Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.Cl.Cl[CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[O:19]1[CH2:20][CH2:21][N:16]([CH2:15][CH2:14][O:1][C:2]2[CH:3]=[CH:4][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:10][CH:11]=2)[CH2:17][CH2:18]1
Reactant: COC(=O)c1ccc(O)cc1
Reactant: ClCCN1CCOCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COC(=O)c1ccc(OCCN2CCOCC2)cc1
Temperature: 50 °C
Yield: 141.7 %

Procedure:
To a stirring solution of methyl 4-hydroxybenzoate 191 (1.08 g, 7.10 mmol) and 4-(2-chloroethyl)morpholine hydrochloride 192 (1.45 g, 7.82 mmol) in acetonitrile was added potassium carbonate (2.95 g, 21.3 mmol). The reaction mixture was heated to 50° C. overnight then cooled to rt and the resulting precipitate was filtered and washed with methanol to provide methyl 4-(2-morpholinoethoxy)benzoate 193 (2.67 g, 142%). 1H NMR: (DMSO) δ (ppm): 400 MHz, (DMSO) d (ppm): 7.87 (s, J=9.0 Hz, 2 h), 7.03 (d, J=9.0 Hz, 2H), 4.15 (t, J=5.7 Hz, 2H), 3.80 (s, 3H), 3.56 (t, J=4.5 Hz, 4H), 2.69 (t, J=5.7 Hz, 4H), 2.47 (m, 4H). MS: 265.13 (calc), 266.1 (obs).
Reaction SMILES: [F:1][C:2]([F:13])([C:6]([F:12])([F:11])[C:7]([F:10])([F:9])[F:8])[C:3]([OH:5])=[O:4].[CH3:14]S(O)(=O)=O>CO>[F:1][C:2]([F:13])([C:6]([F:11])([F:12])[C:7]([F:8])([F:9])[F:10])[C:3]([O:5][CH3:14])=[O:4]
Reactant: O=C(O)C(F)(F)C(F)(F)C(F)(F)F
Reactant: CS(=O)(=O)O
Solvent: CO
Product: COC(=O)C(F)(F)C(F)(F)C(F)(F)F

Procedure:
Perfluorobutyric acid (55 g, 0.26 m) in 25 ml of methanol containing 0.1 g of methane sulfonic acid was refluxed for 16 hours. The product was washed with a sodium carbonate solution and dried over magnesium carbonate. IR analysis showed the following major absorption bands: 2970, 1785, 1310, 1225, 1145, 1085 cm-1.
Reaction SMILES: [CH:1]1([C:5]([C:7]2[CH:8]=[N:9][C:10]3[C:15]([C:16]=2Cl)=[N:14][C:13]([Cl:18])=[CH:12][CH:11]=3)=[O:6])[CH2:4][CH2:3][CH2:2]1.[CH3:19][N:20]([CH2:22][C@H:23]1[CH2:28][CH2:27][C@H:26]([NH2:29])[CH2:25][CH2:24]1)[CH3:21]>>[Cl:18][C:13]1[N:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([C:5]([CH:1]1[CH2:4][CH2:3][CH2:2]1)=[O:6])=[C:16]2[NH:29][CH:26]1[CH2:27][CH2:28][CH:23]([CH2:22][N:20]([CH3:21])[CH3:19])[CH2:24][CH2:25]1
Reactant: O=C(c1cnc2ccc(Cl)nc2c1Cl)C1CCC1
Reactant: CN(C)C[C@H]1CC[C@H](N)CC1
Product: CN(C)CC1CCC(Nc2c(C(=O)C3CCC3)cnc3ccc(Cl)nc23)CC1

Procedure:
(6-Chloro-4-((4-((dimethylamino)methyl)cyclohexyl)amino)-1,5-naphthyridin-3-yl)(cyclobutyl)methanone was prepared with conditions described in Example 131 using cyclobutyl(4,6-dichloro-1,5-naphthyridin-3-yl)methanone and trans-4-((dimethylamino)methyl)cyclohexanamine.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:12]3[CH:17]=[C:16]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[N:15]=[C:14]([NH2:25])[N:13]=3)[CH2:9]2)=[CH:4][CH:3]=1.[CH3:26][N:27]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[N:28]1>>[CH3:24][N:21]1[CH2:22][CH2:23][N:18]([C:16]2[CH:17]=[C:12]([N:8]3[CH2:7][CH2:6][C:5]4[C:10](=[CH:11][C:2]([C:30]5[CH:29]=[N:28][N:27]([CH3:26])[CH:31]=5)=[CH:3][CH:4]=4)[CH2:9]3)[N:13]=[C:14]([NH2:25])[N:15]=2)[CH2:19][CH2:20]1
Reactant: CN1CCN(c2cc(N3CCc4ccc(Br)cc4C3)nc(N)n2)CC1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Product: CN1CCN(c2cc(N3CCc4ccc(-c5cnn(C)c5)cc4C3)nc(N)n2)CC1

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 2 starting from 4-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (Aldrich, Cat. No. 595214). LCMS (M+H)+: m/z=405.4.
Reaction SMILES: Br[CH2:2][CH2:3][N:4]1[C:17](=[O:18])[C:16]2[C:15](=[O:19])[C:14]3[CH:13]=[CH:12][C:11]([Cl:20])=[CH:10][C:9]=3[NH:8][C:7]=2[C:6]([OH:21])=[N:5]1.[C:22]1(=[O:32])[NH:26][C:25](=[O:27])[C:24]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:23]12.[K].Cl>CN(C=O)C>[Cl:20][C:11]1[CH:12]=[CH:13][C:14]2[C:15](=[O:19])[C:16]3[C:17](=[O:18])[N:4]([CH2:3][CH2:2][N:26]4[C:25](=[O:27])[C:24]5=[CH:28][CH:29]=[CH:30][CH:31]=[C:23]5[C:22]4=[O:32])[N:5]=[C:6]([OH:21])[C:7]=3[NH:8][C:9]=2[CH:10]=1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: O=c1c2ccc(Cl)cc2[nH]c2c(O)nn(CCBr)c(=O)c12
Agent: Cl
Agent: [K]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCn1nc(O)c2[nH]c3cc(Cl)ccc3c(=O)c2c1=O
Yield: 78.9 %

Procedure:
2-(2-Bromoethyl)-7-chloro-4-hydroxy-1,2,5,10-tetrahydropyridazino[4,5-b]-quinoline-1,10-dione (5.00 g, 13.50 mM) and potassium phthalimide (10.50 g, 56.70 mH) were stirred and refluxed in DMF (100 mL) for 22 hours. The cooled yellow suspension was poured into dilute hydrochloric acid (1N, 1.0 L) with good stirring. A white precipitate formed and was collected. This solid was resuspended in aqueous methanol (50%, 1.0 L) and stirred/sonicated to give a fine white suspension. Filtration and resuspension in methanol (0.25 L) gave a free-flowing white suspension after sonication and brief warming. The solids were finally collected and washed with methanol to give the title compound (4.65 g, 79%) as a white powder, mp 349-352° C.; MS(CI): 437 (M+H).
Reaction SMILES: C([Si](C)(C)[O:6][C:7]1[CH:8]=[C:9]([OH:13])[CH:10]=[CH:11][CH:12]=1)(C)(C)C.Br[C:17]1[N:22]=[CH:21][C:20]2[N:23]=[C:24]([C:28]3[C:29]([NH2:33])=[N:30][O:31][N:32]=3)[N:25]([CH2:26][CH3:27])[C:19]=2[CH:18]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1>[NH2:33][C:29]1[C:28]([C:24]2[N:25]([CH2:26][CH3:27])[C:19]3[CH:18]=[C:17]([O:6][C:7]4[CH:8]=[C:9]([OH:13])[CH:10]=[CH:11][CH:12]=4)[N:22]=[CH:21][C:20]=3[N:23]=2)=[N:32][O:31][N:30]=1
Reactant: CC(C)(C)[Si](C)(C)Oc1cccc(O)c1
Reactant: CCn1c(-c2nonc2N)nc2cnc(Br)cc21
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: c1cnc2c(c1)ccc1cccnc12
Solvent: Cc1ccccc1
Product: CCn1c(-c2nonc2N)nc2cnc(Oc3cccc(O)c3)cc21
Temperature: 120 °C
Yield: 7 %

Procedure:
The product from Step 1 (46 mg, 0.20 mmol) in toluene (10 mL) was treated with the product from Step 2 (42 mg, 0.14 mmol), cuprous iodide (26 mg, 0.14 mmol), 1,10-phenanthroline (43 mg, 0.24 mmol), and cesium carbonate (88 mg, 0.27 mmol). The resulting mixture was heated to 120° C. for 48 hours in a sealed tube. After concentration the residue was purified by reverse phase HPLC to give the title compound (3.3 mg, 7%). MS (ES+) m/e 339 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[C@H:19]([CH3:30])[CH2:18]3)=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.FC(F)(F)C(O)=O.[OH-].[Na+]>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([N:17]3[CH2:22][CH2:21][NH:20][C@H:19]([CH3:30])[CH2:18]3)=[CH:15][N:16]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1
Reactant: C[C@@H]1CN(c2ccc(Nc3cc(Br)cn(C)c3=O)nc2)CCN1C(=O)OC(C)(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: C[C@@H]1CN(c2ccc(Nc3cc(Br)cn(C)c3=O)nc2)CCN1
Reaction time: 8 h
Yield: 61 %

Procedure:
To a mixture of 108c (624 mg, 1.3 mmol) in dichloromethane (8 mL) was added trifluoroacetic acid dropwise (300 mg, 2.6 mmol) at room temperature. Then the mixture was stirred for overnight. 2.0 N NaOH was added to adjust pH to greater than 10. Then the mixture was extracted with ethyl acetate (50 mL×2). The combined organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford 108d as a brown solid (300 mg, 61%). LCMS: [M+H]+ 380
Reaction SMILES: N#N.[C:3]([O:9][CH3:10])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].[CH2:11](O)[CH:12]=C>>[C:3]([O:9][CH2:10][CH:11]=[CH2:12])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6]
Reactant: C=CCO
Reactant: COC(=O)CC(C)=O
Agent: N#N
Product: C=CCOC(=O)CC(C)=O
Yield: 72.8 %

Procedure:
In a 2 l flask equipped with a magnetic stirrer, equipped for a Vigreaux column for distillation, a heating mantle and N2, there was added 4.0 mole (432 ml) of methyl acetoacetate and 8.0 mole (464.6 g) of allyl alcohol. The reaction mixture was distilled for 12 hours at 92° C. There was added 136 ml (2.0 mole) of allyl alcohol and the mixture was distilled 23 hours. There was then added 136 ml (2.0 mole) of allyl alcohol and the mixture was distilled 16 hours. The reaction mixture was then distilled under vacuum and product was collected at 105°-110° C./35 mm Hg. There was obtained 414 g of allyl acetoacetate (73% yield). ##STR230##
Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:8]=[C:9]([OH:13])[CH:10]=[CH:11][CH:12]=2)=[CH:4][CH:3]=1.[CH3:16][S:17]Cl.CSSC.ClCl>C(Cl)Cl>[Br:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([S:17][CH3:16])=[C:9]([OH:13])[CH:8]=2)=[CH:4][CH:3]=1
Reactant: Oc1cccc(Oc2ccc(Br)cc2)c1
Reactant: CSCl
Agent: ClCl
Solvent: CSSC
Solvent: ClCCl
Product: CSc1ccc(Oc2ccc(Br)cc2)cc1O
Temperature: -20 °C
Reaction time: 0.5 h

Procedure:
3-(4-Bromophenoxy)phenol (0.1 mole) and methylene chloride (200 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer and addition funnel. The mixture is stirred until dissolved and cooled to about -20° C. A solution of methyl sulfenyl chloride freshly prepared by reacting dimethyl disulfide (0.15 mole) with chlorine (0.18 mole) in methylene chloride (100 ml) is then added dropwise to the reaction vessel over a period of about 40 minutes. After the addition is completed stirring is continued for 30 minutes with cooling and 30 minutes at room temperature. After this time the reaction mixture is washed with water (200 ml), with 5% aqueous sodium bicarbonate (200 ml) and again with water (200 ml). The washed solution is then dried by passing it through a phase separator. The dried solution is stripped of solvent under reduced pressure and the residue chromatographed using a clay column and hexane/ethyl acetate as the eluant. The fractions containing the product are combined and stripped of solvent to yield the desired product 5-(4-bromophenoxy) 2-(methylthio)phenol as the residue.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][CH:12]([C:15]([OH:17])=O)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(C(C)C)CC)(C)C.[CH3:49][N:50]([CH:67]([C:75](=[O:78])[NH:76][CH3:77])[CH2:68][C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)[C:51](=[O:66])[CH:52]([NH:64][CH3:65])[CH2:53][C:54]1[CH:63]=[CH:62][C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[CH:55]=1>ClCCl.CN(C)C=O>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]1[CH2:10][CH2:11][CH:12]([C:15](=[O:17])[N:64]([CH3:65])[C@@H:52]([C:51](=[O:66])[N:50]([C@@H:67]([C:75](=[O:78])[NH:76][CH3:77])[CH2:68][C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[CH3:49])[CH2:53][C:54]2[CH:63]=[CH:62][C:61]3[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=3)[CH:55]=2)[CH2:13][CH2:14]1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)NC1CCC(C(=O)O)CC1
Reactant: CNC(=O)C(Cc1ccccc1)N(C)C(=O)C(Cc1ccc2ccccc2c1)NC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CNC(=O)[C@@H](Cc1ccccc1)N(C)C(=O)[C@@H](Cc1ccc2ccccc2c1)N(C)C(=O)C1CCC(NC(=O)OC(C)(C)C)CC1
Reaction time: 0.33 h
Yield: 81.9 %

Procedure:
To a suspension of 4-tert-butoxycarbonylamino cyclohexanecarboxylic acid (115 mg, 0.47) in 5 ml of dichloromethane was added 1-hydroxy-7-azabenzotriazole (64 mg, 0.47 mmol) in 0.5 ml N,N-dimethylformamide. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (100 mg, 0.52) was added and the solution was stirred for 20 min. Diisopropylethylamine (120 mg, 0.94 mmol) and N-methyl-2-methylamino-N-(1-methylcarbamoyl-2-phenylethyl)-3-(2-naphthyl)propionamide (191 mg, 0.47 mmol) in 5 ml of dichloromethane was added and the mixture was alloved to stand overnight at room temperature. The mixture was washed with water (5 ml), sodium bicarbonate (5 ml) water (2×5 ml) and brine (5 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was chromatographed on silica (20 g) with ethyl acetate as eleuent to give 242 mg of (4-[N-Methyl-N-{(1R)-1-(N-methyl-[(1R)-1-(methylcarbamoyl)-2-phenylethyl]carbamoyl)-2-(2-naphtyl)ethyl}-carbamoyl]cyclohexyl)carbamic acid tert-butyl ester.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:22])[C:8]=2[NH:12][C:13](=[O:21])[CH2:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)[N:3]=1.[NH:23]1[CH2:27][CH2:26][C@H:25]([NH2:28])[CH2:24]1>>[NH2:28][C@H:25]1[CH2:26][CH2:27][N:23]([C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[C:7]([CH3:22])[C:8]=3[NH:12][C:13](=[O:21])[CH2:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)[N:3]=2)[CH2:24]1
Reactant: N[C@H]1CCNC1
Reactant: Cc1ccc2nc(Cl)ccc2c1NC(=O)CC1CCCCC1
Product: Cc1ccc2nc(N3CC[C@H](N)C3)ccc2c1NC(=O)CC1CCCCC1
Yield: 68.7 %

Procedure:
Prepared according to the method of example 30, using N-(2-Chloro-6-methyl-5-quinolinyl)-cyclohexaneacetamide (Example 15(a)) (0.2 g) and (3S)-3-pyrrolidinamine (0.163 g) which after recrystallisation from ethanol afforded the title compound (0.159 g).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[CH:9][N:8]([C:11]3[N:16]=[C:15]4[N:17]([C@@H:28]([C:30]5[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=5)[CH3:29])[C:18](=[O:27])[N:19](C(OC(C)(C)C)=O)[C:14]4=[CH:13][CH:12]=3)[C:7]=2[CH:36]=1)#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[O:27]=[C:18]1[N:17]([C@@H:28]([C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)[CH3:29])[C:15]2=[N:16][C:11]([N:8]3[C:7]4[CH:36]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]=4[N:10]=[CH:9]3)=[CH:12][CH:13]=[C:14]2[NH:19]1
Reactant: C[C@H](c1cccnc1)n1c(=O)n(C(=O)OC(C)(C)C)c2ccc(-n3cnc4ccc(C#N)cc43)nc21
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C[C@H](c1cccnc1)n1c(=O)[nH]c2ccc(-n3cnc4ccc(C#N)cc43)nc21
Yield: 86.4 %

Procedure:
A solution of tert-butyl 5-(6-cyano-1H-benzo[d]imidazol-1-yl)-2-oxo-3-((R)-1-(pyridin-3-yl)ethyl)-2,3-dihydroimidazo[4,5-b]pyridine-1-carboxylate (72) (57 mg) in methylene chloride (1 mL) was treated with TFA (1 mL) for one hour. The mixture was concentrated and the resulting TFA salt was converted to the HCl salt by dissolving it in 5 mL EtOH and adding 0.5 mL of conc. HCl, then concentrating the solution in vacuo. The process was repeated and the resulting residue was dissolved in a minimum amount of methanol and triturated with the addition of ethyl ether. After 3 triturations, 3-(2-oxo-3-((R)-1-(pyridin-3-yl)ethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-3H-benzo[d]imidazole-5-carbonitrile (73) HCl salt (39 mg) was isolated as a tan colored solid: 1H-NMR (CD3OD) δ 9.9 (br s, 1H), 9.2 (s, 1H), 9.0 (m, 2H), 8.5 (s, 1H), 8.3 (m, 1H), 8.2 (m, 1H), 8.1 (d, 1H), 7.9 (d, 1H), 7.8 (d, 1H), 6.3 (q, 1H), 2.3 (d, 3H).
Reaction SMILES: C([Mg]Br)C.[Mg].C(Br)C.[CH2:9]([N:11]([CH2:14][C:15]#[CH:16])[CH2:12][CH3:13])[CH3:10].[CH:17](=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CCOCC.O1CCCC1.C(OCC)(=O)C.O>[C:18]1([CH:17]([OH:24])[C:16]#[C:15][CH2:14][N:11]([CH2:12][CH3:13])[CH2:9][CH3:10])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=Cc1ccccc1
Reactant: C#CCN(CC)CC
Agent: CC[Mg]Br
Agent: [Mg]
Solvent: CCBr
Solvent: O
Solvent: C1CCOC1
Product: CCN(CC)CC#CC(O)c1ccccc1
Temperature: 25 °C

Procedure:
To a solution of ethyl magnesium bromide in anhydrous ether, prepared from magnesium (584 mg) in ether (25 ml) and ethyl bromide (3.00 g) in ether (5 ml) in a conventional manner, was added a solution of N,N-diethyl propargylamine (2.70 g) in anhydrous tetrahydrofuran (8 ml) with stirring at room temperature, and the resulting mixture was stirred under reflux for 30 minutes. To the resulting solution was added dropwise a solution of benzaldehyde (2.54 g) in anhydrous tetrahydrofuran (7 ml) at a temperature below 10° C., and the mixture was stirred at room temperature for 2 hours. The cooled reaction mixture was diluted with ethyl acetate (50 ml), and water was added thereto in order to decompose metal complexes. The reaction mixture was dried over sodium sulfate and filtered. The filtrate was evaporated and chromatographed to afford N-(4-phenyl-4-hydroxy-2-butynyl)-N,N-diethylamine, b.p., 134°-137° C./0.12 mmHg. M.P., 52°-53.5° C.
Reaction SMILES: Cl[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[N:13]1[C:22]2[C:17](=[CH:18][C:19]([CH2:23][NH:24][S:25]([C:28]3[CH:37]=[CH:36][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:30][CH:29]=3)(=[O:27])=[O:26])=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1>>[Cl:8][C:7]1[C:2]([N:24]([CH2:23][C:19]2[CH:18]=[C:17]3[C:22](=[CH:21][CH:20]=2)[N:13]=[CH:14][CH:15]=[CH:16]3)[S:25]([C:28]2[CH:29]=[CH:30][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:36][CH:37]=2)(=[O:26])=[O:27])=[N:3][CH:4]=[C:5]([C:9]([F:12])([F:11])[F:10])[CH:6]=1
Reactant: FC(F)(F)c1cnc(Cl)c(Cl)c1
Reactant: COC(=O)c1ccc(S(=O)(=O)NCc2ccc3ncccc3c2)cc1
Product: COC(=O)c1ccc(S(=O)(=O)N(Cc2ccc3ncccc3c2)c2ncc(C(F)(F)F)cc2Cl)cc1

Procedure:
The titled compound was prepared according to the procedure described in step-2 of Example 1 from 2,3-dichloro-5-(trifluoromethyl)pyridine and methyl 4-(N-(quinolin-6-ylmethyl)sulfamoyl)benzoate (step-1 of Example 39).
Reaction SMILES: [Cl:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[S:11][N:10]=2)=[CH:5][CH:4]=1.[S].[NH2:19][CH2:20][CH2:21][CH2:22][NH2:23].Cl>C1(C)C=CC=CC=1>[ClH:1].[NH:19]1[CH:20]=[CH:21][CH2:22][NH:23][CH:2]1[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[S:11][N:10]=2)=[CH:5][CH:4]=1
Reactant: NCCCN
Reactant: ClCc1ccc(-c2nsc3ccccc23)cc1
Agent: Cl
Agent: [S]
Solvent: Cc1ccccc1
Product: C1=CNC(c2ccc(-c3nsc4ccccc34)cc2)NC1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
26 g of 3-(4-chloromethylphenyl)-1,2-benzisothiazole, 6.4 g of sulfur and 300 ml of toluene are heated to 50° C. 15 g of 1,3-diaminopropane are added slowly at the same temperature. The reaction mixture is then stirred for 20 hours under reflux. 20 g of hydrogen chloride gas are then passed in over one hour, the mixture is cooled to room temperature and the resulting solid is filtered off. After recrystallization from water in the presence of active charcoal, 18 g of 3-[4-tetrahydropyrimidin-2-yl)-phenyl]-1,2-benzisothiazole hydrochloride, melting, with decomposition, at 314° C., are obtained. The yield corresponds to 54.6% of theory.
Reaction SMILES: ClC1C(Cl)=CC=C(Cl)N=1.ClC1C=CC=C(Cl)N=1.[Cl:18][C:19]1[N:24]=[C:23]([Cl:25])[C:22]([Cl:26])=[C:21](Cl)[C:20]=1[Cl:28].NN.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C(O)C.C(N(CC)CC)C.[OH-].[Na+]>[Cl:25][C:23]1[C:22]([Cl:26])=[CH:21][C:20]([Cl:28])=[C:19]([Cl:18])[N:24]=1
Reactant: Clc1nc(Cl)c(Cl)c(Cl)c1Cl
Agent: Clc1ccc(Cl)c(Cl)n1
Agent: Clc1cccc(Cl)n1
Agent: NN
Solvent: CCO
Solvent: CCN(CC)CC
Product: Clc1cc(Cl)c(Cl)nc1Cl

Procedure:
2,3,6-Trichloropyridine is obtained, for example, in the chlorination of 2,6-dichloropyridine (EP Patent 239,904), in the treatment of pentachloropyridine with hydrazine in ethanol/triethylamine and sodium hydroxide solution (U.S. Pat. No. 3,947,457), and selectively in the reduction of pentachloropyridine with lithium aluminum hydride (F. Binns, S.M. Roberts, H. Suschitzky, J. Chem. Soc. C, (1970) (10), 1375-1380; J. Chem. Soc. D (1969) (20), 1211-1212). 2,3,5,6-Tetrachloropyridine can also be obtained in this way if less reductant is employed.
Reaction SMILES: C(O[C:4](=[C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[NH:13][C:12]1=[O:23])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)C.[CH2:24]([O:26][C:27]([CH2:29][NH:30][CH2:31][C:32]1[CH:33]=[C:34]([CH:36]=[CH:37][CH:38]=1)[NH2:35])=[O:28])[CH3:25]>CN(C=O)C>[CH2:24]([O:26][C:27]([CH2:29][NH:30][CH2:31][C:32]1[CH:33]=[C:34]([NH:35]/[C:4](=[C:11]2\[C:12](=[O:23])[NH:13][C:14]3[C:19]\2=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=3)/[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:36]=[CH:37][CH:38]=1)=[O:28])[CH3:25]
Reactant: CCOC(=O)CNCc1cccc(N)c1
Reactant: CCOC(=C1C(=O)Nc2ccc([N+](=O)[O-])cc21)c1ccccc1
Solvent: CN(C)C=O
Product: CCOC(=O)CNCc1cccc(N/C(=C2\C(=O)Nc3ccc([N+](=O)[O-])cc32)c2ccccc2)c1

Procedure:
Prepared analogously to Example 89 from 3-(1-ethoxy-1-phenyl-methylidene)-5-nitro-2-indolinone and 3-ethoxycarbonylmethylaminomethyl-aniline in DMF.
Reaction SMILES: [C:1]1([S:7]([NH:10][C:11]2[S:19][C:18]3[CH2:17][CH2:16][O:15][CH2:14][C:13]=3[C:12]=2[C:20]([O:22]C)=[O:21])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(S(N(S(C2C=CC=CC=2)(=O)=O)C2SC3CCOCC=3C=2C(OC)=O)(=O)=O)C=CC=CC=1>>[C:1]1([S:7]([NH:10][C:11]2[S:19][C:18]3[CH2:17][CH2:16][O:15][CH2:14][C:13]=3[C:12]=2[C:20]([OH:22])=[O:21])(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC(=O)c1c(NS(=O)(=O)c2ccccc2)sc2c1COCC2
Agent: COC(=O)c1c(N(S(=O)(=O)c2ccccc2)S(=O)(=O)c2ccccc2)sc2c1COCC2
Product: O=C(O)c1c(NS(=O)(=O)c2ccccc2)sc2c1COCC2

Procedure:
Prepared by proceeding in a similar manner to Example 2, starting from a mixture of methyl 2-benzenesulphonylamino-6,7-dihydro-4H-thieno[3,2-c]pyran-3-carboxylate and methyl 2-[bis-(benzenesulphonyl)amino]-6,7-dihydro-4H-thieno[3,2-c]pyran-3-carboxylate (Intermediate 14)
Reaction SMILES: [C:1]([C:5]([CH3:28])([CH3:27])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([OH:26])([CH2:22][C:23]([OH:25])=[O:24])[CH2:18][C:19]([OH:21])=[O:20])(OC)=[O:2].C(C(C)(C)CCCCCCCCCCCC(O)(CC(O)=O)CC(O)=O)(O)=O>>[OH:2][CH2:1][C:5]([CH3:28])([CH3:27])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([OH:26])([CH2:22][C:23]([OH:25])=[O:24])[CH2:18][C:19]([OH:21])=[O:20]
Reactant: COC(=O)C(C)(C)CCCCCCCCCCCC(O)(CC(=O)O)CC(=O)O
Agent: CC(C)(CCCCCCCCCCCC(O)(CC(=O)O)CC(=O)O)C(=O)O
Product: CC(C)(CO)CCCCCCCCCCCC(O)(CC(=O)O)CC(=O)O

Procedure:
##STR10## 3-(12-Carbomethoxy-12-methyl-tridecyl)-3-hydroxy glutaric acid; ##STR11## 3-(12-Carboxy-12-methyl-tridecyl)-3-hydroxy glutaric acid; ##STR12## and Dimethyl 3-(12-carbomethoxy-12-methyl-tridecyl)-3-hydroxy glutarate. ##STR13##
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][NH2:17])[C:13]([OH:15])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:19]O>>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][NH2:17])[C:13]([O:15][CH3:19])=[O:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NC[C@H](NC(=O)OCc1ccccc1)C(=O)O
Reactant: CO
Agent: Cl
Product: COC(=O)[C@H](CN)NC(=O)OCc1ccccc1
Temperature: 20 °C
Reaction time: 2 h

Procedure:
A solution of 2(S)-benzyloxycarbonylamino-3-aminopropionoic acid (2.4 g) in methanol at 0° C. was saturated with HCl gas. After stirring for 2 h at 20° C. the solution was evaporated to obtain the title compound. 1H NMR (300 MHz, CD3OD ) δ 7.35 (5H, m), 5.13 (2H, s), 4.50 (1H, m), 3.77 (3H, s), 3.45 (1H, m), 3.22 (1H, m).
Reaction SMILES: [OH:1][CH2:2][C:3]1[C:4]([I:20])=[C:5]([C:7]([I:19])=[C:8]([C:11]([NH:13][CH2:14][CH:15]([OH:18])[CH2:16][OH:17])=[O:12])[C:9]=1[I:10])[NH2:6].C(Cl)Cl>C(OC(=O)C)(=O)C.N1C=CC=CC=1>[C:2]([O:1][CH2:2][C:3]1[C:4]([I:20])=[C:5]([C:7]([I:19])=[C:8]([C:11]([NH:13][CH2:14][CH:15]([O:18][C:16](=[O:17])[CH3:15])[CH2:16][O:17][C:11](=[O:12])[CH3:8])=[O:12])[C:9]=1[I:10])[NH2:6])(=[O:1])[CH3:3]
Reactant: Nc1c(I)c(CO)c(I)c(C(=O)NCC(O)CO)c1I
Solvent: CC(=O)OC(C)=O
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)OCc1c(I)c(N)c(I)c(C(=O)NCC(COC(C)=O)OC(C)=O)c1I
Temperature: 25 °C
Reaction time: 24 h

Procedure:
3-Hydroxymethyl-5-(2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodoaniline (1.89 g, 3.06 mmol) prepared according to Example 3d, was dissolved in a mixture of acetic anhydride (5 ml) and pyridine (5 ml). The mixture was stirred at room temperature for 24 h, CH2Cl2 (100 ml) was added and the solution was washed with water (3×25 ml), with a saturated aqueous solution of NaHCO3, dried (Na2SO4) and evaporated. The product was purified by flash chromatography on silica gel using a mixture of CH2Cl2 and methanol (98:2) as the eluent. Yield: 1.30 g (57%).