Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC1C=CC(S(O[CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[C:20]([C:32]([NH:34][C:35]3[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=3)=[O:33])[CH:19]=2)(=O)=O)=CC=1.[CH3:41][C:42]([O:45][C:46]([NH:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[O:47])([CH3:44])[CH3:43].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C)C=O.O>[C:26]1([CH2:25][O:24][C:21]2[CH:22]=[CH:23][C:18]([O:17][CH2:16][CH2:15][O:14][CH2:13][CH2:12][N:48]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[C:46]([O:45][C:42]([CH3:41])([CH3:43])[CH3:44])=[O:47])=[CH:19][C:20]=2[C:32]([NH:34][C:35]2[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=2)=[O:33])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: Cc1ccc(S(=O)(=O)OCCOCCOc2ccc(OCc3ccccc3)c(C(=O)Nc3cccnc3)c2)cc1
Reactant: CC(C)(C)OC(=O)NC(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N(CCOCCOc1ccc(OCc2ccccc2)c(C(=O)Nc2cccnc2)c1)C(=O)OC(C)(C)C
Temperature: 60 °C

Procedure:
2-{[2-({4-[(Phenylmethyl)oxy]-3-[(3-pyridinylamino)carbonyl]phenyl}oxy)ethyl]oxy}ethyl 4-methylbenzenesulfonate (may be prepared as described in Description 76; 500 mg, 0.89 mmol) was dissolved in N,N-dimethylformamide (10 ml). Di-tert-butyl iminodicarbonate (193 mg, 0.89 mmol) and Cs2CO3 (290 mg, 0.89 mmol) were added. The reaction mixture was heated at 60° C. for 3 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried over Na2SO4, and concentrated under reduced pressure to yield the title compound as an oil. 360 mg.
Reaction SMILES: [Br:1][C:2]1[C:3]([F:17])=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9](I)=[CH:10]3)[C:6]=2[CH:16]=1.C[Si](N[Si](C)(C)C)(C)C.C[N:28](C)[CH:29]=[O:30]>>[Br:1][C:2]1[C:3]([F:17])=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([C:29]([NH2:28])=[O:30])=[CH:10]3)[C:6]=2[CH:16]=1
Reactant: Fc1cc2c(cc1Br)-c1nc(I)cn1CCO2
Reactant: CN(C)C=O
Agent: C[Si](C)(C)N[Si](C)(C)C
Product: NC(=O)c1cn2c(n1)-c1cc(Br)c(F)cc1OCC2
Temperature: 80 °C
Reaction time: 8 h
Yield: 30 %

Procedure:
Into a 5000-mL pressure tank reactor (10 atm) purged and maintained with an inert atmosphere of nitrogen was placed 9-Bromo-8-fluoro-2-iodo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (204 g, 498.79 mmol, 1.00 equiv), HMDS (403.5 g, 2.50 mol, 5.00 equiv), Pd(PPh3)Cl2 (11 g, 25.02 mmol, 0.05 equiv), and N,N-dimethylformamide (3 L). To the above CO (10 atm) was introduced in. The resulting solution was stirred overnight at 80° C. and quenched by the addition of 5 L of water. The solids were collected by filtration. The crude product was re-crystallized from 800 mL of EA. The mixture was stirred at 50° C. for 3 h. The solids were collected by filtration, washed with 3×100 mL of EA and dried to afford 48.5 g (30%) of 9-Bromo-8-fluoro-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a yellow solid. LC-MS: 326 [M+H]+; 1H-NMR (DMSO, 300 MHz, ppm): δ 8.75 (d, J=8.4 Hz, 1H), 7.79 (s, 1H), 7.61 (s, 1H), 7.16-7.11 (m, 2H), 4.49-4.50 (m, 4H).
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][C@H:6]([C:11]([OH:13])=O)[C:7]([CH3:10])([CH3:9])[CH3:8])=[O:4].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[S:28]1[C:32]([C:33]2[CH:38]=[CH:37][C:36]([CH2:39][N:40]([NH:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:41][C@H:42]([OH:52])[C@@H:43]([NH2:51])[CH2:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)=[CH:35][CH:34]=2)=[CH:31][N:30]=[CH:29]1>CN(C=O)C>[S:28]1[C:32]([C:33]2[CH:38]=[CH:37][C:36]([CH2:39][N:40]([NH:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:41][C@H:42]([OH:52])[C@@H:43]([NH:51][C:11](=[O:13])[C@H:6]([C:7]([CH3:8])([CH3:9])[CH3:10])[NH:5][C:3]([O:2][CH3:1])=[O:4])[CH2:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)=[CH:35][CH:34]=2)=[CH:31][N:30]=[CH:29]1
Reactant: COC(=O)N[C@H](C(=O)O)C(C)(C)C
Reactant: CC(C)(C)OC(=O)NN(Cc1ccc(-c2cncs2)cc1)C[C@H](O)[C@@H](N)Cc1ccccc1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)CN(Cc1ccc(-c2cncs2)cc1)NC(=O)OC(C)(C)C)C(C)(C)C
Reaction time: 0.25 h

Procedure:
Under an nitrogen atmosphere, 1.36 g (7.2 mmol) of N-methoxycarbonyl-(L)-tert-leucine (Example 2e), 2.59 g (13.5 mmol) of EDC and 1.22 g (9.0 mmol) of HOBT are dissolved in 20 ml of DMF. After 15 min, 3.79 ml (27 mmol) of TEA are added and then a solution of 2.11 g (4.5 mmol) of 1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexane in 41 ml of DMF is added dropwise. After 3 hours the reaction mixture is concentrated by evaporation. The resulting oil is dissolved in ethyl acetate and a small amount of THF and washed with 2× water, sat. NaHCO3 solution, 2× water and brine. The aqueous phases are extracted with ethyl acetate; the combined organic phases are dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2 ; methylene chloride/THF 5:1) and crystallisation from ethyl acetate/DIPE yield the title compound: HPLC20-100 : tRet =16.0; FAB MS (M+H)+ =640.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8](Cl)=[O:9])[CH:2]=1.[CH:11]1([NH:17][C:18]2[N:23]3[N:24]=[C:25]([NH2:27])[N:26]=[C:22]3[CH:21]=[CH:20][CH:19]=2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.N1C=CC=CC=1.CCOCC>C(Cl)Cl.O>[CH:11]1([NH:17][C:18]2[N:23]3[N:24]=[C:25]([NH:27][C:8](=[O:9])[CH2:7][C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)[N:26]=[C:22]3[CH:21]=[CH:20][CH:19]=2)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]1
Reactant: O=C(Cl)Cc1cccnc1
Reactant: Nc1nc2cccc(NC3CCCCC3)n2n1
Solvent: CCOCC
Solvent: c1ccncc1
Solvent: O
Product: O=C(Cc1cccnc1)Nc1nc2cccc(NC3CCCCC3)n2n1
Temperature: 55 °C
Yield: 41.4 %

Procedure:
A mixture of pyridin-3-ylacetyl chloride (120.07 mg; 0.77 mmol; 1.50 eq.) and N5-cyclohexyl[1,2,4]triazolo[1,5-a]pyridine-2,5-diamine ((A9); 119 mg; 0.51 mmol; 1.0 eq.) in DCM (1 mL) in presence of pyridine (1244; 1.54 mmol; 3 eq.) was heated in a sealed tube at 55° C. for 3 h. Et2O and Water were then added to the mixture, the precipitate obtained was filtered, washed with water, Et2O, Acetonitrile and dried under vacuum at 40° C. to give the title compound as an off-white powder (74 mg, 41%). HPLC, Rt: 2.49 min. (purity 98.0%). LC/MS, M+(ESI): 350.9, M−(ESI): 348.9.
Reaction SMILES: OO.[CH2:3]([O:10][C:11]([NH:13][CH:14]([CH2:28][F:29])[CH2:15][C@H:16]([Se]C1C=CC=CC=1)[C:17]([O:19][CH3:20])=[O:18])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>CC(C)=O>[CH2:3]([O:10][C:11]([NH:13][C@H:14]([CH2:28][F:29])/[CH:15]=[CH:16]/[C:17]([O:19][CH3:20])=[O:18])=[O:12])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: COC(=O)[C@H](CC(CF)NC(=O)OCc1ccccc1)[Se]c1ccccc1
Agent: OO
Solvent: CC(C)=O
Product: COC(=O)/C=C/[C@@H](CF)NC(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
4.2 ml of 30% hydrogen peroxide solution was added to a stirred solution of 1.4 g of 26A in 25 ml of acetone, at 0° C. The resulting solution was stirred at 0° C. for one hour, warmed to room temperature and the solvent was evaporated. The residue was diluted with 50 ml of cold water and 20 ml of 1N sodium bicarbonate solution and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water, 1N sodium bicarbonate solution and water, dried (MgSO4) and the solvent was evaporated. The residue was chromatographed on silica gel, first eluting with n-hexane, then with 25% ethyl acetate/n-hexane, to give, on work-up, methyl (S)-(E)-4-(benzyloxycarbonylamino)-5-fluoro-2-pentenoate (26B), as a pale yellow viscous oil.
Reaction SMILES: CCN(C(C)C)C(C)C.[NH2:10][CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].[Cl:24][CH2:25][C:26](Cl)=[O:27]>C(Cl)Cl>[Cl:24][CH2:25][C:26]([NH:10][CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:27]
Reactant: O=C(Cl)CCl
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1CN
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CCC[C@@H]1CNC(=O)CCl
Reaction time: 1 h

Procedure:
DIPEA (1.34 ml, 7.5 mmol) was added to a solution of 1,1-dimethylethyl (2R)-2-(aminomethyl)-1-pyrrolidinecarboxylate (1 g, 5 mmol) in 50 ml of DCM; then chloroacetyl chloride (0.418 ml, 5.25 mmol) was slowly added and the reaction mixture stirred 1 h before being worked up. DCM was added and the organic phase was washed with a saturated solution of ammonium chloride. The crude was purified by flash chromatography eluting with cyclohexane/ethyl acetate 8/2 affording 1.28 g of the target material.
Reaction SMILES: [O:1]=[S:2]1(=[O:25])[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:20]4[N:21]=[C:22]([NH2:24])[N:23]=[C:19]4[CH:18]=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.Br[C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1>>[O:25]=[S:2]1(=[O:1])[CH2:3][CH2:4][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:20]4[N:21]=[C:22]([NH:24][C:27]5[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=5)[N:23]=[C:19]4[CH:18]=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:6][CH2:7]1
Reactant: COc1ccc(Br)cc1
Reactant: Nc1nc2cccc(-c3ccc(CN4CCS(=O)(=O)CC4)cc3)n2n1
Product: COc1ccc(Nc2nc3cccc(-c4ccc(CN5CCS(=O)(=O)CC5)cc4)n3n2)cc1
Yield: 43.1 %

Procedure:
5-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}[1,2,4]triazolo[1,5-a]pyridin-2-amine was prepared from 5-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (368 mg, 1.73 mmol) and 4-[(4-boronophenyl)methyl]-thiomorpholine 1,1-dioxide (0.512 mg, 1.90 mmol), in a manner analogous to Step 73c. The residue was purified on a 12 g Isco silica gel column using a gradient of 0-15% methanol in dichloromethane as an eluent. 5-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}[1,2,4]triazolo[1,5-a]pyridin-2-amine (490 mg, 79%) was isolated as a beige foam. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 7.93 (d, J=8.5 Hz, 2H), 7.50 (m, 3H), 7.37 (d, J=7.8 Hz, 1H), 7.07 (d, J=7.8 Hz, 1H), 6.02 (s, 2H), 3.78 (s, 2H), 3.15 (s, 4H), 2.91 (s, 4H). MS=358 (MH)+. 95b) 5-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}[1,2,4]triazolo[1,5-a]pyridin-2-amine (50 mg, 0.140 mmol) and 1-bromo-4-methoxy benzene (29 mg, 0.154 mmol) were combined in a manner analogous to Example 77 to yield 5-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}-N-(4-methoxyphenyl)[1,2,4]triazolo[1,5-a]pyridin-2-amine (28 mg, 42%) as a beige solid. The material was purified via trituration with methanol. MP=241° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.37 (s, 1H), 8.03 (d, J=8.1 Hz, 2H), 7.51-7.67 (m, 6H), 7.17 (d, J=6.4 Hz, 1H), 6.85 (d, J=8.6 Hz, 2H), 3.80 (s, 2H), 3.69 (s, 3H), 3.15 (br s, 4H), 2.92 (br s, 4H). MS=464 (MH)+.
Reaction SMILES: Cl[C:2]1[CH:27]=[CH:26][C:5]([C:6]([NH:8]C2C=CC(Cl)=C(NC(=O)C3C=CC=C(Cl)C=3)C=2)=[O:7])=[C:4]([CH3:28])[N:3]=1.C[C@H]1CNC[C@@H](C)N1>>[CH3:28][C:4]1[N:3]=[CH:2][CH:27]=[CH:26][C:5]=1[C:6]([NH2:8])=[O:7]
Reactant: Cc1nc(Cl)ccc1C(=O)Nc1ccc(Cl)c(NC(=O)c2cccc(Cl)c2)c1
Agent: C[C@@H]1CNC[C@H](C)N1
Product: Cc1ncccc1C(N)=O

Procedure:
6-chloro-N-(4-chloro-3-(3-chlorobenzamido)phenyl)-2-methylnicotinamide (0.14 mmol) was used in general procedure 3 with cis-2,6-dimethylpiperazine (0.70 mmol). The product was purified by RP-HPLC to give N-(4-chloro-3-(3-chlorobenzamido)phenyl))-6-(3S,5R)-3-5-dimethylpiperazine-1-yl)-2-methylnicotinamide. MS (Q1) 512.0 (M)+
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:8][S:9]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=2[O:22][CH3:23])(=[O:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.C[Li].[CH3:26][C:27]([CH3:29])=[O:28].C(O)(=O)C>C1COCC1.C(OCC)C.C(OCC)(=O)C>[CH3:23][O:22][C:15]1[CH:16]=[C:17]([O:20][CH3:21])[CH:18]=[CH:19][C:14]=1[CH2:13][NH:12][S:9]([CH:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=1)[C:27]([OH:28])([CH3:29])[CH3:26])(=[O:10])=[O:11]
Reactant: CC(C)=O
Reactant: COc1ccc(CNS(=O)(=O)Cc2cccc(Br)c2)c(OC)c1
Agent: [Li]C
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: COc1ccc(CNS(=O)(=O)C(c2cccc(Br)c2)C(C)(C)O)c(OC)c1
Reaction time: 0.17 h

Procedure:
Under inert gas, 7.00 g of C-(3-bromophenyl)-N-(2,4-dimethoxybenzyl)methanesulfonamide were initially charged in 120 ml of THF, and then, at a temperature of −78° C., 25.14 ml of a 1.6 N methyllithium solution in diethyl ether were added dropwise and the mixture was stirred at constant temperature for 10 minutes. Subsequently, 7 ml of acetone were added. After stirring for 5 minutes, the reaction solution was admixed with 5 ml of acetic acid and stirred for a further 5 minutes, and 100 ml of ethyl acetate were added to the mixture, which was washed with 1×100 ml and 1×50 ml of a saturated aqueous sodium hydrogencarbonate solution and 2×50 ml of a saturated aqueous sodium chloride solution. The organic phase was dried over MgSO4 and concentrated by rotary evaporation. The residue (8.63 g) was used in the next reaction without further purification.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[C:5]([C:8]1[CH:29]=[CH:28][C:11]([O:12][CH2:13][C:14]2([NH:17][C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])[CH2:16][CH2:15]2)=[C:10]([O:30][CH3:31])[CH:9]=1)(=[O:7])[CH3:6]>CC(OC(C)=O)=O>[C:5]([C:8]1[C:29]([N+:1]([O-:4])=[O:2])=[CH:28][C:11]([O:12][CH2:13][C:14]2([NH:17][C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])[CH2:16][CH2:15]2)=[C:10]([O:30][CH3:31])[CH:9]=1)(=[O:7])[CH3:6]
Reactant: O=[N+]([O-])O
Reactant: COc1cc(C(C)=O)ccc1OCC1(NC(=O)OCc2ccccc2)CC1
Solvent: CC(=O)OC(C)=O
Product: COc1cc(C(C)=O)c([N+](=O)[O-])cc1OCC1(NC(=O)OCc2ccccc2)CC1
Temperature: 0 °C
Reaction time: 2 h
Yield: 56 %

Procedure:
A solution of HNO3 (65%, 3 mL) in Ac2O (2 mL) at 0° C. was slowly added with a suspension of the compound of Example 1 (1.1 g, 2.9 mmol) in Ac2O (3 mL) After stirring at 0° C. for 2 h, the reaction mixture was poured into 50 mL of ice/water and the precipitate was recovered by filtration. The resulting yellow solid was recrystallized with 95% EtOH (5 mL) to give 1-[(4-acetyl-2-methoxy-5-nitrophenoxy)methyl]-N-benzyloxycarbonyl-1-aminocyclopropane (0.69 g, yield: 56%) as a yellow solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(Cl)(=O)C(Cl)=O.[CH:17]1([CH2:20][NH2:21])[CH2:19][CH2:18]1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([NH:21][CH2:20][CH:17]1[CH2:19][CH2:18]1)=[O:9]
Reactant: O=C(O)c1cncc(Br)c1
Reactant: NCC1CC1
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(NCC1CC1)c1cncc(Br)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 71.1 %

Procedure:
To a solution of 5-bromonicotinic acid (XXVIII) (1.01 g, 5 mmol) in dry DCM (10 mL) under nitrogen was added oxalyl chloride (0.654 mL, 7.5 mmol) followed by dry DMF (0.1 mL). The solution was stirred at r.t. for 30 min. The solvent was evaporated under vacuum before adding dry pyridine (10 mL) followed by cyclopropylmethanamine (0.39 mL, 4.5 mmol). The solution was stirred at r.t. under nitrogen for 2 h. The solution was poured into ice water, basified with sat. aq. NaHCO3 and extracted with DCM. The combined organic phases were dried over MgSO4, concentrated and dried under vacuum to yield 5-bromo-N-(cyclopropylmethyl) nicotinamide (XXIX) as an off-white solid (0.82 g, 3.2 mmol, 71% yield). 1H NMR (DMSO-d6) δ ppm −0.07-0.07 (m, 2H), 0.15-0.29 (m, 2H), 0.68-0.88 (m, 1H), 2.93 (t, J=6.22 Hz, 2H), 8.20 (t, J=1.88 Hz, 1H), 8.62 (d, J=1.70 Hz, 2H), 8.75 (s, 1H); ESIMS found C10H11BrN2O m/z 254, 256 (M+, M+2).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]([CH3:9])=[CH:4][C:3]=1[C:10]1[CH2:15][CH:14]([C:16]2[CH:21]=[C:20]([CH3:22])[C:19]([OH:23])=[CH:18][C:17]=2[CH3:24])[CH2:13][CH2:12][CH:11]=1.CC(C1C=CC=CC=1)=C>C(C(C)=O)C(C)C.[C].[Pd]>[CH3:24][C:17]1[CH:18]=[C:19]([OH:23])[C:20]([CH3:22])=[CH:21][C:16]=1[C:14]1[CH:13]=[CH:12][CH:11]=[C:10]([C:3]2[CH:4]=[C:5]([CH3:9])[C:6]([OH:8])=[CH:7][C:2]=2[CH3:1])[CH:15]=1
Reactant: Cc1cc(C2=CCCC(c3cc(C)c(O)cc3C)C2)c(C)cc1O
Agent: [Pd]
Agent: C=C(C)c1ccccc1
Solvent: CC(=O)CC(C)C
Product: Cc1cc(-c2cccc(-c3cc(C)c(O)cc3C)c2)c(C)cc1O
Temperature: 150 °C
Reaction time: 6 h
Yield: 46.3 %

Procedure:
3.0 g of the 98.7% pure 1,5-bis(2,5-dimethyl-4-hydroxyphenyl)-1-cyclohexene obtained in Step (D) of Example 5, 30 g of methyl isobutyl ketone, 3.0 g of α-methyl styrene, and 0.63 g of 5% palladium carbon were introduced to an autoclave and then heated to 150° C. to be reacted for 46.5 hours at the same temperature under agitation. After heating, 0.63 g of 5% palladium carbon was added after 18 hours and again after 34 hours, respectively. The mixture was heated further to 190° C. and agitated for 6 hours at the same temperature to cause reaction, after which the palladium carbon was filtered out and the obtained filtrate was condensed. The obtained residue was dissolved in methyl isobutyl ketone to separate the crystal, which was then filtered out and dried to obtain 1.4 g of 2,2″,5,5″-tetramethyl-4,4″-dihydroxy-m-terphenyl of 94.5% purity (according to high-speed liquid chromatography).
Reaction SMILES: [C:1]1(=[O:11])[O:6][C:4](=[O:5])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[C:12]1([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCCl>[CH2:30]([O:29][C:27]([CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][C:12]1[CH:13]=[CH:14][C:15]([C:4]([C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=2[C:1]([OH:6])=[O:11])=[O:5])=[CH:16][CH:17]=1)=[O:28])[CH3:31]
Reactant: CCOC(=O)CCCCCCCCCc1ccccc1
Reactant: O=C1OC(=O)c2ccccc21
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCCl
Product: CCOC(=O)CCCCCCCCCc1ccc(C(=O)c2ccccc2C(=O)O)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 91.2 %

Procedure:
At 0°-3° C., 9.6 g of phthalic anhydride are added to a solution of 18 g of ethyl 10-phenyldecanoate in 100 ml of 1,2-dichloroethane, after which 26 g of aluminium chloride are added in portions over a period of 1 hour. After stirring for 20 hours at room temperature, the mixture is poured onto ice/2N hydrochloric acid and extracted with methylene chloride. Washing of the organic phase with saturated sodium chloride solution, drying and evaporation gives 25.1 g of 2-[4'-(9"-ethyoxycarbonylnonyl)benzoyl]benzoic acid as a waxy solid which can be used for the next step without purification.
Reaction SMILES: [O:1]=[C:2]1[NH:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]=3)=[CH:10][C:4]=2[NH:3]1>CO.[Ni]>[O:1]=[C:2]1[NH:6][C:5]2[CH:7]=[CH:8][C:9]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[NH:3]1
Reactant: CC(C)(C)OC(=O)N1CC=C(c2ccc3[nH]c(=O)[nH]c3c2)CC1
Agent: [Ni]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(c2ccc3[nH]c(=O)[nH]c3c2)CC1
Reaction time: 12 h
Yield: 90 %

Procedure:
For synthesis from compound 16, following the same procedure adopted for the synthesis of 13, the title compound 17 was obtained from the reaction of compound 16 with CDI. Yield: 62%, off-white solid. For synthesis from compound 13, to a solution of compound 13 (0.94 g, 3 mmol) in CH3OH (30 mL) was added Ra—Ni (0.20 g, 10% wet basis), and the mixture was subjected to hydrogenation in a Parr apparatus at 60 psi for 12 hours. After filtering over the pad of celite, the solution was concentrated and recrystallized from diethyl ether to get compound 17. Yield: 90%, off-white solid, mp>250° C. IR (KBr, cm1) 3290, 3175 (CONH), 3030 (Ar—H), 2989 (Alph-H), 1691 (CO), 1613, 1515, 1416 (C═C), 1220 (C—N), 1167 (C-0); 1H NMR (500 MHz, DMSO d6) δ 1.38 (s, 9H, OC(CH3)3), 1.86 (m, al, CH2), 2.06 (m, 211, CH2), 2.40-2.48 (m, 3H, CH, CH2), 3.44 (obscured by H2O, 2H, CH2), 6.70-6.80 (m, 3H, H-4, H-6, H-7), 10.49 (br. s, 1H, NH), 10.53 (br. s, 1H, NH). 13C NMR (125.7 MHz, DMSO d6) δ 28.15 (OC(CH3)3), 29.25 (CH2), 33.24 (CH2), 41.72 (CH2), 78.72 (OC(CH3)3), 106.93 (C-4), 108.48 (C-7), 119.0 (C-6), 128.09 (C-8), 129.89 (C-9), 138.49 (C-5), 154.05 (CO), 155.61 (CO). Anal. Calcd for C17H23N3O3: C, 64.33; H, 7.30; N, 13.24%. Found: C, 64.25; H, 7.35; N, 13.15%.
Reaction SMILES: [CH3:1][C:2]1[NH:6][CH:5]=[N:4][C:3]=1[CH2:7][S:8][CH2:9][CH2:10][NH2:11].[C:12](=[S:14])=[S:13]>C(O)C>[CH3:1][C:2]1[NH:6][CH:5]=[N:4][C:3]=1[CH2:7][S:8][CH2:9][CH2:10][NH:11][C:12](=[S:13])[SH:14]
Reactant: S=C=S
Reactant: Cc1[nH]cnc1CSCCN
Solvent: CCO
Product: Cc1[nH]cnc1CSCCNC(=S)S
Reaction time: 8 h

Procedure:
A solution of 2-((5-methyl-4-imidazolyl)methylthio)ethylamine (10.2 g) in ethanol (75 ml) was added slowly, with stirring, to carbon disulphide (200 ml). The mixture was set aside overnight at room temperature and the solid formed was collected and recrystallised from aqueous isopropyl alcohol to afford N-[2-((5-methyl-4-imidazolyl)methylthio)ethyl]dithiocarbamic acid (9.8 g), m.p. 127°-129°. This was treated with dicyclohexylcarbodiimide in dry pyridine at -10°, and the mixture was filtered. The filtrate was evaporated to dryness and the residue was treated sith ethanolic hydrogen chloride to give 5-methyl-4-(2-isothiocyanatoethylthiomethyl)imidazole hydrochloride.
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:16]1([SH:22])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN1CCN(C)C1=O>[C:16]1([S:22][C:8]2[CH:9]=[CH:2][CH:3]=[CH:4][C:5]=2[CH:6]=[O:7])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Sc1ccccc1
Reactant: O=Cc1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCN(C)C1=O
Product: O=Cc1ccccc1Sc1ccccc1
Temperature: 120 °C
Reaction time: 2.5 h

Procedure:
To a solution of 4-fluorobenzaldehyde (0.443 mL) in 1,3-dimethyl-2-imidazolidinone (6.4 mL) was added potassium carbonate (0.659 g). Then benzenethiol (0.326 mL) was added, and the resulting mixture was stirred at 120° C. for 2.5 hours. The reaction mixture was cooled to room temperature and then partitioned between diethyl ether (60 mL) and water (15 mL). The organic layer was washed successively with water (15 mL×2) and brine (15 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound (0.826 g).
Reaction SMILES: [C:1]1(=[O:29])[N:5]([NH:6][CH2:7][CH2:8][NH:9][CH2:10][CH2:11][NH:12][N:13]2[C:17](=[O:18])[C:16]3=[CH:19][CH:20]=[CH:21][CH:22]=[C:15]3[C:14]2=[O:23])[C:4](=[O:24])[C:3]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:2]12.C(=O)([O-])[O-].[K+].[K+].[CH2:36](Br)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.O>CN(C)C=O.ClCCCl>[C:17]1(=[O:18])[N:13]([NH:12][CH2:11][CH2:10][N:9]([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:8][CH2:7][NH:6][N:5]2[C:4](=[O:24])[C:3]3=[CH:25][CH:26]=[CH:27][CH:28]=[C:2]3[C:1]2=[O:29])[C:14](=[O:23])[C:15]2=[CH:22][CH:21]=[CH:20][CH:19]=[C:16]12
Reactant: O=C1c2ccccc2C(=O)N1NCCNCCNN1C(=O)c2ccccc2C1=O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: O=C1c2ccccc2C(=O)N1NCCN(CCNN1C(=O)c2ccccc2C1=O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
36.34 g (100 mmol) of 1,7-bis(phthalimido)-1,4,7-triazaheptane [produced according to J. Org. Chem. USSR, 23:3302 (1987)] is dissolved in 500 ml of dimethylformamide. Then, 16.6 g (120 mmol) of potassium carbonate as well as 20.53 g (120 mmol) of benzyl bromide are added to it and stirred overnight at 25° C. It is poured in ice water, the precipitated product is suctioned off, rewashed with water, taken up in 1,2-dichloroethane, dried on sodium sulfate and evaporated to dryness in a vacuum. The title compound is obtained as solid.