Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:7]2[C:8](=[O:26])[N:9]3[CH2:25][CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[S:17][CH:18]=[C:19]([CH2:21]Cl)[N:20]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[NH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1>O1CCCC1>[Cl:1][C:2]1[C:7]2[C:8](=[O:26])[N:9]3[CH2:25][CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[S:17][CH:18]=[C:19]([CH2:21][N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[N:20]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: O=C1c2c(Cl)cccc2-n2cnc(-c3nc(CCl)cs3)c2[C@@H]2CCCN12
Reactant: C1CCNC1
Solvent: C1CCOC1
Product: O=C1c2c(Cl)cccc2-n2cnc(-c3nc(CN4CCCC4)cs3)c2[C@@H]2CCCN12
Reaction time: 96 h
Yield: 44 %

Procedure:
A solution of 1.3 g (0.0032mol) of (S)-8-chloro-1-(4-chloromethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one in 15 ml of tetrahydrofuran was treated with 4 ml (0.048 mol) of pyrrolidine and stirred at 50° for 96 hrs. All volatiles were removed in a water-jet vacuum and the residue was taken up with ethyl acetate and water. The organic phase was dried over magnesium sulphate, concentrated and the residue remaining was chromatographed over silica gel with methylene chloride/methanol 95:5 as the eluent. After recrystallization from ethyl acetate there was obtained 0.62 g (44%) of (S)-8-chloro-1-(4-pyrrolidin-1-ylmethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one in the form of white crystals; m.p. 213-214° and [α]D20 =-71.2° (MeOH, c=1%).
Reaction SMILES: [NH2:1][C:2]1[CH:14]=[CH:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][C:10]=3[F:15])[CH2:5][C:4]=2[CH:3]=1>CCCCCC.CCOC(C)=O>[F:15][C:10]1[C:11]2[C:12]3=[CH:13][C:14]4[C:2](=[CH:3][C:4]3=[CH:5][C:6]=2[CH:7]=[CH:8][CH:9]=1)[NH:1][C:4]([CH3:5])([CH3:12])[CH2:3][C:2]=4[CH3:14]
Reactant: Nc1ccc2c(c1)Cc1cccc(F)c1-2
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CC1=c2cc3c(cc2NC(C)(C)C1)=Cc1cccc(F)c1-3

Procedure:
This compound was prepared according to General Method 3 (EXAMPLE 16) from 2-amino-5-fluorofluorene (structure 15, where R2, R4-6=H, R3=F, X=CH2) (360 mg, 1.72 mmol) to 125 mg (26%) of Compound 126 as a light brown solid. Data for Compound 126: Rf=0.63 (silca gel, hexane/EtOAc, 3:1); 1H NMR (400 MHz, acetone-d6): 7.55 (s, 1H), 7.25 (d, J=7.3, 1H), 7.12 (m, 1H), 7.02 (d, J=10, 10, 1H) 6.73 (s, 1H), 5.39 (s, 1H), 3.81 (s, 2H), 2.87 (s, 3H), 1.28 (s, 6H).
Reaction SMILES: [F:1][C:2]1[C:7]2[CH2:8][O:9][CH:10]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)=[CH:24][CH:23]=3)[C:11]3[C:12](=[CH:13][CH:14]=[C:15]4[C:20]=3[CH:19]=[CH:18][C:17]([OH:21])=[CH:16]4)[C:6]=2[CH:5]=[C:4]([F:37])[C:3]=1[Si](C)(C)C.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[ClH:61].CCOCC>C(#N)C>[ClH:61].[F:1][C:2]1[C:7]2[CH2:8][O:9][CH:10]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]4[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]4)=[CH:24][CH:23]=3)[C:11]3[C:12](=[CH:13][CH:14]=[C:15]4[C:20]=3[CH:19]=[CH:18][C:17]([OH:21])=[CH:16]4)[C:6]=2[CH:5]=[C:4]([F:37])[CH:3]=1
Reactant: C[Si](C)(C)c1c(F)cc2c(c1F)COC(c1ccc(OCCN3CCCCC3)cc1)c1c-2ccc2cc(O)ccc12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: Cl
Agent: [F-]
Solvent: CCOCC
Solvent: O
Solvent: CC#N
Product: Oc1ccc2c3c(ccc2c1)-c1cc(F)cc(F)c1COC3c1ccc(OCCN2CCCCC2)cc1
Temperature: 70 °C
Yield: 92.9 %

Procedure:
Dissolve 1,3-difluoro-11-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-2-trimethylsilanyl-11,13-dihydro-12-oxa-benzo[3,4]cyclohepta[1,2-a]naphthalen-8-ol (2.2 g, 3.8 mmol) in acetonitrile (100 mL) and add tetrabutylammonium fluoride hydrate (2.0 g, 7.6 mmol) and heat to 70° C. for 4 hours. Cool the reaction to room temperature and partition between water and ethyl acetate. Extract the organic layer with water three times. Dry with sodium sulfate, filter and concentrate in vacuo. Dissolve the residue in methylene chloride (8 mL) and add HCl (2M in ether, 3.8 mL, 7.6 mmol). Add the solution slowly to vigorously stirred ether and collect the precipitate. Dry at 50° C. under vacuum over night to yield 1.9 g (93%) of the title compound as a tan solid. 1H NMR (d6-DMSO) δ10.09 (s, 1H), 10.02 (bs, 1H), 8.36 (d, J=9.2 Hz, 1H), 7.92 (d, J=8.6 Hz, 1H), 7.57 (d, J=8.6 Hz, 1H), 7.31 (d, J=2.5 Hz, 1H), 7.22 (dd, J=9.4, 2.7 Hz, 1H), 7.13 (td, J=9.6, 2.3 Hz, 1H), 6.99 (m, 2H), 6.64 (m, 4H), 4.97 (d, J=12.3 Hz, 1H), 4.19 (t, J=5.2 Hz, 2H), 4.07 (d, J=12.3 Hz, 1H), 3.37 (m, 4H), 2.91 (m, 2H), 1.70 (m, 5H), 1.57 (m, 1H). mass spectrum (apci) m/z-502.3 (M−HCl+H). HPLC (5 to 95) Rt (purity at 254 nm)=2.76 min (>99%). Analysis calculated for C31H30ClF2NO3.H2O: C, 66.96; H, 5.80; N, 2.52. Found: C, 67.00; H, 6.20; N, 2.83.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:4]=1[CH2:5][N:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([N:16]3[CH2:20][CH2:19][CH2:18][C@H:17]3[CH2:21][OH:22])[N:14]=2)[C:9](=[O:23])[C:8]([C:24]([O:26]CC)=[O:25])=[CH:7]1.[OH-].[Li+].Cl.O>C(O)C>[CH3:1][O:2][C:3]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:4]=1[CH2:5][N:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([N:16]3[CH2:20][CH2:19][CH2:18][C@H:17]3[CH2:21][OH:22])[N:14]=2)[C:9](=[O:23])[C:8]([C:24]([OH:26])=[O:25])=[CH:7]1
Reactant: CCOC(=O)c1cn(Cc2ccc(OC)cc2OC)c2nc(N3CCC[C@H]3CO)ccc2c1=O
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: COc1ccc(Cn2cc(C(=O)O)c(=O)c3ccc(N4CCC[C@H]4CO)nc32)c(OC)c1

Procedure:
A mixture of EXAMPLE 1C (2 g) and 0.1M lithium hydroxide (80 mL) in ethanol (100 mL) at 25° C. was stirred for 24 hours, adjusted to pH 3 with 1M hydrochloric acid, treated with water, and filtered.
Reaction SMILES: [NH2:1][C:2]1[C:3]([Cl:22])=[CH:4][C:5]([F:21])=[C:6]([N:8]2[C:13](=[O:14])[CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[N:10]([CH3:19])[C:9]2=[O:20])[CH:7]=1.C(N(CC)CC)C.[C:30](Cl)(Cl)=[S:31]>C1(C)C=CC=CC=1>[Cl:22][C:3]1[CH:4]=[C:5]([F:21])[C:6]([N:8]2[C:13](=[O:14])[CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[N:10]([CH3:19])[C:9]2=[O:20])=[CH:7][C:2]=1[N:1]=[C:30]=[S:31]
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2cc(N)c(Cl)cc2F)c1=O
Reactant: S=C(Cl)Cl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: Cn1c(C(F)(F)F)cc(=O)n(-c2cc(N=C=S)c(Cl)cc2F)c1=O
Temperature: 0 °C
Reaction time: 5 h
Yield: 97.9 %

Procedure:
A mixture of 3-(5-amino-4-chloro-2-fluorophenyl)-1-methyl-6-(trifluoromethyl)-2,4 (1H,3H)-pyrimidinedione (1.0 g, 2.96 mmol) in toluene is cooled to 0° C., treated sequentially with triethylamine (0.91 mL, 6.52 mmol) and thiophosgene (0.25 mL, 3.26 mmol), warmed to and stirred at room temperature for 5 hours, and filtered to remove solids. The resultant filtrate is concentrated in vacuo to give the title product as an orange solid (1.1 g, 98% yield) which is identified by 1H NMR spectral analysis.
Reaction SMILES: [F:1][CH2:2][S:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=1)=O.[CH3:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=1[CH3:19].FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[H+].[B-:36]([F:40])([F:39])([F:38])[F:37]>C(OCC)C>[F:37][B-:36]([F:40])([F:39])[F:38].[CH3:12][C:13]1[CH:14]=[C:15]([S+:3]([CH2:2][F:1])[C:5]2[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=2)[CH:16]=[CH:17][C:18]=1[CH3:19]
Reactant: Cc1ccccc1C
Reactant: Cc1ccc(S(=O)CF)cc1
Agent: F[B-](F)(F)F
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: [H+]
Solvent: CCOCC
Product: Cc1ccc([S+](CF)c2ccc(C)c(C)c2)cc1

Procedure:
1-((Fluoromethyl)sulfinyl)-4-methylbenzene (576 mg, 3.34 mmol) of example 5 was dissolved in dry diethyl ether (15 mL) under argon atmosphere. O-Xylene (0.445 mL, 1.10 eq) was added to the previous solution. The mixture was cooled to a temperature below −50° C. After stabilizing the temperature below −50° C., trifluoromethanesulfonic anhydride (0.562 mL, 1 eq) was added slowly maintaining the same temperature. The mixture was stirred, until the reaction was complete. HBF4 in diethyl ether solution (54%, 0.921 mL, 2 eq) was added. The resulting suspension was stirred for 30 minutes. The precipitate tetrafluoroborate salt was isolated by filtration and washed with diethyl ether at 0° C. The desired product was obtained as an oily solid (1.42 g).
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:3]=1[C:4]#[N:5].[CH2:14]1[O:24][C:18]2([CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[O:17][CH:15]1[CH3:16]>C1COCC1.CCOCC.C(=O)([O-])[O-].[Na+].[Na+]>[CH2:14]1[O:24][C:18]2([CH2:23][CH2:22][N:21]([C:2]3[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:3]=3[C:4]#[N:5])[CH2:20][CH2:19]2)[O:17][CH:15]1[CH3:16]
Reactant: CC1COC2(CCNCC2)O1
Reactant: N#Cc1cc(C(F)(F)F)ccc1F
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC1COC2(CCN(c3ccc(C(F)(F)F)cc3C#N)CC2)O1

Procedure:
A solution of 2-fluoro-5-trifluoromethylbenzonitrile (2.01 g, 10.61 mmol) and 4-piperidone propylene ketal (1.71 g, 10.9 mmol) in THF (10 mL) was stirred at room temperature (1 h). The resulting mixture was diluted with ether and sodium carbonate solution. The aqueous layer was extracted with two portions of ether and the combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure to afford the title compound (24).
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:17])=[CH:4][C:5]2[C:6]([CH3:16])([CH3:15])[CH2:7][CH:8]=[C:9]([CH:12]([CH3:14])[CH3:13])[C:10]=2[CH:11]=1.I[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5](=[CH:4][C:3]=1[O:17][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C:6]([CH3:15])([CH3:16])[CH2:7][CH:8]=[C:9]2[CH:12]([CH3:13])[CH3:14]
Reactant: CC(C)C1=CCC(C)(C)c2cc(O)c(Br)cc21
Reactant: CCCCCCI
Product: CCCCCCOc1cc2c(cc1Br)C(C(C)C)=CCC2(C)C
Yield: 39 %

Procedure:
Following General Procedure O, 3-bromo-5-isopropyl-8,8-dimethyl-7,8-dihydronaphthalen-2-ol (Compound 97, 0.11 g, 0.37 mmol) was reacted with 1-iodohexane to afford 0.058 g (39%) of the title compound as a clear oil.
Reaction SMILES: CC1C(C#C)=CC2C(C)(C)CCC(C)(C)C=2C=1.CN(C)S(N1C=C(I)N=C1)(=O)=O.[CH3:30][C:31]1[C:32](/[C:45](/[CH3:58])=[CH:46]/[C:47]2[N:48]=[CH:49][N:50]([S:52](=[O:57])(=[O:56])[N:53]([CH3:55])[CH3:54])[CH:51]=2)=[CH:33][C:34]2[C:35]([CH3:44])([CH3:43])[CH2:36][CH2:37][C:38]([CH3:42])([CH3:41])[C:39]=2[CH:40]=1.C([Li])CCC.Cl[C:65]([O:67][CH2:68][CH3:69])=[O:66]>>[CH3:30][C:31]1[C:32](/[C:45](/[CH3:58])=[CH:46]/[C:47]2[N:48]=[C:49]([C:65]([O:67][CH2:68][CH3:69])=[O:66])[N:50]([S:52](=[O:56])(=[O:57])[N:53]([CH3:55])[CH3:54])[CH:51]=2)=[CH:33][C:34]2[C:35]([CH3:44])([CH3:43])[CH2:36][CH2:37][C:38]([CH3:41])([CH3:42])[C:39]=2[CH:40]=1
Reactant: CCOC(=O)Cl
Reactant: C/C(=C\c1cn(S(=O)(=O)N(C)C)cn1)c1cc2c(cc1C)C(C)(C)CCC2(C)C
Agent: C#Cc1cc2c(cc1C)C(C)(C)CCC2(C)C
Agent: CN(C)S(=O)(=O)n1cnc(I)c1
Agent: [Li]CCCC
Product: CCOC(=O)c1nc(/C=C(\C)c2cc3c(cc2C)C(C)(C)CCC3(C)C)cn1S(=O)(=O)N(C)C

Procedure:
It should be noted in connection with Reaction Schemes 1, 2 and 3 that in all of these reaction schemes heterocycle derivatives corresponding respectively to Formula 7, 11 and 15 can be employed where in the A-B' substituent A is (CH2)n, n is 0, and B' is hydrogen. A carboxylic acid group is then introduced into the molecule, after coupling with the tetrahydronaphthalene moiety, by reaction with strong base (such as n-butyl lithium) and carbon dioxide or ethyl chloroformate. Reaction Scheme 4 illustrates specifically the synthesis of Compound 3 and Compound 4 of the present application. In accordance with this scheme (5,6,7,8-tetrahydro-3,5,5,8,8-pentamethylnaphthalen-2-yl)acetylene (Compound 10) is reacted with trimethylaluminum in the presence zirconocene dichloride. The resulting "carboaluminated adduct" (not shown in Scheme 4) is reacted in the presence of tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) catalyst, with 1-(N,N-dimethylsulfamoyl)-4-iodoimidazole (Compound 11) which is obtained by iodination from 1-(N,N-dimethylsulfamoyl)imidazole. The latter compound can be obtained in accordance with the chemical literature: Chadwick et al. J. Chem. Soc., Perkin Trans. I 1984, 481-486. The result of the coupling reaction between between the carboaluminated adduct derived from Compound 10 and Compound 11 is (E)-4-[2-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethylnaphthalen-2-yl)propen-1-yl]-1-(N,N-dimethylsulfamoyl)imidazole (Compound 12). The carboxylic acid ethyl ester moiety is introduced into the molecule by reacting the anion of Compound 12 generated with strong base such as n-butyl lithium, with ethyl chloroformate, to yield ethyl (E)-4-[2-(5,6,7,8-tetrahydro- 3,5,5,8,8-pentamethylnaphthalen-2-yl)propen-1-yl]-1-(N,N-dimethylsulfamoyl)-2-imidazolecarboxylate (Compound 4). The dimethylsulfamoyl group is removed from the imidazole nitrogen by treatment with acid, to yield ethyl (E)-4-[2-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethylnaphthalen-2-yl)propen-1-yl]-2-imidazolecarboxylate (Compound 3). ##STR10##
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1.[Cl:20][CH:21]([Cl:25])[C:22]([OH:24])=[O:23]>>[Cl:20][C:21]([Cl:25])([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)[C:22]([OH:24])=[O:23]
Reactant: O=C(O)C(Cl)Cl
Reactant: Clc1ccc(OCCCCCCCCCCBr)cc1
Product: O=C(O)C(Cl)(Cl)CCCCCCCCCCOc1ccc(Cl)cc1
Yield: 50 %

Procedure:
Analogously to the preparation of 62, 13.6 g (65%) 63 was obtained from 7.7 g (60 mmol) 4-chlorophenol and 18 g (60 mmol) 1,10-dibromodecane. 13.3 g (38.0 mmol) 63 was reacted with dichloroacetic acid according to example 9. 5.9 g (50%) 11, melting point 63-64° C. was obtained.
Reaction SMILES: [C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.C(=O)=O.CC(C)=O.[F:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([C:48]2[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=2)=[C:32]([N:37]2[C:41]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[N:40][N:39]=[N:38]2)[CH:33]=[CH:34][CH:35]=[O:36])=[CH:27][CH:26]=1.Cl.[NH4+].[Cl-]>O1CCCC1>[F:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([C:48]2[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=2)=[C:32]([N:37]2[C:41]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[N:40][N:39]=[N:38]2)[CH:33]=[CH:34][CH:35]([OH:36])[CH2:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6])=[CH:27][CH:26]=1
Reactant: O=CC=CC(=C(c1ccc(F)cc1)c1ccc(F)cc1)n1nnnc1-c1ccccc1
Reactant: CCOC(=O)CC(C)=O
Agent: Cl
Agent: O=C=O
Agent: [Cl-]
Solvent: CC(C)=O
Solvent: C1CCOC1
Product: CCOC(=O)CC(=O)CC(O)C=CC(=C(c1ccc(F)cc1)c1ccc(F)cc1)n1nnnc1-c1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 68 %

Procedure:
The dianion of ethyl acetoacetate was generated by adding 0.93 mL (7.3 mmoles) of purified ethyl acetoacetate to a suspension of 0.29 g (60% by weight in oil suspension, 7.3 mmoles) of sodium hydride in tetrahydrofuran (10 mL) at 0° C. under argon followed by the addition of 2.93 mL (7.3 mmoles) of 2.5M n-butyllithium. The orange solution was stirred at 0° C. for one hour then cooled to -80° C. (dry ice-acetone). The dianion solution was added to a solution of 1.01 g (2.4 mmoles) of 5,5-bis(4-fluorophenyl)-4-(5-phenyl-1H-tetrazol1-yl)-2,4-pentadienal in 20 mL of tetrahydrofuran at -80° C. under argon. After stirring for 10 minutes, the mixture was neutralized with 4 mL of 2M HCl and 4 mL of saturated aqueous NH4Cl solution. The desired product was extracted with ethyl acetate and purified by silica gel column chromatography using a gradient elution of ethyl acetate-hexanes to yield 0.90 g (68%) of the title compound.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6](/[CH:10]=[CH:11]/[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][O:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=3)[N:13]=2)[CH:7]=[CH:8][CH:9]=1)([O-])=O>CO>[NH2:1][C:4]1[CH:5]=[C:6](/[CH:10]=[CH:11]/[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][O:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=3)[N:13]=2)[CH:7]=[CH:8][CH:9]=1
Reactant: Cc1ccc(CCCCOCc2cccc(/C=C/c3cccc([N+](=O)[O-])c3)n2)cc1
Solvent: CO
Product: Cc1ccc(CCCCOCc2cccc(/C=C/c3cccc(N)c3)n2)cc1
Yield: 84.4 %

Procedure:
To 1.6 g of 2-[(E)-2-(3-nitrophenyl)ethenyl]-6-[4-(4-methylphenyl)butoxy]methylpyridine was added 10 ml of methanol and then added 3 g of stannous chloride dihydride in 10 ml of methanol, and the mixture was stirred under reflux for 3.5 hours. After completion of the reaction, the solvent was distilled off and the residue was made alkaline with an aqueous sodium hydroxide solution. To the solution was added ethyl acetate and the mixture was filtered by sellaite. The organic layer was separated, washed with water, and dried over anhydrous magnesium sulfate and then the solvent was distilled off to give 1.6 g of a crude oily substance. The crude oily substance was purified on chromatography by passing chloroform and then a mixture of chloroform and ethanol(50:1) to give 1.25 g of 2-[(E)-2-(3-aminophenyl)ethenyl]-6-[4-(4-methylphenyl) butoxy]methylpyridine as an oily substance.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:13]([CH3:17])([CH3:16])[CH2:14]O)[CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH:8]=[CH:7]2.C(N(S(F)(F)[F:24])CC)C.O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([C:13]([CH3:17])([CH3:16])[CH2:14][F:24])[CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH:8]=[CH:7]2
Reactant: CCN(CC)S(F)(F)F
Reactant: CC(C)(CO)c1cc(F)c2c(=O)[nH]ccc2c1
Solvent: O
Solvent: ClCCl
Product: CC(C)(CF)c1cc(F)c2c(=O)[nH]ccc2c1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 80 %

Procedure:
8-fluoro-6-(1-hydroxy-2-methylpropan-2-yl)isoquinolin-1(2H)-one (114 mg, 485 μmol) was dissolved in DCM (dry) and cooled to −78° C. under argon. To this solution was added the diethylaminosulfur trifluoride (90 μl, 678 μmol) and the reaction was stirred for about 10 min before removal of the cooling bath. The reaction was warmed to ambient and stirred at this temperature for 2 hrs. To the reaction mixture was added 25 ml water and 20 ml DCM. The mixture was shaken and the organics collected. The organics were washed with 25 ml brine. The aqueous phase was extracted (2×20 ml DCM). The combined organics were dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by preparative tlc (2 plates, eluted with 4.5% MeOH/DCM) to afford 92 mg of the desired product as an off-white powder.
Reaction SMILES: [CH:1]1([C:6]2[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:15])[CH3:14])=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(OC(=O)C)(=O)C.[N+:23]([O-])([OH:25])=[O:24]>O>[CH:1]1([C:6]2[CH:7]=[CH:8][C:9]([NH:12][C:13](=[O:15])[CH3:14])=[C:10]([N+:23]([O-:25])=[O:24])[CH:11]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=[N+]([O-])O
Reactant: CC(=O)Nc1ccc(C2CCCC2)cc1
Solvent: CC(=O)OC(C)=O
Solvent: O
Product: CC(=O)Nc1ccc(C2CCCC2)cc1[N+](=O)[O-]
Reaction time: 4 h

Procedure:
To a suspension of N-(4-cyclopentylphenyl)acetamide (Preparation 97, 18.5 g, 91.0 mmol) in acetic anhydride (148 mL, 1570 mmol) cooled in an ice/brine bath was added dropwise a solution of nitric acid (5.7 mL, 140 mmol) in acetic anhydride (40 mL, 400 mmol). After stirring for 4 hours, the reaction mixture was added water and extracted with methylene chloride (3×). The organic layers were combined, dried over anhydrous magnesium sulphate, filtered, and concentrated in vacuo. This provided product (19.48 g, 86%) as a brown oil that was used without further purification.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]([CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=3)[C:17]([CH3:20])=[CH:18][CH:19]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]([CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:42][CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH3:31])=[CH:25][CH:24]=3)[C:17]([CH3:20])=[CH:18][CH:19]=2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1ccc(-c2ccc(OCc3ccccc3)cc2)n1CCc1ccc(O)cc1
Reactant: CCCCCCCCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCCCCCCCOc1ccc(CCn2c(C)ccc2-c2ccc(OCc3ccccc3)cc2)cc1
Yield: 59.3 %

Procedure:
A solution of 4-{2-[2-(4-benzyloxyphenyl)-5-methyl-1H-pyrrol-1-yl]ethyl}phenol (1.50 g, 3.91 mmol), 1-bromododecane (1.41 ml, 5.87 mmol) and potassium carbonate (811 mg, 5.87 mmol) in DMF (15 ml) was stirred at 80° C. for 4 hours. The reaction solution was poured into water and the mixture was extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate anhydride and solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=30:1) to give the object compound as an oily substance. 1.28 g (yield: 59.3%)
Reaction SMILES: [I:1][C:2]1[C:7]([C:8]([O-:10])=[O:9])=[C:6]([I:11])[C:5]([I:12])=[C:4]([C:13]([O-:15])=[O:14])[C:3]=1[I:16].[Na+].[Na+].[I-].[Na+]>ClCC(O)CO>[I:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[C:6]([I:11])[C:5]([I:12])=[C:4]([C:13]([OH:15])=[O:14])[C:3]=1[I:16]
Reactant: O=C([O-])c1c(I)c(I)c(C(=O)[O-])c(I)c1I
Agent: OCC(O)CCl
Agent: [I-]
Agent: [Na+]
Product: O=C(O)c1c(I)c(I)c(C(=O)O)c(I)c1I
Yield: 85 %

Procedure:
19.4 g Di-sodium tetra-iodoterephthalate (0.0272 mole) and 0.5 g sodium iodide were stirred in 35 ml 3-chloro-1,2-propanediol for 20 hours at 100° C, the reaction mixture was worked up as in Example 1, and the bis-2,3-dihydroxypropyl ester of tetra-iodoterephthalic acid was obtained in an amount of 18.9 g (85% yield). When recrystallized from ethanol, it melted at 230° C (decomp.), gave an Rf value of 0.60, and was identified by elementary analysis:
Reaction SMILES: [O:1]([C:9]1[CH:14]=[CH:13][C:12]([CH:15](C(OCC2C=CC=CC=2)=O)[CH2:16][CH2:17][CH2:18][NH2:19])=[CH:11][CH:10]=1)[CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH3:8]>C(O)C.[Pd]>[O:1]([C:9]1[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][CH2:17][CH2:18][NH2:19])=[CH:13][CH:14]=1)[CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH3:8]
Reactant: COCCOCCOc1ccc(C(CCCN)C(=O)OCc2ccccc2)cc1
Agent: [Pd]
Solvent: CCO
Product: COCCOCCOc1ccc(CCCCN)cc1
Reaction time: 5 h
Yield: 99.1 %

Procedure:
Compound 106 (800 mg, 2.0 mmol) in ethanol (20 mL), was subjected to 1 atmosphere of H2 in the presence of 10% palladium on carbon (100 mg, cat.) with stirring for 5 h. After standing overnight, the reaction was purged with N2 then suction filtered through celite and washed off the celite with methylene chloride. The solvents were evaporated and chromatographed (silica gel, 200:10:1 methylene chloride/methanol/concentrated ammonium hydroxide) to afford 530 mg (>99%) of amine 107. 1H NMR (300 MHz, CDCl3) δ 1.31 (br s, 2H), 1.41-1.52 (m, 2H), 1.55-1.67 (m, 2H), 2.56 (t, J=7.7 Hz, 2H), 2.70 (t, J=7.0 Hz, 2H), 3.39 (s, 3H), 3.58 (m, 2H), 3.72 (m, 2H), 3.84 (t, J=4.9 Hz, 2H), 4.12 (t, J=5.3 Hz, 2H), 6.83 (d, J=8.7 Hz, 2H), 7.07 (d, J=8.7 Hz, 2H). CI MS m/z=268 [C15H25NO3+H]+.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11][C:12]#[N:13])=[CH:7][C:6]=1[N+:14]([O-:16])=[O:15])(=[O:3])[CH3:2].CN(C)C=O.[Na].BrC1[S:25][CH:26]=[CH:27]N=1>O>[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11][C:12]2[S:25][CH:26]=[CH:27][N:13]=2)=[CH:7][C:6]=1[N+:14]([O-:16])=[O:15])(=[O:3])[CH3:2]
Reactant: Brc1nccs1
Reactant: CC(=O)Nc1ccc(SC#N)cc1[N+](=O)[O-]
Agent: [Na]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)Nc1ccc(Sc2nccs2)cc1[N+](=O)[O-]
Reaction time: 1 h

Procedure:
To a solution of 2.37 g. of 1-acetamido-2-nitro-4-thiocyanatobenzene in 10 ml. dimethylformamide, there is added under nitrogen at less than 30°C., 0.38 g. of sodium borohydrode. The mixture is stirred at 20°-30°C. for 1 hour, then 3.2 ml. of 2-bromothiazole is added. The mixture is heated to 130°-135°C. for 1 hour, then cooled and diluted with water. The crude product is filtered off and recrystallized from methanol yielding 1-acetamido-2-nitro-4-(thiazol-2-ylthio)benzene.