Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC(C)CCN.[N:7]1[CH:8]=[CH:9][N:10]2[CH:15]=[CH:14][C:13]([CH2:16][NH:17][C:18](=[O:28])[NH:19][C:20]3[S:21][C:22]([C:25]([OH:27])=O)=[CH:23][N:24]=3)=[CH:12][C:11]=12.[N+:29]([C:32]1C=[CH:39][C:35](C(O)=O)=[CH:34][CH:33]=1)([O-])=O>>[N:7]1[CH:8]=[CH:9][N:10]2[CH:15]=[CH:14][C:13]([CH2:16][NH:17][C:18]([NH:19][C:20]3[S:21][C:22]([C:25]([N:29]4[CH2:32][CH2:33][CH2:34][CH2:35][CH2:39]4)=[O:27])=[CH:23][N:24]=3)=[O:28])=[CH:12][C:11]=12
Reactant: O=C(NCc1ccn2ccnc2c1)Nc1ncc(C(=O)O)s1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Agent: CC(C)CCN
Product: O=C(NCc1ccn2ccnc2c1)Nc1ncc(C(=O)N2CCCCC2)s1

Procedure:
The title compound was prepared as described in Example 1A, substituting piperidine for 3-methylbutan-1-amine and 2-(3-(imidazo[1,2-a]pyridin-7-ylmethyl)ureido)thiazole-5-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.91 (s, 1H), 8.49 (d, J=7.1 Hz, 1H), 7.89 (s, 1H), 7.62 (s, 1H), 7.52 (d, J=0.8 Hz, 1H), 7.39 (s, 1H), 7.11-7.18 (m, 1H), 6.83 (dd, J=6.9, 1.4 Hz, 1H), 4.39 (d, J=6.0 Hz, 2H), 3.54-3.61 (m, 4H), 1.47-1.67 (m, 6H); MS (ESI(+)) m/e 385 (M+H)+.
Reaction SMILES: [CH2:1](I)[CH3:2].[CH2:4]([NH:6][S:7]([C:10]1[NH:14][C:13]2[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=2[N:11]=1)(=[O:9])=[O:8])[CH3:5].C(=O)([O-])[O-].[Na+].[Na+]>CC(C)=O.O>[CH2:1]([N:14]1[C:13]2[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=2[N:11]=[C:10]1[S:7]([NH:6][CH2:4][CH3:5])(=[O:9])=[O:8])[CH3:2]
Reactant: CCNS(=O)(=O)c1nc2ccccc2[nH]1
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: CCNS(=O)(=O)c1nc2ccccc2n1CC
Yield: 74.7 %

Procedure:
46.8 g (0.3 mol) of ethyl iodide are added to a suspension of 67.5 g (0.3 mol) of N-ethyl-1H-benzimidazole-sulfonamide and 47.7 g (0.45 mol) of sodium carbonate In 450 ml of acetone and 20 ml of water. The mixture is left under reflux for 20 hours, the acetone is evaporated off, 200 ml of water are added and the product is extracted with methylene chloride. The organic layer is dried (Na2SO4) and evaporated. The residue is recrystallized from an ethanol/water mixture (2:1) to give 56.8 g (75%) of 1,N-diethyl-1H-benzimidazole-2-sulfonamide melting at 135°-9° C.
Reaction SMILES: [CH3:1][C:2]([O:4][C@H:5]1[C:14]2[C@@:15]3([CH3:30])[C@@H:26]([CH2:27][O:28][CH3:29])[O:25][C:23](=[O:24])[C:17]4=[CH:18][O:19][C:20]([C:21](=[O:22])[C:13]=2[C@@H:8]2[CH2:9][CH2:10][C@H:11]([OH:12])[C@@:7]2([CH3:31])[CH2:6]1)=[C:16]34)=[O:3].[CH2:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:35][CH2:34][NH:33]1>C(Cl)Cl>[C:2]([O:4][C@H:5]1[C:14]2[C@:15]3([CH3:30])[C:16](/[C:17](=[CH:18]\[N:33]4[CH2:34][CH2:35][C:36]5[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=5)[CH2:32]4)/[C:23](=[O:24])[O:25][C@@H:26]3[CH2:27][O:28][CH3:29])=[C:20]([OH:19])[C:21](=[O:22])[C:13]=2[CH:8]2[C@@:7]([CH3:31])([C@@H:11]([OH:12])[CH2:10][CH2:9]2)[CH2:6]1)(=[O:3])[CH3:1]
Reactant: COC[C@H]1OC(=O)c2coc3c2[C@@]1(C)C1=C(C3=O)[C@@H]2CC[C@H](O)[C@@]2(C)C[C@H]1OC(C)=O
Reactant: c1ccc2c(c1)CCNC2
Solvent: ClCCl
Product: COC[C@H]1OC(=O)/C(=C/N2CCc3ccccc3C2)C2=C(O)C(=O)C3=C([C@H](OC(C)=O)C[C@@]4(C)C3CC[C@@H]4O)[C@]21C
Temperature: 25 °C
Reaction time: 8 h
Yield: 13.3 %

Procedure:
To a solution of 50 mg (0.12 mmol) 17-hydroxywortmannin in 0.5 mL CH2Cl2 is added 32 mg (0.24 mmol) 1,2,3,4-tetrahydroisoquinoline. The reaction mixture is stirred at room temperature overnight. CH2Cl2 is removed in vacuo. The residue is triturated with Et2O to give 9 mg (13.3%) product as an orange powder. MS (ESI) m/z 564.25 (M+1).
Reaction SMILES: CO[CH2:3][N:4]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:5][Si](C)(C)C.[Cl:17][C:18]1[CH:23]=[CH:22][C:21](/[CH:24]=[CH:25]/[N+:26]([O-:28])=[O:27])=[CH:20][C:19]=1[Cl:29].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:10]([N:4]1[CH2:5][CH:25]([N+:26]([O-:28])=[O:27])[CH:24]([C:21]2[CH:22]=[CH:23][C:18]([Cl:17])=[C:19]([Cl:29])[CH:20]=2)[CH2:3]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=[N+]([O-])/C=C/c1ccc(Cl)c(Cl)c1
Reactant: COCN(Cc1ccccc1)C[Si](C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=[N+]([O-])C1CN(Cc2ccccc2)CC1c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 62.2 %

Procedure:
A solution of N-(methoxymethyl)-N-(phenylmethyl)-N-(trimethylsilyl)methylamine (1.96 g, 8.2 mmol) in CH2Cl2 (10 ml) was added drop wise, over a 30 minutes period, to a stirred solution of 1,2-dichloro-4-((E)-2-nitro-vinyl)-benzene (1.0 g, 4.58 mmol) and trifluoroacetic acid (52 mg, 4.45 mmol) in CH2Cl2 (5 ml) at 0° C. The ice bath was removed, and the solution was stirred at 25° C. for an additional 48 h. It was then concentrated and purification by flash chromatography (SiO2, EtOAc/H 1:4) afforded 1.00 g (62%) of the title compound as a colorless oil. ES-MS m/e: 351.4 (M+H+).
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1.C(N(CC)CC)C>C(O)C>[N+:8]([C:7]1[C:2]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[N:3][CH:4]=[CH:5][CH:6]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1cccnc1Cl
Reactant: NCc1ccccn1
Solvent: CCN(CC)CC
Solvent: CCO
Product: O=[N+]([O-])c1cccnc1NCc1ccccn1
Yield: 95.1 %

Procedure:
To a stirred solution of 2-chloro-3-nitropyridine (26.56 g, 0.168 mol) in absolute ethanol (250 mL) was added 2-(aminomethyl)pyridine (20.0 g, 0.185 mol) and triethylamine (16.99 g, 0.168 mol). The solution was heated at reflux for 2 hr and evaporated under reduced pressure. The residue was triturated in ethyl acetate several times and filtered. The filtrate was washed 3 times with a saturated sodium chloride solution, dried (sodium sulfate), filtered and evaporated under reduced pressure to give 36.8 g of N-(3-nitro-2-pyridinyl)-2-pyridinemethanamine (95% yield). A 1.0 g portion of the solid was recrystallized from isopropyl ether and dried under high vacuum to give 0.57 g of N-(3-nitro-2-pyridinyl)-2-pyridinemethanamine, mp 112°-115° C.
Reaction SMILES: Cl.[CH2:2]([O:9][C:10](=[O:23])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:22])[C@@H:17]1[CH2:21][CH2:20][CH2:19][NH:18]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.[C:31]1([S:37](Cl)(=[O:39])=[O:38])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(Cl)Cl>[CH2:2]([O:9][C:10](=[O:23])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:22])[C@@H:17]1[CH2:21][CH2:20][CH2:19][N:18]1[S:37]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)(=[O:39])=[O:38])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: O=C(OCc1ccccc1)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(OCc1ccccc1)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1S(=O)(=O)c1ccccc1
Reaction time: 1 h
Yield: 98.1 %

Procedure:
L-prolyl-L-proline benzylester hydrochloride (1.69 g, 5 mmole) was dissolved in methylene chloride (30 ml), and triethylamine (1.11 g, 11 mmole) was added thereto at -30° C. Methylene chloride (10 ml) solution of benzene sulfonyl chloride (0.86 g, 5 mmole) was added dropwise to the solution. The mixture was stirred for 1 hour at less than 0° C., and next for 5 hours at room temperature, and methylene chloride (60 ml) was added thereto. The solution was washed with 5% aqueous sodium bicarbonate (100 ml, twice), 1N aqueous hydrochloric acid (100 ml, twice) and water (100 ml) in the order given, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain N-benzenesulfonyl-L-prolyl-L-proline benzylester(yield: 2.17 g, 98.1%)
Reaction SMILES: [CH2:1]([N:8]1[C:13](=[O:14])[C:12]([C:15]([OH:17])=O)=[C:11]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:10]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:35][NH:36][CH3:37]>>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]([C:15](=[O:17])[N:36]([CH3:37])[CH3:35])=[C:11]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:10]([C:26]2[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=2)=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(-c2nn(Cc3ccccc3)c(=O)c(C(=O)O)c2-c2ccc(OC)cc2)cc1
Reactant: CNC
Agent: Cl
Product: COc1ccc(-c2nn(Cc3ccccc3)c(=O)c(C(=O)N(C)C)c2-c2ccc(OC)cc2)cc1
Yield: 42.1 %

Procedure:
Using 2-benzyl-5,6-bis(4-methoxyphenyl)-4-carboxy-2H-pyridazin-3-one and dimethylamine hydrochloride as starting materials, the procedures of Example 22 were repeated likewise, whereby the title compound was obtained in a yield of 42.1%.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([CH:9]=1)[C:7]#[N:8].[NH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.O>CN(C)C=O>[N+:10]([C:5]1[CH:4]=[CH:3][C:2]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)=[CH:9][C:6]=1[C:7]#[N:8])([O-:12])=[O:11]
Reactant: C1CCNCC1
Reactant: N#Cc1cc(Cl)ccc1[N+](=O)[O-]
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1cc(N2CCCCC2)ccc1[N+](=O)[O-]
Temperature: 50 °C
Reaction time: 0.5 h

Procedure:
63.9 g of 5-chloro-2-nitrobenzonitrile was dissolved in 200 ml of dimethylformamide, and 95 ml of piperidine was added to the solution. The mixture was stirred at 50° C. for 30 minutes while externally cooling because of heat generation. The reaction mixture was poured into water, and the precipitate thus formed was collected, washed with water and then with methanol, and dried to obtain 80 g of 2-nitro-5-piperidinobenzonitrile (melting point: 126°-127° C.).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]([OH:13])=O.S(Cl)(Cl)=O.[NH3:18]>CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]([NH2:18])=[O:13]
Reactant: O=C(O)CCc1ccc(F)cc1F
Reactant: N
Solvent: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: NC(=O)CCc1ccc(F)cc1F
Temperature: 50 °C
Reaction time: 1 h

Procedure:
27.9 g (0.15 mol) of 3-(2,4-difluorophenyl)propanoic acid are mixed in a sulfation flask with 50 ml (0.69 mol) of thionyl chloride and 0.5 ml of dimethylformamide, and the mixture is stirred at room temperature for one hour, at 50° C. for one hour and under reflux for half an hour. The excess thionyl chloride is then removed by distillation in vacuo. The orange-brown oily residue is dissolved in toluene and then cooled to -15° C. At this temperature, 7.0 g (0.41 mol) of ammonia gas are passed in over about one hour. The temperature is then allowed to rise to room temperature. The partially crystalline reaction mixture is then poured into 500 ml of ice-water. The residue is filtered, washed with a little toluene and dried in vacuo. 21.7 (78% of theory) of white crystals of melting point 107°-108° C. are obtained. After recrystallization from water, the product melts at 109°-110° C.
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[C:15]([O:17][CH2:18][CH:19]=[C:20]([Cl:22])[Cl:21])[CH:14]=[C:13]([Cl:23])[C:3]=1[O:4][CH2:5][CH2:6][CH2:7][CH2:8][O:9][CH2:10][CH:11]=[O:12].[Cl:24][C:25](Cl)(Cl)[C:26](F)([F:28])[F:27].[Cl-].[Al+3].[Cl-].[Cl-]>CN(C)C=O.[Zn]>[Cl:1][C:2]1[CH:16]=[C:15]([O:17][CH2:18][CH:19]=[C:20]([Cl:22])[Cl:21])[CH:14]=[C:13]([Cl:23])[C:3]=1[O:4][CH2:5][CH2:6][CH2:7][CH2:8][O:9][CH2:10][CH:11]([OH:12])[C:25]([Cl:24])=[C:26]([F:28])[F:27]
Reactant: O=CCOCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Reactant: FC(F)(F)C(Cl)(Cl)Cl
Agent: [Al+3]
Agent: [Cl-]
Agent: [Zn]
Solvent: CN(C)C=O
Product: OC(COCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl)C(Cl)=C(F)F
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 34.8 %

Procedure:
Then, 19.54 g of 4-(2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)butyloxyacetaldehyde was dissolved in 200 ml of N,N-dimethylformamide, to which 25.3 g of 1,1,1-trichlorotrifluoroethane, 17.6 g of zinc dust and 2.0 g of aluminum chloride were added. After stirring at room temperature for 1.5 hours, the reaction mixture was filtered. The filtrate was poured into diluted hydrochloric acid and extracted twice with diethyl ether. The diethyl ether layers were combined, washed with water, dried over magnesium sulfate and then concentrated to give a crude product. The crude product was subjected to silica gel chromatography, which afforded 8.46 g of 3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-(4-(3-chloro-4,4-difluoro-2-hydoxy-3-butenyloxy)butyloxy)benzene (yield, 38%), nD22.5 1.5302.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:13]([C:14]([NH2:16])=[O:15])=[CH:12][NH:11][N:10]=2)=[CH:4][CH:3]=1.O=[S:18]1(=O)[CH2:23][CH2:22][C:21](=[CH:24][C:25]#[N:26])[CH2:20][CH2:19]1.C1CCN2C(=NCCC2)CC1>CC#N>[C:25]([CH2:24][C:21]1([N:11]2[CH:12]=[C:13]([C:14]([NH2:16])=[O:15])[C:9]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[N:10]2)[CH2:22][CH2:23][S:18][CH2:19][CH2:20]1)#[N:26]
Reactant: N#CC=C1CCS(=O)(=O)CC1
Reactant: NC(=O)c1c[nH]nc1Nc1ccc(F)cc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: N#CCC1(n2cc(C(N)=O)c(Nc3ccc(F)cc3)n2)CCSCC1
Temperature: 80 °C

Procedure:
3-[(4-Fluorophenyl)amino]-1H-pyrazole-4-carboxamide (Intermediate 31-7) (100 mg, 0.45 mmol) was added to a mixture of 2-(1,1-dioxidodihydro-2H-thiopyran-4(3H)-ylidene)acetonitrile (160 mg, 0.91 mmol) in MeCN (1.51 mL). DBU (0.068 mL, 0.45 mmol) was then added, the reaction vessel was capped and the reaction mixture was heated to 80° C. for 4 hours. The reaction mixture was cooled to ambient temperature, and purified by reverse phase preparative HPLC (using a gradient elution of MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were combined, basified with saturated aqueous NaHCO3, and extracted with EtOAc. The organic layer was dried over anhydrous NaSO4, filtered, and concentrated in vacuo to afford the title compound, Example #7.
Reaction SMILES: [C:1]1([C:7]2[O:8][C:9]3[CH:15]=[C:14]([CH:16]=O)[CH:13]=[CH:12][C:10]=3[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(OP([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[O:34][C:35]3[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:36]=3[N:37]=2)=[CH:29][CH:28]=1)(OCC)=O)C.O>CN(C)C=O>[C:1]1([C:7]2[O:8][C:9]3[CH:15]=[C:14]([CH:16]=[CH:26][C:27]4[CH:28]=[CH:29][C:30]([C:33]5[O:34][C:35]6[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:36]=6[N:37]=5)=[CH:31][CH:32]=4)[CH:13]=[CH:12][C:10]=3[N:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=Cc1ccc2nc(-c3ccccc3)oc2c1
Reactant: CCOP(=O)(Cc1ccc(-c2nc3cc(Cl)ccc3o2)cc1)OCC
Solvent: O
Solvent: CN(C)C=O
Product: Clc1ccc2oc(-c3ccc(C=Cc4ccc5nc(-c6ccccc6)oc5c4)cc3)nc2c1
Yield: 33.4 %

Procedure:
A solution of 4.46 g (0.02 mole) of 2-phenyl-6-formyl-benzoxazole of the formula ##STR29## (melting point: 133°-135° C.) and 7.59 g (0.02 mole) of 2-(p-diethylphosphonomethylphenyl)-5-chloro-benzoxazole of the formula ##STR30## (melting point: 96°-98°) in 80 ml of dimethyl formamide is heated to 40° C. Then 2.1 g (0.022 mole) of sodium tert.butylate are added in small amounts to the solution over the course of 30 minutes and the resultant suspension is further stirred for 4 hours at 40° C. The reaction mixture is poured into water and the precipitate is collected by filtration, washed with water and subsequently with a total amount of 110 ml of methanol. The product is recrystallised form a solvent mixture of nonane/xylene (1:1) with the addition of fuller's earth, affording 3 g (30% of theory) of 1-(2-phenylbenzoxazol-6-yl)-2-[4'-(5-chlorbenzoxazol-2-yl)-phenyl]-ethylene of the formula ##STR31## in the form of pale yellow flakes having a melting point of 241°-242° C.
Reaction SMILES: C(O[C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][CH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)=[CH:13][CH:12]=[CH:11][C:10]=2[O:22][CH3:23])=[O:5])C.[C:24]1([N:30]=[C:31]=[O:32])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH:17]1([N:16]2[C:15]3[C:14]4[CH:13]=[CH:12][CH:11]=[C:10]([O:22][CH3:23])[C:9]=4[N:8]=[CH:7][C:6]=3[C:4](=[O:5])[N:30]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:31]2=[O:32])[CH2:18][CH2:19][CH2:20][CH2:21]1
Reactant: CCOC(=O)c1cnc2c(OC)cccc2c1NC1CCCC1
Reactant: O=C=Nc1ccccc1
Product: COc1cccc2c1ncc1c(=O)n(-c3ccccc3)c(=O)n(C3CCCC3)c12
Yield: 74.9 %

Procedure:
1-Cyclopentyl-7-methoxy-3-phenyl-1H-pyrimido[5,4-c]quinoline-2,4-dione (29 mg) was prepared from 4-cyclopentylamino-8-methoxy-quinoline-3-carboxylic acid ethyl ester (0.10 mmol) and phenyl isocyanate (0.4 mmol) following general procedure C. LCMS: m/z 388 [M+1]+.
Reaction SMILES: Cl.[F:2][C:3]1[CH:4]=[C:5]([S:9]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][NH:23][CH3:24])[CH2:17][CH2:16][CH2:15]3)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.[CH3:25][S:26](Cl)(=[O:28])=[O:27]>C(Cl)Cl.N1C=CC=CC=1>[F:2][C:3]1[CH:4]=[C:5]([S:9]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][N:23]([CH3:24])[S:26]([CH3:25])(=[O:28])=[O:27])[CH2:17][CH2:16][CH2:15]3)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1
Reactant: CNC[C@@H]1CCCc2cc(S(=O)(=O)c3cccc(F)c3)ccc21
Reactant: CS(=O)(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CN(C[C@@H]1CCCc2cc(S(=O)(=O)c3cccc(F)c3)ccc21)S(C)(=O)=O
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
[(R)-6-(3-Fluoro-benzenesulfonyl)-1,2,3,4-tetrahydro-naphthalen-1-ylmethyl]-methyl-amine hydrochloride (0.4 g, 1.13 mmol) was dissolved in 10 mL methylene chloride and 2.0 mL pyridine, and the mixture was cooled in an ice bath. Methanesulfonyl chloride (0.2 mL) was added dropwise, and the reaction mixture was stirred for 10 minutes at ice bath temperature, then allowed to warm to room temperature. The reaction mixture was quenched by addition of water, and was extracted with methylene chloride. The organic layer was washed with 1% aqueous HCl, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was eluted through silica gel at medium pressure with 1:1: EtOAc/hexanes to give 310 mg of N—[(R)-6-(3-Fluoro-benzenesulfonyl)-1,2,3,4-tetrahydro-naphthalen-1-ylmethyl]-N-methyl-methanesulfonamide, M+H=412.
Reaction SMILES: [C@@H:1]1([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.O[N:19]1[C:23](=[O:24])[C:22]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:21]2[C:20]1=[O:29].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>CN(C=O)C>[C:23]1(=[O:24])[N:19]([O:7][CH2:6][C@H:5]2[O:8][C@@H:1]([N:9]3[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]3=[O:11])[CH2:2][C@@H:3]2[OH:4])[C:20](=[O:29])[C:21]2=[CH:28][CH:27]=[CH:26][CH:25]=[C:22]12
Reactant: Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Reactant: O=C1c2ccccc2C(=O)N1O
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: Cc1cn([C@H]2C[C@H](O)[C@@H](CON3C(=O)c4ccccc4C3=O)O2)c(=O)[nH]c1=O
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a stirred solution of thymidine (24.22 g, 0.1 mol), N-hydroxyphthalimide (21.75 g, 0.13 mol), triphenylphosphine (34 g, 0.13 mol) in dry DMF (400 ml) was added diisopropylazodicarboxylate (30 ml, 0.15 mol) over a period of 3 h at 0° C. After complete addition the reaction mixture was warmed up to room temperature and stirred for 12 h. The solution was concentrated under vacuum (0.1 mm, <40° C.) to furnish an orange-red residue. The residual gum was washed several times with Et2O and washing were discarded. The semi-solid residue was suspended in EtOH (500 ml) and heated (90° C.) to dissolve the product. On cooling 30.98 g (80%) of 5′-O-phthalimidothymidine was collected in 3-crops as white crystalline material, mp 233-235° C. (decomp.); H NMR (DMSO-d6) δ 11.29 (s, 1, NH), 7.85 (m , 4, ArH), 7.58 (s, 1, C6H), 6.20 (t, 1, H1′, J1′,2′=7.8 Hz, J11′,2″=6.5 Hz), 5.48 (d, 1, OH3′), 4.36 (m, 3, H4′,5′,5″), 4.08 (m, 1, H3′), 2.09-2.13 (m, 2, H2′,2″), and 1.79 (s, 3, CH3). Anal. Calcd. for C18H17O7N3.0.7 H2O: C, 54.05; H, 4.64; N, 10.51. Found: C, 53.81; H, 4.25; N, 10.39.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12](=[O:25])[C:13]2[CH:18]=[CH:17][C:16]([CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[CH:15][CH:14]=2)[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:26][C:27]1([CH3:34])[CH2:32][C:31](=[O:33])[O:30][C:28]1=[O:29].C(C1C=C(NC(C2C=CC(N3CCN(C(=O)CC(C)(C)C(O)=O)CC3)=NC=2)=O)C=CC=1)(C)(C)C>>[C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12]([C:13]2[CH:14]=[CH:15][C:16]([CH:19]3[CH2:24][CH2:23][N:22]([C:31](=[O:33])[CH2:32][C:27]([CH3:34])([CH3:26])[C:28]([OH:30])=[O:29])[CH2:21][CH2:20]3)=[CH:17][CH:18]=2)=[O:25])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC1(C)CC(=O)OC1=O
Reactant: CC(C)(C)c1cccc(NC(=O)c2ccc(C3CCNCC3)cc2)c1
Agent: CC(C)(CC(=O)N1CCN(c2ccc(C(=O)Nc3cccc(C(C)(C)C)c3)cn2)CC1)C(=O)O
Product: CC(C)(CC(=O)N1CCC(c2ccc(C(=O)Nc3cccc(C(C)(C)C)c3)cc2)CC1)C(=O)O

Procedure:
4-{4-[4-(3-tert-Butyl-phenylcarbamoyl)-phenyl]-piperidin-1-yl}-2,2-dimethyl-4-oxo-butyric acid was synthesized from N-(3-tert-butyl-phenyl)-4-piperidin-4-yl-benzamide and 2,2-dimethylsuccinic anhydride in a method similar to the one described in the synthesis of 4-{4-[5-(3-tert-butyl-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-2,2-dimethyl-4-oxo-butyric acid above. LCMS calcd for C28H36N2O4 (m/e) 464, obsd 465 (M+H).
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].[C:16]([C:20]1[CH:21]=[C:22](O)[CH:23]=[C:24]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:25]=1)([CH3:19])([CH3:18])[CH3:17]>N1C=CC=CC=1>[O:6]([C:22]1[CH:21]=[C:20]([C:16]([CH3:18])([CH3:17])[CH3:19])[CH:25]=[C:24]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:23]=1)[S:3]([C:2]([F:15])([F:14])[F:1])(=[O:5])=[O:4]
Reactant: CC(C)(C)c1cc(O)cc(C(C)(C)C)c1
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: c1ccncc1
Product: CC(C)(C)c1cc(OS(=O)(=O)C(F)(F)F)cc(C(C)(C)C)c1
Temperature: 25 °C

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: [NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([O:13]C)[CH:8]=2)[S:4][C:3]=1[C:15]([NH2:17])=[O:16].C[Si]([N:22]=[C:23]=[O:24])(C)C.CN(C)C=O>ClCCl>[NH2:22][C:23]([NH:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([OH:13])[CH:8]=2)[S:4][C:3]=1[C:15]([NH2:17])=[O:16])=[O:24]
Reactant: COc1cccc(-c2cc(N)c(C(N)=O)s2)c1
Reactant: C[Si](C)(C)N=C=O
Solvent: ClCCl
Solvent: CN(C)C=O
Product: NC(=O)Nc1cc(-c2cccc(O)c2)sc1C(N)=O
Reaction time: 72 h

Procedure:
3-Amino-5-(3-methoxyphenyl)-2-thiophenecarboxamide (0.5 g), trimethylsilylisocyanate (2 mL), dimethylformamide (2 mL) and dichloromethane were heated at reflux for 3 days. After cooling the solid was filtered off, suspended in dichloromethane (100 mL) and treated with boron tribromide (5 mL of a 1M solution in dichloromethane). After 3 days. methanol (50 mL) was added. After 1 h, the solvent was evaporated and the residue was triturated with 2M hydrochloric acid. The title urea was filtered off (0.35 g).