Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([NH:7][C:8]1[N:9]=[C:10]([OH:28])[C:11]2[CH:17]=[C:16]([CH:18]=[CH:19][CH2:20][O:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[CH:15]=[N:14][C:12]=2[N:13]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].I[C:30]1[CH:51]=[CH:50][C:33]([C:34]([NH:36][C@H:37]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])=[O:35])=[CH:32][CH:31]=1.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(N(CC)CC)C.C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:23]1[CH2:24][CH2:25][CH2:26][CH2:27][CH:22]1[O:21][CH2:20][C:19]([C:30]1[CH:51]=[CH:50][C:33]([C:34]([NH:36][C@H:37]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])=[O:35])=[CH:32][CH:31]=1)=[CH:18][C:16]1[CH:15]=[N:14][C:12]2[N:13]=[C:8]([NH:7][C:1](=[O:6])[C:2]([CH3:4])([CH3:5])[CH3:3])[N:9]=[C:10]([OH:28])[C:11]=2[CH:17]=1
Reactant: CC(C)(C)C(=O)Nc1nc(O)c2cc(C=CCOC3CCCCO3)cnc2n1
Reactant: CCOC(=O)CC[C@H](NC(=O)c1ccc(I)cc1)C(=O)OCC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCOC(=O)CC[C@H](NC(=O)c1ccc(C(=Cc2cnc3nc(NC(=O)C(C)(C)C)nc(O)c3c2)COC2CCCCO2)cc1)C(=O)OCC
Reaction time: 12 h

Procedure:
A mixture containing 3.48 g (9 mm) of 2-pivaloylamino-4-hydroxy-6-(3-tetrahydropyr-2-yloxyprop-1-en-1-yl)-pyrido[2,3-d]pyrimidine, 3.12 g, (1.2 equiv.) of diethyl N-(4-iodobenzoyl)glutamate, 546 mg (20%) of tris(2-methylphenyl)phosphine, 201 mg (10%) of palladium acetate and 85.5 mg (5%) of cuprous iodide in 15 ml of triethylamine and 240 ml of acetonitrile was heated at reflux under nitrogen. After 12 hours., 1.17 g of diethyl N-(4-iodobenzoyl)glutamate was added and the reaction mixture was heated at reflux under nitrogen for an additional 12 hours. The reaction mixture then was concentrated under reduced pressure and the residue was chromatographed on silica gel, eluting with 20:1 ethyl acetate:hexane. (Recovered starting material can be recycled through the foregoing procedure.) The concentrated material was dissolved in 1:5 ethyl acetate:ether and this solution was refrigerated for 15 hours. The solid which formed was collected by filtration, washed with cold ethyl acetate and dried to yield diethyl N-[4-{1-(tetrahydropyr-2-yloxy)-3-(2-pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidin-6-yl)prop-2-en-2-yl}benzoyl]glutamate. mp. 273°-275° C. Analysis calculated for C36H45N4O9 ; C, 62.50; H, 6.56; N, 10.12. Found: C, 62.21; H, 6.34; N, 9.83. NMR (CDCL3), delta, 1.24 (t, 3H, J=7 Hz), 1.32 (t 3H, J=7 Hz), 1.32 (s, 9H), 1.53-1.87 (m, 6H), 2.11-2.22 (m, 1H), 2.29-2.41 (m 1H), 2.42-2.58 (m, 2H), 3.53-3.59 (m, 1H), 3.80-3.88 (m, 1H), 4.13 (q, 2H, J=7 Hz), 4.25 (q, 2H, J=7 Hz), 4.33 (d, 1H, J=14 Hz), 4.62 (d, 1H, J=14 Hz), 4.75-4.83 (m, 2H), 6.84 (s, 1H), 7.12 (brs, 1H, NH, J =7 Hz), 7.31 (d, 2H, J=8.1 Hz), 7.79 (d, 2H, J=8.1 Hz), 8.13 (d, 1H, J=1.6 Hz), 8.34 (brs, NH), 8.42 (d, 1H, J=1.6 Hz), 11.99 (brs, NH).
Reaction SMILES: [H-].[Na+].[CH2:3]1[N:14]2[C:15]3[CH:7]([CH2:8][CH2:9][C:10](=[O:16])[C:11]=3[CH:12]=[CH:13]2)[CH2:6][NH:5][CH2:4]1.I[CH3:18]>CN(C)C=O>[CH3:18][CH:9]1[CH2:8][CH:7]2[CH2:6][NH:5][CH2:4][CH2:3][N:14]3[C:15]2=[C:11]([CH:12]=[CH:13]3)[C:10]1=[O:16]
Reactant: CI
Reactant: O=C1CCC2CNCCn3ccc1c32
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1CC2CNCCn3ccc(c32)C1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 731.3 %

Procedure:
Add sodium hydride (0.78 g, 1.9 mmol, 60% in mineral oil) to 1,2,4,5-tetrahydro-6H-[1,4]diazepino[6,7,1-hi]indol-7-one (3.05 g, 1.62 mmol) in dry dimethylformamide (77 mL). Stir for 30 minutes at room temperature and then add iodomethane (2.0 mL, 3.2 mmol). Stir at room temperature for 134 minutes. Partition between ethyl acetate (1 L) and water (500 mL). Wash the organic phase with saturated aqueous sodium chloride, dry over sodium sulfate, and concentrate under reduced pressure. Subject the residue to chromatography (pre-packed silica gel), eluting with a gradient 1:0-9:1 ethyl acetate/methanol to provide the desired compound (2.42 g, 74%) as an off-white solid.
Reaction SMILES: [Cl:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[C:3]=1[CH2:20][C:21]#[N:22].S(=O)(=O)(O)[OH:24]>>[Cl:1][C:2]1[N:6]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[C:3]=1[CH2:20][C:21]([NH2:22])=[O:24]
Reactant: O=S(=O)(O)O
Reactant: N#CCc1c(-c2ccc(Cl)cc2)nn(-c2ccccc2)c1Cl
Product: NC(=O)Cc1c(-c2ccc(Cl)cc2)nn(-c2ccccc2)c1Cl
Temperature: 0 °C
Yield: 99 %

Procedure:
5 g of 5-chloro-3-p-chlorophenyl-1-phenyl-pyrazole-4-acetonitrile and 10 ml of 96 % sulfuric acid are stirred for 4 hours at room temperature. The batch is added to 50 g of ice, the precipitate is separated by vacuum filtering and washed with water. 5-Chloro-3-p-chlorophenyl-1-phenyl-pyrazole-4-acetamide is obtained with a 99% yield; F 192°-193°.
Reaction SMILES: [C-:1]1([C:6]#[C:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10](C#C[C-]3C=CC=C3)[CH:9]=2)[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH-:21]1[CH:25]=[CH:24][CH:23]=[CH:22]1.[Fe+2:26].[CH-]1C=CC=C1.[Fe+2].C([C-]1C=CC=C1)#C.[CH-]1C=CC=C1.[Fe+2].[I:46]C1C=CC=C(I)C=1>>[C-:1]1([C:6]#[C:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([I:46])[CH:9]=2)[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH-:21]1[CH:25]=[CH:24][CH:23]=[CH:22]1.[Fe+2:26]
Reactant: Ic1cccc(I)c1
Reactant: C(#C[c-]1cccc1)c1cccc(C#C[c-]2cccc2)c1
Agent: [Fe+2]
Agent: C#C[c-]1cccc1
Agent: c1cc[cH-]c1
Product: Ic1cccc(C#C[c-]2cccc2)c1

Procedure:
Example 11 describes the procedure for producing 1,3-bis(ferrocenylethynyl) benzene 516. Ethynylferrocene 500 was reacted with 1,3-diiodobenzene 502 to form 1-(ferrocenylethynyl)-3-iodobenzene 504. Sufficient ethynylferrocene 500 was present such that the second step of the reaction immediately proceeded. 1-(Ferrocenylethynyl)-3-iodobenzene 504 reacted with ethynylferrocene 514 to form 1,3-bis(ferrocenylethynyl) benzene 516. The reaction procedure is shown in FIG. 5.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:3][CH:2]=1.Cl>C(O)C.[H][H].[Pt]=O>[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:3][CH2:2]1
Reactant: [H][H]
Reactant: CCOC(=O)Cc1ccncc1
Agent: O=[Pt]
Agent: Cl
Solvent: CCO
Product: CCOC(=O)CC1CCNCC1
Reaction time: 1 h
Yield: 162.3 %

Procedure:
16.5 g (0.1 mol) Ethyl 4-pyridylacetate, 8.4 mL (0.1 mol) 12 N hydrochloric acid and 2.5 g platinum oxide were dissolved in absolute ethanol and hydrogenated at 40 psi hydrogen on a Parr shaker. After 1 hour, the contents of the vessel were filtered and concentrated in vacuo yielding 27.79 g of ethyl 4-piperidinylacetate.
Reaction SMILES: [NH3:1].CS(O[CH:7]1[CH2:10][N:9]([CH:11]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[CH2:8]1)(=O)=O>CO>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([CH:11]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[N:9]2[CH2:10][CH:7]([NH2:1])[CH2:8]2)=[CH:13][CH:14]=1
Reactant: N
Reactant: CS(=O)(=O)OC1CN(C(c2ccc(Cl)cc2)c2ccc(Cl)cc2)C1
Solvent: CO
Product: NC1CN(C(c2ccc(Cl)cc2)c2ccc(Cl)cc2)C1
Temperature: -60 °C
Reaction time: 24 h

Procedure:
1-[Bis(4-chlorophenyl)methyl]azetidin-3-yl-amine may be obtained in the following manner: 400 cm3 of a mixture of methanol and liquid ammonia (50/50 by volume) are added to 27 g of 1-[bis(4-chlorophenyl)methyl]azetidin-3-yl methylsulfonate contained in an autoclave previously cooled to around −60° C. The reaction medium is then stirred at 60° C. for 24 hours and then abandoned in the open air to allow the evaporation of the ammonia and finally concentrated under reduced pressure (2.7 kPa). The residue is taken up in 500 cm3 of a 0.37 N aqueous sodium hydroxide solution and extracted with four times 500 cm3 of ethyl ether. The combined organic phases are washed successively with twice 100 cm3 of distilled water and 100 cm3 of a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2.7 kPa). The residue obtained is purified by flash chromatography on silica gel [eluant: dichloromethane/methanol (95/5 by volume)]. 14.2 g of 1-[bis(4-chlorophenyl)methyl]azetidin-3-ylamine are obtained in the form of an oil which solidifies into a cream-colored solid.
Reaction SMILES: Cl[C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][C:8]([O:12][CH3:13])=[CH:7]2.C(=O)([O-])[O-].[K+].[K+].[CH3:20][O:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][NH2:27])=[CH:24][CH:23]=1>CN(C)C=O>[CH3:13][O:12][C:8]1[CH:9]=[N:10][C:11]2[C:6]([CH:7]=1)=[CH:5][CH:4]=[N:3][C:2]=2[NH:27][CH2:26][C:25]1[CH:28]=[CH:29][C:22]([O:21][CH3:20])=[CH:23][CH:24]=1
Reactant: COc1cnc2c(Cl)nccc2c1
Reactant: COc1ccc(CN)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(CNc2nccc3cc(OC)cnc23)cc1
Temperature: 100 °C
Reaction time: 24 h
Yield: 90.1 %

Procedure:
To a solution of 8-chloro-3-methoxy-1,7-naphthyridine (1 g, 5.14 mmol) in N,N-dimethylformamide (10.28 mL) was added potassium carbonate (1.42 g, 10.28 mmol) followed by 4-methoxybenzylamine (1.47 ml, 11.3 mmol). The reaction was stirred at 100° C. for 24 hours and then concentrated to generate a brown residue. This was partitioned between ethyl acetate and water. The organic layer was concentrated and purified by silica-gel chromatography, eluting with 1-5% methanol in DCM, to provide the title compound (1.37 g, 4.63 mmol) as a tan solid. LC/MS (ESI+) m/z=296 (M+H).
Reaction SMILES: CN(C)[CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[F:13])=[O:6].[Br:15][C:16]1[CH:21]=[CH:20][C:19]([C@@H:22]([NH2:24])[CH3:23])=[CH:18][CH:17]=1.O>CCO>[Br:15][C:16]1[CH:21]=[CH:20][C:19]([C@@H:22]([NH:24][CH2:3][CH2:4][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[F:13])=[O:6])[CH3:23])=[CH:18][CH:17]=1
Reactant: C[C@H](N)c1ccc(Br)cc1
Reactant: CN(C)CCC(=O)c1ccccc1F
Solvent: CCO
Solvent: O
Product: C[C@H](NCCC(=O)c1ccccc1F)c1ccc(Br)cc1
Yield: 3.3 %

Procedure:
A solution of 3-dimethylamino-1-(2-fluoro-phenyl)-propan-1-one (17 g, 0.087 mol) and (S)-1-(4-bromophenyl)ethanamine (17 g, 0.087 mol) in EtOH (50 mL)/H2O (50 mL) was refluxed at 80° C. over night. The solvent was removed under vacuum. The residue was purified by column chromatography to afford (S)-3-(1-(4-bromophenyl)ethylamino)-1-(2-fluorophenyl)propan-1-one (1 g, 3%).
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][S:6][C:7]1[CH:8]=[C:9]([O:15][CH3:16])[C:10]([O:13][CH3:14])=[N:11][CH:12]=1.BrCC1C=CC([F:28])=CC=1>>[F:28][C:19]1[CH:18]=[CH:17][C:4]([CH2:5][S:6][C:7]2[CH:8]=[C:9]([O:15][CH3:16])[C:10]([O:13][CH3:14])=[N:11][CH:12]=2)=[CH:3][CH:2]=1
Reactant: Fc1ccc(CBr)cc1
Reactant: COc1cc(SCc2cccc(Cl)c2)cnc1OC
Product: COc1cc(SCc2ccc(F)cc2)cnc1OC

Procedure:
Prepared as described for 5-(3-chlorobenzylthio)-2,3-dimethoxypyridine (Intermediate 8) but using 1-(bromomethyl)-4-fluorobenzene instead of 1-(bromomethyl)-3-chlorobenzene.
Reaction SMILES: [Si:1]([O:8][C@@H:9]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)[CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Si:38]([O:55][CH2:56][C@H:57]1[N:62]([CH2:63][CH2:64][C@@H:65]([NH:74][C:75]2[CH:80]=[CH:79][C:78]([S:81]([NH2:84])(=[O:83])=[O:82])=[CH:77][C:76]=2[S:85]([C:88]([F:91])([F:90])[F:89])(=[O:87])=[O:86])[CH2:66][S:67][C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)[CH2:61][CH2:60][O:59][CH2:58]1)([C:51]([CH3:54])([CH3:53])[CH3:52])([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Si:1]([O:8][C@@H:9]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)[CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:24]=[CH:23][C:19]([C:20]([NH:84][S:81]([C:78]3[CH:79]=[CH:80][C:75]([NH:74][C@H:65]([CH2:64][CH2:63][N:62]4[CH2:61][CH2:60][O:59][CH2:58][C@H:57]4[CH2:56][O:55][Si:38]([C:51]([CH3:52])([CH3:53])[CH3:54])([C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=4)[C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[CH2:66][S:67][C:68]4[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=4)=[C:76]([S:85]([C:88]([F:89])([F:90])[F:91])(=[O:86])=[O:87])[CH:77]=3)(=[O:83])=[O:82])=[O:21])=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)O[C@@H](c1ccccc1-c1ccc(Cl)cc1)C1CCN(c2ccc(C(=O)O)cc2)CC1
Reactant: CC(C)(C)[Si](OC[C@@H]1COCCN1CC[C@H](CSc1ccccc1)Nc1ccc(S(N)(=O)=O)cc1S(=O)(=O)C(F)(F)F)(c1ccccc1)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: ClCCCl
Product: CC(C)(C)[Si](C)(C)O[C@@H](c1ccccc1-c1ccc(Cl)cc1)C1CCN(c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H](CCN4CCOC[C@H]4CO[Si](c4ccccc4)(c4ccccc4)C(C)(C)C)CSc4ccccc4)c(S(=O)(=O)C(F)(F)F)c3)cc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 253 %

Procedure:
To a solution of (R)-4-(4-((tert-butyldimethylsilyloxy)(4′-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 13, 183 mg, 0.34 mmol) in DCM (3 ml) were added sequentially DMAP (125 mg, 1.02 mmol), 4-((R)-4-((S)-3-((tert-butyldiphenylsilyloxy)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 105, 280 mg, 0.34 mmol) and EDC (131 mg, 0.68 mmol). The resulting solution was stirred at room temperature overnight. Evaporation of the volatiles under reduced pressure gave a residue which was purified by column chromatography (ISCO, 27 g silica gel column, eluting with 0→20% EtOAc/hexanes) to give 4-(4-((R)-(tert-butyldimethylsilyloxy)(4′-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)-N-(4-((R)-4-((S)-3-((tert-butyldiphenylsilyloxy)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide (EXAMPLE 24, STEP 1,153 mg) which was used in the preparation of EXAMPLE 24, STEP 2 without further purification.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([NH2:12])=[O:11])[CH:5]=[CH:6][C:7]=1[CH3:8].Br[CH2:14][C:15](=O)[C:16]([O:18][CH2:19][CH3:20])=[O:17]>CN(C=O)C.CCOC(C)=O>[OH:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[O:11][CH:14]=[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:12]=2)[CH:5]=[CH:6][C:7]=1[CH3:8]
Reactant: Cc1ccc(NC(N)=O)cc1O
Reactant: CCOC(=O)C(=O)CBr
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)c1coc(Nc2ccc(C)c(O)c2)n1
Temperature: 60 °C
Yield: 50 %

Procedure:
A solution containing 1-(3-hydroxy-4-methylphenyl)urea (150 mg, 0.9 mmol) and ethyl 3-bromopyruvate (0.11 mL, 0.9 mmol) in dry DMF (3.611E) was heated at 60° C. for 6 h. The reaction mixture was diluted with EtOAc and washed with brine and saturated NaHCO3 solution and the combined organic layers were dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography on silica gel (hexane:EtOAc 6/4) to give the product in 50% yield (119 mg).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[C:13]1([C:19]2[C:32]3[C:23](=[C:24]4[C:29](=[CH:30][CH:31]=3)[C:28]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:27][CH:26]=[N:25]4)[N:22]=[CH:21][CH:20]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.O>C1COCC1>[C:2]1([C:26]2[CH:27]=[C:28]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:29]3[C:24](=[C:23]4[C:32](=[CH:31][CH:30]=3)[C:19]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[CH:20][CH:21]=[N:22]4)[N:25]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Brc1ccccc1
Reactant: c1ccc(-c2ccnc3c2ccc2c(-c4ccccc4)ccnc23)cc1
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: c1ccc(-c2cc(-c3ccccc3)c3ccc4c(-c5ccccc5)ccnc4c3n2)cc1
Temperature: -78 °C
Yield: 37.2 %

Procedure:
To a three-necked flask of 250 ml, 0.97 g (6.16 mmol) of bromobenzene and 70 ml of THF were charged, then 3.9 ml (22 mmol) n-butyllithium (1.6M in Hexane solution) was dropped under stirring at −78° C. in a nitrogen atmosphere. The mixture was stirred for one hour at −78° C., and a solution of 1.86 g (5.6 mmol) 4,7-diphenyl-1,10-phenanthroline in 30 ml THF was dropped. Then the mixture was stirred at room temperature for overnight and was added with water. The organic layer was extracted with Dichloromethane and dried with anhydrous magnesium sulfate, the solvent was removed by rotary evaporation. The product was purified by column chromatography on alumina using Dichloromethane/Hexane as eluent and dried in vacuo, obtaining white powder compound 0.85 g (yield of 37.21%).
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:4]=[CH:5][C:6]2[N:12]3[C:13]([CH2:16]Cl)=[N:14][N:15]=[C:11]3[CH2:10][N:9]=[C:8]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:7]=2[CH:24]=1.[I-].[K+].[CH2:27]([NH2:30])[CH:28]=[CH2:29]>O1CCCC1>[CH3:1][S:2][C:3]1[CH:4]=[CH:5][C:6]2[N:12]3[C:13]([CH2:16][NH:30][CH2:27][CH:28]=[CH2:29])=[N:14][N:15]=[C:11]3[CH2:10][N:9]=[C:8]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:7]=2[CH:24]=1
Reactant: CSc1ccc2c(c1)C(c1ccccc1)=NCc1nnc(CCl)n1-2
Reactant: C=CCN
Agent: [I-]
Agent: [K+]
Solvent: C1CCOC1
Product: C=CCNCc1nnc2n1-c1ccc(SC)cc1C(c1ccccc1)=NC2

Procedure:
In the manner given in Example 31, 8-(methylthio)-1-(chloromethyl)-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine, potassium iodide and allylamine in tetrahydrofuran are reacted to give 8-(methylthio)-1-[(allylamino)-methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[C:9]([CH2:12][O:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[CH:16]=[C:17]([C:23](O)=[O:24])[NH:18]4)=[CH:10][O:11][C:7]=2[CH:6]=[C:5]([O:26][CH3:27])[CH:4]=1.Cl.Cl.Cl.[NH2:31][CH:32]1[CH2:37][CH2:36][N:35]([CH2:38][C@@H:39]([N:41]2[CH2:46][CH2:45][CH:44]([OH:47])[CH2:43][CH2:42]2)[CH3:40])[CH2:34][CH2:33]1>>[OH:47][CH:44]1[CH2:43][CH2:42][N:41]([C@@H:39]([CH3:40])[CH2:38][N:35]2[CH2:34][CH2:33][CH:32]([NH:31][C:23]([C:17]3[NH:18][C:19]4[C:15]([CH:16]=3)=[C:14]([O:13][CH2:12][C:9]3[C:8]5[C:3]([O:2][CH3:1])=[CH:4][C:5]([O:26][CH3:27])=[CH:6][C:7]=5[O:11][CH:10]=3)[CH:22]=[CH:21][CH:20]=4)=[O:24])[CH2:37][CH2:36]2)[CH2:46][CH2:45]1
Reactant: COc1cc(OC)c2c(COc3cccc4[nH]c(C(=O)O)cc34)coc2c1
Reactant: C[C@@H](CN1CCC(N)CC1)N1CCC(O)CC1
Agent: Cl
Product: COc1cc(OC)c2c(COc3cccc4[nH]c(C(=O)NC5CCN(C[C@H](C)N6CCC(O)CC6)CC5)cc34)coc2c1

Procedure:
This compound is synthesized analogously to example 1 from 4-(4,6-dimethoxy-benzofuran-3-ylmethoxy)-1H-indole-2-carboxylic acid, 126 (see example 99) and amine 50.
Reaction SMILES: Br[C:2]1[C:3]([F:21])=[C:4]([F:20])[C:5]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].C(N(CC)C(C)C)(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH2:73]([SH:80])[C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:73]([S:80][C:2]1[C:3]([F:21])=[C:4]([F:20])[C:5]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8])[C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1
Reactant: SCc1ccccc1
Reactant: COC(=O)c1cc(Br)c(F)c(F)c1Nc1ccccc1F
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1cc(SCc2ccccc2)c(F)c(F)c1Nc1ccccc1F
Temperature: 100 °C
Reaction time: 8 h
Yield: 87.5 %

Procedure:
To a solution of methyl 5-bromo-3,4-difluoro-2-((2-fluorophenyl)amino)benzoate (12.85 g, 35.80 mmol) in anhydrous 1,4-dioxane (30 mL) was added N,N-diisopropylethylamine (9.21 g, 71.60 mmol). Then Pd2(dba)3 (1.63 g, 1.78 mmol) followed by Xantphos (2.06 g, 3.56 mmol) and BnSH (4.44 g, 35.80 mmol) was added under nitrogen atmosphere. The mixture was stirred overnight at 100° C. under N2 atmosphere. Then the reaction was allowed to warm to ambient temperature and quenched with water (150 mL). The aqueous layer was extracted with ethyl acetate (200 mL×3). The combined organic layers were washed with water (200 mL×3) and brine (200 mL) sequentially, dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 50:1, v/v) to give the desired product (white solid, 12.64 g, 88% yield). 1H NMR (400 MHz, CDCl3) δ 9.04 (s, 1H), 7.68 (dd, J=7.5, 2.1 Hz, 1H), 7.21-7.14 (m, 5H), 7.05-6.89 (m, 4H), 3.97 (s, 2H), 3.80 (s, 3H).
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:14])([CH3:13])[CH2:7][CH2:8][C:9]2=O)=[CH:4][CH:3]=1.[C:15]([Mg]Cl)([CH3:18])([CH3:17])[CH3:16].C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:14])([CH3:13])[CH2:7][CH:8]=[C:9]2[C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1
Reactant: CC1(C)CCC(=O)c2cc(Br)ccc21
Reactant: CC(C)(C)[Mg]Cl
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: C1CCOC1
Product: CC(C)(C)C1=CCC(C)(C)c2ccc(Br)cc21

Procedure:
Reaction Scheme 9 discloses the preferred method of synthesis of a starting material from which certain examples for compounds of the invention within the scope of Formula 6 are preferably made. In accordance with this scheme 7-bromo-3,4-dihydro-4,4-dimethylnaphthalen-1(2H)-one (Compound G) is reacted with t-butylmagnesium chloride in tetrahydrofuran in the presence of 1,3-dimethyl-3,4,5,6-tetrahydro-2(H)-pyrimidinone (DMPU). Thereafter, the resulting intermediate tertiary alcohol is heated in the presence of acid (p-toluenesulfonic acid) to give 7-bromo-1-(1,1-dimethylethyl)-3,4-dihydro-4,4-dimethylnaphthalene (Compound C42). Compound C42 is reacted with 1-ethoxyvinyltributyltin (EVTB) in the presence of Pal(0) catalyst to yield after acidic work-up 7-acetyl-1-(1,1-dimethylethyl)-3,4-dihydro-4,4-dimethylnaphthalene (Compound C43). Compound C43 is subjected to a sequence of reactions of the type described above in connection with Reaction Scheme 8, starting with a Horner Emmons reaction with diethyl cyanomethylphosphonate, to eventually provide ethyl 7-[4,4-dimethyl-3,4-dihydro-1-(1,1-dimethylethyl)-naphth-7-yl]-3,7-dimethyl-hepta-2(E),4(E),6(E)-trienoate (Compound C46). Compound C46 of the invention is within the scope of Formula 6. ##STR24##
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([O-:10])(=[O:9])=[O:8])=[CH:3][CH:2]=1.[F:12][C:13]([F:27])([F:26])[C:14]1[CH:15]=[CH:16][C:17]2[S:21][C:20]([CH3:22])=[N+:19]([CH2:23][CH3:24])[C:18]=2[CH:25]=1.CC(C)=O.[C:32]([O:35][CH2:36][CH3:37])(=O)[CH3:33]>>[C:1]1([CH3:11])[CH:2]=[CH:3][C:4]([S:7]([O-:10])(=[O:8])=[O:9])=[CH:5][CH:6]=1.[F:27][C:13]([F:12])([F:26])[C:14]1[CH:15]=[CH:16][C:17]2[S:21][C:20]([CH:22]=[C:36]3[CH:37]=[C:5]([CH3:4])[C:6]4[C:32](=[CH:33][CH:3]=[CH:2][CH:1]=4)[O:35]3)=[N+:19]([CH2:23][CH3:24])[C:18]=2[CH:25]=1
Reactant: CC[n+]1c(C)sc2ccc(C(F)(F)F)cc21
Reactant: CCOC(C)=O
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Solvent: CC(C)=O
Product: CC[n+]1c(C=C2C=C(C)c3ccccc3O2)sc2ccc(C(F)(F)F)cc21
Temperature: 150 °C
Reaction time: 0.67 h
Yield: 46 %

Procedure:
2.37 g of 5-trifluoromethyl-3-ethyl-2-methylbenzothiazolium p-toluenesulfonate and 1.0 g of 4-methylcoumarin-2-thione were reacted under heat at 150° C. for 20 hours, and then 10 ml of metrhanol, 10 ml of acetone, and 20 ml of ethyl acetate were added to the reaction mixture in the order listed to obtain a uniform solution. After cooling to room temperature, crystals precipitated out therefrom. The crystals formed were separated by filtration and washed with a small amount of acetone, and thereafter the crystlas were placed in a mixed solvent comprising 10 ml of methanol, 10 ml of acetone, and 20 ml of ethyl acetate at room temperature, and stirred for 40 minutes. Then, the crystals were again taken out by filtration and washed with acetone, at last to obtain 1.47 g of the desired p-toluenesulfonate product. Yield: 46%. Appearance: brown crystal. M.P.: 272°-273° C. (decomposition).