Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:59])([F:58])[C:3]([NH:5][C:6]1[N:10]([C:11]2[C:12]([F:53])=[CH:13][C:14]([CH3:52])=[C:15]([CH:17]([S:22][CH:23]([C:28]3[CH:33]=[C:32]([N:34]4[C:38]([NH:39][C:40](=[O:45])[C:41]([F:44])([F:43])[F:42])=[N:37][C:36]([C:46]([F:49])([F:48])[F:47])=[N:35]4)[C:31]([F:50])=[CH:30][C:29]=3[CH3:51])[C:24]([F:27])([F:26])[F:25])[C:18]([F:21])([F:20])[F:19])[CH:16]=2)[N:9]=[C:8]([C:54]([F:57])([F:56])[F:55])[N:7]=1)=[O:4].ClC1C=CC=C(C(OO)=[O:68])C=1>C(Cl)(Cl)Cl>[F:42][C:41]([F:44])([F:43])[C:40]([NH:39][C:38]1[N:34]([C:32]2[C:31]([F:50])=[CH:30][C:29]([CH3:51])=[C:28]([CH:23]([S:22]([CH:17]([C:15]3[CH:16]=[C:11]([N:10]4[C:6]([NH:5][C:3](=[O:4])[C:2]([F:1])([F:58])[F:59])=[N:7][C:8]([C:54]([F:55])([F:56])[F:57])=[N:9]4)[C:12]([F:53])=[CH:13][C:14]=3[CH3:52])[C:18]([F:21])([F:20])[F:19])=[O:68])[C:24]([F:27])([F:26])[F:25])[CH:33]=2)[N:35]=[C:36]([C:46]([F:47])([F:48])[F:49])[N:37]=1)=[O:45]
Reactant: Cc1cc(F)c(-n2nc(C(F)(F)F)nc2NC(=O)C(F)(F)F)cc1C(SC(c1cc(-n2nc(C(F)(F)F)nc2NC(=O)C(F)(F)F)c(F)cc1C)C(F)(F)F)C(F)(F)F
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Product: Cc1cc(F)c(-n2nc(C(F)(F)F)nc2NC(=O)C(F)(F)F)cc1C(S(=O)C(c1cc(-n2nc(C(F)(F)F)nc2NC(=O)C(F)(F)F)c(F)cc1C)C(F)(F)F)C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 73.7 %

Procedure:
0.8 g of [5-(5-trifluoroacetylamino-3-trifluoromethyl-1,2,4-triazolyl)-4-fluoro-2-methylphenyl]2,2,2-trifluoroethyl sulfide was dissolved in 50 ml of chloroform, and 0.3 g of m-chloroperbenzoic acid was added at 0° C., followed by stirring at room temperature for 1 hour. The solvent was distilled off under reduced pressure, and the obtained solid was purified by column chromatography (eluent ethyl acetate:hexane=1:1) to obtain 0.6 g of [5-(5-trifluoroacetylamino-3-trifluoromethyl-1,2,4-triazolyl)-4-fluoro-2-methylphenyl]2,2,2-trifluoroethyl sulfoxide as a pale yellow powder (melting point 233 to 237° C.).
Reaction SMILES: F[C:2]1[N:18]=[CH:17][CH:16]=[CH:15][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=1)=[O:5].[ClH:19].Cl.[NH:21]1[C:25]2=[N:26][CH:27]=[CH:28][C:29]([O:30][C:31]3[CH:36]=[CH:35][C:34]([NH:37]C4N=CC=CC=4C(NC4C=CC=CC=4C)=O)=[CH:33][C:32]=3[F:54])=[C:24]2[CH:23]=[CH:22]1>>[ClH:19].[ClH:19].[NH:21]1[C:25]2=[N:26][CH:27]=[CH:28][C:29]([O:30][C:31]3[CH:36]=[CH:35][C:34]([NH:37][C:2]4[N:18]=[CH:17][CH:16]=[CH:15][C:3]=4[C:4]([NH:6][CH2:7][C:8]4[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=4)=[O:5])=[CH:33][C:32]=3[F:54])=[C:24]2[CH:23]=[CH:22]1
Reactant: O=C(NCc1ccc(F)cc1)c1cccnc1F
Reactant: Cc1ccccc1NC(=O)c1cccnc1Nc1ccc(Oc2ccnc3[nH]ccc23)c(F)c1
Agent: Cl
Product: O=C(NCc1ccc(F)cc1)c1cccnc1Nc1ccc(Oc2ccnc3[nH]ccc23)c(F)c1
Yield: 35 %

Procedure:
2-Fluoro-N-(4-fluorobenzyl)nicotinamide (0.050 g, 0.20 mmol) was converted to the title compound (0.035 g, 35%) in a manner similar to the preparation of 2-(4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenylamino)-N-o-tolylnicotinamide (Step B of Example 8). 1H NMR (DMSO-d6) δ 12.63 (s, 1H), 11.17 (s, 1H), 9.44 (t, 1H, J=5.8 Hz), 8.10-8.40 (m, 4H), 7.50-7.60 (m, 1H), 7.30-7.45 (m, 4H), 7.08-7.10 (m, 2H), 6.90-6.95 (m, 1H), 6.66 (d, 1H, J=6.3 Hz), 6.43-6.46 (m, 1H), 4.44 (d, 2H, J=5.7 Hz); HRMS(ESI+), 472.1585 (M+H)+ calc, 472.1587 (M+H)+ found.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]([CH2:16][CH:17]([C:21]1[C:26]([F:27])=[CH:25][CH:24]=[C:23]([F:28])[C:22]=1[F:29])[C:18](=O)[CH3:19])[C:10](OC(C)C)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([NH2:33])(C)C>CS(C)=O>[CH3:19][C@H:18]1[NH:33][C:10](=[O:11])[CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:16][C@H:17]1[C:21]1[C:26]([F:27])=[CH:25][CH:24]=[C:23]([F:28])[C:22]=1[F:29]
Reactant: CC(=O)C(CC(NC(=O)OC(C)(C)C)C(=O)OC(C)C)c1c(F)ccc(F)c1F
Reactant: CC(C)N
Solvent: CS(C)=O
Product: C[C@H]1NC(=O)C(NC(=O)OC(C)(C)C)C[C@H]1c1c(F)ccc(F)c1F
Temperature: 55 °C
Reaction time: 27.5 h

Procedure:
Crude keto ester 19 (23.6 g, 69 wt %, 16.3 g assay, 39 mmol) was dissolved in DMSO (163 mL) and the solution was added to the reactor over 5-10 min. Then the reaction was heated to 55° C. The pH was adjusted to 10.5 according to a handheld pH meter and controlled overnight with an automated pH controller using 8 M aqueous isopropylamine. The reaction was aged for 27.5 hours.
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]1[N:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][NH:11]2)=[CH:6][CH:5]=1.[C-:14]#[N:15].[Na+]>CN(C=O)C.O>[N:13]1[C:12]2[NH:11][CH2:10][CH2:9][CH2:8][C:7]=2[CH:6]=[CH:5][C:4]=1[CH2:3][CH2:2][C:14]#[N:15]
Reactant: [C-]#N
Reactant: ClCCc1ccc2c(n1)NCCC2
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: N#CCCc1ccc2c(n1)NCCC2
Temperature: 85 °C
Yield: 21 %

Procedure:
7-(2-chloroethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (500 mg) and NaCN (150 mg) were dissolved in DMF (in 15 mL) and the mixture was heated at 85° C. for 6 hrs. Cooled to 25° C. and the reaction was diluted with H2O, extracted with CHCl3, and the solution was washed with H2O, dried with MgSO4. The solution was concentrated to a yellow oil. Column purification (Ethyl acetate: Hexane=1:1) to yield a yellow solid 100 mg (8.9%). 1H NMR (DMSO-d6) δ 7.06 (d, 1H), 6.45 (m, 2H), 3.33 (1, 2H), 2.75 (m, 4H), 2.63 (t, 2H), 1.75 (m, 2H).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([N:13]3[CH2:17][CH2:16][CH:15]([NH:18][S:19](=[O:24])(=[O:23])[N:20]([CH3:22])[CH3:21])[CH2:14]3)=[O:12])[S:10][C:3]=12.[CH3:25][C:26]1[NH:27][C:28]2[C:33]([CH:34]=1)=[CH:32][C:31]([NH2:35])=[CH:30][CH:29]=2>>[CH3:25][C:26]1[NH:27][C:28]2[C:33]([CH:34]=1)=[CH:32][C:31]([NH:35][C:2]1[CH:7]=[CH:6][N:5]=[C:4]3[CH:8]=[C:9]([C:11]([N:13]4[CH2:17][CH2:16][CH:15]([NH:18][S:19](=[O:24])(=[O:23])[N:20]([CH3:22])[CH3:21])[CH2:14]4)=[O:12])[S:10][C:3]=13)=[CH:30][CH:29]=2
Reactant: Cc1cc2cc(N)ccc2[nH]1
Reactant: CN(C)S(=O)(=O)NC1CCN(C(=O)c2cc3nccc(Cl)c3s2)C1
Product: Cc1cc2cc(Nc3ccnc4cc(C(=O)N5CCC(NS(=O)(=O)N(C)C)C5)sc34)ccc2[nH]1

Procedure:
The title compound was prepared from (+/−)-dimethylsulfamic acid {1-[7-chloro-thieno[3,2-b]pyridine-2-carbonyl]-pyrrolidin-3-yl}-amide and 2-methyl-1H-indol-5-ylamine by a procedure analogous to Example 1C. MS: 499 (MH+); HPLC Rf: 4.04 min.; HPLC purity 96%.
Reaction SMILES: C(OC(=O)NC[CH2:9][CH2:10][NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]2[CH:24]=[CH:23][N:22]=[C:21]([Cl:25])[N:20]=2)[CH:14]=1)(C)(C)C.[CH:27](N)(C)C>>[Cl:25][C:21]1[N:20]=[C:19]([C:15]2[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=2)[CH2:12][NH:11][CH:10]([CH3:9])[CH3:27])[CH:24]=[CH:23][N:22]=1
Reactant: CC(C)(C)OC(=O)NCCCNCc1cccc(-c2ccnc(Cl)n2)c1
Reactant: CC(C)N
Product: CC(C)NCc1cccc(-c2ccnc(Cl)n2)c1

Procedure:
Intermediate 2 was coupled with isopropylamine following procedure B. LC-MS showed the product had the expected M+H+ of 262.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[C:10]([N:18]=[C:19]=[S:20])(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[C:4]([C:3]1[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=1[NH:1][C:19]([NH:18][C:10](=[O:17])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[S:20])#[N:5]
Reactant: N#Cc1ccccc1N
Reactant: O=C(N=C=S)c1ccccc1
Product: N#Cc1ccccc1NC(=S)NC(=O)c1ccccc1

Procedure:
Prepared as in Example 1a from 2-aminobenzonitrile and benzoyl isothiocyanate as a pale-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 7.35-7.56 (m, 3H), 7.67 (t, 1H), 7.75-7.76 (d, J=5.2 Hz, 2H), 7.89-7.91 (d, J=7.2 Hz, 2H), 7.98-8.01 (dd, J1=1.6 Hz, J2=8.2 Hz, 2H), 11.90 (s, 1H), 12.54 (s, 1H). MS 282 (MH+).
Reaction SMILES: C(OCC)C.C([Li])CCC.Br[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1.[CH:18]([C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][CH:21]=1)=[O:19]>O1CCCC1>[N:14]1[CH:15]=[CH:16][CH:17]=[C:12]([CH:18]([C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:23]=[CH:22][CH:21]=2)[OH:19])[CH:13]=1
Reactant: Brc1cccnc1
Reactant: O=Cc1cccc2ccccc12
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: C1CCOC1
Product: OC(c1cccnc1)c1cccc2ccccc12
Temperature: -120 °C
Reaction time: 0.75 h

Procedure:
To a 500 ml 3-neck flask round bottom flask equipped with an addition funnel, septum, thermometer and an argon inlet is added 100 ml of anhydrous diethyl ether and 62.5 ml of 1.6 molar butyllithium solution (in hexane). The system is cooled to -120° C. and 15.90 gm of 3-bromopyridine in 50 ml of tetrahydrofuran is added over 2 hours. After addition of the 3-bromopyridine, the system is stirred for an additional 45 minutes. At this time, 15.60 gm of 1-formylnaphthalene in 50 ml of tetrahydrofuran is added to the system while still maintaining a temperature of -120° C. The system is kept at -120° C. for an additional 3 hours after addition of the 1-formylnaphthalene and afterwards is allowed to come to room temperature. After 10 hours at room temperature, the system is quenched with saturated ammonium chloride (in water). The system is adjusted to pH 2 with HCl solution. The solution is extracted with diethyl ether. The aqueous solution is made basic with a 5% NaOH solution. The product is extracted with methylene chloride and dried over sodium sulfate. The methylene chloride is removed by stripping and the residue is triturated with hexane to give the 3-pyridyl-1-naphthylcarbinol.
Reaction SMILES: [CH2:1]([O:3][P:4]([CH2:9][O:10][CH2:11][CH2:12]Cl)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[N-:14]=[N+:15]=[N-:16].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH2:1]([O:3][P:4]([CH2:9][O:10][CH2:11][CH2:12][N:14]=[N+:15]=[N-:16])(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]
Reactant: CCOP(=O)(COCCCl)OCC
Reactant: [N-]=[N+]=[N-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCOP(=O)(COCCN=[N+]=[N-])OCC

Procedure:
0,02 mol (2-chloroethoxy)methyl-phosphonic acid diethylester, 3 mmol tetrabutylammoniumbromide and 2,5 g sodiumazide are boiled in 50 ml toluol under reflux for 4 h. After cooling-off it is washed for three times with 25 ml water respectively. The watery phase may be extracted with toluol. The combined toluol phases are dried over sodiumsulfate and the solvent is removed in the vacuum. A yellow oil remains.
Reaction SMILES: [CH3:1][CH:2]([C:8](=[O:10])[CH3:9])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[CH2:13]([Li])[CH2:14][CH2:15]C.C(Br)C=C>O1CCCC1>[CH3:1][CH:2]([C:8](=[O:10])[CH2:9][CH2:15][CH:14]=[CH2:13])[C:3]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: [Li]CCCC
Reactant: CCOC(=O)C(C)C(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: C=CCBr
Solvent: C1CCOC1
Product: C=CCCC(=O)C(C)C(=O)OCC
Yield: 58.9 %

Procedure:
Ethyl 2-methyl-3-oxobutanoate (10 mL, 70.7 mmol) was added dropwise to an anhydrous tetrahydrofuran suspension of sodium hydride (2.83 g, 74.2 mmol) with stirring under ice cooling. The mixture was stirred for 15 minutes in this bath. Then, n-butyllithium (1.59 M hexane solution, 45.3 mL, 72.1 mmol) was added dropwise thereto, and the mixture was further stirred for 30 minutes. Then, allyl bromide (6.73 mL, 77.7 mmol) was added dropwise thereto. After removal of the ice bath, the mixture was stirred for 2 hours, and the reaction was then terminated by pouring dilute hydrochloric acid to the reaction solution. The reaction solution was subjected to extraction with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium bicarbonate, and saturated saline and dried over anhydrous magnesium sulfate, and the solvent was then distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain the compound of interest as a pale yellow oil (7.67 g).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH:5]=[O:6].I[CH2:13][C:14]([F:17])([F:16])[F:15].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:11][O:10][C:9]1[CH:8]=[CH:7][C:4]([CH:5]=[O:6])=[CH:3][C:2]=1[O:1][CH2:13][C:14]([F:17])([F:16])[F:15]
Reactant: FC(F)(F)CI
Reactant: COc1ccc(C=O)cc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(C=O)cc1OCC(F)(F)F
Temperature: 90 °C
Reaction time: 8 h

Procedure:
3-Hydroxy-4-methoxy-benzaldehyde (560, 2.9 g, 19.5 mmol), 2-iodo-1,1,1-trifluoroethane (561, 2.2 mL, 23 mmol), and potassium carbonate (3.7 g, 27 mmol) were dissolved in N,N-dimethylformamide (100 mL). The solution was stirred at 90° C. overnight under an atmosphere of nitrogen. The reaction was poured into water, extracted with ethyl acetate, and washed with brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The compound was isolated by silica gel column chromatography eluting with 25% to 50% ethyl acetate in hexanes to give white powder (562, 1.6 g, 40%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][C:3]=1[C:15]([F:18])([F:17])[F:16].[Li]CCCC.[I:24]I>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:12])[CH3:13])=[C:4]([I:24])[C:3]=1[C:15]([F:16])([F:17])[F:18]
Reactant: II
Reactant: CC(C)(C)C(=O)Nc1ccc(Cl)c(C(F)(F)F)c1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)(C)C(=O)Nc1ccc(Cl)c(C(F)(F)F)c1I
Reaction time: 0.5 h
Yield: 61.9 %

Procedure:
A THF (20 mL) solution of known N-[4-chloro-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide (1.49 g, 5.34 mmol) at ca. −5° C. was treated with n-BuLi (2.5 M, 5.33 mL). After 30 min, the reaction was treated with I2 (2.03 g, 8.01 mmol) dissolved in THF (3 mL). The resulting mixture was then quenched with sat. aqueous NH4Cl after 10 min. Excess I2 was removed with 10% aqueous sodium metabisulfite. The mixture was diluted with EtOAc (20 mL) and H2O (20 mL) and partitioned. The aqueous portion was extracted with EtOAc (20 mL). The combined organic portions were washed with H2O followed by brine. Drying (Na2SO4) was followed by filtration and concentration. 1H NMR of the crude mixture showed a 3.7:1 ratio of the desired (2-iodo) to the undesired regioisomer. Column chromatography (SiO2; hexanes/EtOAc) provided the title compound as a white solid (1.34 g, 62%): 1H NMR (CDCl3) δ 8.33 (d, J=6.0 Hz, 1H), 8.16 (bs, 1H), 7.49 (d, J=6.0 Hz, 1H), 1.38 (s, 9H).
Reaction SMILES: [OH:1][CH2:2][C:3]([F:42])([F:41])[C:4]([F:40])([F:39])[C:5]([F:38])([F:37])[C:6]([F:36])([F:35])[C:7]([F:34])([F:33])[C:8]([F:32])([F:31])[C:9]([F:30])([F:29])[C:10]([F:28])([F:27])[CH2:11][O:12][C:13]1[CH:26]=[CH:25][C:16]([C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:18])=[CH:15][CH:14]=1.[N+:43]([C:46]1[CH:51]=[C:50]([N+:52]([O-:54])=[O:53])[CH:49]=[CH:48][C:47]=1Cl)([O-:45])=[O:44]>CN1C(=O)CCC1>[N+:43]([C:46]1[CH:51]=[C:50]([N+:52]([O-:54])=[O:53])[CH:49]=[CH:48][C:47]=1[O:1][CH2:2][C:3]([F:41])([F:42])[C:4]([F:39])([F:40])[C:5]([F:37])([F:38])[C:6]([F:35])([F:36])[C:7]([F:33])([F:34])[C:8]([F:31])([F:32])[C:9]([F:29])([F:30])[C:10]([F:28])([F:27])[CH2:11][O:12][C:13]1[CH:26]=[CH:25][C:16]([C:17]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:18])=[CH:15][CH:14]=1)([O-:45])=[O:44]
Reactant: O=[N+]([O-])c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: O=C(c1ccccc1)c1ccc(OCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)CO)cc1
Solvent: CN1CCCC1=O
Product: O=C(c1ccccc1)c1ccc(OCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)COc2ccc([N+](=O)[O-])cc2[N+](=O)[O-])cc1

Procedure:
A solution of 4-(10-Hydroxy-2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-hexadecafluorodecyloxy)benzophenone (6.42 g), 2,4-dinitrochlorobenzene (2.42 g) potassium carbonate (2.76 g) and NMP (15 mL) is heated to 75-80° C. for 24 hrs. The solution is further processed as described in Example 2 to give 4-[10-(2,4-dinitrophenoxy)-2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-hexadecafluorodecyloxy]benzophenone.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([OH:12])=O)=[CH:9][C:4]=2[N:3]=[CH:2]1.[C:13]1([C:19]2[CH:32]=[CH:31][C:22]3[C@@H:23]4[C@H:28]([CH2:29][CH2:30][C:21]=3[CH:20]=2)[NH:27][CH2:26][CH2:25][CH2:24]4)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(Cl)Cl.CO>[NH:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([N:27]3[C@@H:28]4[C@@H:23]([C:22]5[CH:31]=[CH:32][C:19]([C:13]6[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=6)=[CH:20][C:21]=5[CH2:30][CH2:29]4)[CH2:24][CH2:25][CH2:26]3)=[O:12])=[CH:9][C:4]=2[N:3]=[CH:2]1
Reactant: c1ccc(-c2ccc3c(c2)CC[C@@H]2NCCC[C@H]32)cc1
Reactant: O=C(O)c1ccc2[nH]cnc2c1
Solvent: CO
Solvent: ClCCl
Product: O=C(c1ccc2[nH]cnc2c1)N1CCC[C@@H]2c3ccc(-c4ccccc4)cc3CC[C@@H]21
Yield: 29 %

Procedure:
The title compound is prepared from 1H-benzoimidazole-5-carboxylic acid and cis-8-phenyl-1,2,3,4,4a,5,6,10b-octahydro-benzo[f]quinoline following a procedure analogous to that described in Example 1. Yield: 29% of theory; TLC: rf=0.49 (silica gel, CH2Cl2/MeOH/32% aqueous NH3 90:10:1); Mass spectrum (ESI+): m/z=408 [M+H]+.
Reaction SMILES: Cl.[NH2:2][C:3]1[C:8]([C:9]#[N:10])=[CH:7][C:6]([C:11](=[O:19])[CH2:12][NH:13][C:14]([CH2:17][CH3:18])([CH3:16])[CH3:15])=[CH:5][C:4]=1[Cl:20]>>[NH2:2][C:3]1[C:8]([C:9]#[N:10])=[CH:7][C:6]([CH:11]([OH:19])[CH2:12][NH:13][C:14]([CH2:17][CH3:18])([CH3:16])[CH3:15])=[CH:5][C:4]=1[Cl:20]
Reactant: CCC(C)(C)NCC(=O)c1cc(Cl)c(N)c(C#N)c1
Agent: Cl
Product: CCC(C)(C)NCC(O)c1cc(Cl)c(N)c(C#N)c1

Procedure:
m.p. of the hydrochloride: 218°-220° C. (decomp.), was prepared from 4'-amino-3'-chloro-5'-cyano-2-tert.pentylaminoacetophenone analogous to Example 48.
Reaction SMILES: [Cl:1][C:2]1[C:11]([I:12])=[CH:10][C:5]2[NH:6][C:7](=[S:9])[NH:8][C:4]=2[CH:3]=1.Br[CH2:14][C:15]([O:17][CH3:18])=[O:16].C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1>[Cl:1][C:2]1[C:11]([I:12])=[CH:10][C:5]2[N:6]=[C:7]([S:9][CH2:14][C:15]([O:17][CH3:18])=[O:16])[NH:8][C:4]=2[CH:3]=1
Reactant: S=c1[nH]c2cc(Cl)c(I)cc2[nH]1
Reactant: COC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1CCOC1
Product: COC(=O)CSc1nc2cc(I)c(Cl)cc2[nH]1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
A mixture of 6-chloro-5-iodo-2-thio-1H-benzo[d]imidazole (Intermediate 2; 4.00 g, 12.9 mmol), methyl bromoacetate (1.2 mL, 12.9 mmol), and Cs2CO3 (8.41 g, 25.8 mmol) in 65 mL of THF was stirred for 2.5 h at rt. The volume of the solvent was reduced by rotary evaporation to about 20 mL, the mixture was diluted with 200 mL of EtOAc and washed with brine, dried (MgSO4) and evaporated. The resulting residue was subjected to chromatography on an 80 g column of SiO2 eluting with 14% EtOAc in hexanes, followed by 20% to provide the title compound as an amorphous solid, which exists as a tautomer mixture in DMSO according to 1H NMR: 1H NMR (500 MHz, DMSO-d6): δ 3.66, 3.72, 3.73 (s each, 3H), 4.24, 4.25, 4.26 (s each, 2H), 7.71, 7.95 (s each, 1H), 7.99, 8.11, 8.22 (s each, 1H), 12.91 (br s, 1H); LC-MS: calculated for C10H8ClIN2O2S 382.6, observed m/e 382.9/384.9 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]2[C:9]([C:13]3[N:23]([S:24]([C:27]4[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=4)(=[O:26])=[O:25])[C:16]4[N:17]=[CH:18][CH:19]=[C:20]([CH:21]=O)[C:15]=4[CH:14]=3)=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1[O:34][CH3:35].[CH3:36][N:37]1[CH2:42][CH2:41][N:40]([C:43]2[CH:50]=[CH:49][C:46]([CH2:47][NH2:48])=[CH:45][CH:44]=2)[CH2:39][CH2:38]1>>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[C:9]([C:13]3[N:23]([S:24]([C:27]4[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=4)(=[O:26])=[O:25])[C:16]4=[N:17][CH:18]=[CH:19][C:20]([CH2:21][NH:48][CH2:47][C:46]5[CH:45]=[CH:44][C:43]([N:40]6[CH2:39][CH2:38][N:37]([CH3:36])[CH2:42][CH2:41]6)=[CH:50][CH:49]=5)=[C:15]4[CH:14]=3)=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1[O:34][CH3:35]
Reactant: CN1CCN(c2ccc(CN)cc2)CC1
Reactant: COc1cc2c(nc1OC)c(-c1cc3c(C=O)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Product: COc1cc2c(nc1OC)c(-c1cc3c(CNCc4ccc(N5CCN(C)CC5)cc4)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C

Procedure:
The product is prepared by following the procedure described in example 34, stage (j), starting with 0.1 g of 2-(5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-carbaldehyde and 0.209 cm3 of 4-(4-methylpiperazino)benzylamine instead of the cyclopropylamine used in example 34, stage (j). After purification by flash-pack chromatography (SiO2, dichloromethane/methanol 90/10 by volume as eluents), 0.083 g of [2-(5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-ylmethyl]-[4-(4-methylpiperazin-1-yl)-benzyl]amine is obtained with the following characteristics:
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].Br[CH2:12][C:13]([NH2:15])=[O:14].C([O-])([O-])=O.[K+].[K+]>CC(C)=O.O>[NH2:15][C:13]([CH2:12][O:10][C:7]1[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1)=[O:14]
Reactant: NC(=O)CBr
Reactant: O=[N+]([O-])c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: NC(=O)COc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 81.6 %

Procedure:
4-Nitrophenol (10 g), bromoacetamide (10 g) and K2CO3 (15 g) were suspended in acetone (30 mL). The yellow solution was stirred at rt for 3 d. The reaction mixture was diluted with water and acetone was removed under reduced pressure. The light-yellow precipitate was collected by filtration, washed with water and dried to give O-aminocarbonylmethyl-4-nitrophenol (11.5 g) as a beige solid.
Reaction SMILES: [CH2:1](Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Br)C1C=CC=CC=1.[OH:17][CH:18]1[CH2:22][CH2:21][O:20][CH2:19]1.[H-].[Na+]>O1CCOCC1>[O:20]1[CH2:21][CH2:22][CH:18]([O:17][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:19]1
Reactant: ClCc1ccccc1
Reactant: OC1CCOC1
Agent: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: c1ccc(COC2CCOC2)cc1

Procedure:
Thus, benzylchloride or benzylbromide can be reacted at elevated temperature with the alkololate from 3-hydroxytetrahydrofurane and sodium hydride, suspended in dioxane to yield the (3-tetrahydrofuryl)-benzylether which is an active herbicide against grassy weeds (German Offenlegungsschrift No. 2724675).
Reaction SMILES: [CH:1](=O)[C:2]#[CH:3].[NH2:5][C:6]1[CH2:11][CH2:10][CH2:9][C:8](=[O:12])[CH:7]=1>CN(C)C=O>[N:5]1[C:6]2[CH2:11][CH2:10][CH2:9][C:8](=[O:12])[C:7]=2[CH:3]=[CH:2][CH:1]=1
Reactant: NC1=CC(=O)CCC1
Reactant: C#CC=O
Solvent: CN(C)C=O
Product: O=C1CCCc2ncccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 54.1 %

Procedure:
The procedure of Rimek and Zymalkowski (Arch. Pharm. 1961, 294, 759-765) was followed. Over a period of 1 hour, 40.9 g (0.757 mol) of freshly-distilled propiolaldehyde was added dropwise to a solution of 42.1 g (0.379 mol) of 3-amino-2-cyclohexenone in 1.5 1 of N,N-dimethylformamide (DMF). The solution was stirred at room temperature for 12 hours. The DMF was evaporated at reduced pressure. Vacuum distillation (bp 60°-65° C. at 0.025-0.050 mmHg) of the resultant black tars gave 30.2 g (54.2%) of 7,8-dihydro-5(6H)-quinolinone as a colorless liquid.