Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]3[CH:29]=[C:30]([NH:37][C:38]4[CH:43]=[CH:42][C:41]([C:44]([N:46]5[CH2:51][CH2:50][O:49][CH2:48][CH2:47]5)=[O:45])=[CH:40][CH:39]=4)[C:31]4[N:32]([CH:34]=[CH:35][N:36]=4)[CH:33]=3)[C:18]=1[CH2:19][O:20]C(=O)C)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].O>CO>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]3[CH:29]=[C:30]([NH:37][C:38]4[CH:39]=[CH:40][C:41]([C:44]([N:46]5[CH2:47][CH2:48][O:49][CH2:50][CH2:51]5)=[O:45])=[CH:42][CH:43]=4)[C:31]4[N:32]([CH:34]=[CH:35][N:36]=4)[CH:33]=3)[C:18]=1[CH2:19][OH:20])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(=O)OCc1c(-c2cc(Nc3ccc(C(=O)N4CCOCC4)cc3)c3nccn3c2)cccc1-n1ncc2cc(C(C)(C)C)cc(F)c2c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: CC(C)(C)c1cc(F)c2c(=O)n(-c3cccc(-c4cc(Nc5ccc(C(=O)N6CCOCC6)cc5)c5nccn5c4)c3CO)ncc2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 16 %

Procedure:
Acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{8-[4-(morpholine-4-carbonyl)-phenylamino]-imidazo[1,2-a]pyridin-6-yl}-benzyl ester (200 mg, 0.29 mmol) was dissolved in methanol (10 ml). To this solution was added K2CO3 (80 mg, 0.58 mmol) and the mixture was stirred at room temperature for 2 hours. After the completion of the reaction, the mixture was poured into water (10 ml), extracted by DCM (100 ml). The organic extracts were washed with saturated aqueous solution of sodium chloride (100 ml), dried over sodium sulfate and concentrated. The residue was purified by silica gel column (petroleum ether:ethyl acetate 1:3) to afford the desired product as a yellow solid (30 mg, yield 16%). 1H NMR (300 MHz, CDCl3): δ 8.37 (d, J=2.7 Hz, 1H), 8.04 (d, J=1.3 Hz, 1H), 7.78 (s, 1H), 7.73 (d, J=1.7 Hz, 1H), 7.61 (d, J=1.7 Hz, 1H), 7.57 (d, J=1.6 Hz, 1H), 7.45 (dd, J=7.7, 5.7 Hz, 3H), 7.36 (dd, J=6.6, 2.7 Hz, 1H), 7.32 (s, 3H), 7.19 (d, J=1.4 Hz, 1H), 4.38 (s, 2H), 3.57 (s, 8H), 1.35 (s, 9H). LC-MS: 647[M+1]+, tR=1.407 min. HPLC: 97.75% at 214 nm, 98.27% at 254 nm, tR=3.633 min.
Reaction SMILES: [OH-].[Na+].C[O:4][C:5]([C:7]1[N:8]=[CH:9][S:10][C:11]=1/[CH:12]=[CH:13]\[S:14][C:15]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:6].Cl.C(OCC)(=O)C>C1COCC1.O>[C:5]([C:7]1[N:8]=[CH:9][S:10][C:11]=1/[CH:12]=[CH:13]\[S:14][C:15]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([OH:6])=[O:4]
Reactant: COC(=O)c1ncsc1/C=C\SC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1ncsc1/C=C\SC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 60 °C
Reaction time: 1 h
Yield: 117.3 %

Procedure:
A 5 N aqueous sodium hydroxide solution (8.30 ml) was added to a suspension of 7.31 g of 4-methoxycarbonyl-5-((Z)-2-tritylthioethen-1-yl)thiazole in THF, and the mixture was stirred at 60° C. for one hr. The mixture was then cooled to room temperature, and 8.50 ml of 5 N hydrochloric acid, 100 ml of ethyl acetate, and 50 ml of water were added thereto, followed by concentration to 150 ml. Hexane (100 ml) was added to the concentrate, and the precipitated solid was collected by filtration and was washed with ethyl acetate-hexane (2:1) to give 8.30 g of 4-carboxy-5-((Z)-2-tritylthioethen-1-yl)thiazole.
Reaction SMILES: [CH2:1]([N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[Cl:13][CH2:14][CH2:15][C:16](=[O:19])[CH2:17][CH3:18].[ClH:20].[CH:21](O)(C)C>>[ClH:13].[ClH:20].[CH2:1]([N:7]1[CH2:8][CH2:9][N:10]([C:14]2[CH2:15][C:16](=[O:19])[CH:17]=[CH:18][CH:21]=2)[CH2:11][CH2:12]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCC(=O)CCCl
Reactant: CCCCCCN1CCNCC1
Reactant: CC(C)O
Agent: Cl
Product: CCCCCCN1CCN(C2=CC=CC(=O)C2)CC1

Procedure:
A mixture of 8.5 g (0.05 mole) of a n-hexyl piperazine and 6.8 g (0.056 mole) of 1-chloro-3-pentanone was heated to 140° for 5 minutes. The reaction product was dissolved in isopropanol and acidified with a solution of HCl in isopropanol. The dihydrochloride salt was filtered and crystallized from acetonitrile to give 11.0 g of white solid with a melting point of 230°-233° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[C:10]1[CH2:15][CH2:14][CH2:13][CH:12](O)[CH:11]=1)([O-:3])=[O:2].[C:17]1(=[O:27])[NH:21][C:20](=[O:22])[C:19]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:18]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1COCC1.C(Cl)Cl>[N+:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[C:10]1[CH2:15][CH2:14][CH2:13][CH:12]([N:21]2[C:17](=[O:27])[C:18]3[C:19](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:20]2=[O:22])[CH:11]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cnccc1C1=CC(O)CCC1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(=O)N1C1C=C(c2ccncc2[N+](=O)[O-])CCC1
Temperature: 0 °C
Reaction time: 3 h
Yield: 98.6 %

Procedure:
To a solution of 3-(3-nitropyridin-4-yl)cyclohex-2-en-1-ol (1.0 g, 4.5 mmol), phthalimide (1.0 g, 6.8 mmol) and triphenylphosphine (1.8 g, 6.8 mmol) in THF (20 mL), di-tert-butyl azodicarboxylate (1.6 g, 6.8 mmol) was added slowly at 0° C. The resulting mixture was stirred at 0° C. for 3 h. After concentrated concentrating under reduced pressure, the crude product was purified by silica gel column chromatography (eluting with 0-70% EtOAc in hexanes) to give a solid, which was further treated with DCM and hexanes to yield sub-title compound (1.55 g, 98%). LCMS calc. for C19H16N3O4 (M+H)+: m/z=350.1. Found: 350.3.
Reaction SMILES: Cl.Cl.[CH3:3][C@H:4]1[C:12]2[C:11]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:10][CH:9]=[N:8][C:7]=2[CH2:6][CH2:5]1.[C:19]([O:23][C:24]([N:26]([CH:39]([CH3:41])[CH3:40])[CH2:27][CH:28]([C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=1)[C:29](O)=[O:30])=[O:25])([CH3:22])([CH3:21])[CH3:20].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.C(N(CC)CC)C>[Cl:38][C:35]1[CH:36]=[CH:37][C:32]([CH:28]([C:29]([N:16]2[CH2:17][CH2:18][N:13]([C:11]3[C:12]4[C@H:4]([CH3:3])[CH2:5][CH2:6][C:7]=4[N:8]=[CH:9][N:10]=3)[CH2:14][CH2:15]2)=[O:30])[CH2:27][N:26]([CH:39]([CH3:40])[CH3:41])[C:24](=[O:25])[O:23][C:19]([CH3:21])([CH3:20])[CH3:22])=[CH:33][CH:34]=1
Reactant: C[C@@H]1CCc2ncnc(N3CCNCC3)c21
Reactant: CC(C)N(CC(C(=O)O)c1ccc(Cl)cc1)C(=O)OC(C)(C)C
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)N(CC(C(=O)N1CCN(c2ncnc3c2[C@H](C)CC3)CC1)c1ccc(Cl)cc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 46.1 %

Procedure:
To a solution of (R)-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochloride (30 mg, 0.1 mmol) in DCM (10 mL) and triethylamine (1 mL) were added 3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (35 mg, 0.1 mmol) and HBTU (39 mg, 0.1 mmol). The mixture was stirred at room temperature for 2 hours. The solvent was removed and the residue was purified by silica gel chromatography, eluting with ethyl acetate to give tert-butyl 2-(4-chlorophenyl)-3-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (25 mg, 44%). 1H NMR (CDCl3, 400 MHz) δ 8.44 (s, 1H), 7.30-7.20 (m, 4H), 3.90-3.18 (m, 9H), 3.18-2.70 (m, 4H), 2.28 (m, 1H), 1.83 (m, 1H), 1.65 (m, 1H), 1.47 (s, 9H), 1.12 (m, 3H), 0.98 (m, 3H), 0.68 (m, 3H). MS (APCI+) [M+H]+542.
Reaction SMILES: [N:1]1([C:6]2[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=2)[C:9]([OH:11])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].[N+:21]([CH2:23][C:24]([O:26][CH3:27])=[O:25])#[C-:22].C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1>CN(C=O)C.C1(C)C=CC=CC=1.CCOC(C)=O>[N:1]1([C:6]2[CH:7]=[C:8]([C:9]3[O:11][CH:22]=[N:21][C:23]=3[C:24]([O:26][CH3:27])=[O:25])[CH:12]=[CH:13][CH:14]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: [C-]#[N+]CC(=O)OC
Reactant: O=C(O)c1cccc(N2CCCC2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC(=O)c1ncoc1-c1cccc(N2CCCC2)c1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To a suspension of 3-(pyrrolidin-1-yl)benzoic acid (1.0 g, 5.23 mmol) and K2CO3 1.75 g (12.55 mmol) in DMF (10.8 ml) was added methyl isocyanoacetate (551 mg, 5.23 mmol) in DMF (6.8 mL). The resulting mixture was stirred at rt for 5 min and then cooled to 0° C. A solution of DPPA (1.13 mL, 5.23 mmol) in DMF (6.8 mL) was added dropwise. The resulting mixture was stirred at 0° C. for 2 h and then at rt overnight. It was then diluted with toluene-EtOAc 1:1 (110 mL) and the organic layer was washed with water (55 mL) and aq. sat. NaHCO3-solution (45 mL), dried (MgSO4), filtered and concentrated to dryness. The residue was purified by FC (DCM/MeOH 9:1; Rf=0.41) to afford methyl 5-(3-(pyrrolidin-1-yl)phenyl)oxazole-4-carboxylate as a orange oil. LC-MS conditions A: tR=0.93 min, [M+H]+=273.04.
Reaction SMILES: Cl.Cl[CH2:3][C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:7]=[CH:6][N:5]=1.[NH:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1.[OH-].[K+].ClCCl>O>[C:10]1([C:8]2[CH:7]=[CH:6][N:5]=[C:4]([CH2:3][N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH:9]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: ClCc1cc(-c2ccccc2)ccn1
Reactant: C1CCNC1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: c1ccc(-c2ccnc(CN3CCCC3)c2)cc1
Reaction time: 1 h

Procedure:
The product from stage (i) (14.0 g) was added to a solution of pyrrolidine (17.0 ml) in water (80 ml) at 22°. The solution was stirred for 1 h at 22° and then potassium hydroxide (40 g), dichloromethane (200 ml) and water (200 ml) were added. The mixture was stirred for 0.25 h and the phases were separated. The aqueous phase was extracted with dichloromethane (100 ml) and the combined organic extracts were washed with water (2×100 ml), saturated brine, dried and evaporated to leave an oil (15.2 g), a portion of which (0.5 g) was purified by flash chromatography eluting with dichloromethane, ethanol and ammonia (200:8:1) to give the title compound as an oil (0.4 g). T.l.c. Silica (Dichloromethane, ethanol and ammonia 200:8:1) Rf 0.4.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][CH:6]=1)(=[O:4])=[O:3].C[Al](C)C.[C:16]([C:18]1[CH:23]=[CH:22][C:21]([C:24]2[S:25][CH:26]=[CH:27][CH:28]=2)=[CH:20][CH:19]=1)#[N:17]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl.CO>[CH3:1][S:2]([C:5]1[CH:11]=[CH:10][C:8]([NH:9][C:16]([C:18]2[CH:19]=[CH:20][C:21]([C:24]3[S:25][CH:26]=[CH:27][CH:28]=3)=[CH:22][CH:23]=2)=[NH:17])=[CH:7][CH:6]=1)(=[O:3])=[O:4]
Reactant: CS(=O)(=O)c1ccc(N)cc1
Reactant: N#Cc1ccc(-c2cccs2)cc1
Agent: C[Al](C)C
Solvent: ClC(Cl)Cl
Solvent: CO
Solvent: Cc1ccccc1
Product: CS(=O)(=O)c1ccc(NC(=N)c2ccc(-c3cccs3)cc2)cc1
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
To a suspension of 4-(methylsulfonyl)aniline (0.428 g, 2.5 mmol) in toluene (15 mL) at 0° C. was added over 5 minutes trimethylaluminum (3.83 mL, 0.98 M solution in hexane, 3.75 mmol). The reaction mixture was warmed to room temperature and stirred for 3.5 hours. A solution of 2-(4-cyanophenyl)thiophene (0.926 g, 5 mmol, prepared according to the method of Heterocycles, 1990, 31, 1951) in toluene (10 mL) was added over 5 minutes and the reaction mixture heated to 70° C. After 18.5 hours, the reaction mixture was cooled to room temperature and poured over a slurry of silicagel in chloroform-methanol (2:1, 150 mL). After filtration, the residue was washed with a mixture of CH2Cl2—methanol (2:1, 75 mL). The combined filtrates were concentrated in vacuo, and the resulting yellowish solid was washed with hexane-ether (2:1, 100 mL) to give the subtitle compound (0.711 g).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[C:34]([O:38][C:39](=[O:46])[C@H:40]([CH2:42][CH:43]([CH3:45])[CH3:44])[NH2:41])([CH3:37])([CH3:36])[CH3:35]>CN(C=O)C.C(Cl)CCl>[C:34]([O:38][C:39](=[O:46])[C@@H:40]([NH:41][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([N+:11]([O-:13])=[O:12])[CH:4]=1)[CH2:42][CH:43]([CH3:44])[CH3:45])([CH3:36])([CH3:35])[CH3:37]
Reactant: O=C(O)c1ccc(F)c([N+](=O)[O-])c1
Reactant: CC(C)C[C@H](N)C(=O)OC(C)(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Product: CC(C)C[C@H](NC(=O)c1ccc(F)c([N+](=O)[O-])c1)C(=O)OC(C)(C)C
Reaction time: 4 h
Yield: 99.6 %

Procedure:
To a solution of 9.26 g of 4-fluoro-3-nitro-benzoic acid in 100 ml of dry DMF 7.43 g of HOBT, 10.54 g of EDC and 8.9 ml of DIPEA were added at 0° C. After 30 min 12.31 g of L-leucin-tert.-butylester-hydrochloride and 8.9 ml of DIPEA were added and the reaction was stirred at it for 4 h. The reaction was then concentrated to about a fifth of its volume and poured into water. It was then extracted with ethyl acetate three times. The combined organic phases were washed with saturated aqueous sodium carbonate solution and brine, dried over magnesium sulphate and concentrated to yield 17.65 g (100%) of (S)-2-(4-Fluoro-3-nitro-benzoylamino)-4-methyl-pentanoic acid tert-butyl ester as a brown oil, which was used without further purification in the subsequent step.
Reaction SMILES: [C:1]([N:8]1[CH2:16][CH2:15][CH:11]([C:12]([OH:14])=O)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:17][C:18]1([CH3:26])[O:25][C:23](=[O:24])[CH2:22][C:20](=[O:21])[O:19]1.C(P(=O)(OCC)OCC)#N.C(N(CC)CC)C>CN(C=O)C>[CH3:17][C:18]1([CH3:26])[O:25][C:23](=[O:24])[C:22](=[C:12]([OH:14])[CH:11]2[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:16][CH2:15]2)[C:20](=[O:21])[O:19]1
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)O)CC1
Reactant: CC1(C)OC(=O)CC(=O)O1
Agent: CCOP(=O)(C#N)OCC
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCC(C(O)=C2C(=O)OC(C)(C)OC2=O)CC1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A cooled (0° C.) solution of Boc-isonipecotic acid (5.97 g, 26.0 mmol) and Meldrum's acid (3.75 g, 26.0 mmol) in DMF (54 mL) was treated dropwise with diethyl cyanophosphonate (4.34 mL, 28.6 mmol) and triethylamine (11.2 mL, 80.7 mmol). After stirring at 0° C. for an additional 30 min the reaction mixture was permitted to warm to rt and stir over 3 days. The reaction mixture was concentrated under reduced pressure and ether and 1N HCl solution were added. The aqueous layer was extracted again with ether and the ethereal layers were combined and washed with 1N HCl solution, twice with water, and lastly with brine. He ethereal layer was then dried over anhydrous MgSO4, filtered, and concentrated to give tert-butyl 4-[(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)(hydroxy)methyl]piperidine-1-carboxylate which contained approximately 10% of Boc-isonipecotic acid.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][C:11]23[CH2:22][CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[C:10]2=[CH:9]1)[C:14]1[CH:23]=[CH:24][CH:25]=[CH:26][C:13]3=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.C([BH3-])#N.[Na+].Cl>C(O)(=O)C>[CH2:1]([N:8]1[CH2:12][C:11]23[CH2:22][CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[CH:10]2[CH2:9]1)[C:14]1[CH:23]=[CH:24][CH:25]=[CH:26][C:13]3=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C1=C2c3ccccc3C3CC2(CN1Cc1ccccc1)c1ccccc13
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: c1ccc(CN2CC3c4ccccc4C4CC3(C2)c2ccccc24)cc1

Procedure:
A mixture of 37.7 g of finely powdered 2-benzyl-2,3-dihydro-8H-3a, 8-methanodibenzo[3,4:6,7]cyclohepta[1,2-c] pyrrole (5e), 300 ml of methanol, and 40 ml of acetic acid is cooled with ice, and 14.8 g of sodium cyanoborohydride is added slowly with stirring. The mixture is stirred at room temperature for 3 hours, cooled, and treated with 50 ml of conc. hydrochloric acid. After stirring at room temperature for 0.5 hour the mixture is made basic and extracted several times with methylene chloride. Removal of the solvent from the dried extracts gives 37.5 g of 2-benzyl-2,3,8,12b-tetrahydro-1H-3a,8-methanodibenzo[3,4:6,7]-cyclohepta[1,2-c]pyrrole, identical by nmr spectroscopy with the product obtained in Example 4. The hydrochloride melts with decomposition at 195°-200° after crystallization from ethanol.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6](Cl)(=[O:8])=[O:7].[C:10]([NH2:14])([CH3:13])([CH3:12])[CH3:11].C1(C)C=CC=CC=1>C(Cl)(Cl)Cl>[C:10]([NH:14][S:6]([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)(=[O:8])=[O:7])([CH3:13])([CH3:12])[CH3:11]
Reactant: CC(C)(C)N
Reactant: O=S(=O)(Cl)c1cccs1
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Product: CC(C)(C)NS(=O)(=O)c1cccs1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Thiophene-2-sulfonyl chloride (15 g, 0.082 mol) was dissolved in CHCl3 (200 mL) under N2 atmosphere and then cooled to 0° C. tert-Butylamine (25.9 mL, 0.246 mol) dissolved in CHCl3 (50 mL) was then added dropwise to the reaction mixture. The reaction mixture was stirred for 1 h at room temperature and then at reflux for 10 min. Toluene (700 mL) was added and the organic phase was washed with water (3×50 mL), dried, and concentrated in vacuo. The sub-title product was used without further purification in the next step.
Reaction SMILES: C(C1C=C(C#CC2C=C(C)C(C#CC3C=C(C(C)(C)C)C=C(C(C)(C)C)C=3)=CC=2C(OC)=[O:41])C=C(C(C)(C)C)C=1)(C)(C)C.[N+]([O-])(O)=O.[Br:48][C:49]1[CH:54]=[C:53]([CH3:55])[C:52]([Br:56])=[CH:51][C:50]=1[CH3:57].[OH2:58]>>[Br:48][C:49]1[CH:54]=[C:53]([CH3:55])[C:52]([Br:56])=[CH:51][C:50]=1[C:57]([OH:41])=[O:58]
Reactant: Cc1cc(Br)c(C)cc1Br
Reactant: O
Reactant: COC(=O)c1cc(C#Cc2cc(C(C)(C)C)cc(C(C)(C)C)c2)c(C)cc1C#Cc1cc(C(C)(C)C)cc(C(C)(C)C)c1
Solvent: O=[N+]([O-])O
Product: Cc1cc(Br)c(C(=O)O)cc1Br

Procedure:
Molecules of the present invention can be synthesized using well-known organic synthesis methods. FIG. 8 shows a method for synthesizing a molecule belonging to the subclass shown in FIG. 6 according to one embodiment of the present invention. A detailed description of the organic synthesis is described below in an experimental subsection called “Synthesis of 1,4-bis[3′,5′-di-tert-butylphenylethynyl]-5-methyl-2-methoxycarbonylbenzene.” The organic synthesis includes adding nitric acid and water to a solution of 2,5-dibromo-p-xylene 802, which is refluxed to obtain in solution 2,5-dibromo-4-methylbenzoic acid 804. Methanol and concentrated sulfuric acid are added to the solution of 2,5-dibromo-4-methylbenzoic acid 804, which is refluxed to obtain a solution of methyl 2,5-dibromo-4-methylbenzoate 806. In a separate part of the synthesis, trifluoromethanesulfonic anhydride and pyridine are added to a solution of 3,5-di-tert-butylphenol 808 and the solution is warmed to room temperature to obtain 3,5-di-tert-butylphenyl triflate 810. A solution of 3,5-di-tert-butylphenyl triflate 810, PdCl2, (PPH3)2, CuI, tetrabutylammonium iodide, and trimethylsilylacetylene are stirred to obtain 1-[3′,5′-di-tert-butylphenyl-2-trimethylsilylacetylene 812. Combining 1-[3′,5′-di-tert-butylphenyl-2-trimethylsilylacetylene 812, methyl 2,5-dibromo-4-methylbenzoate 806, PdCl2, (PPH3)2, CuI, triethylamine, tetrahydrofuran, and tetrabutylammonium fluoride and stirring at room temperature yields the desired molecule 1,4-bis[3′,5′-di-tert-butylphenylethynyl]-5-methyl-2-methoxycarbonylbenzene 814.
Reaction SMILES: C(OCC)(=O)C.C(O)(=O)C.[CH3:11][NH2:12].[Cl:13][C:14]1[CH:15]=[C:16]([CH3:26])[C:17]2[NH:22]C(=O)[O:20][C:19](=O)[C:18]=2[CH:25]=1>O>[NH2:22][C:17]1[C:16]([CH3:26])=[CH:15][C:14]([Cl:13])=[CH:25][C:18]=1[C:19]([NH:12][CH3:11])=[O:20]
Reactant: CN
Reactant: Cc1cc(Cl)cc2c(=O)oc(=O)[nH]c12
Solvent: CC(=O)O
Solvent: O
Solvent: CCOC(C)=O
Product: CNC(=O)c1cc(Cl)cc(C)c1N
Temperature: 37.5 °C
Reaction time: 0.33 h
Yield: 95.6 %

Procedure:
A 300-mL flask equipped with a thermometer and nitrogen bubbler was charged with ethyl acetate (100 mL) and 12.6 g (0.21 mol) of acetic acid. Anhydrous methylamine (6.3 g, 0.20 mol) was added below the surface of the liquid mixture, which was cooled to maintain the temperature below 35° C. Then 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (21 g, 0.10 mol) (i.e. the product of Example 1) was added in portions while maintaining the reaction mixture at 35-40° C. After completion of the addition of the 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione the temperature was maintained at 40-45° C., and the progress of the reaction was monitored by HPLC analysis. After about 20 minutes, when no more than 0.5% 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione remained, water (50 mL) was added. A distillation head was attached, moderate vacuum was applied, and ethyl acetate was distilled out at an internal temperature of about 46-60° C. and pressure of about 30 to 50 kPa. To replace the ethyl acetate removed by distillation, water was added to maintain the original liquid volume in the reactor. When a significant amount of water began to distill, the aqueous slurry was cooled to 10° C. The solid was collected by filtration and dried at 60° C. and 13.3 kPa to afford the title compound as a white crystalline solid (19 g, ca. 95% yield, >98% purity by peak area in HPLC analysis).
Reaction SMILES: [C:1]([N:11]1[CH2:18][CH2:17][CH2:16][C@H:12]1[C:13]([OH:15])=O)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].ClC(O[CH2:23][CH:24](C)C)=O.C[N:28]1[CH2:33][CH2:32][O:31]CC1>C1COCC1>[C:1]([N:11]1[CH2:18][CH2:17][CH2:16][C@H:12]1[C:13]([NH:28][C@@H:33]([CH2:32][OH:31])[CH2:23][CH3:24])=[O:15])([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]
Reactant: O=C(O)[C@@H]1CCCN1C(=O)OCc1ccccc1
Reactant: CN1CCOCC1
Reactant: CC(C)COC(=O)Cl
Solvent: C1CCOC1
Product: CC[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)OCc1ccccc1
Yield: 60.5 %

Procedure:
4.98 g (20 mmol) N-carbobenzoxy-L-proline, 2.73 g (20 mmol) isobutyl chloroformate, 2.03 g (20 mmol) N-methylmorpholine, and 1.78 g (20 mmol) 1-(-)-2-amino-1-butanol were contacted and reacted in THF substantially according to the mixed anhydride procedure described in Example 1. The resulting crude product, 5.58 g, was recrystallized from a mixture of 40 mL ethyl acetate and 60 mL n-hexane, providing 3.87 g (12.1 mmol, 60.4%) of colorless crystalline N-carbobenzoxy-L-prolyl-D-homoalaninol; m.p. 99.5°-101.5°, α25D-28.5° (C=1.00 g/100 mL of acetone).
Reaction SMILES: [CH2:1]([OH:7])[CH2:2][CH2:3][CH2:4][CH2:5][OH:6].[H-].[Na+].[CH3:10][O:11][CH2:12][CH2:13][O:14][CH2:15]Cl.O>CN(C)C=O>[CH3:10][O:11][CH2:12][CH2:13][O:14][CH2:15][O:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:1][OH:7]
Reactant: OCCCCCO
Reactant: COCCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COCCOCOCCCCCO
Temperature: 25 °C
Reaction time: 1 h
Yield: 52.4 %

Procedure:
A solution of 50.00 g of 1,5-pentanediol dissolved in 100 ml of dimethylformamide was added dropwise to a mixture of 23.00 g of sodium hydride (as a 55% w/w dispersion in mine al oil) in 300 ml of dimethylformamide, whilst ice-cooling at 5° to 7° C. The mixture was stirred at room temperature for one hour, after which 65.79 g of 2-methoxyethoxymethyl chloride dissolved in 100 ml of dimethylformamide were added dropwise, whilst ice-cooling at 5° to 7° C. The mixture was stirred at room temperature for 3 hours, after which it was poured into 2.5 liters of water and then extracted five times with methylene chloride. The combined extracts were washed with water, dried and concentrated by evaporation under reduced pressure. The residue was subjected to column chromatography through 850 g of silica gel and 48.40 g of the title compound were obtained from the fractions eluted with a mixtures of methylene chloride and methanol ranging from 98:2 to 95:5 by volume, as a colorless oil.