Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[N:2](C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:24])([F:23])[F:22])[CH:15]=2)[N:8]=1)=O.[F:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33]N)=[CH:29][CH:28]=1>>[F:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[C:5]([C:7]3[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:24])([F:23])[F:22])[CH:15]=4)[N:8]=3)=[CH:4][CH:3]=[N:2]2)=[CH:29][CH:28]=1
Reactant: CN(C)/C=C/C(=O)c1nn(-c2cccc(OC(F)(F)F)c2)ccc1=O
Reactant: NNc1ccc(F)cc1
Product: O=c1ccn(-c2cccc(OC(F)(F)F)c2)nc1-c1ccnn1-c1ccc(F)cc1

Procedure:
Reaction of 3-((E)-3-dimethylamino-acryloyl)-1-(3-trifluoromethoxy-phenyl)-1H-pyridazin-4-one (A-6) and (4-fluoro-phenyl)-hydrazine according to example 43 gave the desired product. MS: M=416.9 (M+H)+
Reaction SMILES: Cl[C:2]1[C:7]2[O:8][CH2:9][CH2:10][CH2:11][O:12][C:6]=2[CH:5]=[C:4]([CH2:13][NH:14][CH2:15][CH:16]([CH3:18])[CH3:17])[CH:3]=1.[C:19]1([NH:25][CH:26]2[CH2:30][CH2:29][CH:28]([C:31]([OH:33])=O)[CH2:27]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.Cl.C(N=C=NCCCN(C)C)C.O>CN(C1C=CN=CC=1)C.ClCCl>[O:8]1[C:7]2[CH:2]=[CH:3][C:4]([CH2:13][N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:31]([CH:28]3[CH2:29][CH2:30][CH:26]([NH:25][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH2:27]3)=[O:33])=[CH:5][C:6]=2[O:12][CH2:11][CH2:10][CH2:9]1
Reactant: CC(C)CNCc1cc(Cl)c2c(c1)OCCCO2
Reactant: O=C(O)C1CCC(Nc2ccccc2)C1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: O
Solvent: ClCCl
Product: CC(C)CN(Cc1ccc2c(c1)OCCCO2)C(=O)C1CCC(Nc2ccccc2)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The mixture of N-(9-chloro-3,4-dihydro-2H-1,5-benzodioxepin-7-ylmethyl)-2-methylpropan-1-amine (17 mg), 3-phenylaminocyclopentanecarboxylic acid (15 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (20 mg), and N,N-dimethyl-4-aminopyridine (12 mg) in 5 ml dichloromethane was stirred at room temperature overnight. After addition of water (5 mL), the mixture was extracted with ethyl acetate (10 ml×2). The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Preparative thin layer chromatography on silica (33% ethyl acetate in hexane) gave the product as a resin: MS (m+1)=423.3; H NMR (500 MHz, CDCl3) 0.95 (m, 6H), 1.30 (m, 4H), 1.75 (m, 2H), 1.90 (m, 1H), 1.95 (m, 1H), 2.15 (m, 1H), 2.30 (m, 1H), 2.65 (m, 2H), 3.00 (m, 1H), 4.00 (m, 2H), 4.40 (m, 2H), 4.15 (m, 4H), 5.20 (s, 1H), 6.6-6.8 (m, 3H), 7.1-7.6 (m, 5H).
Reaction SMILES: [NH2:1][CH:2]1[C:8](=[O:9])[N:7]([CH3:10])[C:6]2[CH:11]=[CH:12][CH:13]=[CH:14][C:5]=2[C:4]2[CH:15]=[CH:16][CH:17]=[CH:18][C:3]1=2.[CH3:19][CH:20]([C:24]([NH:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=1)=[O:25])[C:21](O)=[O:22]>>[F:34][C:30]1[CH:29]=[C:28]([CH:33]=[CH:32][CH:31]=1)[CH2:27][NH:26][C:24](=[O:25])[CH:20]([CH3:19])[C:21]([NH:1][CH:2]1[C:8](=[O:9])[N:7]([CH3:10])[C:6]2[CH:11]=[CH:12][CH:13]=[CH:14][C:5]=2[C:4]2[CH:15]=[CH:16][CH:17]=[CH:18][C:3]1=2)=[O:22]
Reactant: CN1C(=O)C(N)c2ccccc2-c2ccccc21
Reactant: CC(C(=O)O)C(=O)NCc1cccc(F)c1
Product: CC(C(=O)NCc1cccc(F)c1)C(=O)NC1C(=O)N(C)c2ccccc2-c2ccccc21

Procedure:
The title compound, MS: m/e=446.2 (M+H+), was prepared in analogy to example 16 from 7-amino-5-methyl-5H,7H-dibenzo[b,d]azepin-6-one and 2-methyl-N-(3-fluoro-benzyl)-malonamic acid.
Reaction SMILES: Cl[S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)(=[O:4])=[O:3].[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1>ClCCl>[O:18]1[CH2:19][CH2:20][N:15]([S:2]([C:5]2[CH:6]=[C:7]3[C:11](=[CH:12][CH:13]=2)[NH:10][C:9](=[O:14])[CH2:8]3)(=[O:4])=[O:3])[CH2:16][CH2:17]1
Reactant: O=C1Cc2cc(S(=O)(=O)Cl)ccc2N1
Reactant: C1COCCN1
Solvent: ClCCl
Product: O=C1Cc2cc(S(=O)(=O)N3CCOCC3)ccc2N1
Temperature: 25 °C
Reaction time: 3 h
Yield: 74.9 %

Procedure:
A suspension of 2.3 g of 5-chlorosulfonyl-2-oxindole and 2.2 g of morpholine in 50 mL of dichloromethane was stirred at room temperature for 3 hours. The white precipitate was collected by vacuum filtration, washed with ethyl acetate and hexane and dried under vacuum at 40° C. overnight to give 2.1 g (74% yield) of 5-(morpholinosulfonyl)-2-oxindole.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][C:12]1([S:15]([N:18]2[CH2:21][CH:20]([OH:22])[CH2:19]2)(=[O:17])=[O:16])[CH2:14][CH2:13]1.C(N(CC)CC)C>C(Cl)Cl>[CH3:11][C:12]1([S:15]([N:18]2[CH2:19][C:20](=[O:22])[CH2:21]2)(=[O:17])=[O:16])[CH2:14][CH2:13]1
Reactant: CC1(S(=O)(=O)N2CC(O)C2)CC1
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: ClCCl
Product: CC1(S(=O)(=O)N2CC(=O)C2)CC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of oxalyl chloride (59 μL, 0.69 mmol) in methylene chloride (1.5 mL) at −78° C. was added dimethyl sulfoxide (0.10 mL, 1.5 mmol) slowly dropwise. The reaction was stirred for 15 minutes following complete addition. A solution of 1-[(1-methylcyclopropyl)-sulfonyl]azetidin-3-ol (64 mg, 0.33 mmol) in methylene chloride (1.0 mL) was added dropwise and the reaction mixture was stirred for 45 min at −60° C. Triethylamine (0.28 mL, 2.0 mmol) was added dropwise and the reaction was stirred for 15 minutes and the bath was removed and the solution allowed to warm to ambient temperature. The solvent was removed in vacuo and ethyl acetate was added. The solution was washed sequentially with saturated sodium bicarbonate solution, water and brine, dried over sodium sulfate, decanted and concentrated. The crude product was used without further purification in Step 6.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[Br:15][C:16]1[N:17]=[CH:18][NH:19][CH:20]=1.O>CN(C=O)C>[Br:15][C:16]1[N:17]=[CH:18][N:19]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH:20]=1
Reactant: Clc1ccnc(Cl)n1
Reactant: Brc1c[nH]cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Clc1nccc(-n2cnc(Br)c2)n1
Temperature: 0 °C
Yield: 23.1 %

Procedure:
To a solution of 2,4-dichloropyrimidine (0.447 g, 3 mmol) in anhydrous DMF (4 ml) was added potassium carbonate (0.415 g, 3 mmol). The reaction mixture was cooled (0° C.) under an inert atmosphere before the addition of 4-bromo-1-H-imidazole (0.441 g, 3 mmol) as solution in DMF (2 ml). The reaction was then allowed to stir at this temperature for a further 3 hours whereupon water (3 ml) was added. The resultant white precipitate was removed from the mixture by filtration and washed with water before being dried to give the title compound as a white solid (0.18 g, 23%) which was suitably pure to be used without further purification. m/z (LC-MSW, ESP):259.2,261.2 (bromine isotopes) [M+H]+, R/T=3.47 mins.
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH:13][CH3:14])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:27][CH2:28][C:29]1([OH:37])[CH:34]2[CH2:35][CH2:36][N:31]([CH2:32][CH2:33]2)[CH2:30]1.CN(C)C=O>O1CCCC1>[Cl:1][C:2]1[C:3]([NH:13][CH3:14])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([NH:27][CH2:28][C:29]1([OH:37])[CH:34]2[CH2:33][CH2:32][N:31]([CH2:36][CH2:35]2)[CH2:30]1)=[O:9]
Reactant: NCC1(O)CN2CCC1CC2
Reactant: CNc1cc(OC)c(C(=O)O)cc1Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CNc1cc(OC)c(C(=O)NCC2(O)CN3CCC2CC3)cc1Cl
Reaction time: 1 h
Yield: 53.9 %

Procedure:
A solution of 5-chloro-2-methoxy-4-(methylamino)benzoic acid (3.02 g, 0.014 mole) in anhydrous tetrahydrofuran (15 ml) under nitrogen was treated with 1,1'-carbonyldiimidazole (2.35 g, 0.0145 mole) and stirred for one hour. A solution/suspension of 3-aminomethyl-1-azabicyclo[2.2.2]octan-3-ol (2.34 g, 15 mole) in tetrahydrofuran (15 ml) containing a little N,N-dimethylformamide for solubility was added slowly over a few minutes, and the mixture was stirred overnight (18 hours) at room temperature and for one hour at 60° C., then concentrated in vacuo. The white solid was partitioned between 1.0N sodium carbonate (100 ml) and methylene chloride (200 ml) containing a little methanol, and the organic layer was separated. The aqueous solution was extracted with methylene chloride (2×50 ml) containing a little methanol, and the combined organic solution was dried (sodium sulfate) and passed through a short column of alumina (eluted with 10% methanol/methylene chloride). The filtrate was concentrated in vacuo, triturated from ether, and triturated from acetonitrile to afford 2.67 g (54%) of the title compound as a colorless solid; mp 236°-237° C. (dec).
Reaction SMILES: [SH:1][C:2]1[N:3]([CH3:12])[C:4](=[O:11])[C:5]2[S:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[OH-].[Na+].CN(C=O)C.[Cl:20][C:21]1[CH:36]=[CH:35][C:24]([C:25]([C:27]2[CH:34]=[CH:33][C:30]([CH2:31]Br)=[CH:29][CH:28]=2)=[O:26])=[CH:23][CH:22]=1>C(O)C.O>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([C:25]([C:27]2[CH:34]=[CH:33][C:30]([CH2:31][S:1][C:2]3[N:3]([CH3:12])[C:4](=[O:11])[C:5]4[S:10][CH:9]=[CH:8][C:6]=4[N:7]=3)=[CH:29][CH:28]=2)=[O:26])=[CH:35][CH:36]=1
Reactant: O=C(c1ccc(Cl)cc1)c1ccc(CBr)cc1
Reactant: Cn1c(S)nc2ccsc2c1=O
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: CN(C)C=O
Solvent: O
Product: Cn1c(SCc2ccc(C(=O)c3ccc(Cl)cc3)cc2)nc2ccsc2c1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 69.6 %

Procedure:
To a solution of 2-mercapto-3-methylthieno[3,2-d]pyrimidin-4-(3H)-one (1.0 g) and sodium hydroxide (205 mg) in 50% ethanol (12 ml)-DMF (20 ml) was added 4-(4-chlorobenzoyl)benzyl bromide (1.56 g) and the mixture was stirred at room temperature for 1 hour. This reaction mixture was poured in water and the resulting crystals were collected by filtration, rinsed with water and methanol, and recrystallized from methanol to provide the title compound as colorless solid (1.497 g) . 1H-NMR (CDCl3) δ: 3.61(3H,s), 4.58(2H,s), 7.23(1H,d,J=5.2Hz), 7.45(2H,d,J=8.6Hz), 7.59(2H,d,J=8.2Hz), 7.70-7.80(5H,m).
Reaction SMILES: F[C:2]1[CH:17]=[CH:16][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=2)=[O:7])=[CH:4][C:3]=1[N+:18]([O-:20])=[O:19].[OH-].[K+].[C:23]([O:27][C:28](=[O:37])[NH:29][C:30]1[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=1)([CH3:26])([CH3:25])[CH3:24]>CS(C)=O.O>[C:23]([O:27][C:28](=[O:37])[NH:29][C:30]1[CH:31]=[CH:32][C:33]([O:36][C:2]2[CH:17]=[CH:16][C:5]([C:6](=[O:7])[NH:8][C:9]3[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=3)=[CH:4][C:3]=2[N+:18]([O-:20])=[O:19])=[CH:34][CH:35]=1)([CH3:26])([CH3:24])[CH3:25]
Reactant: Cc1ccc(NC(=O)c2ccc(F)c([N+](=O)[O-])c2)cc1
Reactant: CC(C)(C)OC(=O)Nc1ccc(O)cc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: Cc1ccc(NC(=O)c2ccc(Oc3ccc(NC(=O)OC(C)(C)C)cc3)c([N+](=O)[O-])c2)cc1
Temperature: 80 °C

Procedure:
To the product from Example 86B (1.77 g, 5.45 mmol), KOH (736 mg, 12.9 mmol), and (4-Hydroxy-phenyl)-carbamic acid tert-butyl ester (1.35 g, 6.45 mmol) were dissolved in DMSO and heated to 80° C. for 2 hrs. At this time the reaction mixture was cooled to room temperature and diluted with water. The title compound was then collected by filtration (380 mg, 12.7%).
Reaction SMILES: [CH:1]([Mg]Br)=[CH2:2].[N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][CH:6]=1.[Cl:15][C:16]1[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[CH:18][CH:17]=1>>[Cl:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]([N:5]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]=[CH:7][CH:6]2[CH:1]=[CH2:2])=[O:21])=[CH:18][CH:17]=1
Reactant: c1ccc2ncccc2c1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Reactant: C=C[Mg]Br
Product: C=CC1C=Cc2ccccc2N1C(=O)c1ccc(Cl)cc1
Temperature: 40 °C
Reaction time: 1 h

Procedure:
A solution of vinyl magnesium bromide (4.65 mL in 1M THF solution) under nitrogen gas at ambient conditions is treated with quinoline dropwise. The reaction mixture is warmed to 40° C. and stirred for 1 h. The reaction mixture is then allowed to attain ambient conditions and 4-chlorobenzoyl chloride (591 μL) is then added dropwise and reaction mixture stirred overnight. The reaction mixture is then cooled to 0° C. and quenched with saturated aqueous ammonium chloride solution. The reaction mixture is then partitioned between diethyl ether and water and the organic layer is washed successively with 1N hydrochloric acid and 1N sodium hydroxide solution and then dried over sodium sulfate. The organic solvent is removed under reduced pressure and the crude product is purified by liquid chromatography (gradient elution of acetonitrile (0.02% trifluoroacetic acid/water (0.02% trifluoroacetic acid) through a reverse phase. (M+H)+−296.
Reaction SMILES: Br[C:2]1[C:9]([O:10][CH3:11])=[C:8]([O:12][CH3:13])[C:7]([O:14][CH3:15])=[CH:6][C:3]=1[CH:4]=[O:5].[CH3:16][S:17]([O:20][C:21]1[C:26]([O:27][CH3:28])=[CH:25][CH:24]=[C:23](Br)[C:22]=1[CH:30]=[O:31])(=[O:19])=[O:18]>CN(C=O)C.C(OCC)(=O)C.[Cu]>[CH3:16][S:17]([O:20][C:21]1[C:22]([CH:30]=[O:31])=[C:23]([C:2]2[C:3]([CH:4]=[O:5])=[CH:6][C:7]([O:14][CH3:15])=[C:8]([O:12][CH3:13])[C:9]=2[O:10][CH3:11])[CH:24]=[CH:25][C:26]=1[O:27][CH3:28])(=[O:19])=[O:18]
Reactant: COc1cc(C=O)c(Br)c(OC)c1OC
Reactant: COc1ccc(Br)c(C=O)c1OS(C)(=O)=O
Agent: [Cu]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1ccc(-c2c(C=O)cc(OC)c(OC)c2OC)c(C=O)c1OS(C)(=O)=O
Temperature: 165 °C
Reaction time: 3 h
Yield: 43.7 %

Procedure:
To a suspension of copper bronze (0.646 g, 10 mmol) in anhydrous DMF (2 mL) was added a solution of 2-bromo-3,4,5-trimethoxybenzaldehyde (0.80 g, 2.91 mmol) and 3-bromo-2-formyl-6-methoxyphenyl methanesulfonate (0.30 g, 0.97 mmol) in anhydrous DMF (1 mL) and the suspension was stirred at 165° C. for 3 hours. TLC indicated the presence of unreacted 3-bromo-2-formyl-6-methoxyphenyl methanesulfonate and a further portion of 2-bromo-3,4,5-trimethoxybenzaldehyde (100 mg) was added. After a further 1 hour at 165° C. the reaction was complete and the reaction mixture was cooled and diluted with ethyl acetate (20 mL). The resulting suspension was filtered through Celite® (3 g) and the filtrate concentrated in vacuo. The residue was chromatographed over silica gel (70 g), eluting with hexane-ethyl acetate (gradient 2:1 to 1:1), followed by crystallisation (ethyl acetate) yielded 2,6′-diformyl-4,2′,3′,4′-tetramethoxybiphenyl-3-yl methanesulfonate (180 mg, 44%); m.p. 130-131° C.; Elemental Analysis Found: C, 53.7; H, 4.8; S, 7.8 (C19H20O9S requires C, 53.77; H, 4.75; S, 7.56%); NMR Spectrum δH (300 MHz, CDCl3) 10.18 (1H, s, 2-CHO), 9.63 (1H, s, 6′-CHO), 7.36 (1H, s, 5′-H), 7.26 (1H, d, J 8.4 Hz, 6-H), 7.15 (1H, d, J 8.4 Hz, 5-H), 4.03 (3H, s, OCH3), 3.98 (3H, s, OCH3), 3.57 (3H, s, OCH3), 3.43 (3H, s, SCH3); NMR Spectrum δC (100 MHz, CDCl3) 50.2, 56.5, 56.9, 61.2, 61.5, 106.2, 116.8, 127.5, 130.0, 130.7, 131.0, 132.1, 139.8, 147.6, 151.1, 152.6, 154.0, 189.3, 190.5; νmax/cm−1 (thin film) 2934, 2843, 1701, 1682, 1588, 1561, 1480, 1371, 1336, 1285, 1169, 1111, 1072; m/z (ES) 447 (MNa+, 100%), 379 (5); Rf (hexane-ethyl acetate 1:2) 0.20.
Reaction SMILES: N12CCCCC1C=NCCC2.[CH3:12][C:13]1([CH3:26])[O:17][C:16]2[C:18]([S:22](=[O:25])(=[O:24])[NH2:23])=[CH:19][CH:20]=[CH:21][C:15]=2[CH2:14]1.[CH3:27][N:28]=[C:29]=[O:30].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O>[CH3:12][C:13]1([CH3:26])[O:17][C:16]2[C:18]([S:22]([NH:23][C:29]([NH:28][CH3:27])=[O:30])(=[O:25])=[O:24])=[CH:19][CH:20]=[CH:21][C:15]=2[CH2:14]1
Reactant: CC1(C)Cc2cccc(S(N)(=O)=O)c2O1
Reactant: CN=C=O
Agent: C1=NCCCN2CCCCC12
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CNC(=O)NS(=O)(=O)c1cccc2c1OC(C)(C)C2
Reaction time: 2 h
Yield: 89.5 %

Procedure:
6.54 ml of 1,5-diazabicyclo(5,4,0)undec-5-ene are added to 9.9 g (0.0436 mole) of 2,3-dihydro-2,2-dimethyl-7-sulfamoylbenzo[b]furan (compound 1.4) in dioxan. While cooling with ice, 2.65 ml of methyl isocyanate are added dropwise. The reaction mixture is stirred for 2 hours at 20° to 25° C., then diluted with water, neutralised with 10 ml of 5% sodium carbonate solution, and filtered. Acidification of the filtrate yields 11.1 g (89.5% of theory) of N-(2,3-dihydro-2,2-dimethylbenzo[b]furan-7-ylsulfonyl)-N'-methylurea.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:13]=[CH:12][S:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[I:14]N1C(=O)CCC1=O.CCCCCC.CCOC(C)=O>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:13]=[CH:12][S:11][C:10]=1[I:14])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C1CCC(=O)N1I
Reactant: CC(C)(C)OC(=O)Nc1ccsc1
Solvent: CCCCCC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)Nc1ccsc1I
Reaction time: 0.33 h
Yield: 92.3 %

Procedure:
In a manner analogous to Campaigne, E. and Monroe, P. A. J.A.C.S., 76, 2447-2450 (1954), to a boiling solution of (tert-butoxy)-N-(3-thienyl)carboxamide (21.0 g, 0.1 mol, preparation 5) in methylene chloride (400 mL) is added N-iodosuccinimide (23.7 g, 0.1 mol) in small portions. The heating bath is then set to 65° C. for 20 min. TLC (Hexane/AcOEt 9:1) shows complete consumption of starting material. The reaction is taken to room temperature, the solvent is evaporated and the crude is purified by flash chromatography (Silica gel-Hexane/EtOAc 9:1) to obtain 30.0 g (88%) of title compound as a white solid.
Reaction SMILES: [Cl:1]C1C=C2C(C=CN=C2)=CC=1F.[ClH:13].[NH:14]1[CH2:19][CH2:18][CH:17]([O:20][C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[CH:27]=[N:26][CH:25]=[CH:24]3)[CH2:16][CH2:15]1>>[ClH:1].[Cl:13][C:30]1[CH:29]=[C:28]2[C:23]([CH:24]=[CH:25][N:26]=[CH:27]2)=[CH:22][C:21]=1[O:20][CH:17]1[CH2:18][CH2:19][NH:14][CH2:15][CH2:16]1
Reactant: c1cc2cc(OC3CCNCC3)ccc2cn1
Reactant: Fc1cc2ccncc2cc1Cl
Agent: Cl
Product: Clc1cc2cnccc2cc1OC1CCNCC1

Procedure:
Starting from 7-Chloro-6-fluoro-isoquinoline (150), the title compound was prepared by the same synthetic route as for compound 124. Rt=0.66 min (Method #1), detected mass: 263.1/265.1 (M+H+).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[CH:10][NH:11]2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].CC(C)([O-])C.[K+].[NH2:20]Cl>CN(C=O)C.CCOCC>[CH3:1][S:2]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[CH:10][N:11]2[NH2:20])=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)c1ccc2cc[nH]c2c1
Reactant: NCl
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CS(=O)(=O)c1ccc2ccn(N)c2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 51 %

Procedure:
A solution of 6-methanesulfonyl-1H-indole (2.66 mmol) and potassium tert-butoxide (5.32 mmol) in DMF (15 mL) is stirred at rt under N2 for 2 h. 0.15 M NH2Cl in ether (26.6 mL) is added drop-wise for 15 minutes at rt and the reaction mixture is stirred at rt for 2 h. The reaction mixture is quenched with 10% Na2S2O3 aqueous solution, and extracted with ether (3×20 mL). The combined organic layer is washed with brine (20 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue is triturated with EtOAc to give 6-methanesulfonyl-indole-1-ylamine (270 mg, 51%) as a solid. MS: 211 (M+H); 1H NMR (300 MHz, CDCl3): δ 3.09 (s, 3H), 6.49 (d, H), 7.41 (m, H), 7.61 (d, H), 7.71 (d, H), 8.12 (s, H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[CH:6]=O.[C:13]([O-])(=O)C.[NH4+].[N+:18](C)([O-:20])=[O:19]>C(O)(=O)C>[CH3:1][O:2][C:3]1[C:4]([N+:18]([O-:20])=[O:19])=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[CH:6]=[CH2:13]
Reactant: CC(=O)[O-]
Reactant: COc1ccc(C=O)cc1OC
Reactant: C[N+](=O)[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Product: C=Cc1ccc(OC)c(OC)c1[N+](=O)[O-]

Procedure:
207.0 g of 3,4-dimethoxybenzaldehyde, 100.0 g of ammonium acetate and 125 ml of nitromethane are heated to boiling for 34 h in 1.0 l of glacial acetic acid. After cooling in an ice bath, the precipitate is filtered off with suction, rinsed with glacial acetic acid and petroleum ether and dried. M.p.: 140-141° C.
Reaction SMILES: [CH3:1][N:2]([CH3:11])[CH2:3][CH2:4][NH:5][CH2:6][C:7]([CH3:10])([NH2:9])[CH3:8].C1N=CN([C:17](N2C=NC=C2)=[O:18])C=1.CO>C(Cl)Cl>[CH3:11][N:2]([CH3:1])[CH2:3][CH2:4][N:5]1[CH2:6][C:7]([CH3:8])([CH3:10])[NH:9][C:17]1=[O:18]
Reactant: CN(C)CCNCC(C)(C)N
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: CO
Solvent: ClCCl
Product: CN(C)CCN1CC(C)(C)NC1=O
Reaction time: 20 h
Yield: 1.8 %

Procedure:
To a solution of N1-(2-(dimethylamino)ethyl)-2-methylpropane-1,2-diamine (23.2 mmol) in CH2Cl2 (50 ml) was added CDI (4.51 g, 27.8 mmol). The solution was stirred for 20 h, concentrated in vacuo, the resulting residue suspended in 800 ml diethyl ether, washed with 3× 200 ml 1M Na2CO3, 200 ml sat. NaCl, dried on MgSO4, and concentrated in vacuo. Flash chromatography (2.5%→20% MeOH:CH2Cl2) afforded the title compound as a clear oil (79.3 mg, 0.428 mmol, 2%) as well as additional material heavily contaminated with imidazole g). 1H NMR (CDCl3, 400 MHz) δ 1.24 (s, 6H), 2.23 (s, 6H), 2.41 (m, 2H), 3.24 (s, 2H), 3.34 (m, 2H), 4.96 (s, 1H). ESI/APCI (pos) expected for C9H19N3O: 185.15. Found: 186 (MH+).
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=O.[NH:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1.O>C1(C)C=CC=CC=1>[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[N:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: O=C1Cc2ccccc2C1
Reactant: C1CCNC1
Solvent: O
Solvent: Cc1ccccc1
Product: C1=C(N2CCCC2)Cc2ccccc21

Procedure:
A mixture of 2-indanone (2.0 g, 15.1 mmol) and pyrrolidine (1.6 mL, 19.7 mmol) in anhydrous toluene (61 mL) was refluxed under nitrogen with azeotropic removal of water (Dean-Stark apparatus) for 2 h. The mixture was then cooled and concentrated to dryness in vacuo to give the title compound. MS:m/z=186.2 (M+1).
Reaction SMILES: [CH2:1]([N:8]1[C:20]2[CH:19]=[C:18]3[CH:21]=[CH:22][CH:23]=[CH:24][C:17]3=[C:16]([OH:25])[C:15]=2[C:14]2[C:13]([C:26]([NH2:28])=[O:27])=[CH:12][CH:11]=[CH:10][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:30][C:31]([O:33][CH3:34])=[O:32].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([N:8]1[C:20]2[CH:19]=[C:18]3[CH:21]=[CH:22][CH:23]=[CH:24][C:17]3=[C:16]([O:25][CH2:30][C:31]([O:33][CH3:34])=[O:32])[C:15]=2[C:14]2[C:9]1=[CH:10][CH:11]=[CH:12][C:13]=2[C:26](=[O:27])[NH2:28])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)CBr
Reactant: NC(=O)c1cccc2c1c1c(O)c3ccccc3cc1n2Cc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)COc1c2ccccc2cc2c1c1c(C(N)=O)cccc1n2Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.03 h
Yield: 53.7 %

Procedure:
40% Methanolic Triton B (0.378 mL, 0.832 mM) was added to a solution of 5-benzyl-11-hydroxy-5H-benzo[b]carbazole-1-carboxylic acid amide, (0.235 g, 0.64 mM) in 5 mL DMF at room temperature. After 2 minutes, methyl bromoacetate (0.125 mL, 0.202 g, 1.28 mM) was added and the resultant mixture stirred at room temperature for 2 h. Cesium carbonate (0.105 g, 0.32 mM) was then added as a solid, and the mixture allowed to stir at room temperature for an additional 1 h. The mixture was diluted with ethyl acetate, washed with H2O, 1N HCl, saturated aqueous NaHCO3 solution, and saturated brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting brown residue-was purified by column chromatography on silica gel (elution with ethyl acetate) to afford 0.151 g (53%) of the title compound (5-benzyl-1-carbamoyl-5H-benzo[b]carbazol-11-yloxy)-acetic acid, methyl ester as a brown foam (MP 120–125° C., MW 438.49).