Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1]/[N:2]=[C:3](\[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[O:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1)/[C:4]([NH:6][CH3:7])=[O:5].[C:22](=O)([O-])[O-].[K+].[K+].COS(OC)(=O)=O.O>CC(C)=O>[CH3:22][O:1]/[N:2]=[C:3](\[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[O:14][C:15]1[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=1)/[C:4]([NH:6][CH3:7])=[O:5]
Reactant: O=C([O-])[O-]
Reactant: CNC(=O)/C(=N/O)c1ccccc1Oc1ccc(C)cc1
Agent: [K+]
Solvent: COS(=O)(=O)OC
Solvent: CC(C)=O
Solvent: O
Product: CNC(=O)/C(=N/OC)c1ccccc1Oc1ccc(C)cc1
Yield: 91.9 %

Procedure:
E-2-hydroxyimino-N-methyl-2-[2-(4-methylphenoxy)phenyl] acetoamide (1.00 g, 0.0035 mole) was dissolved in dried acetone (7 ml), and potassium carbonate (0.63 g, 0.0046 mole) and dimethylsulfate (0.53 g, 0.0042 mole) were added to the mixture, which was reacted at room temperature for 22 hours. After completion of the reaction, water was added to the reaction mixture, which was extracted twice with methylene chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to obtain E-2-methoxyimino-N-methyl-2-[2-(4-methylphenoxy)phenyl]-acetamide as colorless crystals (0.96 g, yield: 92.3%).
Reaction SMILES: [ClH:1].Cl.C1(NC(C2C3C=C(C4C([Cl:24])=CN=C(NCCC5CCN(CC)CC5)N=4)SC=3C=CC=2)=O)CC1.[CH:36]1([NH:39][C:40]([C:42]2[C:50]3[CH:49]=[C:48]([C:51]4[C:56]([CH3:57])=[CH:55][N:54]=[C:53]([NH:58][CH2:59][CH2:60][CH2:61][CH:62]5[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]5)[N:52]=4)[S:47][C:46]=3[CH:45]=[CH:44][CH:43]=2)=[O:41])[CH2:38][CH2:37]1.Br[CH2:69][CH2:70][F:71]>>[ClH:24].[ClH:1].[CH:36]1([NH:39][C:40]([C:42]2[C:50]3[CH:49]=[C:48]([C:51]4[C:56]([CH3:57])=[CH:55][N:54]=[C:53]([NH:58][CH2:59][CH2:60][CH2:61][CH:62]5[CH2:63][CH2:64][N:65]([CH2:69][CH2:70][F:71])[CH2:66][CH2:67]5)[N:52]=4)[S:47][C:46]=3[CH:45]=[CH:44][CH:43]=2)=[O:41])[CH2:37][CH2:38]1
Reactant: CCN1CCC(CCNc2ncc(Cl)c(-c3cc4c(C(=O)NC5CC5)cccc4s3)n2)CC1
Reactant: FCCBr
Reactant: Cc1cnc(NCCCC2CCNCC2)nc1-c1cc2c(C(=O)NC3CC3)cccc2s1
Agent: Cl
Product: Cc1cnc(NCCCC2CCN(CCF)CC2)nc1-c1cc2c(C(=O)NC3CC3)cccc2s1

Procedure:
Using the method of 2-{5-chloro-2-[2-(1-ethylpiperidin-4-yl)-ethylamino]-pyrimidin-4-yl}-benzo[b]thiophene-4-carboxylic acid cyclopropylamide di-hydrochloride, the title compound is synthesized from 2-[5-methyl-2-(3-piperidin-4-yl-propylamino)-pyrimidin-4-yl]-benzo[b]thiophene-4-carboxylic acid cyclopropylamide and 1-bromo-2-fluoroethane and isolated as a yellow solid. ES+(m/z) 496 [M(free base)+H].
Reaction SMILES: [OH:1][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]=[CH:5][CH:4]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[N:33]1[C:37](=[O:38])[C:36]2=[CH:39][CH:40]=[CH:41][CH:42]=[C:35]2[C:34]1=[O:43].CCOC(/N=N/C(OCC)=O)=O>C1COCC1.CCOCC>[N:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]([CH2:2][O:1][N:33]2[C:34](=[O:43])[C:35]3=[CH:42][CH:41]=[CH:40][CH:39]=[C:36]3[C:37]2=[O:38])=[CH:4][CH:5]=1
Reactant: OCc1ccnc2ccccc12
Reactant: O=C1c2ccccc2C(=O)N1O
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCOCC
Product: O=C1c2ccccc2C(=O)N1OCc1ccnc2ccccc12
Reaction time: 8 h
Yield: 88.4 %

Procedure:
4-(hydroxymethyl)quinoline (1.20 g, 7.55 mmol), triphenyl phosphine (2.27 g, 8.66 mmol, 1.15 equiv) and N-hydroxyphthalimide (1.42 g, 8.71 mmol, 1.15 equiv) were dissolved in 40 mL of dry THF. Diethylazodicarboxylate (1.44 mL, 9.15 mmol, 1.21 equiv) was then added dropwise and the reaction was stirred overnight. The reaction mixture was then diluted with 50 mL of Et2O and filtered. The resulting solid was dissolved in dichloromethane and washed with 1N NaOH, H2O and brine. The organic portion was dried over Na2SO4 and concentrated under reduced pressure to give the title compound (2.03 g) as a fluffy white solid. MS(CI) m/e 305 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH2:24])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:27])[F:26].[C:29]1([N:35]=[C:36]=[O:37])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH:24][C:36]([NH:35][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:37])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:26])([F:28])[F:27]
Reactant: O=C=Nc1ccccc1
Reactant: Cc1ccccc1-c1cnc2c(C(F)(F)F)cccc2c1-c1cccc(N)c1
Product: Cc1ccccc1-c1cnc2c(C(F)(F)F)cccc2c1-c1cccc(NC(=O)Nc2ccccc2)c1

Procedure:
The title compound was prepared from {3-[3-(2-methylphenyl)-8 (trifluoromethyl)quinolin-4-yl]phenyl}amine and phenyl isocyanate in substantially the same manner as described in Example 65; off-white solid: mp 192-195° C.; MS (EI) m/z 498 (M+H)+.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([OH:10])[CH:7]=[CH:8][CH:9]=1)([CH3:3])[CH3:2].[N+:11]([O-])([O-:13])=[O:12].[Na+].S(=O)(=O)(O)O.N([O-])=O.[Na+]>C(Cl)Cl>[N+:11]([C:7]1[CH:8]=[CH:9][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:5][C:6]=1[OH:10])([O-:13])=[O:12]
Reactant: O=[N+]([O-])[O-]
Reactant: CC(C)c1cccc(O)c1
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)c1ccc([N+](=O)[O-])c(O)c1
Reaction time: 24 h
Yield: 27.3 %

Procedure:
3-isopropylphenol (3.00 g, 22 mmol) was dissolved in methylene chloride(40 ml) followed by the addition of sodium nitrate (2.06 g, 24 mmol). The addition of sulfuric acid (25 mL/3M) is then made, followed by addition of a catalytic amount of sodium nitrite. The mixture was allowed to stir. After 24 h, the reaction mixture is diluted with methylene chloride and extracted with water. The organic layer is dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4% MeOH/CH2Cl2) gave the desired product(1.09 g, 27%). 1H NMR (CD3COCD3): δ 7.95 (d,1H), 7.62 (d,1H), 7.11 (d, 1H), 2.95 (m, 1H), 1.24 (d, 6H).
Reaction SMILES: [Cl:1][C:2]1[C:11]([Cl:12])=[C:10]2[C:5]([C:6](=[O:13])[CH2:7][CH2:8][O:9]2)=[CH:4][CH:3]=1.[Br-:14].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>C(O)C.C(Cl)(Cl)Cl>[Br:14][CH:7]1[C:6](=[O:13])[C:5]2[C:10](=[C:11]([Cl:12])[C:2]([Cl:1])=[CH:3][CH:4]=2)[O:9][CH2:8]1
Reactant: O=C1CCOc2c1ccc(Cl)c2Cl
Reactant: [Br-]
Agent: c1cc[nH+]cc1
Solvent: ClC(Cl)Cl
Solvent: CCO
Product: O=C1c2ccc(Cl)c(Cl)c2OCC1Br
Reaction time: 0.5 h

Procedure:
A mixture of 100 mg. (0.46 mmol) 7,8-dichlorochroman-4-one was dissolved in anhydrous ethanol (5 ml) and Chloroform (5 ml). To this solution was added pyridinium tribromide (0.442 g, 1.38 mmol, 3 equiv). The reddish brown mixture was heated with stirring at 50 C for 30 min. The reaction mixture was then cooled and the solvent was evaporated. Then water (20 ml) was added to the residue and it was then extracted with 20 ml of dichloromethane. The dichloromethane layer was then washed with 5% sodium bicarbonate solution followed by water (20 ml). The organic layer was then dried and the solvent was evaporated in vacuum to yield the crude product which was purified by column chromatography.
Reaction SMILES: [CH3:1][N:2]([CH:4]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:5]1[CH:6]=[C:7]([CH2:11][C:12](O)=[O:13])[CH:8]=[CH:9][CH:10]=1)[CH3:3].S(Cl)([Cl:23])=O>>[CH3:1][N:2]([CH:4]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:5]1[CH:6]=[C:7]([CH2:11][C:12]([Cl:23])=[O:13])[CH:8]=[CH:9][CH:10]=1)[CH3:3]
Reactant: CN(C)C(c1ccccc1)c1cccc(CC(=O)O)c1
Reactant: O=S(Cl)Cl
Product: CN(C)C(c1ccccc1)c1cccc(CC(=O)Cl)c1

Procedure:
1.5 g of 3-(dimethylaminophenylmethyl)phenylacetic acid are heated at reflux temperature for 1/2 an hour in 15 ml of thionyl chloride with stirring. Thionyl chloride not consumed in the reaction is distilled off. The residue is taken up in toluene and the solvent is distilled again.
Reaction SMILES: C([O:8][C:9]1[C:14]2[NH:15][C:16](=[O:19])[CH2:17][O:18][C:13]=2[C:12]([C:20](=[O:24])[CH:21](O)O)=[CH:11][CH:10]=1)C1C=CC=CC=1.[CH3:25][O:26][C:27]1[CH:37]=[CH:36][CH:35]=[CH:34][C:28]=1[CH2:29][C:30]1([NH2:33])[CH2:32][CH2:31]1.FC(F)(F)C([O-])=O>>[OH:8][C:9]1[C:14]2[NH:15][C:16](=[O:19])[CH2:17][O:18][C:13]=2[C:12]([CH:20]([OH:24])[CH2:21][NH:33][C:30]2([CH2:29][C:28]3[CH:34]=[CH:35][CH:36]=[CH:37][C:27]=3[O:26][CH3:25])[CH2:32][CH2:31]2)=[CH:11][CH:10]=1
Reactant: O=C1COc2c(C(=O)C(O)O)ccc(OCc3ccccc3)c2N1
Reactant: COc1ccccc1CC1(N)CC1
Agent: O=C([O-])C(F)(F)F
Product: COc1ccccc1CC1(NCC(O)c2ccc(O)c3c2OCC(=O)N3)CC1

Procedure:
Prepared according to general method 3 from 329 mg (1 mmol) 5-benzyloxy-8-(2,2-dihydroxy-acetyl)-4H-benzo[1,4]oxazin-3-one and 177 mg (1 mmol) 1-(2-methoxy-benzyl)-cyclopropylamine. Yield: 100 mg (20%, trifluoroacetate); mass spectroscopy: [M+H]+=385.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][C:5]([N:7]1[C:16]2[CH2:15][CH2:14][C:13]3[CH:17]=[C:18]([Cl:21])[CH:19]=[CH:20][C:12]=3[C:11]=2[CH2:10][CH2:9][CH2:8]1)=[O:6].C(N(CC)CC)C.[C:29](Cl)(=[O:31])[CH3:30]>C(Cl)Cl>[Cl:21][C:18]1[CH:19]=[CH:20][C:12]2[C:11]3[CH2:10][CH2:9][CH2:8][N:7]([C:5](=[O:6])[CH2:4][CH2:3][CH2:2][NH:1][C:29](=[O:31])[CH3:30])[C:16]=3[CH2:15][CH2:14][C:13]=2[CH:17]=1
Reactant: NCCCC(=O)N1CCCC2=C1CCc1cc(Cl)ccc12
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)NCCCC(=O)N1CCCC2=C1CCc1cc(Cl)ccc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a suspension of 5.09 g (0.015 mol) of 4-(4-aminobutyryl)-8-chloro-1,2,3,4,5,6-hexahydrobenzo[f]quinoline in 50 ml of methylene chloride are added 5 ml (0.036 mol) of triethylamine and then at 0° 1.33 ml (0.019 mol) of acetyl chloride dissolved in 15 ml of methylene chloride, and the mixture is stirred at room temperature for 1 hour. Then, the mixture is extracted with methylene chloride/water, dried with magnesium sulfate and the solvent is distilled in a vacuum. Crystallization from methylene chloride/ether, chromatography on silica gel with ethyl acetate/methanol (9:1) and renewed crystallization from methylene chloride/ether gives N-[4-[8-chloro-2,3,5,6,-tetrahydrobenzo[f]quinolin-4(1H)-yl]-4-oxobutyl]acetamide as white crystals with melting point 142°-143°.
Reaction SMILES: [CH2:1]([S:8][CH2:9][CH:10]([CH2:14][CH2:15][C:16]([OH:18])=[O:17])[C:11]([OH:13])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=[O:27])C=1>ClCCl>[CH2:1]([S:8]([CH2:9][CH:10]([CH2:14][CH2:15][C:16]([OH:18])=[O:17])[C:11]([OH:13])=[O:12])=[O:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)CCC(CSCc1ccccc1)C(=O)O
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: O=C(O)CCC(CS(=O)Cc1ccccc1)C(=O)O
Temperature: 25 °C
Yield: 68.9 %

Procedure:
To a cooled mixture (-78° C.) of 2-[(benzylsulfanyl)methyl]pentanedioic acid (5.2 g, 19.4 mmol) in dichloromethane (100 ml) was added 3-chloroperbenzoic acid (85%, 3.9 g, 19.4 mmol) with stirring. The reaction mixture was allowed to stir for 1 hour at -78° C., then allowed to warm to room temperature. If starting material was still present according to analysis by TLC, the reaction was cooled again to -78° C. and additional 3-chloroperbenzoic acid (2-4 mmol depending on the intensity of the starting material spot) added and the reaction mixture allowed to warm at room temperature. This was repeated until no more starting material was detected by TLC. The dichloromethane was removed under reduced pressure and the resulting residue was purified by column chromatography to yield 3.8 g (69%) of white solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:17]1[S:18][CH:19]=[C:20]([C:22]2SC=C(C(=O)N)N=2)C=1)([OH:16])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.[NH:30]1C=NC=N1.[H-].[Na+].[F:37][C:38]1[CH:43]=[C:42]([F:44])C=[CH:40][C:39]=1C(C1SC=C(C2SC=C(C(OCC)=O)N=2)C=1)(O)CN1C=NC=N1>O.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:17]1[S:18][CH:19]=[C:20]([C:22]2[CH:40]=[CH:39][C:38]([F:37])=[CH:43][C:42]=2[F:44])[N:30]=1)([OH:16])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1
Reactant: NC(=O)c1csc(-c2csc(C(O)(Cn3cncn3)c3ccc(F)cc3F)c2)n1
Reactant: CCOC(=O)c1csc(-c2csc(C(O)(Cn3cncn3)c3ccc(F)cc3F)c2)n1
Reactant: c1nc[nH]n1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: OC(Cn1cncn1)(c1nc(-c2ccc(F)cc2F)cs1)c1ccc(F)cc1F
Temperature: 60 °C

Procedure:
After 4-(2,4-difluorophenyl)thiazole (330 mg) was dissolved in diethyl ether (3 ml), and the resultant solution was cooled to -78° C. in a nitrogen atmosphere, a 1.6M solution (1.06 ml) of n-butyllithium in hexane was added, and the resultant mixture was stirred for about 10 minutes. After a solution of 2-chloro-2',4'-difluoroacetophenone (306 mg) in tetrahydrofuran was added dropwise to this mixture, the liquid reaction mixture was heated to -20° C. to add an aqueous solution of ammonium chloride. The reaction mixture was extracted with ethyl acetate. After drying an organic layer over magnesium sulfate, the solvent was distilled out under reduced pressure. The residue was dissolved in dimethylformamide (3 ml) to form a solution (A). On the other hand, a dimethylformamide solution (3 ml) (B) containing 1,2,4-triazole (350 ml) and 60% sodium hydride (135 mg) was prepared. The solution (B) was then added to the solution (A), and the mixture was heated at 60° C. for 6 hours. After ethyl acetate and water were added to the liquid reaction mixture, and an organic layer was washed several times with water, the solvent was distilled out. The residue was subjected to column chromatography on silica gel to recrystallize a fraction containing the intended compound from diethyl ether, thereby obtaining the title compound (390 mg). Its physical properties are shown in Table 1 which will be described subsequently.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][C:7]1[CH:16]=[CH:15][C:10]([C:11](=[N:13][OH:14])[NH2:12])=[CH:9][CH:8]=1.[C:17]([O:21][C:22]([NH:24][CH:25]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:26]1[CH:27]=[C:28]([CH:34]=[CH:35][CH:36]=1)[O:29][CH2:30][C:31](O)=O)=[O:23])([CH3:20])([CH3:19])[CH3:18]>C(#N)C.N1C=CC=CC=1.[Cl-].[Na+].O>[C:17]([O:21][C:22](=[O:23])[NH:24][CH:25]([C:26]1[CH:36]=[CH:35][CH:34]=[C:28]([O:29][CH2:30][C:31]2[O:14][N:13]=[C:11]([C:10]3[CH:15]=[CH:16][C:7]([CH2:6][CH:2]4[O:3][CH2:4][CH2:5][O:1]4)=[CH:8][CH:9]=3)[N:12]=2)[CH:27]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([CH3:20])([CH3:19])[CH3:18]
Reactant: CC(C)(C)OC(=O)NC(c1ccccc1)c1cccc(OCC(=O)O)c1
Reactant: NC(=NO)c1ccc(CC2OCCO2)cc1
Agent: [Cl-]
Agent: [Na+]
Solvent: CC#N
Solvent: c1ccncc1
Solvent: O
Product: CC(C)(C)OC(=O)NC(c1ccccc1)c1cccc(OCc2nc(-c3ccc(CC4OCCO4)cc3)no2)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a stirred solution of 4-((1,3-dioxolan-2-yl)methyl)-N′-hydroxybenzimidamide (0.747 g, 3.35 mmol) and 2-(3-(((tert-butoxycarbonyl)amino)(phenyl)methyl)phenoxy)-acetic acid (Example 59 Step 2, 1.0 g, 2.79 mmol)) in acetonitrile (5 mL), was added 1-ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride (0.8 g, 4.18 mmol). The reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was diluted with pyridine (1 mL) and heated at 150° C. for 30 minutes in a microwave. The reaction was diluted with saturated brine and extracted with ethyl acetate (×3). The combined organic fractions were dried with magnesium sulphate, and the solvent evaporated at reduced pressure. Material used directly in the next step without further purification (1.01 g, 65%).
Reaction SMILES: Br[C:2]1[S:3][C:4]2[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[C:14]([Cl:19])[CH:13]=3)[C:5]=2[N:6]=1.Cl.Cl.[Cl:22][C:23]1[CH:28]=[C:27]([N:29]2[CH2:34][CH2:33][CH:32]([NH2:35])[CH2:31][CH2:30]2)[CH:26]=[CH:25][N:24]=1.C(N(CC)CC)C>CC(N(C)C)=O.ClCCl>[Cl:19][C:14]1[CH:13]=[C:12]([C:7]2[C:5]3[N:6]=[C:2]([NH:35][CH:32]4[CH2:33][CH2:34][N:29]([C:27]5[CH:26]=[CH:25][N:24]=[C:23]([Cl:22])[CH:28]=5)[CH2:30][CH2:31]4)[S:3][C:4]=3[CH:10]=[C:9]([CH3:11])[CH:8]=2)[CH:17]=[CH:16][C:15]=1[F:18]
Reactant: Cc1cc(-c2ccc(F)c(Cl)c2)c2nc(Br)sc2c1
Reactant: NC1CCN(c2ccnc(Cl)c2)CC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CC(=O)N(C)C
Product: Cc1cc(-c2ccc(F)c(Cl)c2)c2nc(NC3CCN(c4ccnc(Cl)c4)CC3)sc2c1
Temperature: 175 °C
Yield: 20.5 %

Procedure:
To a solution of 2-bromo-4-(3-chloro-4-fluorophenyl)-6-methylbenzo[d]thiazole (0.06 g, 0.2 mmol) in dimethylacetamide (1 mL) was added 1-(2-chloropyridin-4-yl)piperidin-4-amine dihydrochloride (0.05 g, 0.2 mmol) followed by triethylamine (70 L, 0.5 mmol) and the mixture was heated to 175° C. for 1 h in a microwave. The reaction was then diluted with dichloromethane, washed with water, brine, dried with sodium sulfate and concentrated. The product was purified by preparative HPLC to yield the title compound as light yellow solid (0.02 g, 24%).
Reaction SMILES: C[N:2]([CH2:6][CH2:7]O)[CH2:3]CO.[NH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11].C([O-])(=O)CCCC[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26].C([O-])(=[O:41])CCCCCCCCCCC.C([Sn+2][CH2:48][CH2:49][CH2:50][CH3:51])CCC>CN1CCCC1=O>[NH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11].[NH2:2][C:10]([NH2:9])=[O:12].[CH2:22]1[CH:21]([CH2:20][CH:49]2[CH2:48][CH2:7][CH:6]([N:2]=[C:3]=[O:41])[CH2:51][CH2:50]2)[CH2:26][CH2:25][CH:24]([N:9]=[C:10]=[O:12])[CH2:23]1
Reactant: CCCC[Sn+2]CCCC
Reactant: CN(CCO)CCO
Reactant: CCCCCCCCCCCC(=O)[O-]
Agent: CCOC(N)=O
Solvent: CN1CCCC1=O
Product: NC(N)=O
Product: O=C=NC1CCC(CC2CCC(N=C=O)CC2)CC1

Procedure:
A cationic poly(urethane-urea) lacquer was prepared as follows: 400 parts by weight of a 1000 molecular weight poly(1,4-butanediol adipate) was charged to a suitable reaction vessel along with 85.7 parts by weight of methyl diethanolamine, 0.44 parts by weight of dibutyltin dilaurate urethane-forming catalyst, 3.88 parts by weight of N-methyl pyrrolidone solvent and 419 parts by weight of HYLENE W. The reaction mixture was heated to 95° C. under a nitrogen atmosphere for a 4-1/2 hour period. The reaction mixture was then cooled to room temperature and the NCO-polymer which was formed was quaternized with 100.8 parts by weight of dimethyl sulfate. The quaternizing agent was added to the reaction mixture in a dropwise fashion. After quaternizing the NCO-containing polymer, it was thinned by combining it with 280 parts by weight of N-methyl pyrrolidone. The thinned NCO-containing polymer was dispersed and chain extended by charging it to a solution of 24 parts by weight of hydrazine hydrate dissolved in 1245 parts by weight of deionized water. The mixture dispersed very well, increasing in viscosity halfway through addition such that an additional 2500 parts by weight of water were added during the addition to reduce the viscosity. The final dispersion had a solids content of 19.8 percent, a pH of 6.75, a Brookfield viscosity at 23° C. (1000 rpm's) of 4200 centipoises. The resin was essentially free of NCO groups as determined by an infrared scan.
Reaction SMILES: [CH2:1]([C:3]1[C:4]([NH2:13])=[C:5]([S:9]([NH2:12])(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1)[CH3:2].[Cl:14]N1C(=O)CCC1=O.C1(=O)NC(=O)CC1.[K+].[Br-]>C(#N)C.C(OCC)(=O)C>[Cl:14][C:7]1[CH:8]=[C:3]([CH2:1][CH3:2])[C:4]([NH2:13])=[C:5]([S:9]([NH2:12])(=[O:10])=[O:11])[CH:6]=1
Reactant: O=C1CCC(=O)N1Cl
Reactant: CCc1cccc(S(N)(=O)=O)c1N
Agent: O=C1CCC(=O)N1
Agent: [Br-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CCc1cc(Cl)cc(S(N)(=O)=O)c1N

Procedure:
To a solution of 3-ethyl-2-aminobenzenesulfonamide (0.5043 g, 2.52 mmol) in 10 mL acetonitrile was added N-chlorosuccinimide (0.3163 g, 2.37 mmol). The mixture was stirred at reflux for 1 2.5 h, cooled, filtered, and concentrated in vacuo. Reaction was incomplete by 1H NMR; the purple solids were redissolved in acetonitrile and additional NCS (0.1019 g, 0.76 mmol) was added. The mixture was refluxed for 1 5 minutes and worked up as before. Column chromatography on the mixture of succinimide and D (40% ethyl acetate:hexanes) gave pure D (0.5224 g, 94%), m.p. 134-135° C. 1H NMR (300 MHz, DMSO): δ7.45 (3H, s), 7.19 (1H, d, J=2.1 Hz), 5.76 (2H, s), 2.53 (2H, q, J=7.3 Hz), 1.14 (3H, i, J=7.3 HZ). 13C NMR (300 MHz, DMSO): δ141.9, 131.8, 131.2, 125.4, 124.8, 118.1, 23.4, 12.7. FT-IR (KBr): 3457.8, 3427.9, 3358.4, 3268.9, 3080.1, 2970.8, 2364.5, 2334.7, 1630.6. 1556.1, 1541.2. 1451.7. 1312.6. 1188.3, 1148.6, 905.1, 875.3, 762.2, 611.3 cm-1. HRMS: M+ calculated=234.0230, found=234.0227.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[NH:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1C=CC=CC=1>O>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH:15]=[C:14]([N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[CH2:13][CH2:12]2)=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)c1ccc(N2CCC(=O)CC2)cc1
Reactant: C1CCNC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Solvent: O
Product: CS(=O)(=O)c1ccc(N2CC=C(N3CCCC3)CC2)cc1
Yield: 78 %

Procedure:
A solution of 24 g (0.0947 mol) of the compound of (b), 12 ml (10.2 g/0.143 mol) of pyrrolidine, 240 mg of p-toluenesulfonic acid and 150 ml of benzene is heated at reflux with the azeotropic removel of water for 6 hours. After cooling the resulting precipitate is collected and triturated with ethyl ether to afford 22.5 g (78%) of title compound: m.p. 141°-143° C.; IR (KBr) 1650, 1580, 1300, and 1130 cm-1 ; NMR (CDCl3)δ 7.75 (d, 2H), 6.85 (d, 2H), 4.30-4.10 (m, 1H), 3.95-3.45 (m, 4H), 3.25-2.85 (m, 4H) 3.05 (s, 3H), 2.65-2.30 (m, 2H), and 1.95-1.70 (m, 4H).
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:7]([CH:8]=[CH:9][CH:10]=1)=[N:6][N:5]([CH3:11])[CH:4]=2.[Cl:12][C:13]1[NH:14][CH2:15][CH2:16][N:17]=1.S(O)(O)(=O)=O.ClC1NCCN=1.[OH-].[Na+]>C1COCC1.C(Cl)Cl>[ClH:12].[NH:17]1[CH2:16][CH2:15][N:14]=[C:13]1[NH:1][C:2]1[C:3]2[C:7]([CH:8]=[CH:9][CH:10]=1)=[N:6][N:5]([CH3:11])[CH:4]=2
Reactant: ClC1=NCCN1
Reactant: Cn1cc2c(N)cccc2n1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: C1CCOC1
Product: Cl
Product: Cn1cc2c(NC3=NCCN3)cccc2n1

Procedure:
4 g 4-amino-2-methyl-indazole is dissolved in 120 ml THF. The solution is treated with a solution of 2-chloro-imidazoline base, which is prepared from 10 g 2-chloro-imidazoline sulfate (prepared according to J. Heteroc. Chem. 11, 258) with 2 n NaOH in methylene chloride.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[CH:9]3[O:14][CH:8]3[C:7]=2[CH:15]=1)#[N:2].[CH3:16][O:17][C:18]1[CH2:22][NH:21][C:20](=[O:23])[CH:19]=1.[H-].[Na+].O>C(OCC)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[C@@H:9]([OH:14])[C@H:8]([N:21]3[CH2:22][C:18]([O:17][CH3:16])=[CH:19][C:20]3=[O:23])[C:7]=2[CH:15]=1)#[N:2]
Reactant: COC1=CC(=O)NC1
Reactant: CC1(C)Oc2ccc(C#N)cc2C2OC21
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Product: COC1=CC(=O)N([C@@H]2c3cc(C#N)ccc3OC(C)(C)[C@H]2O)C1
Temperature: 25 °C
Reaction time: 5 h
Yield: 17.1 %

Procedure:
A solution of 6-cyano-3,4-dihydro-2,2-dimethyl-3,4-epoxy-2H-1-benzopyran (15 g) and 4-methoxy-3-pyrrolin-2-one (8.5 g) in dimethylsufoxide (40 ml) was stirred and sodium hydride (80% dispersion in oil, 2.2 g) was added. The mixture was stirred at room temperature for 5 hours. Water (50 ml) was slowly added, and the resulting solution extracted with ethyl acetate (2×50 ml). After drying the organic layer with sodium sulfate the solvent was removed under reduced pressure and the residual oil chromatographed on silica gel (4% methanol in methylene chloride). The product obtained was dissolved in diethylether and precipitated with pentane to afford 4 g of 6-cyano-3,4-dihydro-2,2-dimethyl-trans-3-hydroxy-4-(4-methoxy-2-oxo-3-pyrrolin-1-yl)-2H-1-benzopyran, m.p. 256° C.