Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]([O:5]C(=O)OC(Cl)(Cl)Cl)(Cl)Cl.[CH2:13]([O:15][CH2:16][CH2:17][OH:18])[CH3:14].N1C=CC=CC=1>O1CCCC1>[C:2]([Cl:1])(=[O:5])[O:18][CH2:17][CH2:16][O:15][CH2:13][CH3:14]
Reactant: CCOCCO
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: CCOCCOC(=O)Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 84.5 %

Procedure:
To a solution (20 mL) of bis(trichloromethyl)carbonate (2.97 g) in tetrahydrofuran was dropwise added a solution (10 mL) of 2-ethoxyethanol (1.80 g) in tetrahydrofuran under ice-cooling. Then a solution (10 mL) of pyridine (2.43 mL) in tetrahydrofuran was added dropwise, and the mixture was stirred at room temperature for 2 hrs. The reaction mixture was concentrated under reduced pressure and water (50 mL) was added to the residue. The mixture was extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with 0.2N hydrochloric acid (20 mL) and saturated brine (50 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 2-ethoxyethyl chlorocarbonate (1.29 g). A solution (15 mL) of tert-butyl 2-hydroxyethyl(methyl)carbamate (1.23 g) obtained in Reference Example 1 in tetrahydrofuran was added pyridine (0.68 mL), and a solution (5 mL) of 2-ethoxyethyl chlorocarbonate obtained above in tetrahydrofuran was dropwise added to the mixture, and the mixture was stirred at room temperature for 3 days. After concentration of the reaction mixture under reduced pressure, water (50 mL) was added thereto and the mixture was extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with a 5% aqueous citric acid solution (50 mL) and saturated brine (50 mL), dried over anhydrous magnesium sulfate. The mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (eluted with ethyl acetate:hexane=1:5, then 2:3). The purified product (1.60 g) was dissolved in diethyl ether (3 mL) and a 4N hydrogen chloride-ethyl acetate solution (3 mL) was added. The mixture was stirred overnight at room temperature, and the precipitated solid was collected by filtration and dried under reduced pressure to give the title compound (0.94 g) as a white solid.
Reaction SMILES: [N:1]1([C:7]([N:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=3)[CH2:12][CH:11]([C:26](O)=[O:27])[CH2:10]2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:29]([NH:32][NH2:33])(=[O:31])[CH3:30]>>[C:29]([NH:32][NH:33][C:26]([CH:11]1[CH2:12][CH:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:23])([F:25])[F:24])=[CH:17][CH:16]=2)[CH2:14][N:9]([C:7]([N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)=[O:8])[CH2:10]1)=[O:27])(=[O:31])[CH3:30]
Reactant: CC(=O)NN
Reactant: O=C(O)C1CC(c2ccc(OC(F)(F)F)cc2)CN(C(=O)N2CCOCC2)C1
Product: CC(=O)NNC(=O)C1CC(c2ccc(OC(F)(F)F)cc2)CN(C(=O)N2CCOCC2)C1

Procedure:
100 mg (0.25 mmol) of the compound from Example 44A and 37 mg (0.50 mmol) of acetohydrazide were reacted according to the General Method 11A. Yield: 106 mg (93% of theory)
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH3:13])[CH:8]=2)[N:3]=1.[CH3:14][NH:15][C:16]1[CH:21]=[CH:20][C:19](B2OC(C)(C)C(C)(C)O2)=[CH:18][CH:17]=1>>[CH3:13][O:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([C:19]1[CH:20]=[CH:21][C:16]([NH:15][CH3:14])=[CH:17][CH:18]=1)[CH:11]=[CH:10]2
Reactant: CNc1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Reactant: COc1ccc2nc(Cl)ccc2c1
Product: CNc1ccc(-c2ccc3cc(OC)ccc3n2)cc1

Procedure:
4-(6-Methoxyquinolin-2-yl)-N-methylaniline T523 was prepared using general procedure A from 2-chloro-6-methoxyquinoline (39 mg, 0.2 mmol) and N-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (46 mg, 0.2 mmol). T523 was obtained as a brown solid (27 mg, 51%). NMR (400 MHz, CDCl3): δ 8.03-7.99 (m, 4H), 7.75 (d, J=8.4 Hz, 1H), 7.33 (dd, J=9.2, 2.8 Hz, 1H), 7.04 (d, J=2.8 Hz, 1H), 6.71 (m, 2H), 3.92 (s, 3H), 2.89 (s, 3H); MS (ESI): 235 (M+H+).
Reaction SMILES: [Li+].CC([N-]C(C)C)C.[C:9]([O:15][CH2:16][CH3:17])(=[O:14])[CH2:10][C:11]([CH3:13])=[O:12].[Cl:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22]Br.Cl>O1CCCC1>[Cl:18][C:19]1[CH:20]=[C:21]([CH2:22][CH2:13][C:11](=[O:12])[CH2:10][C:9]([O:15][CH2:16][CH3:17])=[O:14])[CH:24]=[CH:25][CH:26]=1
Reactant: CCOC(=O)CC(C)=O
Reactant: Clc1cccc(CBr)c1
Agent: CC(C)[N-]C(C)C
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: CCOC(=O)CC(=O)CCc1cccc(Cl)c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of LDA (2.0M solution in heptanes/tetrahydrofuran/ethylbenzene, 500 ml) in tetrahydrofuran (2 L) at 0° C. was added ethyl acetoacetate (62 ml). After 40 min 3-chlorobenzyl bromide (100 g) was added dropwise and the mixture was stirred at 0° C. for 1 hour. The reaction mixture was acidified with 2N HCl and the organic phase was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with water and brine, dried (MgSO4) and evaporated. Purification was by chromatography eluting with 5-10% ethyl acetate in isohexane.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[N:21]=[C:22]4[C:28]([C:29]([OH:31])=O)=[CH:27][N:26]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:23]4=[N:24][CH:25]=3)=[N:7][N:8]2[CH2:11][C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:13])=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:52]([NH2:56])([CH3:55])([CH3:54])[CH3:53]>C1COCC1>[C:52]([NH:56][C:29]([C:28]1[C:22]2[C:23](=[N:24][CH:25]=[C:20]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=4)[N:8]([CH2:11][C:12]([N:14]4[CH2:19][CH2:18][O:17][CH2:16][CH2:15]4)=[O:13])[N:7]=3)[N:21]=2)[N:26]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:37])([CH3:38])[CH3:39])[CH:27]=1)=[O:31])([CH3:55])([CH3:54])[CH3:53]
Reactant: C[Si](C)(C)CCOCn1cc(C(=O)O)c2nc(-c3nn(CC(=O)N4CCOCC4)c4cc(F)ccc34)cnc21
Reactant: CC(C)(C)N
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CC(C)(C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-c3nn(CC(=O)N4CCOCC4)c4cc(F)ccc34)nc12
Temperature: 60 °C
Reaction time: 0.75 h
Yield: 68.9 %

Procedure:
In a 15 ml round-bottomed flask, 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (110 mg, 0.20 mmol) was suspended in THF (3 ml) and 1,1′-carbonyldiimidazole (39 mg, 0.24 mmol) was added. The light yellow suspension was stirred at 60° C. for 45 min during which time all solids dissolved. The reaction mixture was cooled to room temperature, tert-butylamine (0.20 ml, 1.9 mmol) was added, and the reaction was stirred at room temperature overnight. The reaction mixture was quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-80% EtOAc) to afford 84 mg (70%) of 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as an off-white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8](=[O:11])[CH2:9][CH3:10])[CH:5]=[CH:6][CH:7]=1.CO[CH:14](OC)[N:15]([CH3:17])[CH3:16]>>[Cl:1][C:2]1[CH:3]=[C:4]([C:8](=[O:11])[C:9]([CH3:10])=[CH:14][N:15]([CH3:16])[CH3:17])[CH:5]=[CH:6][CH:7]=1
Reactant: COC(OC)N(C)C
Reactant: CCC(=O)c1cccc(Cl)c1
Product: CC(=CN(C)C)C(=O)c1cccc(Cl)c1

Procedure:
A mixture of 75.0 g of m-chloropropiophenone and 200 ml of N,N-dimethylformamide dimethyl acetal was stirred and heated at reflux for 16 hours. The mixture was evaporated in vacuo to give a black oil. The oil was subjected to Kugelrohr distillation at 0.5 mm of mercury and the fraction that boils at 110° C. was removed. The residue from the distillation was collected to give 35.0 g of 3'-chloro-3-dimethylamino-2-methylacrylophenone as a black oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[CH:26]=[C:12]2[C:13]([NH:17]C3C=C(NC)N=CN=3)=[N:14][CH:15]=[CH:16][C:11]2=[N:10]1.ClC1C2=CN(C3C(Cl)=CC=CC=3Cl)N=C2C=CN=1.N>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[CH:26]=[C:12]2[C:13]([NH2:17])=[N:14][CH:15]=[CH:16][C:11]2=[N:10]1
Reactant: CNc1cc(Nc2nccc3nn(-c4c(Cl)cccc4Cl)cc23)ncn1
Agent: Clc1cccc(Cl)c1-n1cc2c(Cl)nccc2n1
Agent: N
Product: Nc1nccc2nn(-c3c(Cl)cccc3Cl)cc12
Yield: 53 %

Procedure:
Following the procedure described for N-[2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-yl]-N′-methylpyrimidine-4,6-diamine, 4-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine and 33% aqueous ammonia (1.5 mL) were reacted to afford the title compound as a white solid (139 mg, 53% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.66 (d, J=0.9 Hz, 1H), 7.79-7.77 (m, 2H), 7.67 (dd, J=9.0, 7.3 Hz, 1H), 7.58 (d, J=6.5 Hz, 1H), 7.10 (br s, 2H), 6.74 (dd, J=6.5, 1.0 Hz, 1H). LCMS (Method B): RT=2.54 min, m/z: 279 [M+H+].
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[S:10])=[CH:4][CH:3]=1.[CH3:11][NH:12][NH2:13]>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([N:12]([CH3:11])[NH2:13])=[S:10])=[CH:4][CH:3]=1
Reactant: CNN
Reactant: S=C=Nc1ccc(Cl)cc1
Solvent: CCO
Product: CN(N)C(=S)Nc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 4-chlorophenylisothiocyanate (17.0 g, 0.10 mole) and methylhydrazine (5.0 g, 0.11 mole) in 80 ml of ethanol was stirred at room temperature for two hours. The reaction mixture was filtered to collect colorless crystalline N-(4-chlorophenyl)-1-methylhydrazinecarbothioamide (18.4 g, mp 152°-154° C.).
Reaction SMILES: C[N:2]1[CH:6]2[CH2:7][C:8]([CH2:10][CH:3]1[CH2:4][CH2:5]2)=[O:9].Cl[C:12]([O:14][CH2:15][CH3:16])=[O:13]>C1C=CC=CC=1>[CH2:15]([O:14][C:12]([N:2]1[CH:6]2[CH2:5][CH2:4][CH:3]1[CH2:10][C:8](=[O:9])[CH2:7]2)=[O:13])[CH3:16]
Reactant: CN1C2CCC1CC(=O)C2
Reactant: CCOC(=O)Cl
Solvent: c1ccccc1
Product: CCOC(=O)N1C2CCC1CC(=O)C2
Yield: 88.4 %

Procedure:
56.5 g of tropinone are dissolved in 330 ml of anhydrous benzene and heatedto 70° C. under a nitrogen atmosphere. A solution of 88 g of freshly-distilled ethyl chloroformate in 200 ml of benzene is added dropwise within one hour, with stirring. After a further 4 hours' heating under reflux, cooling is effected, followed by filtration; the filtrate isconcentrated in a vacuum, and the residue is purified by vacuum distillation to obtain 70.75 g (88.4 percent) of (e) as colorless oil (b.p. 91° to 93° C. at 12 Pa.)
Reaction SMILES: [CH2:1]([O:8][CH2:9][C:10](Cl)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:13][O:14][C:15](=[O:29])[CH:16]([C:18]1[CH:27]=[CH:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([OH:28])[CH:24]=2)[CH:19]=1)[CH3:17].C(N(CC)CC)C>CC(C)=O>[CH3:13][O:14][C:15](=[O:29])[CH:16]([C:18]1[CH:27]=[CH:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([O:28][C:10](=[O:11])[CH2:9][O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:24]=2)[CH:19]=1)[CH3:17]
Reactant: COC(=O)C(C)c1ccc2cc(O)ccc2c1
Reactant: O=C(Cl)COCc1ccccc1
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Product: COC(=O)C(C)c1ccc2cc(OC(=O)COCc3ccccc3)ccc2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 63.8 %

Procedure:
Benzyloxy acetyl chloride (24 gm, 86.95 mmol) was added drop-wise to a mixture of 2-(6-Hydroxynaphthalen-2-yl)propionic acid methyl ester 6 (20 g, 86.95 mmol) and triethylamine (22.5 g, 222.35 mmol) in acetone (300 ml) and stirred for 2 hrs at room temp. Solids were filtered off, acetone distilled off, and water (100 ml) added. Crude 99 was extracted into chloroform, washed with 5% sodium bicarbonate (2×50 ml), water (2×50 ml), dried over sodium sulphate and distilled. Crude 99 was purified by recrystallising in chloroform:hexane (1:6) to get pure 99 (21 g, 63.9%) as a white powder. M.p: 58-60° C.
Reaction SMILES: [CH:1]([NH:4][CH2:5][CH:6]([OH:17])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][N:10]=1)([CH3:3])[CH3:2].N>CO.[Ni]>[NH2:16][CH2:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][CH:6]([OH:17])[CH2:5][NH:4][CH:1]([CH3:2])[CH3:3])=[N:10][CH:11]=1
Reactant: CC(C)NCC(O)COc1ccc(C#N)cn1
Agent: [Ni]
Agent: N
Solvent: CO
Product: CC(C)NCC(O)COc1ccc(CN)cn1

Procedure:
12.5 g of 2-(3'-isopropylamino-2'-hydroxy-propoxy)-5-cyano-pyridine are dissolved in 100 ml of methanol. 5-7 g of ammonia are added to the solution and after adding 3 g of Raney nickel hydrogenation is carried out at 70°-80° C. and 40 bars initial pressure of hydrogen, until the absorption of hydrogen ceases. The catalyst is filtered off, the solution is evaporated and the residue is distilled in a bulb tube at 140° C./0.01 mm Hg. 5-Aminomethyl-2-(3'-isopropylamino-2'-hydroxy-propoxy)-pyridine is thus obtained as a slightly yellowish oil.
Reaction SMILES: NCCOCCOCC[O:10][CH2:11][CH2:12][NH:13][C:14]([CH2:16][CH2:17][C@H:18]([NH:26][C:27]([C:29]1[CH:34]=[CH:33][C:32]([N:35](C(OCC2C=CC=CC=2)=O)[CH3:36])=[CH:31][CH:30]=1)=[O:28])[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:15].NCCO[CH2:51][CH2:52][O:53][CH2:54][CH2:55][O:56][CH2:57][CH2:58][O:59][CH2:60][CH2:61][O:62][CH2:63][CH2:64][N:65]=[N+]=[N-]>>[NH2:65][CH2:64][CH2:63][O:62][CH2:61][CH2:60][O:59][CH2:58][CH2:57][O:56][CH2:55][CH2:54][O:53][CH2:52][CH2:51][O:10][CH2:11][CH2:12][NH:13][C:14]([CH2:16][CH2:17][C@H:18]([NH:26][C:27]([C:29]1[CH:34]=[CH:33][C:32]([NH:35][CH3:36])=[CH:31][CH:30]=1)=[O:28])[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:15]
Reactant: CN(C(=O)OCc1ccccc1)c1ccc(C(=O)N[C@@H](CCC(=O)NCCOCCOCCOCCN)C(=O)OC(C)(C)C)cc1
Reactant: [N-]=[N+]=NCCOCCOCCOCCOCCOCCN
Product: CNc1ccc(C(=O)N[C@@H](CCC(=O)NCCOCCOCCOCCOCCOCCN)C(=O)OC(C)(C)C)cc1

Procedure:
Compound 26 was synthesized by an analogous procedure as employed for compound 12, but using 1-amino-17-azido-3,6,9,12,15-pentaoxaheptadecane instead of 1-amino-11-azido-3,6,9-trioxaundecane in the first step of synthesis.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.[CH:12]1([NH:17][CH2:18][C:19]([F:26])([CH3:25])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16][CH2:15][CH2:14][CH2:13]1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([N:17]([CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16]2)[CH2:18][C:19]([F:26])([CH3:25])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1
Reactant: CCOC(=O)C(C)(F)CNC1CCCC1
Reactant: O=[N+]([O-])c1cnc(Cl)nc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)C(C)(F)CN(c1nc(Cl)ncc1[N+](=O)[O-])C1CCCC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of 2,4-dichloro-5-nitropyrimidine (2.14 g, 11.0 mmol) in anhydrous acetone (30 ml) at 0° C., was added dropwise a solution of compound ethyl 3-(cyclopentylamino)-2-fluoro-2-methylpropanoate (2 g, 9.22 mmol) in acetone (10 mL) over 10 min. After which, potassium carbonate (3.8 g, 27.7 mmol) was added and the whole was stirred at rt for 18 h. After evaporation in vacuo, the residue was partitioned between ethyl acetate (200 ml) and water (200 ml). The organic layer was washed with NaHCO3, brine and water, dried over Na2SO4 and concentrated in vacuo to give a red residue which was used directly for next step. [M+H] calc'd for C15H20ClFN4O4, 375; found 375.
Reaction SMILES: C(O[C:4]([C:6]1([CH2:13][CH2:14]OC)[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]1)=[O:5])C.[CH:17]([O:20][C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=1)([CH3:19])[CH3:18]>>[OH:12][CH:9]1[CH2:8][CH2:7][C:6]2([C:4](=[O:5])[N:27]([C:24]3[CH:23]=[CH:22][C:21]([O:20][CH:17]([CH3:19])[CH3:18])=[CH:26][CH:25]=3)[CH2:14][CH2:13]2)[CH2:11][CH2:10]1
Reactant: CCOC(=O)C1(CCOC)CCC(O)CC1
Reactant: CC(C)Oc1ccc(N)cc1
Product: CC(C)Oc1ccc(N2CCC3(CCC(O)CC3)C2=O)cc1

Procedure:
The title compound was prepared in analogy to example 108, step 3 from 4-hydroxy-1-(2-methoxy-ethyl)-cyclohexanecarboxylic acid ethyl ester (obtained in example 2, step 3) by treatment with 4-isopropoxy-phenylamine as a mixture of cis and trans diastereomers. White solid. MS (m/e): 304.190 [MH+].
Reaction SMILES: [C:1]([C:4]1[S:5][CH:6]=[CH:7][CH:8]=1)(=O)[CH3:2].[CH:9]1([NH2:15])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.C(O)=O>C1(C)C=CC=CC=1>[CH:9]1([N:15]=[C:1]([C:4]2[S:5][CH:6]=[CH:7][CH:8]=2)[CH3:2])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: CC(=O)c1cccs1
Reactant: NC1CCCCC1
Solvent: Cc1ccccc1
Solvent: O=CO
Product: CC(=NC1CCCCC1)c1cccs1
Yield: 101.3 %

Procedure:
378 g (3 moles) of acetylthiophene, 594 g (6 moles) of cyclohexylamine and 6 ml of formic acid are azeotropically dehydrated by means of 1 liter of toluene. When all the water has been removed, the solution is cooled and the toluene and excess amine are removed under reduced pressure of 18 mm of mercury, without exceeding 120° C. in the reactor. In this way, 630 g of acetylthiophene N-cyclohexylimine are obtained, titrating 94.5% by gas phase chromatography, namely a yield of 97%. NMR spectrum in carbon tetrachloride
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[CH2:2].P(Cl)(Cl)(Cl)=O.[Cl:23][C:24]([Cl:29])(Cl)[C:25](Cl)=[O:26]>C(OCC)C.[Cu].[Zn]>[CH2:11]([O:10][C:4]1[CH:5]=[CH:6][C:7]([F:9])=[CH:8][C:3]=1[CH:1]1[CH2:2][C:25](=[O:26])[C:24]1([Cl:29])[Cl:23])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: O=C(Cl)C(Cl)(Cl)Cl
Reactant: C=Cc1cc(F)ccc1OCc1ccccc1
Agent: [Cu]
Agent: [Zn]
Solvent: O=P(Cl)(Cl)Cl
Solvent: CCOCC
Product: O=C1CC(c2cc(F)ccc2OCc2ccccc2)C1(Cl)Cl
Temperature: 40 °C
Reaction time: 2 h

Procedure:
Zinc-copper couple (1.71 g, 13.1 mmol) was added to a solution of benzyl 2-ethenyl-4-fluorophenyl ether (C17) (1.0 g, 4.38 mmol) in diethyl ether (15 mL). To this mixture was added drop-wise a mixture of phosphorus oxychloride (446 μL, 4.82 mmol) and trichloroacetyl chloride (978 μL, 8.76 mmol) in diethyl ether (5 mL). The mixture was stirred at 40° C. for 2 hours, cooled to room temperature and stirred for an additional 18 hours. The solution was filtered through Celite, and the filtrate was washed with water (2×100 mL) and saturated aqueous sodium chloride solution (100 mL), dried over magnesium sulfate and concentrated in vacuo to afford the title compound as a colorless oil. Yield: 1.4 g, 4.13 mmol, 94%. 1H NMR (400 MHz, CDCl3) δ 3.57 (dd, half of ABX pattern, J=18.0, 10.5 Hz, 1H), 3.65 (dd, half of ABX pattern, J=18.0, 9.4 Hz, 1H), 4.49 (dd, J=10.1, 9.8 Hz, 1H), 5.14 (AB quartet, JAB=12.0 Hz, ΔνAB=12.2 Hz, 2H), 6.91-6.95 (m, 2H), 7.01 (ddd, J=9.0, 7.8, 2.9 Hz, 1H), 7.32-7.44 (m, 3H), 7.45-7.49 (m, 2H).
Reaction SMILES: [NH2:1][S:2]([C:5]1[C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][S:8][C:9]=1[CH3:10])(=[O:4])=[O:3].C(N=[C:21]=[O:22])CCCC.C(Cl)(Cl)=O>>[N:1]([S:2]([C:5]1[C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][S:8][C:9]=1[CH3:10])(=[O:4])=[O:3])=[C:21]=[O:22]
Reactant: COC(=O)c1csc(C)c1S(N)(=O)=O
Reactant: CCCCCN=C=O
Agent: O=C(Cl)Cl
Product: COC(=O)c1csc(C)c1S(=O)(=O)N=C=O

Procedure:
Under the conditions specified above, 23.5 g of methyl 4-(aminosulfonyl)-5-methylthiophene -3-carboxylate (1) were reacted with 11.3 g of pentyl isocyanate (100 mmol) in the presence of phosgene to give methyl 4-(isocyanatosulfonyl)-5-methylthiophene-3-carboxylate (2). 22 g of this isocyanate (83% of theory, content: 99%, b.p.: 120° C., 0.4 mbar) were likewise obtained. The identification and the determination of content were conducted by means of derivatization with methanol to the corresponding carbamate (1H NMR (400 MHz, d6DMSO): 2.72 (s), 3.61 (s), 3.79 (s), 8.00 (s), 11.96 (s)).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:22])=[C:6]([NH:8][C:9](=[O:21])[CH2:10][C:11]23[CH2:20][CH:15]4[CH2:16][CH:17]([CH2:19][CH:13]([CH2:14]4)[CH2:12]2)[CH2:18]3)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][C:31]([O:33]CC)=[O:32].[OH-].[Na+].[ClH:38]>C(OCC)(=O)C.O1CCOCC1>[ClH:38].[CH3:22][C:5]1[CH:4]=[CH:3][C:2]([O:1][CH2:30][C:31]([OH:33])=[O:32])=[CH:7][C:6]=1[NH:8][C:9](=[O:21])[CH2:10][C:11]12[CH2:20][CH:15]3[CH2:14][CH:13]([CH2:19][CH:17]([CH2:16]3)[CH2:18]1)[CH2:12]2
Reactant: CCOC(=O)CBr
Reactant: Cc1ccc(O)cc1NC(=O)CC12CC3CC(CC(C3)C1)C2
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: Cc1ccc(OCC(=O)O)cc1NC(=O)CC12CC3CC(CC(C3)C1)C2
Temperature: 80 °C

Procedure:
To a solution of N-(5-Hydroxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-acetamide from Example 12 (0.20 g) was added potassium carbonate (0.106 g) and ethyl bromoacetate (0.3 ml). The reaction mixture was stirred and heated at 80° C. for 24 hours. Once cooled, the reaction mixture was diluted with ethyl acetate and washed with saturated brine. The organic phase was separated, dried over magnesium sulphate (MgSO4) and evaporated under reduced pressure to leave a residue which was purified by silica gel chromatography eluting with iso-hexane/diethyl ether (1:1) to give a white solid. The solid was dissolved in dioxane (20 ml) and the solution treated with 2M sodium hydroxide solution, the reaction mixture was stirred at ambient temperature for 24 hours, acidified (2M hydrochloric acid) and extracted into ethyl acetate. The organic phase was washed with brine, dried over magnesium sulphate (MgSO4) and evaporated under reduced pressure. The residue was triturated with diethyl ether to leave the title compound as a white solid (0.070 g).
Reaction SMILES: [Cl:1][C:2]1[CH:13]=[C:12]([Cl:14])[C:11]([NH:15][C:16]([NH:18][C:19]2[CH2:23][CH2:22][CH2:21][C:20]=2[C:24](OCC)=[O:25])=[O:17])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5].[Na]>C(O)(C)C>[Cl:1][C:2]1[CH:13]=[C:12]([Cl:14])[C:11]([N:15]2[C:24](=[O:25])[C:20]3[CH2:21][CH2:22][CH2:23][C:19]=3[NH:18][C:16]2=[O:17])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:8])[CH3:9])=[O:5]
Reactant: CCOC(=O)C1=C(NC(=O)Nc2cc(C(=O)OC(C)C)c(Cl)cc2Cl)CCC1
Agent: [Na]
Solvent: CC(C)O
Product: CC(C)OC(=O)c1cc(-n2c(=O)[nH]c3c(c2=O)CCC3)c(Cl)cc1Cl

Procedure:
using isopropyl 2,4-dichloro-5-{3-[2-(ethoxycarbonyl)-1-cyclopenten-1-yl]ureido}-benzoate with sodium isopropylate in isopropanol there is obtained isopropyl 2,4-dichloro-5-(1,2,4,5,6,7-hexahydro-2,4-dioxo-3H-cyclopenta[d]pyrimidin-3-yl)-benzoate, m.p. 186°-189° C.,
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH:10]([CH3:15])[CH2:11][C:12](O)=[O:13])=[CH:5][CH:4]=1.O.[NH2:18][NH2:19]>C(O)(C)C>[CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]([CH3:15])[CH2:11][C:12](=[O:13])[NH:18][N:19]=2)=[CH:5][CH:4]=1
Reactant: NN
Reactant: CSc1ccc(C(=O)C(C)CC(=O)O)cc1
Solvent: O
Solvent: CC(C)O
Product: CSc1ccc(C2=NNC(=O)CC2C)cc1

Procedure:
2.3 g (0.01 mole) of 4-(4-methylthio-phenyl)-4-oxo-3-methyl-butyric acid and 1 ml of hydrazine hydrate are heated under reflux in 20 ml of isopropanol for 2 hour. After the mixture has been cooled, the product is filtered off with suction and dried.
Reaction SMILES: CC1C=CC(S([O:11][CH2:12][CH2:13][O:14][CH:15]2[CH2:20][CH2:19][N:18](C(OCC3C=CC=CC=3)=O)[CH2:17][CH2:16]2)(=O)=O)=CC=1.[O:31]1[CH2:36][CH2:35][O:34][CH2:33][CH:32]1[CH2:37]O>>[O:31]1[CH2:36][CH2:35][O:34][CH2:33][CH:32]1[CH2:37][O:11][CH2:12][CH2:13][O:14][CH:15]1[CH2:16][CH2:17][NH:18][CH2:19][CH2:20]1
Reactant: Cc1ccc(S(=O)(=O)OCCOC2CCN(C(=O)OCc3ccccc3)CC2)cc1
Reactant: OCC1COCCO1
Product: C1CC(OCCOCC2COCCO2)CCN1
Yield: 118.8 %

Procedure:
Using benzyl 4-(2-{[(4-methylphenyl)sulfony]oxy}ethoxy)piperidine-1-carboxylate (7.8 g, 18.0 mmol) produced in Reference Example 1 (1c) and 1,4-dioxan-2-ylmethanol (1.78 g, 15.1 mmol), the desired title compound (4.4 g, yield 61%) was obtained by the same method as in Reference Examples 1 (1d) and 1 (1e).