH]c(=O)c2c2cc(Br)ccc12)C(C)(C)C
Temperature: 45 °C
Reaction time: 0.5 h

Procedure:
9-bromo-4-iodo-6-[(1,2,2-trimethylpropyl)amino]benzo[c]-1,6-naphthyridin-1(2H)-one (5.03 g, 10.06 mmol), copper(I) iodide (0.230 g, 1.207 mmol), Pd(allyl)Cl dimer (0.221 g, 0.603 mmol) and tri(2-furyl)phosphine (0.280 g, 1.207 mmol) were combined in a 10-dram vial that was then flushed with nitrogen and kept under a nitrogen atmosphere. MeCN (101 ml) was then added followed by diisopropylamine (4.30 ml, 30.2 mmol) and cyclopropylacetylene (2.57 ml, 30.2 mmol). The resulting solution was then heated to 45° C. and stirred in the dark for 30 min. Then, the reaction was poured into ethyl acetate (350 mL) and washed with sat NaHCO3, water, brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting oil was purified by column chromatography on silica gel, eluting with EtOAc/Hexanes to afford the title compound as a pale yellow solid. LRMS (ESI) calc'd for (C23H25BrN3O) [M+H]+, 438.1; found 438.0.
Reaction SMILES: [Cl:1]Cl.[Cl:3][CH2:4][S:5]([C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1)(=[O:7])=[O:6].O>C(O)(=O)C>[Cl:1][C:12]1[CH:13]=[C:8]([S:5]([CH2:4][Cl:3])(=[O:6])=[O:7])[CH:9]=[CH:10][C:11]=1[OH:14]
Reactant: O=S(=O)(CCl)c1ccc(O)cc1
Reactant: ClCl
Solvent: O
Solvent: CC(=O)O
Product: O=S(=O)(CCl)c1ccc(O)c(Cl)c1
Reaction time: 0.17 h
Yield: 92.9 %

Procedure:
14.2 g (0.2 mole) of chlorine was passed into a solution of 41.5 g (0.2 mole) of 4-chloromethylsulphonylphenol in 200 ml acetic acid at 20° C. The mixture was stirred for a further 10 minutes and the solvent was then stripped off under reduced pressure. 100 ml of water were added to the residue and after crystallization the product was filtered off. 44.8 g (93% of theory) of 2-chloro-4-chloromethylsulfonylphenol were obtained in the form of a beige powder of melting point 108° C.