Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[CH3:10][C:11]1([CH3:19])[O:18][C:16](=[O:17])[CH2:15][C:13](=[O:14])[O:12]1.N1CCCC1C(O)=O.[F:28][C:29]1[C:37]([CH2:38][S:39][CH3:40])=[C:36]2[C:32]([CH:33]=[CH:34][NH:35]2)=[CH:31][CH:30]=1>C(#N)C>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]([C:33]2[C:32]3[C:36](=[C:37]([CH2:38][S:39][CH3:40])[C:29]([F:28])=[CH:30][CH:31]=3)[NH:35][CH:34]=2)[CH:15]2[C:16](=[O:17])[O:18][C:11]([CH3:19])([CH3:10])[O:12][C:13]2=[O:14])=[CH:4][CH:3]=1
Reactant: CC1(C)OC(=O)CC(=O)O1
Reactant: CSCc1c(F)ccc2cc[nH]c12
Reactant: O=Cc1ccc(Cl)cc1
Agent: O=C(O)C1CCCN1
Solvent: CC#N
Product: CSCc1c(F)ccc2c(C(c3ccc(Cl)cc3)C3C(=O)OC(C)(C)OC3=O)c[nH]c12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1.44 g (10.24 mmol) of 4-chlorobenzaldehyde, 1.48 g (10.24 mmol) of Meldrum's acid and 0.06 g (0.51 mmol) of D,L-proline were added to a solution of 2.00 g (10.24 mmol) of the compound from Example 9A in 15 ml of acetonitrile. The reaction mixture was stirred at RT overnight. The precipitated solid was filtered off with suction, washed with acetonitrile and dried under high vacuum. 3.32 g (67% of theory) of the title compound were obtained.
Reaction SMILES: C([Li])CCC.[CH2:6]([NH:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH2:7][CH2:8][CH3:9].[O:15]1[C:19]([CH3:26])([CH2:20][CH2:21][CH2:22][CH:23]([CH3:25])[CH3:24])[CH:16]1[CH2:17][OH:18]>O1CCCC1>[CH2:6]([N:10]([CH2:11][CH2:12][CH2:13][CH3:14])[CH:16]([C:19]([CH3:26])([OH:15])[CH2:20][CH2:21][CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:17][OH:18])[CH2:7][CH2:8][CH3:9]
Reactant: CC(C)CCCC1(C)OC1CO
Reactant: CCCCNCCCC
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCCCN(CCCC)C(CO)C(C)(O)CCCC(C)C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 79.7 %

Procedure:
Under nitrogen atmosphere, 65 ml of n-butyllithium (1.6 M in hexane) was added dropwise to a solution of 12.9 g of di-n-butylamine in 30 ml of tetrahydrofuran at -78° C. and after completion of addition, the mixture was stirred at 0° C. for 30 minutes. To this solution was added a solution of 8.6 g of 2,3-epoxy-3,7-dimethyl-1octanol in 20 ml of tetrahydrofuran slowly in portions at 0° C. The mixture was then stirred at room temperature for 2 hours, after which it was poured into ice-water and extracted with diethyl ether. The extract was washed with water and after drying over anhydrous magnesium sulfate, the solvent was distilled off. The residue was further distilled under reduced pressure to give 12 g of 2-(dibutylamino)-3,7-dimethyl-1,3-octanediol [Compound (59)]. Yield 80%. ##STR195##
Reaction SMILES: [C:1]([CH:5]([NH:12][NH:13][C:14](=[O:24])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[C:16]=1[CH3:23])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])([CH3:4])([CH3:3])[CH3:2].[CH3:25][C:26]1[CH:27]=[C:28]([CH:32]=[C:33]([CH3:35])[CH:34]=1)[C:29](Cl)=[O:30].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[C:1]([CH:5]([N:12]([C:29](=[O:30])[C:28]1[CH:32]=[C:33]([CH3:35])[CH:34]=[C:26]([CH3:25])[CH:27]=1)[NH:13][C:14](=[O:24])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[C:16]=1[CH3:23])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCCCCCC(NNC(=O)c1cccc(OC)c1C)C(C)(C)C
Reactant: Cc1cc(C)cc(C(=O)Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: CCCCCCC(N(NC(=O)c1cccc(OC)c1C)C(=O)c1cc(C)cc(C)c1)C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 85.9 %

Procedure:
164 mg (0.49 mmol) of 3-methoxy-2-methyl-benzoic acid N′-(1-tert-butyl-heptyl)-hydrazide and 82 mg 3,5-dimethylbenzoyl chloride were dissolved in 10 mL CH2Cl2. 7 mL of 25% K2CO3 were added, and the reaction mixture was stirred at room temperature overnight. The reaction was monitored by TLC. The phases were separated, adding additional CH2Cl2 and/or water as needed to aid manipulation. The CH2Cl2 layer was dried and solvent was removed in vacuo to provide 240 mg of crude product. This material was purified by silica gel column chromatography, eluting with a step gradient of 5-20% ethyl acetate in hexane. The desired product eluted in the 15% ethyl acetate fraction, TLC Rf=0.62 (1:1 ethyl acetate:hexane), to yield 195 mg 3,5-dimethyl-benzoic acid N-(1-tert-butyl-heptyl)-N′-(3-methoxy-2-methyl-benzoyl)-hydrazide. 1H NMR (500 MHz, CDCl3) δ (ppm): 7.2 (s, NH), 7.05 (s, 2H), 7.03 (m, 1H), 7.01 (s, 1H), 6.83 (d, 1H), 6.25 (d, 1H), 4.67 (d, 1H), 3.81 (s, 3H), 2.28 (s, 6H), 1.79 (s, 3H), 1.55 (br m, 2H), 1.3 (br, 8H), 1.34+1.07 (s+s, 9H), 0.089 (br s, 3H).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])=[CH:4][CH:3]=1.[CH:16]1[CH:21]=[CH:20][CH:19]=[C:18]2[NH:22][C:23]3[C:24](=[CH:25][C:26]4[NH:27][C:28]5[C:33]([C:34]=4[CH:35]=3)=[CH:32][CH:31]=[CH:30][CH:29]=5)[C:17]=12.C1O[CH2:52][CH2:51]OCCOCCOCCOCCOC1.C([O-])([O-])=O.[K+].[K+]>O1CCCC1.[Cu].ClC1C=CC=CC=1Cl>[CH2:8]([C:5]1[CH:6]=[CH:7][C:2]([N:27]2[C:26]3[C:34](=[CH:35][C:23]4[N:22]([C:2]5[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:51][CH3:52])=[CH:6][CH:7]=5)[C:18]5[C:17]([C:24]=4[CH:25]=3)=[CH:16][CH:21]=[CH:20][CH:19]=5)[C:33]3[C:28]2=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:3][CH:4]=1)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: c1ccc2c(c1)[nH]c1cc3c(cc12)[nH]c1ccccc13
Reactant: C1COCCOCCOCCOCCOCCO1
Reactant: CCCCCCCCc1ccc(I)cc1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Clc1ccccc1Cl
Solvent: C1CCOC1
Product: CCCCCCCCc1ccc(-n2c3ccccc3c3cc4c(cc32)c2ccccc2n4-c2ccc(CCCCCCCC)cc2)cc1
Temperature: 25 °C
Yield: 359.2 %

Procedure:
A mixture of 1-iodo-4-octylbenzene (16.09 g, 35.1 mmol, 69% of purity) as prepared above, 5,11-dihydridoindolo[3,2-b]carbazole (3.00 g, 11.7 mmol), 18-crown-6 (0.62 g, 2.34 mmol), K2CO3 (12.94 g, 93.6 mmol), copper (2.97 g, 46.8 mmol), and 1,2-dichlorobenzene (50 mL) was charged into an argon-filled 200 mL flask fitted with a condenser. The mixture was heated under reflux in an argon atmosphere for 24 h. Subsequently, the reaction mixture was cooled down to room temperature, diluted with tetrahydrofuran, and filtered. A viscous liquid, obtained after removal of solvent on a rotary evaporator, was added to 400 mL of methanol with vigorous stirring. The precipitated yellow solid was filtered, washed several times with water and methanol, dissolved in 400 mL of hexane by heating, and filtered to remove the insoluble impurities. The filtrate was concentrated to about 50 mL and allowed to cool down to room temperature, and then chilled at 0° C. overnight. The crystallized yellow product was filtered, washed with a small amount of hexane, and dried to yield 5.32 g of 5,11-bis(4-octylphenyl)indolo[3,2-b]carbazole, compound (2), which was subject to train sublimation to obtain electrically pure compound for OTFT fabrication. DSC showed a melting point at 131° C. on first heating. 1H NMR (CDCl3): δ 8.12 (d, J=7.6 Hz, 2H), 8.05 (s, 2H), 7.58 (d, J=8.3 Hz, 4H), 7.47 (d, J=8.3 Hz, 4H), 7.39-7.40 (m, 4H), 7.19-7.21 (m, 2H), 2.78 (t, J=7.8 Hz, 4H), 1.78 (pent, J=7.4 Hz, 4H), 1.30-1.50 (m, 20H), 0.92 (m, 6H); IR (NaCl): 3047, 2956, 2923, 2852, 1517, 1451, 1324, 1236, 842, 731 cm−1.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([OH:12])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[CH:13]1(O)[CH2:17][CH2:16][CH2:15][CH2:14]1.[N:19]1[C:27]2[C:22](=[N:23][CH:24]=[CH:25][CH:26]=2)[S:21][C:20]=1[NH2:28]>>[CH:13]1([O:12][C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[N:5]=[CH:4][N:3]=[C:2]3[NH:28][C:20]2[S:21][C:22]3[C:27]([N:19]=2)=[CH:26][CH:25]=[CH:24][N:23]=3)[CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: Nc1nc2cccnc2s1
Reactant: OC1CCCC1
Reactant: Oc1ccc2ncnc(Cl)c2c1
Product: c1cnc2sc(Nc3ncnc4ccc(OC5CCCC5)cc34)nc2c1

Procedure:
The compound of Example 26 was manufactured by the same method as in Example 22, by a similar method thereto or by a combination of such a method with a conventional method using 4-chloro-6-hydroxy-quinazoline, cyclopentanol and thiazolo[5,4-b]pyridin-2-yl-amine.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[OH:12])[C:7]#[N:8])(=[O:3])[CH3:2].[OH-].[Na+]>C1(C)C=CC=CC=1.C(C(CC)=O)C.N1CCCC1>[CH2:1]([C:4]1([CH2:11][CH3:10])[CH2:2][C:1](=[O:3])[C:4]2[CH:5]=[C:6]([C:7]#[N:8])[CH:9]=[CH:10][C:11]=2[O:12]1)[CH3:2]
Reactant: CC(=O)c1cc(C#N)ccc1O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCNC1
Solvent: CCC(=O)CC
Solvent: Cc1ccccc1
Product: CCC1(CC)CC(=O)c2cc(C#N)ccc2O1
Temperature: 25 °C

Procedure:
A solution of 16,1 g of 3-acetyl-4-hydroxybenzonitrile in 200 ml of toluene, 21 ml of diethylketone and 10 ml of pyrrolidin is refluxed for 31/2 hours in a Dean-Stark apparatus. The reaction solution cooled to room temperature is made alkaline with a 2N aq. sodium hydroxide solution and extracted with dichloroethane. The combined organic phases are washed with sodium hydroxidesolution and water, dried over sodiumsulfate and concentrated. The obtained residue is chromatographed on silica gel/dichloromethane. Recristallisation of the eluate from ether/hexane yields 2,2-diethyl-3,4-dihydro-4-oxo-2H-1-benzopyran-6-carbonitrile having a m.p. of 71°-72° C.
Reaction SMILES: [C:1]([CH2:9][CH:10]([CH3:21])[C:11]([N:13]1[CH2:20][CH2:19][CH2:18][C@H:14]1[C:15]([OH:17])=[O:16])=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)C.[Br:26]Br.CCCCCC>ClCCl>[C:1]([CH:9]([Br:26])[CH:10]([CH3:21])[C:11]([N:13]1[CH2:20][CH2:19][CH2:18][C@H:14]1[C:15]([OH:17])=[O:16])=[O:12])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: BrBr
Reactant: CC(CC(=O)c1ccccc1)C(=O)N1CCC[C@H]1C(=O)O
Solvent: CCCCCC
Solvent: ClCCl
Solvent: CC(=O)O
Product: CC(C(=O)N1CCC[C@H]1C(=O)O)C(Br)C(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a mixture of 1.25 g. of 1-(3-benzoyl-2-methylpropionyl)-L-proline (isomer A of Example 9) in 30 ml. of acetic acid, is added 0.7 g. of bromine in 10 ml. of acetic acid. The mixture is stirred at room temperature for 18 hours, the solvent is concentrated in vacuo to 1/2 volume and the mixture is poured into ice and water. This mixture is extracted with dichloromethane. The organic extract is washed with water, then sodium chloride solution, dried over magnesium sulfate and the solvent is removed in vacuo giving a gum. This gum is dissolved in dichloromethane, hexane is added and the solvent is removed at room temperature giving a white glass. This glass is chromatographed on a silica gel column with ethyl acetate-hexane-acetic acid (75:25:2) giving 1.25 g. of the desired product as a white glass (3-bromo derivative of isomer A).
Reaction SMILES: [I:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH2:8]2)=[CH:4][C:3]=1[CH:11]=[O:12].[BH4-].[Na+]>CCO>[I:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH2:8]2)=[CH:4][C:3]=1[CH2:11][OH:12]
Reactant: O=Cc1cc2c(cc1I)CCC2
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: OCc1cc2c(cc1I)CCC2
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 6-iodoindane-5-carbaldehyde (35.5 mg, 0.131 mmol) in anhydrous EtOH (3 mL) under N2 at 0° C., was added sodium borohydride (20 mg, 0.522 mmol) as a powder. The mixture was warmed to room temperature and stirred for 0.5 h. The mixture was quenched with water. The aqueous layer was extracted with EtOAc (3×). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (Si, hexanes/EtOAc) to afford (6-iodo-2,3-dihydro-1H-inden-5-yl)methanol. 1H NMR (500 MHz, CDCl3) δ 7.70 (s, 1H), 7.33 (s, 1H), 4.68 (d, J=6.3 Hz, 2H), 2.92-2.88 (m, 4H), 2.12-2.06 (m, 2H), 1.96 (t, J=6.4 Hz, 1H).
Reaction SMILES: [C:1]([CH:4]1[C:13]2([CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]2)[O:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]1=O)(=O)[CH3:2].[NH2:27][N:28](C)[C:29](=O)OC(C)(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[ClH:49]>C(O)C>[ClH:49].[ClH:49].[CH3:29][N:28]1[C:5]2[C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[O:12][C:13]3([CH2:14][CH2:15][NH:16][CH2:17][CH2:18]3)[C:4]=2[C:1]([CH3:2])=[N:27]1
Reactant: CN(N)C(=O)OC(C)(C)C
Reactant: CC(=O)C1C(=O)c2ccccc2OC12CCN(C(=O)OC(C)(C)C)CC2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cl
Solvent: O
Solvent: CCO
Product: Cc1nn(C)c2c1C1(CCNCC1)Oc1ccccc1-2
Temperature: 80 °C
Reaction time: 1 h

Procedure:
A mixture of tert-butyl 3-acetyl-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (250 mg, 0.70 mmol), tert-butyl N-amino-N-methyl-carbamate (120 μL, 0.84 mmol) and p-toluene sulfonic acid monohydrate (27 mg, 0.14 mmol) in ethanol (8 mL) was heated at 80° C. overnight. Additional tert-butyl N-amino-N-methyl-carbamate (120 μL, 0.84 mmol) was added and the mixture was heated at 80° C. for 6.5 h, then another portion of tert-butyl N-amino-N-methyl-carbamate (120 μL, 0.84 mmol) was added and the mixture was heated at 80° C. for 2 h. HCl (0.87 mL of 4.0 M in dioxane, 3.5 mmol) was added and the mixture was stirred at 80° C. for 1 h. After cooling, the precipitate was collected via filtration and washed with cold EtOH to provide 1,3-dimethyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine] dihydrochloride (295 mg, >100%, may contain some methyl hydrazine HCl salt) as a solid. ESI-MS m/z calc. 269.2, found 270.5 (M+1)+; Retention time: 1.11 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 7.71 (dd, J=7.8, 1.3 Hz, 1H), 7.33-7.27 (m, 1H), 7.17-7.14 (m, 1H), 7.11-7.05 (m, 1H), 4.02 (s, 3H), 3.28-3.15 (m, 4H), 2.40-2.30 (m, 2H), 2.23 (s, 3H), 2.07-1.97 (m 2H).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([OH:12])=O.[C:13]([O:17][C:18](=[O:26])[N:19]([CH3:25])[CH:20]1[CH2:24][CH2:23][NH:22][CH2:21]1)([CH3:16])([CH3:15])[CH3:14].C1N=CN(C(N2C=NC=C2)=O)C=1>C1COCC1>[C:13]([O:17][C:18](=[O:26])[N:19]([CH:20]1[CH2:24][CH2:23][N:22]([C:10]([C:2]2[NH:1][C:9]3[C:4]([CH:3]=2)=[CH:5][CH:6]=[CH:7][CH:8]=3)=[O:12])[CH2:21]1)[CH3:25])([CH3:16])([CH3:14])[CH3:15]
Reactant: CN(C(=O)OC(C)(C)C)C1CCNC1
Reactant: O=C(O)c1cc2ccccc2[nH]1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CN(C(=O)OC(C)(C)C)C1CCN(C(=O)c2cc3ccccc3[nH]2)C1
Reaction time: 18 h
Yield: 82.3 %

Procedure:
To a solution of indole-2-carboxylic acid (388 mg, 2.40 mmol) and methyl-pyrrolidin-3-yl-carbamic acid tert-butyl ester (401 mg, 2.00 mmol) in THF (16 mL) was added CDI (356 mg, 2.20 mmol). After 18 h at rt, the mixture was concentrated, diluted with CH2Cl2, washed with satd. aq. Na2CO3 and water, dried (Na2SO4), and concentrated. The residue was purified by FCC to give the title compound (565 mg, 69%). MS (ESI): mass calcd. for C19H25N3O3, 343.19; m/z found, 344 [M+H]+. 1H NMR (CDCl3): 9.73 (s, 1H), 7.67 (d, J=8.0, 1H), 7.46 (dd, J=8.3, 0.8, 1H), 7.29 (t, J=8.2, 1H), 6.89 (d, J=1.3, 1H), 4.89 (br s, 1H), 4.26-3.49 (m, 4H), 2.85 (s, 3H), 2.36-1.96 (m, 2H), 1.76 (s, 1H), 1.49 (s, 9H). Anal. Calcd for C19H25N3O3: C, 66.45; H, 7.34; N, 12.24. Found: C, 66.42; H, 7.55; N, 12.10.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2([C:14]3[CH:24]=[CH:23][C:17]4[O:18][C:19]([F:22])([F:21])[O:20][C:16]=4[CH:15]=3)[CH2:13][CH2:12]2)=[O:10])[CH:5]=[CH:4][C:3]=1[CH3:25].[OH:26][C:27]1[CH:28]=[C:29]([CH:34]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:36]=1)[C:30]([O:32][CH3:33])=[O:31].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:21][C:19]1([F:22])[O:18][C:17]2[CH:23]=[CH:24][C:14]([C:11]3([C:9]([NH:8][C:6]4[N:7]=[C:2]([C:35]5[CH:34]=[C:29]([CH:28]=[C:27]([OH:26])[CH:36]=5)[C:30]([O:32][CH3:33])=[O:31])[C:3]([CH3:25])=[CH:4][CH:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20]1
Reactant: Cc1ccc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)nc1Cl
Reactant: COC(=O)c1cc(O)cc(B2OC(C)(C)C(C)(C)O2)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: COC(=O)c1cc(O)cc(-c2nc(NC(=O)C3(c4ccc5c(c4)OC(F)(F)O5)CC3)ccc2C)c1
Temperature: 120 °C
Yield: 97.9 %

Procedure:
N-(6-Chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (130 mg, 0.36 mmol) was dissolved in 1,2-dimethoxyethane (3.6 mL) in a reaction tube. Methyl 3-hydroxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (150 mg, 0.55 mmol), aqueous 2 M sodium carbonate (0.37 mL), and (Ph3P)4Pd (21 mg, 0.018 mmol) were added and the reaction mixture was heated at 120° C. for 30 minutes in the microwave. The resulting material was cooled to room temperature, filtered, dried over Na2SO4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (0-30% ethyl acetate in hexane) to yield methyl 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclo-propanecarboxamido)-3-methylpyridin-2-yl)-5-hydroxybenzoate (170 mg, 99%) as a white solid. ESI-MS m/z calc. 482.1, found 483.53 (M+1)+. Retention time 1.83 minutes.
Reaction SMILES: [CH:1]1[C:6]([NH2:7])=[CH:5][CH:4]=[C:3]([NH2:8])[CH:2]=1.[CH2:9](Br)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26].[OH-].[Na+]>O>[CH2:9]([NH:7][C:6]1[CH:5]=[CH:4][C:3]([NH:8][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH3:9])=[CH:2][CH:1]=1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: Nc1ccc(N)cc1
Reactant: CCCCCCCCCCCCCCCCCCBr
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCCCCCCCCCCCCCCCNc1ccc(NCCCCCCCCCCCCCCCCCC)cc1
Yield: 40.7 %

Procedure:
A mixture of 15.6 g of p-phenylenediamine, 15.5 g of stearyl bromide, and 1.96 g of powdered sodium hydroxide was heated to 140° to 150° C. for about 3.5 hours with stirring under nitrogen gas stream. After the reaction was over, 50 ml of water was poured to the reaction mixture and black-purple solids thus formed were recovered by filtration. When the solids were washed with water, ethanol, and methylene chloride and filtered to provide about 5.8 g of a pink powder of N,N'-distearyl-p-phenylenediamine. The structure was confirmed by 1HNMR, IR spectra, and elemental analysis.
Reaction SMILES: C(N(CC)CCC(=O)CCCC1C=CC=[C:12]([O:16]C)[CH:11]=1)C.[O:21]=N.N1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1C=CC=CC=1>[CH3:24][CH:25]1[C:12](=[O:16])[CH2:11][CH2:28][CH2:27][C:26]1=[O:21]
Reactant: c1ccncc1
Reactant: CCN(CC)CCC(=O)CCCc1cccc(OC)c1
Reactant: N=O
Solvent: c1ccccc1
Product: CC1C(=O)CCCC1=O

Procedure:
Add to the crude undistilled ketoamine 1-diethylamino-6-(m-methoxyphenyl)hexan-3-one (2.3 g), the material obtained by hydration of the acetylenic amine, 2-methylcyclohexane-1,3-dione (1 g), pyridine (1 cc) and benzene (12 cc), and reflux the mixture for 15 hours. Cool the mixture and filter off unreacted dione, add a little ether to the filtrate, and wash the ethereal solution with acid, and then water, and dry. Evaporate the solvents to obtain as residue crude 2-(6-m-methoxyphenyl-3-oxohexyl)-2-methylcyclohexane-1,3-dione (1.7 g).
Reaction SMILES: [Cl:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[CH2:21][CH2:20][C:19]3[C:14](=[CH:15][C:16]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:17][CH:18]=3)[CH:13]=2)=[O:11])=[CH:5][CH:4]=1.[C:28]([C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1)#[N:29]>CN(C=O)C>[Cl-:1].[C:28]([C:30]1[CH:35]=[CH:34][N+:33]([CH2:2][C:3]2[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]3[CH2:21][CH2:20][C:19]4[C:14](=[CH:15][C:16]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)=[CH:17][CH:18]=4)[CH:13]=3)=[O:11])=[CH:5][CH:4]=2)=[CH:32][CH:31]=1)#[N:29]
Reactant: N#Cc1ccncc1
Reactant: O=C(Nc1ccc(CCl)cc1)C1=Cc2cc(-c3ccccc3)ccc2CC1
Solvent: CN(C)C=O
Product: N#Cc1cc[n+](Cc2ccc(NC(=O)C3=Cc4cc(-c5ccccc5)ccc4CC3)cc2)cc1
Product: [Cl-]
Reaction time: 24 h
Yield: 78.8 %

Procedure:
In DMF (3 ml) was dissolved N-[4-(chloromethyl)-phenyl]-7-phenyl-3,4-dihydronaphthalene-2-carboxamide (140 mg), and to the mixture was added 4-cyanopyridine (117 mg). The mixture was stirred at 70° for 24 hours and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-methanol to give 4-cyano-1-[4-(7-phenyl-3,4-dihydro-naphthalene-2-carboxamido)benzyl]pyridinium chloride (Compound 21) (141 mg) as pale brown crystals.
Reaction SMILES: CS[C:3]([NH:8][CH2:9][CH2:10][S:11][CH2:12][CH:13]=[C:14]([CH3:31])[CH2:15][CH2:16][CH:17]=[C:18]([CH3:30])[CH2:19][CH2:20][CH:21]=[C:22]([CH3:29])[CH2:23][CH2:24][CH:25]=[C:26]([CH3:28])[CH3:27])=[CH:4][N+:5]([O-:7])=[O:6].[CH3:32][NH2:33]>>[CH3:32][NH:33][C:3]([NH:8][CH2:9][CH2:10][S:11][CH2:12][CH:13]=[C:14]([CH3:31])[CH2:15][CH2:16][CH:17]=[C:18]([CH3:30])[CH2:19][CH2:20][CH:21]=[C:22]([CH3:29])[CH2:23][CH2:24][CH:25]=[C:26]([CH3:28])[CH3:27])=[CH:4][N+:5]([O-:7])=[O:6]
Reactant: CN
Reactant: CSC(=C[N+](=O)[O-])NCCSCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C
Product: CNC(=C[N+](=O)[O-])NCCSCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C
Temperature: 20 °C
Reaction time: 0.5 h
Yield: 96.7 %

Procedure:
2-Methylthio-1-nitro-2-[2-(3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraen-1-ylthio)ethylamino]ethylene [12.5 g, 26.8 mmol, prepared as described in Item a)] was dissolved in 40% methylamine solution (134 ml, 1.34 mol, 40% methanol solution) and stirred at 20° C. for 30 minutes. The reaction mixture was evaporated in vacuo to dryness. The remaining residue was chromatographed on silica gel, eluting with CH2Cl2 /MeOH (30:1) to afford 11.6 g (96.7%) of the desired compound, as a pale yellow oil.
Reaction SMILES: [Cl:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[N:4][N:3]=1.[N+:13]([O-])([OH:15])=[O:14]>>[Cl:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][CH:8]=2)[N:5]=[N:4][N:3]=1
Reactant: O=[N+]([O-])O
Reactant: Clc1nnnn1-c1ccccc1
Product: O=[N+]([O-])c1ccc(-n2nnnc2Cl)cc1
Temperature: 65 °C
Yield: 87 %

Procedure:
5-Chloro-1-phenyl-1H-tetrazole (500 g, 2.78 mol) was carefully added in one portion to stirred white fuming nitric acid (91.5% HNO3, 2.5 L). The internal temperature of the mixture increased steadily to 65° C. then fell. An aliquot was removed and partitioned between water and dichloromethane. TLC analysis (80:20 hexanes/ethyl acetate) indicated consumption of starting material. The mixture was carefully poured into stirred ice (3 L), water (2 L) and dichloromethane (2 L). The layers were separated and the aqueous was extracted with dichloromethane (2 L). The combined organic phase was washed with 5% aqueous sodium bicarbonate solution (1 L), dried (MgSO4), filtered, and concentrated to a solid. The solid was mixed with 90:10 hexanes/ethyl acetate (3 L) and heated to 65° C. The mixture was cooled overnight (2-5° C.). Filtration afforded a white crystalline solid (544 g, 87%). 1H NMR (CDCl3, 300 MHz) δ 8.51 (d, 9.5 Hz, 2 H), 7.91 (d, 8.8 Hz, 2 H); mp 96.5° C.; Rf =0.2 (K).