Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:6][CH:7]=1.[F:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[CH:15]=O>C1(C)C=CC=CC=1>[F:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[CH:15]=[N:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:9])([F:10])[F:11])[CH:3]=1
Reactant: O=Cc1ccccc1F
Reactant: Nc1cccc(C(F)(F)F)c1
Solvent: Cc1ccccc1
Product: Fc1ccccc1C=Nc1cccc(C(F)(F)F)c1
Yield: 104.8 %

Procedure:
To a toluene (200 mL) solution of 3-aminobenzotrifluoride (10.4 grams, 0.06 mol) was added 2-fluorobenzaldehyde (8.0 grams, 0.06 mol). The mixture was heated under reflux with a Dean-Stark trap for 6 hours. The solvent was removed in a rotary evaporator to give 2-fluorobenzylidene 3-trifluoromethylaniline (16.8 grams, 97% yield, yellow liquid) whose structure was confirmed by nuclear magnetic resonance, infra-red spectroscopy, and mass spectroscopy analysis.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][C:9]=2[CH:15](O)[CH3:16].[CH3:18][N:19]1[CH:23]=[CH:22][N:21]=[C:20]1[SH:24].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1.O>[CH3:18][N:19]1[CH:23]=[CH:22][N:21]=[C:20]1[S:24][CH:15]([C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:8]=1[NH:7][C:6]([C:2]1[S:1][CH:5]=[CH:4][N:3]=1)=[CH:14]2)[CH3:16]
Reactant: Cn1ccnc1S
Reactant: CC(O)c1cccc2cc(-c3nccs3)[nH]c12
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: O
Solvent: C1CCOC1
Product: CC(Sc1nccn1C)c1cccc2cc(-c3nccs3)[nH]c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 88.7 %

Procedure:
A solution of 1-[2-(1,3-thiazol-2-yl)-1H-indol-7-yl]ethanol (0.089 g), 1-methyl-1H-imidazole-2-thiol (0.046 g) and tributylphosphine (0.458 g) in tetrahydrofuran (7 mL) was stirred, 1,1′-(azodicarbonyl)dipiperidine (0.584 g) was added, and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70-70:30) to give the title compound (0.110 g, yield 89%) as colorless crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][C:10](=[N:12][OH:13])[NH2:11].[CH:14]1([CH2:17]Br)[CH2:16][CH2:15]1.CC(C)([O-])C.[K+].P([O-])(O)(O)=O.[Na+]>CN(C)C=O>[CH:14]1([CH2:17][C:4]2([Cl:8])[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]2[CH2:9][C:10](=[N:12][OH:13])[NH2:11])[CH2:16][CH2:15]1
Reactant: BrCC1CC1
Reactant: NC(Cc1c(Cl)cccc1Cl)=NO
Agent: CC(C)(C)[O-]
Agent: O=P([O-])(O)O
Agent: [K+]
Solvent: CN(C)C=O
Product: NC(CC1C(Cl)=CC=CC1(Cl)CC1CC1)=NO
Temperature: -20 °C
Reaction time: 1 h

Procedure:
10.0 g (46 mmol) of (2,6-dichlorophenyl)acetamidoxime in 40 ml of dimethylformamide were admixed with 6.5 g (48 mmol) of cyclopropylmethyl bromide. The mixture was cooled to −20° C. and admixed dropwise with 5.4 g (48 mmol) of potassium tert-butoxide in 20 ml of dimethylformamide. The mixture was stirred at −20° C. for 1 h and then at room temperature overnight, poured into aqueous sodium dihydrogen phosphate buffer (pH 6) and extracted 5 times with diethyl ether. The combined extracts were washed twice with water and once with saturated sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. Yield: 12.3 g of a yellow oil which was reacted further without any further purification.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[C:8]([NH2:12])[C:9]([NH2:11])=[CH:10][C:5]=2[CH2:4][O:3][CH2:2]1.C(O[C:16]([S-])=[S:17])C.[K+].C(O)(=O)C>O>[NH:11]1[C:9]2[CH:10]=[C:5]3[CH2:4][O:3][CH2:2][O:1][C:6]3=[CH:7][C:8]=2[N:12]=[C:16]1[SH:17]
Reactant: CCOC(=S)[S-]
Reactant: Nc1cc2c(cc1N)OCOC2
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: Sc1nc2cc3c(cc2[nH]1)COCO3
Reaction time: 1 h
Yield: 81.3 %

Procedure:
21.2 g of 1,3-benzodioxane-6,7-diamine was dissolved while heating in 300 ml of alcohol, then diluted with 75 ml of water, treated with 23.6 g of potassium ethylxanthate and boiled under reflux overnight. Subsequently, there were added thereto 300 ml of water and at 60°-70° C. 20 ml of glacial acetic acid. After stirring at this temperature for 1 hour, the suspension was cooled, suction filtered and washed with water. 21.6 g (81.2% of theory) of 1,8-dihydro-m-dioxino(5,4-f)benzimidazole-2-thiol of melting point 288°-289° C. were obtained.
Reaction SMILES: [CH2:1]([S:3]([C:6]1[N:10]=[CH:9][NH:8][N:7]=1)(=[O:5])=[O:4])[CH3:2].[CH2:11]([N:14]([CH2:18][CH:19]=[CH2:20])[C:15](Cl)=[O:16])[CH:12]=[CH2:13].O1CCCC1>C(N(CC)CC)C>[CH2:11]([N:14]([CH2:18][CH:19]=[CH2:20])[C:15]([N:8]1[CH:9]=[N:10][C:6]([S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])=[N:7]1)=[O:16])[CH:12]=[CH2:13]
Reactant: CCS(=O)(=O)c1nc[nH]n1
Reactant: C=CCN(CC=C)C(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C=CCN(CC=C)C(=O)n1cnc(S(=O)(=O)CC)n1

Procedure:
A mixture of 6.45 g. 3-ethylsulphonyl-1,2,4-triazole, 6.6 g. diallylcarbamoyl chloride, 25 ml. dry tetrahydrofuran and 8 ml. dry triethylamine was refluxed under anhydrous conditions for 1.5 hours. The cooled reaction mixture was filtered and the filtrate distilled under reduced pressure to remove solvent and give a product which distilled at 187°C./0.2 mm. This product solidified and was recrystallized from petroleum ether (b.p. 60° - 80°C.) to give 1-diallylcarbamoyl-3-ethylsulphonyl-1,2,4-triazole, m.p. 39° - 42°C. Elemental analysis satisfactory.
Reaction SMILES: [C@@H:1]1([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.CC(C)=O.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>O>[CH3:22][S:23]([O:4][C@@H:3]1[C@@H:5]([CH2:6][O:7][S:23]([CH3:22])(=[O:25])=[O:24])[O:8][C@@H:1]([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[CH2:2]1)(=[O:25])=[O:24]
Reactant: CS(=O)(=O)Cl
Reactant: Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Solvent: O
Solvent: CC(C)=O
Product: Cc1cn([C@H]2C[C@H](OS(C)(=O)=O)[C@@H](COS(C)(=O)=O)O2)c(=O)[nH]c1=O
Reaction time: 0.75 h
Yield: 98.1 %

Procedure:
To a dry, round-bottom flask purged with nitrogen was added thymidine (10.0 g, 0.0412 mole) and acetone (30 mL). The slurry was stirred and 3, 5-lutidine (17.7 g, 0.165 mole) was added. Then, methanesulfonyl chloride (13.8 g, 0.124 mole) was added over ten minutes with the temperature rising to 40° C. After 45 minutes, the reaction was complete and the thick slurry was diluted with 150 mL of water. The slurry was stirred for 25° C. for 30 minutes, and then cooled at 0°-5° C. for 30 minutes. The solids were collected, washed with water (80 mL) and isopropanol (40 mL), then dried to give 16.1 g (98.2%) of the title compound.
Reaction SMILES: [CH2:1]([N:8]([CH2:13][C@H:14]([OH:18])[CH2:15][O:16][CH3:17])[C@@H:9]([CH3:12])[CH2:10]Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+]>CN(C)C=O>[CH2:1]([N:8]1[C@@H:9]([CH3:12])[CH2:10][O:18][C@H:14]([CH2:15][O:16][CH3:17])[CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC[C@@H](O)CN(Cc1ccccc1)[C@@H](C)CCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC[C@@H]1CN(Cc2ccccc2)[C@@H](C)CO1
Temperature: 0 °C
Reaction time: 1 h
Yield: 52.3 %

Procedure:
A solution of (2S)-1-[N-benzyl-N-[(1S)-2-chloro-1-methylethyl]amino]-3-methoxy-2-propanol (1.90 g) in N,N-dimethylformamide (10 ml) was added to an ice-cooled suspension of sodium hydride (0.45 g, 60% in mineral oil) in N,N-dimethylformamide (10 ml) at 0° C. After being stirred for 1 hour at the same temperature, the mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified is by column chromatography on silica gel using mixed solvents of hexane and ethyl acetate (10:1). The fractions containing the objective compound were collected and evaporated under reduced pressure to give (2S,5S)-4-benzyl-2-methoxymethyl-5-methylmorpholine (0.86 g) as an oil.
Reaction SMILES: Br[C:2]1[C:3]2[CH2:4][CH2:5][N:6]([CH3:31])[C@@H:7]([C@@H:17]3[C:25]4[C:20](=[C:21]([O:28][CH3:29])[C:22]([O:26][CH3:27])=[CH:23][CH:24]=4)[C:19](=[O:30])[O:18]3)[C:8]=2[C:9]([O:15][CH3:16])=[C:10]2[O:14][CH2:13][O:12][C:11]=12.[N-:32]=[N+:33]=[N-:34].[Na+].[I-].[Na+]>CN(C=O)C>[N:32]([C:2]1[C:3]2[CH2:4][CH2:5][N:6]([CH3:31])[C@@H:7]([C@@H:17]3[C:25]4[C:20](=[C:21]([O:28][CH3:29])[C:22]([O:26][CH3:27])=[CH:23][CH:24]=4)[C:19](=[O:30])[O:18]3)[C:8]=2[C:9]([O:15][CH3:16])=[C:10]2[O:14][CH2:13][O:12][C:11]=12)=[N+:33]=[N-:34]
Reactant: [N-]=[N+]=[N-]
Reactant: COc1ccc2c(c1OC)C(=O)O[C@@H]2[C@H]1c2c(c(Br)c3c(c2OC)OCO3)CCN1C
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc2c(c1OC)C(=O)O[C@@H]2[C@H]1c2c(c(N=[N+]=[N-])c3c(c2OC)OCO3)CCN1C
Temperature: 80 °C
Reaction time: 15 h

Procedure:
To a solution of compound 2 (2.0 g, 4.063 mmol) in DMF (20 mL) were added sodium azide (2.641 g, 40.63 mmol) and sodium iodide (0.609 g, 4.063 mmol) and the reaction mixture was stirred at 80° C. for 15 h to attain completion. Then the solvent was removed in vacuo and the resultant residue was dissolved in chlorofrom (40 mL), washed with water (2×40 mL), dried over sodium sulfate and concentrated to obtain the titled compound 3, which was recrystallized with ethanol in hexane (10:90) to afford brown crystals. Yield, 89%; mp 177.2-178.1° C.; IR: 1529, 1362 cm−1; 1H NMR (CDCl3, 400 MHz): δ 7.05 (d, 1H, J=7.0 Hz), 6.4 (d, 1H, J=7.0 Hz), 6.01 (s, 2H), 5.85 (d, 1H, J=4.4 Hz), 4.40 (d, 1H, J=4.4 Hz), 4.15 (s, 3H), 3.88 (s, 3H), 3.84 (s, 3H), 2.75-2.62 (m, 2H), 2.60-2.56 (m, 2H), 2.51 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 169.2, 157.7, 152.6, 147.9, 142.2, 140.5, 135.0, 134.0, 123.5, 121.8, 119.7, 119.3, 114.1, 100.5, 87.4, 64.1, 56.7, 56.5, 56.2, 51.4, 39.2, 27.2; HRMS (ESI): m/z Calcd. for C22H23N4O7 (M+1), 455.4335; Found, 455.4452 (M+1).
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([N:15]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[CH3:32])[C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH:19]=[CH:18][CH:17]=3)=[CH:11][CH:10]=2)O1.Br[C:35]1[CH:40]=[N:39][C:38]([Br:41])=[CH:37][N:36]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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>[Br:41][C:38]1[N:39]=[CH:40][C:35]([C:9]2[CH:10]=[CH:11][C:12]([N:15]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[CH3:32])[C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH:19]=[CH:18][CH:17]=3)=[CH:13][CH:14]=2)=[N:36][CH:37]=1
Reactant: Cc1ccccc1N(c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)c1cccc2ccccc12
Reactant: Brc1cnc(Br)cn1
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: [K+]
Solvent: O
Solvent: C1COCCO1
Product: Cc1ccccc1N(c1ccc(-c2cnc(Br)cn2)cc1)c1cccc2ccccc12
Temperature: 80 °C
Yield: 75 %

Procedure:
A mixture of N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-N-(o-tolyl)naphthalen-1-amine (Compound 22) (0.55 g, 1.26 mmol), 2,5-dibromopyrazine (0.77 g, 3.0 mmol), Pd(PPh3)4 (0.1 g, 0.09 mmol), K2CO3 (0.414 g, 3 mmol) in dioxane/water (40 mL/8 mL) was degassed and heated at 80° C. overnight. The resulting mixture was worked up with ethyl acetate/brine, dried over Na2SO4, loaded on silica gel and purified by flash column using eluents of hexanes/dichloromethane 9:1 to 3:2. After removal of solvents, a yellow solid (Compound 23) was obtained, 0.44 g in 75% yield.
Reaction SMILES: Cl.[Br:2][C:3]1[CH:4]=[C:5]([CH2:9][NH2:10])[CH:6]=[CH:7][CH:8]=1.C[O-].[Na+].[CH2:14]([O:16][CH:17]([O:22][CH2:23][CH3:24])[C:18](=[NH:21])OC)[CH3:15]>CO>[Br:2][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][CH:8]=1)[CH2:9][NH:10][C:18](=[NH:21])[CH:17]([O:22][CH2:23][CH3:24])[O:16][CH2:14][CH3:15]
Reactant: CCOC(OCC)C(=N)OC
Reactant: NCc1cccc(Br)c1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CCOC(OCC)C(=N)NCc1cccc(Br)c1
Yield: 50.7 %

Procedure:
(3-Bromophenyl)methanamine hydrochloride (3.62 g, 15.64 mmol) and sodium methoxide (3.58 mL, 15.64 mmol) were added to a solution of methyl 2,2-diethoxyacetimidate (5.042 g, 31.3 mmol) in methanol (15 mL). The cloudy mixture was heated at 70 C for 1.5 h and the resulting yellow mixture was concentrated. The residue was purified by silica gel chromatography with 100% ethyl acetate. The desired fractions were concentrated to give a yellow viscous oil (2.5 g, 51%). LCMS:R.T.=2.11; [M+2]+=317.06.
Reaction SMILES: [Br:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:13]([OH:15])=O.[C:16](N1C=CN=C1)([N:18]1C=CN=C1)=O.CN>CN(C)C=O>[Br:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:13]([NH:18][CH3:16])=[O:15]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: O=C(O)c1cnn(-c2ccccc2)c1Br
Agent: CN
Solvent: CN(C)C=O
Product: CNC(=O)c1cnn(-c2ccccc2)c1Br
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 41.3 %

Procedure:
Three grams of 5-bromo-1-phenyl-1H-pyrazole-4-carboxylic acid and 2.6 g of carbonyldiimidazole were dissolved in 50 ml of dimethylformamide. The mixture was allowed to stir for 20 minutes and 7 ml of 40% aqueous methylamine was added to the reaction mixture. The mixture was stirred for 2 hours at room temperature and poured into ice water. The precipitated solid was collected by filtration and recrystallized from ethanol/water to afford 1.3 g of 5-bromo-1-phenyl-N-methyl-1H-pyrazole-4-carboxamide. Yield 42%. mp=157°-159° C.
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:12]1[C:44]([CH3:45])=[CH:43][C:15]2[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([C:25]4[CH:26]=[C:27]5[C:32](=[CH:33][CH:34]=4)[N:31]=[C:30](OS(C(F)(F)F)(=O)=O)[CH:29]=[CH:28]5)[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:46]1[CH:51]=[CH:50][C:49]([Cl:52])=[CH:48][CH:47]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:53][NH2:54]>C1COCC1>[C:1]([O:5][C@@H:6]([C:12]1[C:44]([CH3:45])=[CH:43][C:15]2[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([C:25]4[CH:26]=[C:27]5[C:32](=[CH:33][CH:34]=4)[N:31]=[C:30]([NH:54][CH3:53])[CH:29]=[CH:28]5)[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:46]1[CH:47]=[CH:48][C:49]([Cl:52])=[CH:50][CH:51]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]
Reactant: CN
Reactant: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccnc(-c4ccc5nc(OS(=O)(=O)C(F)(F)F)ccc5c4)c3)sc2c1-c1ccc(Cl)cc1
Solvent: C1CCOC1
Product: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccnc(-c4ccc5nc(NC)ccc5c4)c3)sc2c1-c1ccc(Cl)cc1

Procedure:
(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(2-(trifluoromethylsulfonyloxy)quinolin-6-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)acetate (28.0 mg, 0.036 mmol) and 1.0 mL of methylamine at 2M in THF were heating at 80° C. for 3 days. Concentrated in vacuo and then purified by flash column chromatography (silica gel, 0 to 100% ethyl acetate/hexanes) to give the desired product. LCMS-ESI+ (m/z): [M+H]+ calcd for C37H36ClN4O3S: 651.2; found: 651.3.
Reaction SMILES: [NH2:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([N:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][N:11]3[CH:19]=[CH:20][CH:21]=[C:10]3[CH2:9]2)=[O:7])=[CH:4][CH:3]=1.[Cl:24][C:25]1[C:33]([Cl:34])=[CH:32][C:31]([Cl:35])=[CH:30][C:26]=1[C:27](Cl)=[O:28]>>[CH:21]1[CH:20]=[CH:19][N:11]2[CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:8]([C:6]([C:5]3[CH:22]=[CH:23][C:2]([NH:1][C:27](=[O:28])[C:26]4[CH:30]=[C:31]([Cl:35])[CH:32]=[C:33]([Cl:34])[C:25]=4[Cl:24])=[CH:3][CH:4]=3)=[O:7])[CH2:9][C:10]=12
Reactant: O=C(Cl)c1cc(Cl)cc(Cl)c1Cl
Reactant: Nc1ccc(C(=O)N2Cc3cccn3Cc3ccccc32)cc1
Product: O=C(Nc1ccc(C(=O)N2Cc3cccn3Cc3ccccc32)cc1)c1cc(Cl)cc(Cl)c1Cl
Yield: 81.5 %

Procedure:
As described for Example 8, 0.50 g of 10,11-dihydro-10-(4-aminobenzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine is reacted with 0.483 g of 2,3,5-trichlorobenzoyl chloride to give a glass which is crystallized from ethyl acetate to give 0.686 g of crystals, m.p. 231°-234° C.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=CC=CC=2)[CH:3]=[CH:2]1.C([N:17]1[C:29]2[C:28]([OH:30])=[C:27]3[N:31](C(OC(C)(C)C)=O)[C:32]4[CH:33]=[CH:34][C:35]([Cl:38])=[CH:36][C:37]=4[C:26]3=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[C:21]([Cl:46])[CH:22]=2)(OC(C)(C)C)=O>>[Cl:38][C:35]1[CH:36]=[C:37]2[C:32](=[CH:33][CH:34]=1)[NH:31][C:27]1[C:28]([O:30][C@@H:3]3[CH2:4][CH2:9][NH:1][CH2:2]3)=[C:29]3[NH:17][C:18]4[CH:19]=[CH:20][C:21]([Cl:46])=[CH:22][C:23]=4[C:24]3=[CH:25][C:26]2=1
Reactant: c1ccc2[nH]ccc2c1
Reactant: CC(C)(C)OC(=O)n1c2ccc(Cl)cc2c2cc3c4cc(Cl)ccc4n(C(=O)OC(C)(C)C)c3c(O)c21
Product: Clc1ccc2[nH]c3c(O[C@@H]4CCNC4)c4[nH]c5ccc(Cl)cc5c4cc3c2c1

Procedure:
The title compound was prepared in a manner analogous to Example 28 except the starting indole is 5,7-diBOC-2,10-dichloro-6-hydroxyindolo[2,3-b]carbazole and the reagent is (R)-tent-butyl 3-hydroxypyrrolidine-1-carboxylate. 1H-NMR (400 MHz, CD3OD) δ ppm 8.51 (s, 1H), 8.14-8.11 (m, 2H), 7.44 (dd, J=8.4, 0.6 Hz, 2H), 7.31 (dd, J=8.4, 2.2 Hz, 2H), 5.41 (t, J=4.6 Hz, 1H), 3.91-3.72 (m, 2H), 3.56-3.45 (m, 2H), 2.48-2.40 (m, 1H), 1.28-1.16 (m, 1H); MS (ESI) m/z 408.2 (M−H)−; MS (ESI) m/z 410.1 (M+H)+
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].C[O:8][C:9]([CH:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[NH:12]1)=O.[OH-].[Na+].O>C1COCC1.C(OCC)C>[OH:8][CH2:9][CH:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[NH:12]1
Reactant: COC(=O)C1Cc2ccccc2N1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: O
Product: OCC1Cc2ccccc2N1
Yield: 95.9 %

Procedure:
To a suspension of LiAlH4 (4.65 g, 0.122 mol) in THF (100 mL) was added dropwise 2-methoxycarbonylindoline (10.85 g, 0.0613 mol) in THF 260 mL at room temperature. The mixture was refluxed for 3.5 h and then excess reagent was decomposed by addition of aqueous THF. To the mixture was added 1N aqueous NaOH (50 mL), water (100 mL), and diethyl ether (100 mL), successively. The organic layer was separated, washed with brine, dried over magnesium sulfate, and concentrated to give 8.77 g of 2-hydroxymethylindoline (96%): 1H NMR (270 MHz, CDCl3) δ7.08 (d, 1H, J=7 Hz), 7.02 (t, 1H, J=7 Hz), 6,71 (t, 1H, J=7 Hz), 6.64 (d, 1H, J=7 Hz), 4.02 (m, 1H), 3.70 (dd, 1H, J=11, 4 Hz), 3.56 (dd, 1H, J=11, 7 Hz), 3.09 (dd, 1H, J=16, 9 Hz), 2.81 (dd, 1H, J=16, 8 Hz).
Reaction SMILES: [CH3:1][CH2:2][C:3]([CH2:5][CH2:6]/[CH:7]=[C:8](/[CH2:10][CH2:11][CH:12]=[C:13]([CH3:15])[CH3:14])\[CH3:9])=[CH2:4].[C:16]([C:18]([CH3:20])=[O:19])#[CH:17]>>[C:18]([CH:16]1[CH2:17][CH:4]=[C:3]([CH2:5][CH2:6][CH:7]=[C:8]([CH3:9])[CH2:10][CH2:11][CH:12]=[C:13]([CH3:14])[CH3:15])[CH2:2][CH2:1]1)(=[O:19])[CH3:20]
Reactant: C#CC(C)=O
Reactant: C=C(CC)CC/C=C(\C)CCC=C(C)C
Product: CC(=O)C1CC=C(CCC=C(C)CCC=C(C)C)CC1
Temperature: 150 °C
Yield: 50 %

Procedure:
The (E)-β-farnesene-containing product of Example 1 (6.0 g) and methyl ethynyl ketone (1.5 g) are heated together at 150° C. for 16 hours. The mixture is then distilled under reduced pressure to give 1-acetyl-4-(4,8-dimethyl-3,7-nonadienyl)-cyclohex-4-ene as a pale yellow oil (2.3 g, 50%); b.p. 130°-140° C./0.2τ, nD20 1.4998; M+ (m/z as % of base peak): 274 (3.0; δ(CCl4) 1.70 (m, 9H), 2.00-2.80 (m, 15H), 2.22 (s, 3H), 5.20 (m, 2H), 5.50 (br, t, 1H).
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([Cl:11])[C:3]=1[S:12](Cl)(=[O:14])=[O:13].[CH2:16]([NH2:18])[CH3:17].C(N(CC)CC)C>>[CH2:16]([NH:18][S:12]([C:3]1[C:4]([Cl:11])=[CH:5][CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]=1[Cl:1])(=[O:14])=[O:13])[CH3:17]
Reactant: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)Cl)c1Cl
Reactant: CCN
Solvent: CCN(CC)CC
Product: CCNS(=O)(=O)c1c(Cl)ccc([N+](=O)[O-])c1Cl
Yield: 74.2 %

Procedure:
Following the general procedure for sulfonamide formation outlined in example 15, 2,6-dichloro-3-nitrobenzenesulfonyl chloride (800 mg, 2.75 mmol), ethylamine (4.13 mL, 8.26 mmol) and triethylamine(1.5 mL, 8.36 mmol) were reacted to form the desired product (610 mg, 74%). 1H NMR (MeOD-d4): δ 7.92 (d, 1H), 7.78 (d, 1H), 3.08 (q, 2H), 1.11 (t, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:48]=[CH:47][CH:46]=[CH:45][C:3]=1[C:4]([C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=1[N:13]([CH:28]=[N:29][NH:30][C:31](=O)[CH2:32][N:33]1[C:41](=[O:42])[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34]1=[O:43])C(=O)CN1C(=O)C2C(=CC=CC=2)C1=O)=[O:5].FC(F)(F)C(O)=O>>[Cl:1][C:2]1[CH:48]=[CH:47][CH:46]=[CH:45][C:3]=1[C:4](=[O:5])[C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=1[N:13]1[CH:28]=[N:29][N:30]=[C:31]1[CH2:32][N:33]1[C:41](=[O:42])[C:40]2=[CH:39][CH:38]=[CH:37][CH:36]=[C:35]2[C:34]1=[O:43]
Reactant: O=C(CN1C(=O)c2ccccc2C1=O)NN=CN(C(=O)CN1C(=O)c2ccccc2C1=O)c1ccc(Cl)cc1C(=O)c1ccccc1Cl
Solvent: O=C(O)C(F)(F)F
Product: O=C(c1ccccc1Cl)c1cc(Cl)ccc1-n1cnnc1CN1C(=O)c2ccccc2C1=O

Procedure:
In the manner given in Example 7, 1,3-dioxo-2-isoindolineacetic acid, [[N-[2-(o-chlorobenzoyl)-4-chlorophenyl]1,3-dioxo-2-isoindolineacetamido]methylene]hydrazide is heated to 100°-110°C with trifluoroacetic acid to give 2',5-dichloro-2-[3-(phthalimidomethyl)-4H-1,2,4-triazol-4-yl]benzophenone.
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[CH2:4][NH:3][C:2]1=[O:11].C(=O)(O)[O-].[Na+].Cl[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19].Cl>O>[C:18]([N:8]1[CH2:7][CH2:6][C:5]2([O:1][C:2](=[O:11])[NH:3][CH2:4]2)[CH2:10][CH2:9]1)([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19]
Reactant: O=C1NCC2(CCNCC2)O1
Reactant: O=C(Cl)OCc1ccccc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: O=C1NCC2(CCN(C(=O)OCc3ccccc3)CC2)O1
Reaction time: 18 h
Yield: 81.5 %

Procedure:
To a mixture of 9.5 g 1-oxa-3,8-diazaspiro[4.5]decan-2-one and 75 ml water, at 0°, are added 6.3 g sodium bicarbonate and 10.9 g benzyl chloroformate. The mixture is stirred 18 hours at 0°, acidified with 10 N hydrochloric acid and stirred four hours at room temperature. The mixture is extracted with three 50 ml portions of dichloromethane. Removal of solvent affords 14.4 g 8-carbobenzyloxy-1-oxa-3,8-diazaspiro[4.5]decan-2-one, mp 126°-128°.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:9][CH:10]([O:13][CH3:14])[O:11][CH3:12])=[C:6]([NH2:8])[CH:7]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][C:25](=O)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([NH:8][C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[CH2:9][CH:10]([O:13][CH3:14])[O:11][CH3:12])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: COC(Cc1ccc(Cl)cc1N)OC
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Product: COC(Cc1ccc(Cl)cc1NC1CCN(C(=O)OC(C)(C)C)CC1)OC
Reaction time: 5 h
Yield: 40.6 %

Procedure:
To a stirred solution of 2 g of 5-chloro-2-(2,2-dimethoxy-ethyl)-phenylamine, (9.27 mmol) in 50 mL of acetic acid was added 3.7 g of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (18.5 mmol). The reaction mixture was allowed to stir for 1 h at room temperature before the portion wise addition of 5.9 g of sodium triacetoxyborohydride (27.9 mmol). The reaction mixture was allowed to stir an additional 5 h before removing the solvent under reduced pressure. The crude product was partitioned between CH2Cl2 (250 mL) and water. The aqueous layer was further extracted with CH2Cl2 (2×75 mL). The combined organic layers were then washed with 1 N NaOH (2×50 mL), brine, dried over Na2SO4, and concentrated. Purification by chromatography (silica, 10-25% EtOAc/hexanes) afforded 1.5 g (71%) of desired product. TLC (silica, 35% EtOAc/hexanes): Rf=0.49. MS (electrospray): exact mass calculated for C20H31ClN2O4, 398.20. m/z found, 399.2 [M+H]+. 1H NMR (CDCl3, 400 MHz): 6.94 (d, J=7.83 Hz, 1H), 6.61 (dd, J=7.83, 2.02 Hz, 1H), 6.57 (d, J=2.02 Hz, 1H), 4.87 (br s, 1H), 4.40 (t, J=5.31 Hz, 1H), 3.97 (br m, 2H), 3.36 (s, 6H), 3.02 (m, 2H), 2.78 (d, J=5.05 Hz, 2H), 2.00 (m, 2H), 1.47 (s, 9H), 1.37 (m, 2H).