Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]([C:9]2[O:10][C:11]([C:14]3[S:15][CH:16]=[CH:17][C:18]=3[CH3:19])=[N:12][N:13]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.C1COCC1.C(=O)(OC(C)(C)C)[O:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=O>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Br:1][C:2]1[N:3]=[C:4]([C:9]2[O:10][C:11]([C:14]3[S:15][CH:16]=[CH:17][C:18]=3[CH3:19])=[N:12][N:13]=2)[C:5]([NH:8][C:27](=[O:26])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[N:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Reactant: Cc1ccsc1-c1nnc(-c2nc(Br)cnc2N)o1
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Solvent: ClCCl
Product: Cc1ccsc1-c1nnc(-c2nc(Br)cnc2NC(=O)OC(C)(C)C)o1
Temperature: 25 °C
Reaction time: 2 h
Yield: 110.1 %

Procedure:
5-bromo-3-[5-(3-methyl-2-thienyl)-1,3,4-oxadiazol-2-yl]pyrazin-2-amine (11.49 g, 33.98 mmol) and DMAP (415.1 mg, 3.398 mmol) were suspended in DCM (172.4 mL) and THF (172.4 mL) and cooled in an icebath. tert-butoxycarbonyl tert-butyl carbonate (22.24 g, 101.9 mmol) was added portionwise. The reaction mixture was allowed to warm to ambient temperature and stirred for 2 hours. The reaction mixture was filtered through plug of silica gel and concentrated in vacuo. The residue was dissolved in ethylacetate, washed with aq NaHCO3 (×1), brine (×1), dried over MgSO4 and passed through short silica gel column. The mixture was concentrated in vacuo to low bulk, diluted with petrol and stirred at 50° C. for 5 min. The mixture was filtered to give tert-butyl (5-bromo-3-(5-(3-methylthiophen-2-yl)-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)carbamate as a colourless solid (16.4 g, 89%). H NMR (400.0 MHz, DMSO-d6) δ 1.4 (9H, s), 2.7 (3H, s), 7.0 (1H, d), 7.5 (1H, d), 8.7 (1H, s); LC/MS m/z 440.1 [M−100+1]+.
Reaction SMILES: Cl[C:2]1[C:3]2[N:4]([C:8]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([CH2:17][N:18]4[CH2:23][CH2:22][CH:21]([C:24]5[N:28]=[C:27]([C:29]6[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=6)[NH:26][N:25]=5)[CH2:20][CH2:19]4)=[CH:13][CH:12]=3)[N:10]=2)[CH:5]=[CH:6][N:7]=1>CO.[Pd]>[C:35]1([C:8]2[N:4]3[CH:5]=[CH:6][N:7]=[CH:2][C:3]3=[N:10][C:9]=2[C:11]2[CH:12]=[CH:13][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][CH:21]([C:24]4[N:28]=[C:27]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=5)[NH:26][N:25]=4)[CH2:20][CH2:19]3)=[CH:15][CH:16]=2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: Clc1nccn2c(-c3ccccc3)c(-c3ccc(CN4CCC(c5n[nH]c(-c6ccccn6)n5)CC4)cc3)nc12
Agent: [Pd]
Solvent: CO
Product: c1ccc(-c2c(-c3ccc(CN4CCC(c5n[nH]c(-c6ccccn6)n5)CC4)cc3)nc3cnccn23)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of example 26 (0.1 g, 0.18 mM) in 10 mL of methanol is added 40 mg Pd/C(10%). The reaction mixture is stirred at RT under hydrogen atmosphere overnight. The reaction mixture is filtered through celite and concentrated. It is then purified by column chromatography and washed with water to obtain the desired compound.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[Li]CCCC.Cl[P:18]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C1COCC1>[C:25]1([P:18]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[N:10]=[CH:9][CH:8]=[CH:7]3)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: ClP(c1ccccc1)c1ccccc1
Reactant: Brc1cccc2cccnc12
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: c1ccc(P(c2ccccc2)c2cccc3cccnc23)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 60.6 %

Procedure:
To a stirred solution of 8-bromoquinoline (20.8 g, 100 mmol) in dry THF (200 mL) under nitrogen was added n-BuLi (62.5 mL, 1.6 M in hexanes, 100 mmol) at −78° C. and the mixture was stirred for 30 minutes. Chlorodiphenylphosphine (17.9 mL, 100 mmol) was then added and the solution was allowed to warm up to room temperature and stirred for 2 h. The solution was then cooled to −78° C. and quenched by addition of saturated aqueous NH4Cl solution (100 mL). After warming up to room temperature, the solution was filtered, the precipitated solid collected, taken up in CH2Cl2 (200 mL) and filtered over silica gel eluting with further portions of CH2Cl2 (4×200 mL). The combined filtrates were evaporated to give 1 as a light yellow solid (19 g, 60% yield). 1H NMR (400.13 MHz, CDCl3) δ 8.37 (dd, 1H, J=4.0, 1.6 Hz, C2—H), 8.17 (dd, 1H, J=8.0, 1.6 Hz, C3—H), 7.82 (d, 1H, J=8.4 Hz, C5—H), 7.44 (t, 1H, J=7.6 Hz, C6—H), 7.40 (dd, 1H, J=8.0, 4.0 Hz, C4—H), 7.3-7.2 (m, 10H, Ph-H), 7.14 (ddd, 1H, J=7.2, 3.6, 1.6 Hz, C1′—H) ppm; 13C NMR (100.61 MHz, CDCl3) δ 149.8, 149.6 (d, J=17.2 Hz), 138.4 (d, J=12.1 Hz), 137.4 (d, J=11.1 Hz), 136.2, 134.4, 134.2 (d, J=21.2 Hz), 128.8, 128.4 (d, J=19.2), 127.9, 126.57, 121.41 ppm; 31P NMR (161.97 MHz, CDCl3) δ 15.0 ppm.
Reaction SMILES: [H-].[Na+].[CH:3]1([CH:6]([OH:8])[CH3:7])[CH2:5][CH2:4]1.[Br:9][C:10]1[CH:15]=[CH:14][C:13](F)=[CH:12][CH:11]=1>CN(C=O)C>[Br:9][C:10]1[CH:15]=[CH:14][C:13]([O:8][CH:6]([CH:3]2[CH2:5][CH2:4]2)[CH3:7])=[CH:12][CH:11]=1
Reactant: Fc1ccc(Br)cc1
Reactant: CC(O)C1CC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(Oc1ccc(Br)cc1)C1CC1
Temperature: 100 °C
Yield: 94.6 %

Procedure:
To a 0° C. slurry of NaH (460 mg, 11.4 mmol, 60 wt % dispersion in mineral oil) in DMF (14 mL) was added 1-cyclopropylethanol (0.79 mL, 7.41 mmol) dropwise. The cold bath was removed for 30 min before the addition of 1-bromo-4-fluorobenzene (1.00 g, 5.7 mmol). The resulting reaction mixture was heated to 100° C. for 3 h. At completion, the reaction was cooled to room temperature and concentrated. The resulting oil was diluted with water (30 mL) and extracted into EtOAc (3×30 mL). The combined organics were washed with brine (20 mL), then dried over MgSO4 and concentrated to provide 1-bromo-4-(1-cyclopropylethoxy)benzene (1.30 g, 95% yield). The resulting oil was used directly without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12](O)=[O:13])[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17].FC1C(OC(N(C)C)=[N+](C)C)=C(F)C(F)=C(F)C=1F.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[CH3:63][N:64]([CH3:73])[CH2:65][CH2:66][CH:67]1[CH2:72][CH2:71][CH2:70][CH2:69][NH:68]1>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([N:68]1[CH2:69][CH2:70][CH2:71][CH2:72][CH:67]1[CH2:66][CH2:65][N:64]([CH3:63])[CH3:73])=[O:13])[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17]
Reactant: CN(C)CCC1CCCCN1
Reactant: CC(Nc1ncnc2cc(C(=O)O)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1
Agent: CN(C)C(Oc1c(F)c(F)c(F)c(F)c1F)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(Nc1ncnc2cc(C(=O)N3CCCCC3CCN(C)C)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1

Procedure:
Prepared analogously to Example 37a from 6-chloro-4-[1-(5-chloro-1H-benzimidazol-2-yl)-ethylamino]-7-hydroxycarbonyl-quinazoline, pentafluorophenyl-tetramethyluronium-hexafluorophosphate (PFTU), diisopropylethylamine and 2-(2-dimethylamino-ethyl)-piperidine in DMSO at ambient temperature.
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].[CH2:8]([O:10][C:11]([C:13]1[CH:14]=[N:15][C:16]2[CH:17]=[C:18]3[O:28][CH:27]([CH2:29][O:30][CH2:31][CH3:32])[CH2:26][O:25][C:19]3=[C:20]([NH2:24])[C:21]=2[C:22]=1[OH:23])=[O:12])[CH3:9]>C(O)C>[CH2:8]([O:10][C:11]([C:13]1[CH:14]=[N:15][C:16]2[CH:17]=[C:18]3[O:28][CH:27]([CH2:29][O:30][CH2:31][CH3:32])[CH2:26][O:25][C:19]3=[C:20]([NH:24][C:1](=[O:3])[CH3:2])[C:21]=2[C:22]=1[OH:23])=[O:12])[CH3:9]
Reactant: CCOCC1COc2c(cc3ncc(C(=O)OCC)c(O)c3c2N)O1
Reactant: CC(=O)OC(C)=O
Solvent: CCO
Product: CCOCC1COc2c(cc3ncc(C(=O)OCC)c(O)c3c2NC(C)=O)O1
Temperature: 50 °C

Procedure:
3 portions of acetic acid anhydride totalling 3 ml were added at intervals of half an hour to a suspension of 0.13 g of 10-amino-3-(ethoxymethyl)-2,3-dihydro-9-hydroxy-p-dioxino [2,3-g] quinoline-8-carboxylic acid ethyl ester obtained by the method described in Example 29) in 15 ml of 96% ethanol. Before the last addition the reaction mixture was briefly heated to about 50°C, a clear solution being obtained. After the last addition the mixture was stirred for another hour and subsequently concentrated by evaporation in a vacuum. The concentrate was mixed with methylene chloride and water, after which the two layers were separated. The water layer was extracted 2 times with methylene chloride, the entire solution in methylene chloride was then washed thrice with water and subsequently dried over anhydrous sodium sulfate. Subsequently the solvent was distilled off in a vacuum. The residue having the superscribed structure was not purified any further.
Reaction SMILES: C[O:2][C:3]1[C:12]([O:13]C)=[N:11][C:10]2[C:5](=[CH:6][C:7]([N+:20]([O-:22])=[O:21])=[CH:8][C:9]=2[CH2:15][N:16]2[CH2:18][CH:17]2[CH3:19])[N:4]=1.[BrH:23]>C(O)(=O)C.C(OCC)C>[BrH:23].[O:2]=[C:3]1[C:12](=[O:13])[NH:11][C:10]2[C:5](=[CH:6][C:7]([N+:20]([O-:22])=[O:21])=[CH:8][C:9]=2[CH2:15][N:16]2[CH2:18][CH:17]2[CH3:19])[NH:4]1
Reactant: COc1nc2cc([N+](=O)[O-])cc(CN3CC3C)c2nc1OC
Agent: Br
Solvent: CCOCC
Solvent: CC(=O)O
Product: CC1CN1Cc1cc([N+](=O)[O-])cc2[nH]c(=O)c(=O)[nH]c12

Procedure:
180 mg (0.59 mmol) of N-(2,3-dimethoxy-7-nitro-quinoxalin-5-ylmethyl)-2-methylaziridine are stirred in a 33% solution of hydrogen bromide in acetic acid for 2 hours at 70° C. The mixture is diluted with diethyl ether and the solid is filtered off and washed with diethyl ether. After drying, the title compound is obtained in the form of a yellow solid. M.p.=241° C. (decomp.).
Reaction SMILES: C([N:8](CC1C=CC=CC=1)[CH:9]1[CH2:13][CH:12]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:11]([CH2:19][CH3:20])[CH2:10]1)C1C=CC=CC=1>CCO>[NH2:8][CH:9]1[CH2:13][CH:12]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:11]([CH2:19][CH3:20])[CH2:10]1
Reactant: CCOC(=O)C1CC(N(Cc2ccccc2)Cc2ccccc2)CC1CC
Solvent: CCO
Product: CCOC(=O)C1CC(N)CC1CC
Temperature: 50 °C
Reaction time: 1.5 h
Yield: 98.9 %

Procedure:
To a vessel containing a slurry of 20% wet Pd(OH)2—C (12.9 g, 92.0 mmol) in EtOH (1.0 L) was added ethyl 4-(dibenzylamino)-2-ethylcyclopentanecarboxylate (129 g, 352 mmol). The reaction was shaken for about 90 min at about 50° C. under about 30 psi of H2. The resulting mixture was filtered through a pad of Celite® and the filtrate was concentrated under reduced pressure to give ethyl 4-amino-2-ethylcyclopentanecarboxylate (64.5 g, 99%) as a yellow syrup: 1H NMR (CDCl3) δ 4.03-3.88 (m, 2H), 3.17 (m, 1H), 2.68 (m, 1H), 2.09-2.02 (m, 2H), 2.02-1.94 (m, 2H), 1.84 (m, 1H), 1.58-1.48 (m, 1H), 1.32-1.18 (m, 1H), 1.09 (m, 3H), 1.03 (m, 2H), 0.78-0.69 (m, 3H).
Reaction SMILES: [N+:1]([C:4]1[C:12]([CH2:13][CH2:14][CH:15]([CH3:43])[CH:16]([OH:42])[CH:17]([CH3:41])[C:18](=[O:40])[CH:19]([CH2:38][CH3:39])[CH:20]2[CH:24]([CH3:25])[CH2:23][C:22]([CH2:36][CH3:37])([CH:26]3[CH2:31][CH2:30][C:29]([CH2:33][CH3:34])([OH:32])[CH:28]([CH3:35])[O:27]3)[O:21]2)=[C:8]([C:9]([OH:11])=[O:10])[C:7]([OH:44])=[C:6]([CH3:45])[CH:5]=1)([O-])=O.[H][H]>C(O)C.[Ni]>[NH2:1][C:4]1[C:12]([CH2:13][CH2:14][CH:15]([CH3:43])[CH:16]([OH:42])[CH:17]([CH3:41])[C:18](=[O:40])[CH:19]([CH2:38][CH3:39])[CH:20]2[CH:24]([CH3:25])[CH2:23][C:22]([CH2:36][CH3:37])([CH:26]3[CH2:31][CH2:30][C:29]([CH2:33][CH3:34])([OH:32])[CH:28]([CH3:35])[O:27]3)[O:21]2)=[C:8]([C:9]([OH:11])=[O:10])[C:7]([OH:44])=[C:6]([CH3:45])[CH:5]=1
Reactant: CCC(C(=O)C(C)C(O)C(C)CCc1c([N+](=O)[O-])cc(C)c(O)c1C(=O)O)C1OC(CC)(C2CCC(O)(CC)C(C)O2)CC1C
Reactant: [H][H]
Agent: [Ni]
Solvent: CCO
Product: CCC(C(=O)C(C)C(O)C(C)CCc1c(N)cc(C)c(O)c1C(=O)O)C1OC(CC)(C2CCC(O)(CC)C(C)O2)CC1C

Procedure:
A solution of 5.0 g. (7.6 millimole) of 5-nitro-3-methyl-6-{7-ethyl-4-hydroxy-3,5-dimethyl-6-oxo-7-[5-ethyl-3-methyl-5-(5-ethyl-5-hydroxy-6-methyl-2-tetrahydropyranyl)-2-tetrahydrofuryl]-heptyl}salicylic acid in ethanol (450 ml.) was hydrogenated over 2 g. of Raney-nickel with an uptake of 22.2 mm. of hydrogen. The reaction was filtered (over N2) and 17.2 ml. of N HCl was added. The solvent was removed under reduced pressure, and the residue was crystallized from aqueous acetone to give 5-amino-3-methyl-6-{7-ethyl-4-hydroxy-3,5-dimethyl-6-oxo-7-[5-ethyl-3-methyl-5-(5-ethyl-5-hydroxy-6-methyl-2-tetrahydropyranyl)-2-tetrahydrofuryl]-heptyl}salicylic acid, m.p. 223°-225°[α]D25 +17.92° (1%, MeOH).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9][C:10]2[N:14]([CH2:15][C:16]3[C:17]([CH3:22])=[N:18][CH:19]=[CH:20][CH:21]=3)[C:13]([CH2:23][OH:24])=[N:12][C:11]=2[CH:25]([CH3:27])[CH3:26])[CH:5]=[C:6]([Cl:8])[CH:7]=1.ClC(Cl)(Cl)[C:30]([N:32]=C=O)=[O:31].C(N(CC)CC)C.O>O1CCCC1.CO>[C:30]([O:24][CH2:23][C:13]1[N:14]([CH2:15][C:16]2[C:17]([CH3:22])=[N:18][CH:19]=[CH:20][CH:21]=2)[C:10]([S:9][C:4]2[CH:3]=[C:2]([Cl:1])[CH:7]=[C:6]([Cl:8])[CH:5]=2)=[C:11]([CH:25]([CH3:27])[CH3:26])[N:12]=1)(=[O:31])[NH2:32]
Reactant: Cc1ncccc1Cn1c(CO)nc(C(C)C)c1Sc1cc(Cl)cc(Cl)c1
Reactant: O=C=NC(=O)C(Cl)(Cl)Cl
Solvent: O
Solvent: CCN(CC)CC
Solvent: CO
Product: Cc1ncccc1Cn1c(COC(N)=O)nc(C(C)C)c1Sc1cc(Cl)cc(Cl)c1
Temperature: -40 °C

Procedure:
In 20 ml of tetrahydrofuran was dissolved 405 mg of 5-(3,5-dichlorophenylthio)-2-hydroxymethyl-4-isopropyl-1-(2-methylpyridin-3-ylmethyl)-1H-imidazole (119a), and the mixture was cooled to -40° C. With stirring, 171 μl of trichloroacetylisocyanate was added, the mixture was allowed to stand to reach room temperature, and stirred for 30 minutes. There were added 200 μl of triethylamine, 5 ml of water and 10 ml of methanol, and the mixture was stirred at 70° C. for 2 hours. After completion of the reaction, the solution was distilled off under reduced pressure, an aqueous sodium hydrogen carbonate solution was added, extracted with ethyl acetate, the extract was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The crystals were washed with diethyl ether, filtered, and 400 mg of Compound I-133 was obtained (yield 90%). mp 127° C.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[NH:12][C:13](=[O:26])[N:14]([C:15]4[CH:20]=[CH:19][C:18]([C:21]([CH3:25])([CH3:24])[C:22]#[N:23])=[CH:17][CH:16]=4)[C:5]=3[C:4]=2[CH:3]=1.C(N(CC)CC)C.[F:34][C:35]([F:47])([F:46])[C:36]1[CH:37]=[C:38]([S:42](Cl)(=[O:44])=[O:43])[CH:39]=[CH:40][CH:41]=1.O>ClCCl>[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([S:42]([C:38]4[CH:39]=[CH:40][CH:41]=[C:36]([C:35]([F:34])([F:46])[F:47])[CH:37]=4)(=[O:44])=[O:43])[C:13](=[O:26])[N:14]([C:15]4[CH:20]=[CH:19][C:18]([C:21]([CH3:24])([CH3:25])[C:22]#[N:23])=[CH:17][CH:16]=4)[C:5]=3[C:4]=2[CH:3]=1
Reactant: CC(C)(C#N)c1ccc(-n2c(=O)[nH]c3cnc4ccc(Br)cc4c32)cc1
Reactant: O=S(=O)(Cl)c1cccc(C(F)(F)F)c1
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C#N)c1ccc(-n2c(=O)n(S(=O)(=O)c3cccc(C(F)(F)F)c3)c3cnc4ccc(Br)cc4c32)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 2-(4-(8-bromo-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile (Intermediate 1, 50 mg, 0.12 mmol) and triethylamine (24.4 mg, 0.24 mmol) in dichloromethane (6 ml) was added 3-trifluoromethylbenzene-1-sulfonyl chloride (44 mg, 0.18 mmol) at 0° C. The reaction was stirred at RT for 3 hours. The reaction mixture was poured into cold water and organic layer was separated. The aqueous layer was extracted with dichloromethane. The combined organic layer was washed with brine dried over sodium sulfate and evaporated to dryness. The crude product was purified by column chromatography (silica gel, 2% acetone in chloroform) to obtain the title compound. Yield: 45 mg (60%); 1H NMR (DMSO-d6, 300 MHz): δ 9.466 (s, 1H), 8.523-8.550 (d, 1H, J=8.1 Hz), 8.475 (s, 1H), 8.241-8.268 (d, 1H, J=8.1 Hz), 7.971-8.020 (m, 2H), 7.668-7.989 (m, 5H), 6.749-6.756 (d, 1H, J=2.1 Hz), 1.773 (s, 6H); MS: m/z 615 (M+), 617 (M+2).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9][C:10]2[N:14](CC3C=CC(OC)=CC=3)[N:13]=[C:12]([CH3:24])[C:11]=2[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:26])[CH:5]=[C:6]([Cl:8])[CH:7]=1.FC(F)(F)C(O)=O>>[Cl:8][C:6]1[CH:5]=[C:4]([S:9][C:10]2[NH:14][N:13]=[C:12]([CH3:24])[C:11]=2[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:26])[CH:3]=[C:2]([Cl:1])[CH:7]=1
Reactant: COc1ccc(Cn2nc(C)c(C(=O)c3ccccc3)c2Sc2cc(Cl)cc(Cl)c2)cc1
Solvent: O=C(O)C(F)(F)F
Product: Cc1n[nH]c(Sc2cc(Cl)cc(Cl)c2)c1C(=O)c1ccccc1
Yield: 71.3 %

Procedure:
140 mg of [5-(3,5-dichlorophenylthio)-1-(4-methoxybenzyl)-3-methyl-1H-pyrazol-4-yl]-phenyl-methanone was treated with 4 ml of trifluoroacetic acid. The solution was then heated at reflux for 2 h. The solvent was evaporated under reduced pressure. The residue was then partitioned between dichloromethane/saturated sodium hydrogen carbonate, washed with brine then dried over anhydrous magnesium sulphate, filtered and evaporated to give 75 mg of [5-(3,5-dichlorophenylthio)-3-methyl-1H-pyrazol-4-yl]-phenyl-methanone as a yellow solid which was used without further purification. Mass spectrum (ES) m/z 363[M+H]+.
Reaction SMILES: [Cl:1]([O-:5])(=[O:4])(=[O:3])=[O:2].[CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][CH2:8][NH+:7]=1.[C:16](=[C:19]1[CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]1=O)([CH3:18])[CH3:17]>CO>[Cl:1]([O-:5])(=[O:4])(=[O:3])=[O:2].[CH3:18][C:16]1[C:19]2[CH2:27][C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]=2[N+:7]2[CH2:8][CH2:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=3[C:6]=2[CH:17]=1
Reactant: C1=[NH+]CCc2ccccc21
Reactant: CC(C)=C1Cc2ccccc2C1=O
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: CO
Product: Cc1cc2[n+](c3c1Cc1ccccc1-3)CCc1ccccc1-2

Procedure:
3,4-Dihydroisoquinolinium perchlorate (2 g) and 2-isopropylidene-indan-1-one (2 g) were heated together at 150° for 2 hours. The reaction mixture was cooled and diluted with methanol. The product was collected by filtration and recrystallized from methanol.
Reaction SMILES: [CH3:1][CH:2]([CH3:8])/[CH:3]=[CH:4]/[C:5]([OH:7])=[O:6].[CH2:9]=[CH:10][CH:11]=[CH:12][CH3:13].CC(C)C=CC(O)=O.S(=O)(=O)(O)O>CCOCC>[CH:2]([CH:3]1[CH:4]([C:5]([OH:7])=[O:6])[CH:12]([CH3:13])[CH:11]=[CH:10][CH2:9]1)([CH3:8])[CH3:1]
Reactant: C=CC=CC
Reactant: CC(C)/C=C/C(=O)O
Agent: CC(C)C=CC(=O)O
Agent: O=S(=O)(O)O
Solvent: CCOCC
Product: CC(C)C1CC=CC(C)C1C(=O)O
Temperature: 200 °C
Yield: 65.7 %

Procedure:
A mixture of 70 g (0.61 mol) of trans-4-methyl-2-pentenoic acid and 49 g (0.72 mol) of 1,3-pentadiene was heated for 12 hours at approx. 200° C. in an autoclave. After the reaction mixture had cooled, it was checked by means of GLC for the presence of 4-methyl-2-pentenoic acid. A further 25 g (0.36 mol) of 1,3-pentadiene were added, after which the mixture was again heated for 12 hours at 200° C. This procedure was repeated until no further decrease in the content of 4-methyl-2-pentenoic acid was any longer observed. The reaction mixture obtained was dissolved in 300 ml of ether and extracted with 300 ml of 10% NaOH solution. The alkaline solution thus obtained was acidified with 40 g of concentrated sulphuric acid and then extracted three times with ether. The ether extract was washed with water, dried on MgSO4, evaporated down and distilled. 73 g of 6-isopropyl-2-methyl-3-cyclohexene-1-carboxylic acid were obtained, b.p.: 95°-100° C./70 Pa.
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:15])=[C:11](F)[CH:12]=3)[C:7](=[O:16])[C:6]([C:17]([OH:19])=[O:18])=[CH:5]2)[CH2:3][CH2:2]1.Cl.Cl.[OH:22][C:23]1([CH2:29][NH:30][CH3:31])[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:15])=[C:11]([N:26]4[CH2:27][CH2:28][C:23]([OH:22])([CH2:29][NH:30][CH3:31])[CH2:24][CH2:25]4)[CH:12]=3)[C:7](=[O:16])[C:6]([C:17]([OH:19])=[O:18])=[CH:5]2)[CH2:3][CH2:2]1
Reactant: CNCC1(O)CCNCC1
Reactant: O=C(O)c1cn(C2CC2)c2cc(F)c(F)cc2c1=O
Agent: Cl
Product: CNCC1(O)CCN(c2cc3c(cc2F)c(=O)c(C(=O)O)cn3C2CC2)CC1

Procedure:
1-Cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid is reacted with 4-hydroxy-4-methylaminomethylpiperidine dihydrochloride analogously to Example 6 to give 1-cyclopropyl-6-fluoro-1,4-dihydro-7-(4-hydroxy-4-methylaminomethyl-1-piperidinyl)-4-oxo-3-quinolinecarboxylic acid of melting point 162° (with decomposition).
Reaction SMILES: C(O[C:6]([NH:8][CH2:9][C@@H:10]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]([C:24]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:26]([CH3:33])[CH:25]=2)=[O:23])[CH2:11]1)=[O:7])(C)(C)C.[NH2:34][C:35]1[C:43]([Cl:44])=[CH:42][C:38](C(O)=O)=[C:37]([O:45][CH3:46])[CH:36]=1>>[NH2:34][C:35]1[C:43]([Cl:44])=[CH:42][C:38]([C:6]([NH:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]([C:24]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[N:26]([CH3:33])[CH:25]=3)=[O:23])[CH2:11]2)=[O:7])=[C:37]([O:45][CH3:46])[CH:36]=1
Reactant: Cn1cc(C(=O)NCCCCCCN2CC[C@@H](CNC(=O)OC(C)(C)C)C2)c2ccccc21
Reactant: COc1cc(N)c(Cl)cc1C(=O)O
Product: COc1cc(N)c(Cl)cc1C(=O)NC[C@@H]1CCN(CCCCCCNC(=O)c2cn(C)c3ccccc23)C1

Procedure:
N-(6-((3S)-3-tert-Butoxycarbonylaminomethylpyrrolidin-1-yl)-hexyl)-1-methyl-1 H-indole-3-carboxamide (1.00 g) as starting compound was reacted and treated in the same manner as in Example 67 using 4-amino-5-chloro-2-methoxybenzoic acid (0.50 g) to give N-(6-((3S)-3-(4-amino-5-chloro-2-methoxybenzoylaminomethyl)pyrrolidin-1-yl)hexyl)-1-methyl-1 H-indole-3-carboxamide.
Reaction SMILES: Cl.[OH:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C@:6]([CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])([C:13]([O:15][CH2:16][C@H:17]2[CH2:21][CH2:20][CH2:19][NH:18]2)=[O:14])[C:5](=[O:27])[C:4]=1[C:28]1[NH:33][C:32]2[CH:34]=[CH:35][C:36]([NH:38][S:39]([CH3:42])(=[O:41])=[O:40])=[CH:37][C:31]=2[S:30](=[O:44])(=[O:43])[N:29]=1.[CH3:45][O:46][C:47](Cl)=[O:48].C(N(CC)CC)C>ClCCl>[OH:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C@@:6]([C:13]([O:15][CH2:16][C@H:17]2[CH2:21][CH2:20][CH2:19][N:18]2[C:47]([O:46][CH3:45])=[O:48])=[O:14])([CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[C:5](=[O:27])[C:4]=1[C:28]1[NH:33][C:32]2[CH:34]=[CH:35][C:36]([NH:38][S:39]([CH3:42])(=[O:41])=[O:40])=[CH:37][C:31]=2[S:30](=[O:44])(=[O:43])[N:29]=1
Reactant: CC(C)CC[C@@]1(C(=O)OC[C@H]2CCCN2)C(=O)C(C2=NS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)=C(O)c2ccccc21
Reactant: COC(=O)Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)N1CCC[C@@H]1COC(=O)[C@]1(CCC(C)C)C(=O)C(C2=NS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)=C(O)c2ccccc21
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of Example 173 (0.079 mmol) in dry dichloromethane (1 mL) at 0° C. was added methylchloroformate (0.12 mL, 1.55 mmol) and triethylamine (33 μL, 0.24 mmol). The resulting mixture was stirred at rt 3 h and partitioned between H2O (5 mL) and dichloromethane (3×5 mL). The combined organic layers were dried over Na2SO4, the drying agent was filtered off, and the solvent was removed in vacuo. To a solution of the resulting residue in methanol (1 mL) was added K2CO3, and the resulting mixture was stirred at rt 90 min. The mixture was partitioned between N HCl (5 mL) and ethyl acetate (3×5 mL), and the combined organic layers were dried over Na2SO4. The crude product was purified by column chromatography on silica gel using 5% methanol in chloroform, and the title compound was obtained as a lt. yellow solid (48 mg, 88%): 1H NMR (300 MHz, DMSO-d6) δ 0.43 (m, 1 H), 0.67 (m, J=6.62 Hz, 3 H), 0.71 (d, J=6.62 Hz, 3 H), 0.89 (m, 2 H), 1.33 (m, 1 H), 1.45 (m, 3 H), 1.67 (m, 1 H), 2.10 (m, 1 H), 2.40 (m, 1 H), 2.70 (m, 1 H), 3.02 (s, 3 H), 3.74 (m, 1 H), 3.93 (m, 1 H), 4.13 (m, 1 H), 7.16 (m, 1 H), 7.49 (m, 5 H), 8.12 (m, 1 H), 10.01 (s, 1 H), 14.54 (br s, 1 H); MS (ESI) m/z=689 [M+H].