Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[C:6]([N:8]1[CH2:13][CH2:12][C:11](=[C:14]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[O:16][C:17]([CH3:20])=[N:18][N:19]=2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.Cl.[CH3:35][O:36][C:37]1[CH:45]=[N:44][C:43]([C:46]2[NH:47][C:48]([CH3:51])=[N:49][N:50]=2)=[C:42]2[C:38]=1[C:39]([C:52](=[O:56])C(O)=O)=[CH:40][NH:41]2.C(N(CC)CC)(C)C.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1>C(Cl)Cl>[C:21]1([C:14](=[C:11]2[CH2:12][CH2:13][N:8]([C:6](=[O:7])[C:52]([C:39]3[C:38]4[C:42](=[C:43]([C:46]5[NH:47][C:48]([CH3:51])=[N:49][N:50]=5)[N:44]=[CH:45][C:37]=4[O:36][CH3:35])[NH:41][CH:40]=3)=[O:56])[CH2:9][CH2:10]2)[C:15]2[O:16][C:17]([CH3:20])=[N:18][N:19]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: COc1cnc(-c2nnc(C)[nH]2)c2[nH]cc(C(=O)C(=O)O)c12
Reactant: Cc1nnc(C(=C2CCN(C(=O)OC(C)(C)C)CC2)c2ccccc2)o1
Agent: CCN(CC)C(C)C
Agent: Cl
Agent: O=C1OCCN1P(=O)(Cl)N1CCOC1=O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1cnc(-c2nnc(C)[nH]2)c2[nH]cc(C(=O)C(=O)N3CCC(=C(c4ccccc4)c4nnc(C)o4)CC3)c12
Reaction time: 0.5 h
Yield: 17.6 %

Procedure:
To a solution of 4-[1-phenyl-1-(5-methyl-1,3,4-oxadiazol-2-yl)methylene]-piperidine-1-carboxylic acid tert-butyl ester (0.0348 g, 0.098 mmol) in CH2Cl2 (1 mL) was added TFA (0.5 mL) and the reaction mixture was stirred for 30 min. The solvent was then removed in vacuo and the residual material was dissolved in CHCl3 (1 mL). To this solution was then added 4-methoxy-7-(5-methyl-1,3,4-triazol-2-yl)-6-azaindol-3-yl-oxoacetic acid hydrochloride salt (0.0621 g, 0.206 mmol) and iPrNEt2 (0.18 mL, 1.03 mmol), followed by BOP—Cl (0.0670 g, 0.263 mmol). The mixture was stirred at rt for 2 h and then the solvent was removed in vacuo. The residue was diluted with H2O and extracted with EtOAc (×3). The combined organic layers were washed (H2O, brine), dried (Na2SO4) and concentrated, and the residue was purified by preparative HPLC (NH4OAc) to give the title compound (0.0093 g, 18%) as a colorless solid:
Reaction SMILES: [CH3:1][C:2]1([CH3:27])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([C:14]3[NH:15][C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[C:18]([C:23]([O:25][CH3:26])=[O:24])[CH:17]=4)[CH:5]=[CH:4][C:3]1=2.[H-].[Na+].[CH3:30]I.O>C1COCC1>[CH3:30][N:15]1[C:16]2[C:21](=[CH:20][CH:19]=[C:18]([C:23]([O:25][CH3:26])=[O:24])[CH:17]=2)[CH:22]=[C:14]1[C:6]1[CH:5]=[CH:4][C:3]2[C:2]([CH3:27])([CH3:1])[CH2:11][CH2:10][C:9]([CH3:12])([CH3:13])[C:8]=2[CH:7]=1
Reactant: COC(=O)c1ccc2cc(-c3ccc4c(c3)C(C)(C)CCC4(C)C)[nH]c2c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)c1ccc2cc(-c3ccc4c(c3)C(C)(C)CCC4(C)C)n(C)c2c1
Reaction time: 2 h

Procedure:
1.40 g (3.8 mmol) of the ester produced in Example 13, are dissolved in 20 ml of dry THF, and treated with 0.14 g (4.6 mmol) of sodium hydride (80% in oil). This mixture is stirred for 1 hour, at which point 0.65 g (4.4 mmol) of methyl iodide is added. The resulting mixture is stirred for 2 hours and then poured into water (100 ml) and extracted with dichloromethane (3×100 ml). The organic phase is dried and the solvent evaporated. The resulting residue is recrystallized in hexane, yielding methyl 1-methyl-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-6-indole carboxylate. (1.30 g, 91%)
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:34])[C@@H:24]([NH:26][C:27](=[O:33])[C@@H:28]([OH:32])[CH:29]([CH3:31])[CH3:30])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[CH3:35][C@:36]([CH2:42][O:43][C:44]([F:47])([F:46])[F:45])([CH:40]=[CH2:41])[C:37]([OH:39])=[O:38].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>O1CCOCC1>[OH:32][C@@H:28]([CH:29]([CH3:31])[CH3:30])[C:27]([NH:26][C@@H:24]([CH3:25])[C:23]([N:19]1[CH2:20][CH2:21][CH2:22][C@@H:17]([C:15]([NH:14][C@@H:12]([C:8]2[CH:7]=[CH:6][C:5]3[C:10](=[CH:11][C:2](/[CH:41]=[CH:40]/[C@:36]([CH3:35])([CH2:42][O:43][C:44]([F:45])([F:46])[F:47])[C:37]([OH:39])=[O:38])=[CH:3][CH:4]=3)[N:9]=2)[CH3:13])=[O:16])[NH:18]1)=[O:34])=[O:33]
Reactant: C=C[C@](C)(COC(F)(F)F)C(=O)O
Reactant: CC(C)[C@H](O)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H](C(=O)N[C@H](C)c2ccc3ccc(Br)cc3n2)N1
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CC(C)[C@H](O)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H](C(=O)N[C@H](C)c2ccc3ccc(/C=C/[C@](C)(COC(F)(F)F)C(=O)O)cc3n2)N1
Temperature: 25 °C

Procedure:
A solution of (S)-1-[(S)-2-((S)-2-hydroxy-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amide (212 mg, 0.4 mmol), crude (R)-2-methyl-2-trifluoromethoxymethyl-but-3-enoic acid (95 mg), tri(o-tolyl)phosphine (24 mg, 0.08 mmol) and triethylamine (121 mg, 0.17 mL, 1.2 mmol) in 1,4-dioxane (10 mL) was stirred at 50° C. under nitrogen. Trs(dibenzylideneacetone)dipalladium(0) (36 mg, 0.04 mmol) was added and the reaction mixture was heated at reflux for 40 minutes. The reaction mixture was cooled to room temperature and the mixture was filtered through a hydrophobic frit and the filtrate was evaporated to afford crude (E)-(R)-4-{2-[(R)-1-({(S)-1-[(S)-2-((S)-2-hydroxy-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carbonyl}-amino)-ethyl]-quinolin-7-yl}-2-methyl-2-trifluoromethoxymethyl-but-3-enoic acid which was used in the next step. LCMS (m/z) 652.1 [M+H], Tr=2.17 min.
Reaction SMILES: [NH2:1][C:2]1[N:7]2[N:8]=[C:9]([CH2:11][O:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[N:10]=[C:6]2[N:5]([CH2:22][CH3:23])[C:4](=[O:24])[CH:3]=1.[N:25](OCCC(C)C)=[O:26].O>CN(C)C=O>[NH2:1][C:2]1[N:7]2[N:8]=[C:9]([CH2:11][O:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[N:10]=[C:6]2[N:5]([CH2:22][CH3:23])[C:4](=[O:24])[C:3]=1[N:25]=[O:26]
Reactant: CC(C)CCON=O
Reactant: CCn1c(=O)cc(N)n2nc(COCc3ccc(OC)cc3)nc12
Solvent: CN(C)C=O
Solvent: O
Product: CCn1c(=O)c(N=O)c(N)n2nc(COCc3ccc(OC)cc3)nc12
Temperature: 25 °C

Procedure:
3.7 g of the precursor (7-amino-4-ethyl-2-[(4-methoxybenzyloxy)methyl]-s-triazolo[1,5-a]pyrimidin-5-one) are dissolved in 17 ml of dimethylformamide, and 2.69 ml of isoamyl nitrite are added whilst cooling with ice. Afterwards it is stirred at ambient temperature. After the reaction is complete (about 3 hours) 34 ml of water are added at 5-10° C. The solid obtained is separated off, washed with water and diethyl ether and recrystallised from 80 ml of ethanol. 2.0 g of 7-amino-4-ethyl-2-[(4-methoxybenzyloxy)methyl]-6-nitroso-s-triazolo[1,5-a]pyrimidin-5-one are left.
Reaction SMILES: C(OC([C:6]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:9][S:8][C:7]=1[NH2:17])=O)C.C(O)C>[OH-].[K+].O>[C:11]1([C:10]2[CH:6]=[C:7]([NH2:17])[S:8][CH:9]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CCOC(=O)c1c(-c2ccccc2)csc1N
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Nc1cc(-c2ccccc2)cs1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-Amino-4-phenyl-thiophene-3-carboxylic acid ethyl ester (5 g, 20.2 mmol) was suspended in 20% potassium hydroxide solution (100 ml) and heated to reflux. Ethanol (100 ml) was added to aid dissolution. The reaction was stirred overnight and then cooled to room temperature and diluted with water (250 ml). The precipitated solid was collected by filtration and dissolved in DCM/ethyl acetate before drying over magnesium sulfate. The solvent was removed in vacuo to give 4-phenyl-thiophen-2-ylamine. Yield 1.05 g (30%).
Reaction SMILES: FC(F)(F)C(O)=O.[C:8]([O:11][CH2:12][CH2:13][CH2:14][NH:15][C:16](=[O:50])[C@H:17]([N:25]([C:27](=[O:49])[C@H:28]([N:40](C(OC(C)(C)C)=O)[CH3:41])[CH2:29][C:30]1[CH:39]=[CH:38][C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=1)[CH3:26])[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)(=[O:10])[CH3:9]>ClCCl>[C:8]([O:11][CH2:12][CH2:13][CH2:14][NH:15][C:16](=[O:50])[C@H:17]([N:25]([C:27](=[O:49])[C@H:28]([NH:40][CH3:41])[CH2:29][C:30]1[CH:39]=[CH:38][C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=1)[CH3:26])[CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)(=[O:10])[CH3:9]
Reactant: CC(=O)OCCCNC(=O)[C@@H](Cc1ccccc1)N(C)C(=O)[C@@H](Cc1ccc2ccccc2c1)N(C)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CN[C@H](Cc1ccc2ccccc2c1)C(=O)N(C)[C@H](Cc1ccccc1)C(=O)NCCCOC(C)=O
Reaction time: 0.08 h
Yield: 67.7 %

Procedure:
At 0° C., trifluoroacetic acid (3 mL) was added to a solution of 3-((2R)-2-(N-((2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)propionyl)-N-methylamino)-3-phenylpropionylamino)propyl acetate (885 mg, 1.50 mmol) in dichloromethane (3 mL). The reaction mixture was stirred for 5 min. The solvents were removed in vacuo at 20° C. The residue was dissolved in dichloromethane (40 mL). The procedure was repeated twice. The crude product was purified by flash chromatography on silica (45 g) with dichloromethane/methanol/25% solution of ammonia in water (100:10:1) to give 497 mg of 3-((2R)-2-(N-((2R)-2-methylamino-3-(2-naphthyl)propionyl)-N-methylamino)-3-phenylpropionylamino)propyl acetate.
Reaction SMILES: [O:1]=[C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[N:4]=[C:3]1[CH:18]=[O:19].[CH2:20]=[N:21][CH:22](S(C1C=CC(C)=CC=1)(=O)=O)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C([O-])([O-])=O.[K+].[K+]>CC#N.O>[C:23]1([C:22]2[N:21]=[CH:20][O:19][C:18]=2[C:3]2[C:2](=[O:1])[CH:7]=[CH:6][N:5]([C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=3)[N:4]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=Cc1nn(-c2cccc(C(F)(F)F)c2)ccc1=O
Reactant: C=NC(c1ccccc1)S(=O)(=O)c1ccc(C)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: O=c1ccn(-c2cccc(C(F)(F)F)c2)nc1-c1ocnc1-c1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 24.6 %

Procedure:
To a solution of 4-oxo-1-[3-(trifluoromethyl)phenyl]-1,4-dihydropyridazine-3-carbaldehyde (52.8 mg, 0.197 mmol) in MeCN (0.4 mL) were added N-methylidene-1-[(4-methylphenyl)sulfonyl]-1-phenylmethanamine (53.8 mg, 0.197 mmol) and K2CO3 (35.4 mg, 0.256 mmol) at room temperature. The suspension was stirred at room temperature for 1 day. The suspension was diluted with water, extracted with AcOEt, washed with brine, dried over MgSO4, filtered, concentrated in vacuo, purified by column chromatography on silica gel (hexane/AcOEt=90/10 to 0/100) and crystallized with AcOEt/hexane to yield the title compound (18.6 mg, 25% yield) as a solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 6.75 (1H, d, J=8.5 Hz), 7.33-7.43 (3H, m), 7.64-7.70 (2H, m), 7.72-7.83 (2H, m), 7.92-8.01 (2H, m), 8.65 (1H, s), 9.02 (1H, d, J=7.7 Hz). Anal. Calcd for C20H12F3N3O2.0.2H2O: C, 62.08; H, 3.23; N, 10.86. Found: C, 62.08; H, 3.38; N, 10.67.
Reaction SMILES: [OH:1][CH:2]1[CH2:6][CH2:5][CH:4]([CH:7]=[CH:8][CH:9]([OH:15])[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH:3]1[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23].ClC1C=CC=C(C(OO)=[O:34])C=1>ClCCl>[OH:1][CH:2]1[CH2:6][CH2:5][CH:4]([CH:7]2[O:34][CH:8]2[CH:9]([OH:15])[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH:3]1[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCCCCC(O)C=CC1CCC(O)C1CCCCCCC(=O)OC
Solvent: ClCCl
Product: CCCCCC(O)C1OC1C1CCC(O)C1CCCCCCC(=O)OC
Yield: 91.9 %

Procedure:
A solution of methyl 7-[2-hydroxy-5-(3-hydroxy-1-octenyl)cyclopentyl]heptanoate (1.0 g.) [prepared as described in Example 5], metachlorperbenzoic acid (2.0 g.) and dichloromethane (30 ml.) was refluxed for days. The precipitated metachlorbenzoic acid was filtered from the cooled solution and washed with dichloromethane. The filtrate was washed successively with sodium sulphite solution, twice with 5% sodium bicarbonate solution and finally water, dried over sodium sulphate and evaporated to give methyl 7-[2-hydroxy-5-(3-hydroxy-1,2-epoxy-1-octyl)cyclopentyl]heptanoate (0.96 g.,92%), νmax 3450 cm-1, 1730 cm-1 and 1170 cm-1.
Reaction SMILES: [CH:1]1([NH2+:7]C2CCCCC2)CC[CH2:4][CH2:3][CH2:2]1.[CH2:14]([C@H:18]1[O:20][C@@H:19]1[C:21]([O-:23])=O)[CH2:15][CH2:16][CH3:17].C(Cl)(=O)C(C)(C)C.C(N)CCC>O1CCCC1>[CH2:1]([NH:7][C:21]([C@@H:19]1[C@@H:18]([CH2:14][CH2:15][CH2:16][CH3:17])[O:20]1)=[O:23])[CH2:2][CH2:3][CH3:4]
Reactant: CCCC[C@H]1O[C@@H]1C(=O)[O-]
Reactant: C1CCC([NH2+]C2CCCCC2)CC1
Agent: CC(C)(C)C(=O)Cl
Solvent: C1CCOC1
Solvent: CCCCN
Product: CCCCNC(=O)[C@H]1O[C@@H]1CCCC
Reaction time: 0.25 h
Yield: 99.8 %

Procedure:
Under ice-cooling, to 10 ml of an anhydrous tetrahydrofuran solution containing 299 mg (1.84 mmol) of (2S-trans)-3-butyl-oxiranecarboxylic acid-dicyclohexylammonium salt was added 2 ml of an anhydrous tetrahydrofuran solution containing 222 mg (1.84 mmol) of pivaloyl chloride, and the resulting mixture was stirred at the same temperature for 15 minutes. Moreover, the temperature of the reaction mixture was returned to room temperature, and the mixture was stirred for 2 hours. After filtering off insoluble materials in the reaction mixture, the filtrate was added to 10 ml of an anhydrous tetrahydrofuran solution containing 135 mg (1.84 mmol) of n-butylamine under ice-cooling, and the resulting mixture was stirred at room temperature for 2 hours. Under reduced pressure, the reaction mixture was concentrated and ethyl acetate was added to the concentrate, and the resulting mixture was washed successively with a 10% aqueous potassium hydrogen sulfate solution, a saturated aqueous sodium hydrogen carbonate solution and then a saturated NaCl solution. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to obtain 366 mg (Yield: 100%) of the title compound.
Reaction SMILES: [Cl:1][CH2:2][C:3](Cl)=[O:4].[CH3:6][O:7][C:8]1[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[CH:10][C:9]=1[N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+]>C(C(C)=O)C>[Cl:1][CH2:2][C:3]([N:19]1[CH2:18][CH2:17][N:16]([C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([O:14][CH3:15])[C:8]=2[O:7][CH3:6])[CH2:21][CH2:20]1)=[O:4]
Reactant: O=C(Cl)CCl
Reactant: COc1cccc(N2CCNCC2)c1OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: COc1cccc(N2CCN(C(=O)CCl)CC2)c1OC
Yield: 98 %

Procedure:
Compound 50A is prepared according to the procedure described for compound 12, using the following reactants: chloroacetyl chloride (150 ml, 1.87 mmol); 1-(2,3-dimethoxyphenyl)piperazine (29A) (416 mg, 1.87 mmol); potassium carbonate (645 mg, 4.67 mmol); methyl ethyl ketone (20 ml).
Reaction SMILES: C1(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:29]([N:36]1[CH2:40][C:39]([C:41]2([NH:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:43][CH2:42]2)=[C:38]([C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:37]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CO>[CH2:29]([N:36]1[CH2:40][C@H:39]([C:41]2([NH:44][C:45]([O:47][C:48]([CH3:50])([CH3:51])[CH3:49])=[O:46])[CH2:42][CH2:43]2)[C@H:38]([C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:37]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: CCOC(=O)C1=C(C2(NC(=O)OC(C)(C)C)CC2)CN(Cc2ccccc2)C1
Agent: c1ccc(P(CCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Solvent: CO
Product: CCOC(=O)[C@@H]1CN(Cc2ccccc2)C[C@@H]1C1(NC(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 97.8 %

Procedure:
Under a nitrogen gas stream, bis(bicyclo[2.2.1]hepta-2,5-diene)rhodium (I) perchlorate (54.5 mg, 0.14 mmol) and 1,2-bis(diphenylphosphino)ethane (67.4 mg, 0.17 mmol) were dissolved in degassed methanol (25 ml) and stirred at room temperature for 10 minutes. To this catalyst solution was added a solution of ethyl 1-benzyl-4-(1-tert-butoxycarbonylaminocyclopropyl)-3-pyrroline-3-carboxylate (1.090 g, 2.820 mmol) in dry and degassed methanol (15 ml). The thus obtained liquid reaction mixture was then stirred under a hydrogen atmosphere (1 kg/cm2) at room temperature for 2.5 hours. After adding active carbon (1 g), the liquid reaction mixture was allowed to stand at room temperature for 30 minutes and then filtered-through celite (washed with methanol). The filtrate was concentrated under reduced pressure and the residue was subjected to flash silica gel column chromatography (eluent:n-hexane:ethyl acetate=5:1) to obtain 1.071 g (97.8%) of the title compound as colorless crystals.
Reaction SMILES: [CH2:1]([OH:4])[CH2:2]O.O[CH2:6][CH:7]([CH2:9][OH:10])O>>[C:9]([O:10][CH3:1])(=[O:10])[C:7]1[CH:6]=[CH:7][C:2]([C:1]([O:4][CH3:2])=[O:4])=[CH:9][CH:6]=1
Reactant: OCC(O)CO
Reactant: OCCO
Product: COC(=O)c1ccc(C(=O)OC)cc1
Yield: 490.7 %

Procedure:
A polyester is produced in known manner from 388 g of dimethyl terephthalate, 112 g of ethylene glycol and 75 g of glycerin, and mixed with 273 g of the reaction product of Example A, added thereto in two portions at a temperature of 180°-215° C. Subsequently the reaction product is worked up as described in Example 1, the obtained lacquer is diluted to a solid body content of 27% and the viscosity of 55 seconds, and copper wire is lacquered therewith.
Reaction SMILES: [Cl-].C([Al+]CC)C.[F:7][C:8]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:9]=1[NH2:10].[C:16]1(=[O:20])[O:19][CH2:18][CH2:17]1.Cl>ClCCl>[F:7][C:8]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:9]=1[NH:10][C:18](=[O:19])[CH2:17][CH2:16][OH:20]
Reactant: Nc1cc(F)ccc1F
Reactant: O=C1CCO1
Agent: CC[Al+]CC
Agent: Cl
Agent: [Cl-]
Solvent: ClCCl
Product: O=C(CCO)Nc1cc(F)ccc1F
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
4 ml of a solution of diethylaluminum chloride (1M in hexane) is added dropwise at 0° C. to a solution of 0.519 g of 2,5-difluoroaniline in 10 ml of anhydrous dichloromethane. The reaction solution is stirred at room temperature for a further 20 minutes and subsequently cooled back to 0° C. A solution of 0.147 g of propiolactone in 8 ml of dichloromethane is added dropwise and the reaction mixture is stirred at room temperature over a further 2 hours. The reaction mixture is subsequently hydrolysed at 0° C. with 30 ml of 0.2M HCl and the phases are separated. The aqueous phase is re-extracted with 2×50 ml of dichloromethane and the combined organic phases are washed with 50 ml of water, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a beige solid from the residue by means of flash chromatography (SiO2 60F). Rf=0.15 (1:1 EtOAc-heptane); Rt=2.62.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](O)=[O:6].CCN=C=NCCCN(C)C.Cl.[CH3:23][NH:24][O:25][CH3:26].Cl>C(Cl)Cl.O>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([N:24]([O:25][CH3:26])[CH3:23])=[O:6]
Reactant: CNOC
Reactant: O=C(O)c1cccc(F)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: O
Product: CON(C)C(=O)c1cccc(F)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 61 %

Procedure:
To a solution of 3-fluorobenzoic acid (30 g, 214.1 mmol) in DCM (300 mL) were added EDC.HCl (45 g, 235 mmol) and N,O-dimethylhydroxylamine.HCl (23 g, 235 mmol) at 0° C. under N2. The reaction mixture was stirred at rt for 3 h, then diluted with water (1000 mL) and extracted with DCM (3×200 mL). The organics were washed with brine, dried over Na2SO4, and concentrated to obtain the 3-fluoro-N-methoxy-N-methylbenzamide (24 g, 61%). (183.91 [M+H]) 1H NMR: (400 MHz, CDCl3) δ: 3.38 (s, 3H), 3.57 (s, 3H), 7.14-7.19 (m, 1H), 7.37-7.43 (m, 2H), 7.48-7.50 (d, J=7.6, 1H).
Reaction SMILES: [CH2:1]([N:3]([CH2:23][CH3:24])[C:4]([CH:6]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:19][CH2:20][OH:21])[C:10]=2[CH2:9][CH:8]([CH3:22])[CH2:7]1)=[O:5])[CH3:2].N1C=CC=CC=1.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>ClCCl>[CH2:23]([N:3]([CH2:1][CH3:2])[C:4]([CH:6]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:19][CH2:20][O:21][S:32]([CH3:31])(=[O:34])=[O:33])[C:10]=2[CH2:9][CH:8]([CH3:22])[CH2:7]1)=[O:5])[CH3:24]
Reactant: CS(=O)(=O)Cl
Reactant: CCN(CC)C(=O)C1CC(C)Cc2c1c1ccccc1n2CCO
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCN(CC)C(=O)C1CC(C)Cc2c1c1ccccc1n2CCOS(C)(=O)=O
Temperature: 0 °C
Yield: 76.9 %

Procedure:
To a solution of 9-(2-hydroxy-ethyl)-2-methyl-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide (49) (250 mg, 0.8 mmol) in dichloromethane (10 mL) was added pyridine (633 mg, 8.0 mmol, 0.6 mL). The reaction was cooled to 0° C. and methanesulfonyl chloride (367 mg, 3.2 mmol, 0.2 mL) was added. The reaction was allowed to warm to room temperature overnight. The mixture was washed with 2 N HCl (2×20 mL) and water (2×20 mL), dried and concentrated in vacuo. The crude material was purified by silica gel chromatography eluting with petrol (A) and ethyl acetate (B) (0-100% B, 10 g, 34 CV, 30 mL/min) then triturated with diethyl ether to afford 250 mg (80%) of methanesulfonic acid 2-(4-diethylcarbamoyl-2-methyl-1,2,3,4-tetrahydro-carbazol-9-yl)-ethyl ester as a white solid. The structure was confirmed by 13C NMR (75 MHz, CDCl3) δ 12.9, 13.0, 15.2, 22.0, 29.7, 30.2, 36.7, 36.8, 40.8, 41.6, 42.0, 67.8, 108.6, 109.5, 118.6, 119.6, 121.2, 126.4, 136.2, 136.4, 173.7.
Reaction SMILES: [C:1]([NH:3][C@@H:4]1[CH2:9][CH2:8][CH2:7][CH2:6][C@@H:5]1[NH:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH3:21])[CH:19]=2)[N:14]=[C:13]([C:22]([NH:24][CH2:25][CH2:26][O:27][CH3:28])=[O:23])[N:12]=1)#[N:2].Cl.[CH3:30][O:31][NH2:32].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[NH2:2][C:1]([NH:3][C@@H:4]1[CH2:9][CH2:8][CH2:7][CH2:6][C@@H:5]1[NH:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH3:21])[CH:19]=2)[N:14]=[C:13]([C:22]([NH:24][CH2:25][CH2:26][O:27][CH3:28])=[O:23])[N:12]=1)=[N:32][O:31][CH3:30]
Reactant: COCCNC(=O)c1nc(N[C@H]2CCCC[C@H]2NC#N)c2cc(C)ccc2n1
Reactant: CON
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Product: COCCNC(=O)c1nc(N[C@H]2CCCC[C@H]2NC(N)=NOC)c2cc(C)ccc2n1
Temperature: 0 °C
Yield: 77.7 %

Procedure:
To a solution of 1.96 g of 4-{[(1S,2R)-2-(cyanoamino)cyclohexyl]amino}-N-(2-methoxyethyl)-6-methylquinazolin-2-carboxamide and 8.56 g of methoxyamine hydrochloride in 80 ml of ethanol, 10.86 g of sodium carbonate was added and the mixture was heated at reflux for 1 hour. The reaction solution was added to 400 ml of ice water, and the deposited substance was collected by filtration. After the collected deposited substance was washed with water, it was dried under reduced pressure. The obtained powder was washed with a mixed solution of (chloroform:diisopropyl alcohol=1:1), whereby 1.71 g of a desired compound was obtained as a white powder.
Reaction SMILES: [CH2:1]([NH2:9])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:10][O:11][C:12](=[O:31])[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[N:20]=[C:21](Cl)[C:22]3[C:27]([Cl:28])=[C:26]([CH3:29])[S:25][C:23]=3[N:24]=2)=[CH:15][CH:14]=1>>[CH3:10][O:11][C:12](=[O:31])[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[N:20]=[C:21]([NH:9][CH2:1][CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[C:22]3[C:27]([Cl:28])=[C:26]([CH3:29])[S:25][C:23]=3[N:24]=2)=[CH:15][CH:14]=1
Reactant: NCCc1ccccc1
Reactant: COC(=O)c1ccc(-c2nc(Cl)c3c(Cl)c(C)sc3n2)cc1
Product: COC(=O)c1ccc(-c2nc(NCCc3ccccc3)c3c(Cl)c(C)sc3n2)cc1

Procedure:
The reaction procedure as above wherein phenethylamine is reacted with 4-(4-chloro-5-chloro-6-methyl-thieno-[2,3-d]-pyrimidin-2-yl)-benzoic acid methylester yields 4-(4-phenethylamino-5-chloro-6-methyl-thieno-[2,3-d]-pyrimidin-2-yl)-benzoic acid methylester.
Reaction SMILES: [CH3:1][O:2][C@H:3]1[C@@H:8]([N:9]([CH3:11])[CH3:10])[CH2:7][CH2:6][NH:5][CH2:4]1.C(N(CC)CC)C.[Cl:19][CH2:20][CH2:21][CH2:22][C:23](Cl)=[O:24]>ClCCl>[Cl:19][CH2:20][CH2:21][CH2:22][C:23]([N:5]1[CH2:6][CH2:7][C@H:8]([N:9]([CH3:10])[CH3:11])[C@H:3]([O:2][CH3:1])[CH2:4]1)=[O:24]
Reactant: CO[C@@H]1CNCC[C@@H]1N(C)C
Reactant: O=C(Cl)CCCCl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CO[C@@H]1CN(C(=O)CCCCl)CC[C@@H]1N(C)C
Reaction time: 0.5 h
Yield: 100 %

Procedure:
To a stirred and cooled (ice/bath) mixture of 7.9 parts of cis-3-methoxy-N,N-dimethyl-4-piperidinamine, 7 parts of N,N-diethylethanamine, 195 parts of dichloromethane were added dropwise 6.16 parts of 4-chlorobutanoyl chloride (temperature <5° C.). Upon completion, stirring was continued for 30 minutes. The organic layer was washed twice with a saturated sodium chloride solution, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated, yielding 13.7 parts (100%) of cis-1-(4-chloro-1- oxobutyl)-3-methoxy-N,N-dimethyl-4-piperidinamine (int. 29).