Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: IC.[Cl:3][C:4]1[C:5]([CH3:13])=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([OH:9])=[O:8].[C:14](=O)([O-])[O-].[K+].[K+].CN(C)C=O>C(OCC)(=O)C.O>[Cl:3][C:4]1[C:5]([CH3:13])=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([O:9][CH3:14])=[O:8]
Reactant: Cc1c(Cl)cccc1C(=O)O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1cccc(Cl)c1C
Reaction time: 0.5 h
Yield: 94.7 %

Procedure:
Iodomethane (1.96 ml, 31.5 mmol) was added to a mixture of 3-chloro-2-methylbenzoic acid (3.58 g, 21 mmol), potassium carbonate (5.8 g, 42 mmol) and N,N-dimethylformamide (35.9 ml), followed by stirring at mom temperature for 18 hours and 30 minutes. Water and ethyl acetate were added to the reaction liquid, and the organic layer was extracted. The organic layer was sequentially washed with a saturated aqueous ammonium chloride solution and brine, and then dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate) to give the title compound (3.67 g, yield: 97%).
Reaction SMILES: C[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]=[CH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[CH2:16](Cl)Cl>[Ir]>[C:10]1([CH2:9][CH:8]([C:3]2[CH:2]=[CH:7][CH:6]=[CH:5][CH:4]=2)[CH3:16])[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: Cc1ccccc1C=Cc1ccccc1
Reactant: ClCCl
Agent: [Ir]
Product: CC(Cc1ccccc1)c1ccccc1
Yield: 94 %

Procedure:
According to the general procedure, a solution of methyl stilbene (57 mg, 0.29 mmol) and iridium catalyst (S)-32 (9.4 mg, 0.0060 mmol, 2.0 mol %) in CH2Cl2 (3 mL) was hydrogenated. Removal of the solvent in vacuo and standard purification gave 33 (54 mg, 94%) as a colorless oil; [α]20D −55.2 (c 1.00, CHCl3); Chiral GC analysis (Chirasil DEX-CB; program: 100° C. for 5 min, the 0.5° C./min to 140° C. for 5 min, then 2° C./min to 180° C. for 10 min) determined a 86:14 er (72% ee) [tR(minor) 66.26 min, tR(major) 66.66 min]; 1H NMR (300 MHz, CDCl3) 7.37-7.30 (m, 3H), 7.24-7.20 (m, 2H), 7.14 (d, 2H, J=7.2 Hz), 3.13-2.98 (m, 2H), 2.82 (q, 1H, J=7.8 Hz), 1.31 (d, 3H, J=6.6 Hz) ppm; 13C NMR (75 MHz, CDCl3) 147.0, 140.8, 129.1, 128.3, 128.1, 127.0, 126.0, 125.8, 45.0, 41.8, 21.1 ppm.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18](/[C:21](/[CH3:25])=[CH:22]/[CH:23]=O)=[CH:17][CH:16]=1.[C:26]([CH2:28]P(=O)(OCC)OCC)#[N:27]>>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18](/[C:21](/[CH3:25])=[CH:22]/[CH:23]=[CH:28]/[C:26]#[N:27])=[CH:19][CH:20]=1
Reactant: C/C(=C\C=O)c1ccc(OCc2nc(-c3ccccc3)oc2C)cc1
Reactant: CCOP(=O)(CC#N)OCC
Product: C/C(=C\C=C\C#N)c1ccc(OCc2nc(-c3ccccc3)oc2C)cc1

Procedure:
According to the method described for Reference Example 35, (E)-3-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]-2-buten-1-al was allowed to react with diethyl cyanomethylphosphonate gave (E,E)-5-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]-2,4-hexadienenitrile. Recrystallization from ethyl acetate--hexane gave colorless prisms, m.p.134°-136° C.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](C(OC(C)(C)C)=O)[C:6]3[C:18](=[O:21])[CH2:19][CH2:20][C:5]=3[C:4]=2[C:3]=1[Cl:22].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[C:18](=[O:21])[CH2:19][CH2:20][C:5]=3[C:4]=2[C:3]=1[Cl:22]
Reactant: CC(C)(C)OC(=O)n1c2c(c3c(Cl)c(Cl)ccc31)CCC2=O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1CCc2c1[nH]c1ccc(Cl)c(Cl)c21
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 94.7 %

Procedure:
To a solution of tert-butyl 7,8-dichloro-3-oxo-2,3-dihydrocyclopenta[b]indole-4(1H)-carboxylate (intermediate 27c) (0.4 g, 1.1 mmol) in CH2Cl2 (10 mL), cooled to 0° C., TFA (1 mL) mL) was added. The reaction mixture was warmed to room temperature and stirred for 90 min., quenched with saturated NaHCO3 (pH-8) and extracted with CH2Cl2 (3×100 mL). The combined organic extracts were dried over Na2SO4 and concentrated in vacuo to give the crude compound. The crude material was purified by washing with 5% EtOAc-hexane (3×20 mL) to provide the title compound (250 mg, 89%). 1H NMR (500 MHz, DMSO-d6, δ in ppm) 12.16 (s, 1H), 7.48 (d, J=15.0 Hz, 1H), 7.42 (d, J=15.0 Hz, 1H), 3.19 (m, 2H), 2.92 (m, 2H).
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:9]1[C@@:13]2([CH3:29])[CH2:14][CH2:15][C@@H:16]3[C@@:21]4([CH3:27])[CH2:22][CH2:23][C@H:24]([OH:26])[CH2:25][C@:20]54[O:28][C@H:19]5[CH2:18][C@H:17]3[C@@H:12]2[CH2:11][CH2:10]1)[CH2:3][CH2:4][CH2:5][CH:6]([CH3:8])[CH3:7].FC(F)(F)C(O)=O.[CH2:37]([OH:40])[CH2:38][CH3:39]>>[CH2:37]([O:40][C@H:19]1[C@:20]2([OH:28])[C@:21]([CH3:27])([CH2:22][CH2:23][C@H:24]([OH:26])[CH2:25]2)[C@@H:16]2[C@H:17]([C@H:12]3[C@:13]([CH3:29])([CH2:14][CH2:15]2)[C@@H:9]([C@H:2]([CH3:1])[CH2:3][CH2:4][CH2:5][CH:6]([CH3:8])[CH3:7])[CH2:10][CH2:11]3)[CH2:18]1)[CH2:38][CH3:39]
Reactant: CCCO
Reactant: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3C[C@@H]4O[C@@]45C[C@@H](O)CC[C@]5(C)[C@H]3CC[C@]12C
Solvent: O=C(O)C(F)(F)F
Product: CCCO[C@@H]1C[C@H]2[C@@H]3CC[C@H]([C@H](C)CCCC(C)C)[C@@]3(C)CC[C@@H]2[C@@]2(C)CC[C@H](O)C[C@]12O

Procedure:
In a flask (50 ml) fitted with a condenser cholesterol 5α,6α-epoxide (100 mg., 0.25 mmol) in 1-propanol (20 ml) solution containing trifluoroacetic acid (1.0 ml) is refluxed for 1 hour. With vacuum evaporation the solvent is removed. The oily residue is dissolved in benzene (10 ml), extracted with 5% aqueous sodium bicarbonate (2 ml×2) and with water, and dried with anhydrous sodium sulfate. After vacuum evaporation the amorphous solid residue is purified by silica gel G-60 column liquid chromatography employing chloroform-methanol gradient elution. Selected fractions provide the product, 6β-n-propoxy-3β,5α-dihydroxycholestane. (45 mg).
Reaction SMILES: [CH3:1][C:2](=[CH:4][CH2:5][CH2:6]/[C:7](=[CH:9]/[CH:10]=[O:11])/[CH3:8])[CH3:3].CC(=CCC/C(=C\C=O)/C)C>>[CH3:1][C:2](=[CH:4][CH2:5][CH2:6][CH:7]([CH2:9][CH:10]=[O:11])[CH3:8])[CH3:3]
Reactant: CC(C)=CCC/C(C)=C/C=O
Agent: CC(C)=CCC/C(C)=C\C=O
Product: CC(C)=CCCC(C)CC=O

Procedure:
A-7) asymmetrically hydrogenating at least one of geranial and neral to thereby obtain an optically active citronellal having an optical purity of from 70 to 99% e.e.,
Reaction SMILES: OC([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([CH:15]([CH3:17])[CH3:16])[CH:8]=1)S(O)(=O)=O.[Na].O.C1(C)C=CC(S(O)(=O)=[O:27])=CC=1.OO.S(S([O-])=O)([O-])=O.[Na+].[Na+]>CO>[CH:15]([C:9]1[CH:8]=[C:7]([OH:27])[CH:12]=[CH:11][C:10]=1[O:13][CH3:14])([CH3:17])[CH3:16]
Reactant: COc1ccc(C(O)S(=O)(=O)O)cc1C(C)C
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=S([O-])S(=O)[O-]
Agent: OO
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COc1ccc(O)cc1C(C)C
Reaction time: 8 h
Yield: 66.7 %

Procedure:
A 22 L three-necked round bottom flask equipped with mechanical agitation was charged with hydroxy-(3-isopropyl-4-methoxyphenyl)methanesulfonic acid, sodium salt (1300 g, 4.61 moles), p-toluenesulfonic acid monohydrate (908 g, 4.77 moles), and methanol (10.4 L), and the mixture was cooled to 0° to SOC. Hydrogen peroxide (30% aqueous, 1.625 L, 16.12 moles) was added slowly to the reaction mixture over about 2 h. The reaction mixture was stirred overnight and allowed to return to room temperature. The completeness of the reaction was assayed by HPLC; if the reaction was incomplete, further hydrogen peroxide was added to the reaction mixture. The reaction mixture was cooled once more to 0° to 5° C. and then quenched by addition of an aqueous slurry of sodium dithionite (1860 g, 10.68 moles, stirred 1 h at room temperature in 6.5 L deionized water). After stirring at least 0.5 h, the reaction mixture was filtered, and the white solids were washed with ethyl acetate (8 L). The ethyl acetate and the aqueous filtrate were combined, agitated, and allowed to separate. Cyclohexane was added if necessary to facilitate separation. The organic phase was washed with sodium bicarbonate (4 L, 10% aqueous solution), then with saturated aqueous sodium chloride solution (4 L). The solvent was removed by vacuum distillation to afford 3-isopropyl-4-methoxyphenol (510 g, 66.7%).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]([NH:16][C:17]3[S:18][C:19]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:20]([C:22]4[O:23][CH:24]=[CH:25][CH:26]=4)[N:21]=3)=[O:15])[CH2:10][CH2:9]2)[CH:3]=1.[H][H]>C(O)C.[C].[Pd]>[O:23]1[CH:24]=[CH:25][CH:26]=[C:22]1[C:20]1[N:21]=[C:17]([NH:16][C:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:4]3[CH:3]=[CH:2][N:7]=[CH:6][N:5]=3)[CH2:13][CH2:12]2)=[O:15])[S:18][C:19]=1[N:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1
Reactant: O=C(Nc1nc(-c2ccco2)c(N2CCOCC2)s1)C1CCN(c2cc(Cl)ncn2)CC1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: O=C(Nc1nc(-c2ccco2)c(N2CCOCC2)s1)C1CCN(c2ccncn2)CC1
Yield: 76.7 %

Procedure:
Compound 51 (300 mg, 0.63 mmol) was dissolved in ethanol (10 mL), and 10% palladium-carbon (500 mg) was added thereto, followed by stirring in an atmosphere of hydrogen at room temperature for 4 hours. The reaction mixture was filtered through Celite, and the filtrate was distilled away under reduced pressure to afford the entitled Compound 52 (213 mg, 77%).
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH2:53]([NH:59][CH2:60][C:61]1[CH:73]=[CH:72][C:64]2[O:65][C:66]([CH3:71])([CH3:70])[O:67][C:68](=[O:69])[C:63]=2[CH:62]=1)[CH2:54][CH2:55][CH2:56][CH2:57][CH3:58]>C(Cl)Cl>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]#[C:12][C:13]2[CH:14]=[CH:15][C:16]([C:17]([N:59]([CH2:60][C:61]3[CH:73]=[CH:72][C:64]4[O:65][C:66]([CH3:71])([CH3:70])[O:67][C:68](=[O:69])[C:63]=4[CH:62]=3)[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])=[O:19])=[CH:20][CH:21]=2)=[CH:9][CH:10]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ccc(C#Cc2ccc(C(=O)O)cc2)cc1
Reactant: CCCCCCNCc1ccc2c(c1)C(=O)OC(C)(C)O2
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCCCCCN(Cc1ccc2c(c1)C(=O)OC(C)(C)O2)C(=O)c1ccc(C#Cc2ccc(CCCC)cc2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 75.4 %

Procedure:
A solution of 4-(4-butylphenylethynyl)benzoic acid (330 mg, 1.19 mmol), EDC.HCl (231 mg, 1.21 mmol), HOBT (163 mg, 1.21 mmol) and DIEA (256 μl, 1.51 mmol) in DCM (15 mL) was stirred 10 min at rt. Then a solution of 6-[(hexylamino)methyl]-2,2-dimethyl-4H-1,3-benzodioxin-4-one (293 mg, 1.01 mmol) in DCM (5 mL) was added and the resulting mixture was stirred 3 hrs at rt. The reaction mixture was diluted with DCM and washed with a saturated aqueous solution of NaHCO3, an aqueous solution of HCl (1N) and brine. Organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. Purification by flash chromatography on silica gel (EtOAc/c-Hex (20/80)) gave 420 mg (73%) of the title compound. HPLC, Rt: 6.18 min (purity: 92.3%). A second purification by preparative HPLC with a X-Terra column allowed the isolation of the title compound (300 mg, 54% yield) as a white powder. HPLC, Rt: 6.15 min (purity: 99.1%). LC/MS, M+(ESI): 552.7. 1H NMR (CDCl3) δ: 0.82 (m, 3H), 0.91 (t, J=7.3 Hz, 3H), 1.09-1.41 (m, 8H), 1.53 (m, 4H), 1.72 (s, 6H), 2.60 (t, J=7.6 Hz, 2H), 3.16-3.45 (m, 2H), 4.50-4.70 (m, 2H), 6.96 (d, J=8.5 Hz, 1H), 7.15 (d, J=8.1 Hz, 2H), 7.37 (d, J=8.3 Hz, 2H), 7.42 (d, J=7.9 Hz, 2H), 7.52-7.84 (m, 4H).
Reaction SMILES: [O:1]1[CH2:19][CH:2]1[CH2:3][O:4][C:5]1[C:17]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10](=[O:18])[C:9]=2[CH:8]=[CH:7][CH:6]=1.[CH3:20][C:21]1([CH3:28])[CH2:25][CH2:24][C:23]([CH3:27])([CH3:26])[NH:22]1>O1CCOCC1>[OH:1][CH:2]([CH2:19][N:22]1[C:23]([CH3:27])([CH3:26])[CH2:24][CH2:25][C:21]1([CH3:28])[CH3:20])[CH2:3][O:4][C:5]1[C:17]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10](=[O:18])[C:9]=2[CH:8]=[CH:7][CH:6]=1
Reactant: O=C1c2ccccc2-c2c(OCC3CO3)cccc21
Reactant: CC1(C)CCC(C)(C)N1
Solvent: C1COCCO1
Product: CC1(C)CCC(C)(C)N1CC(O)COc1cccc2c1-c1ccccc1C2=O

Procedure:
4 g of 4-(2,3-epoxypropoxy)-9-fluorenone are heated to 150° in an autoclave for 15 hours together with 4 g of 2,2,5,5-tetramethylpyrrolidine in 30 cc of dioxane. After cooling, the reaction mixture is concentrated by evaporation. The residue is taken up in ether and extracted with 2 N hydrochloric acid. The aqueous solution is made alkaline and thoroughly extracted with methylene chloride. The methylene chloride phase is concentrated by evaporation and the residue is crystallized from ethyl acetate/petroleum ether. The title compound has an M.P. of 137°-139°.
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:10]([F:39])=[C:11]([CH:15]2[C:19]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)([C:20]#[N:21])[CH:18]([CH2:29][CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)[NH:17][CH:16]2[C:36]([OH:38])=O)[CH:12]=[CH:13][CH:14]=1.CC1(C)[O:45][C@@H:44]([CH2:46][CH2:47][NH2:48])[CH2:43][O:42]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl>C(Cl)Cl.O1CCCC1>[OH:45][C@H:44]([CH2:43][OH:42])[CH2:46][CH2:47][NH:48][C:36]([CH:16]1[CH:15]([C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([Cl:8])[C:10]=2[F:39])[C:19]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)([C:20]#[N:21])[CH:18]([CH2:29][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[NH:17]1)=[O:38]
Reactant: N#CC1(c2ccc(Cl)cc2)C(CC2CCCCC2)NC(C(=O)O)C1c1cccc(Cl)c1F
Reactant: CC1(C)OC[C@H](CCN)O1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: N#CC1(c2ccc(Cl)cc2)C(CC2CCCCC2)NC(C(=O)NCC[C@H](O)CO)C1c1cccc(Cl)c1F
Yield: 71.1 %

Procedure:
In a manner similar to the method described in Examples 42c, 42d, rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-cyclohexylmethyl-pyrrolidine-2-carboxylic acid trifluoroacetic acid prepared in Example 59c (0.6 g, 1 mmol) was reacted with 2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethylamine (0.3 g, 2 mmol), HATU (0.6 g, 1.6 mmol) and iPr2NEt (0.9 g, 7 mmol) in CH2Cl2 at room temperature for 20 h, then reacted with aqueous HCl solution in tetrahydrofuran at room temperature for 2 h to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-cyclohexylmethyl-pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide as a white solid (0.4 g, 71%).
Reaction SMILES: [F:1][C:2]([F:27])([F:26])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[N:16]=[CH:15][N:14]=[C:13]([C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=3)[C:20](O)=[O:21])[CH:12]=2)=[CH:6][CH:5]=1.[F:28][C:29]([F:39])([F:38])[C:30]1[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=1[CH2:32][NH2:33].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CO.ClCCl>[F:27][C:2]([F:1])([F:26])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[N:16]=[CH:15][N:14]=[C:13]([C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=3)[C:20]([NH:33][CH2:32][C:31]3[CH:34]=[CH:35][CH:36]=[CH:37][C:30]=3[C:29]([F:38])([F:39])[F:28])=[O:21])[CH:12]=2)=[CH:6][CH:5]=1
Reactant: O=C(O)c1cccc(-c2cc(Nc3ccc(OC(F)(F)F)cc3)ncn2)c1
Reactant: NCc1ccccc1C(F)(F)F
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NCc1ccccc1C(F)(F)F)c1cccc(-c2cc(Nc3ccc(OC(F)(F)F)cc3)ncn2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 93.2 %

Procedure:
A mixture of 3-[6-(4-trifluoromethoxy-phenylamino)-pyrimidin-4-yl]-benzoic acid (100 mg, 0.27 mmol), 2-trifluoromethylbenzyl amine (71 mg, 0.40 mmol), HATU (112 mg, 0.30 mmol) and DIPEA (232 μL, 1.33 mmol) in DMF (4 mL) is stirred at room temperature for eight hours. The solvent is then removed and silica gel chromatography (methanol/dichloromethane, 5/95) affords the title compound, 3-[6-(4-Trifluoromethoxy-phenylamino)-pyrimidin-4-yl]-N-(2-trifluoromethyl-benzyl)-benzamide (134 mg, 95% yield); 1H NMR (400 MHz, d-DMSO) δ4.71 (d, J=5.1 Hz, 2H), 7.36 (m, 3H), 7.49 (m, 1H), 7.56 (d, J=7.5 Hz, 1H), 7.67 (m, 2H), 7.75 (d, J=7.9 Hz, 1H), 7.85 (d, J=9.1 Hz, 2H), 8.08 (d, J=7.8 Hz, 1H), 8.23 (d, J=7.7 Hz, 1H), 8.61 (s, 1H), 8.78 (s, 1H), 9.31 (dd, J=5.8, 6.0 Hz, 1H), 9.96 (s, 1H); MS (ES+) m/e 533.1(M+H+).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]2[CH2:18][C:17]([CH3:20])([CH3:19])[N:16]([O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[C:15]([CH3:31])([CH3:30])[CH2:14]2)[N:5]=[C:4]([NH:32][CH2:33][CH2:34][CH2:35][CH2:36][CH:37]2[CH2:42][C:41]([CH3:44])([CH3:43])[N:40]([O:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH3:53])[C:39]([CH3:55])([CH3:54])[CH2:38]2)[N:3]=1.[NH2:56][CH2:57][C:58]([OH:60])=[O:59]>>[CH2:22]([O:21][N:16]1[C:17]([CH3:19])([CH3:20])[CH2:18][CH:13]([CH2:12][CH2:11][CH2:10][CH2:9][NH:8][C:6]2[N:5]=[C:4]([NH:32][CH2:33][CH2:34][CH2:35][CH2:36][CH:37]3[CH2:38][C:39]([CH3:55])([CH3:54])[N:40]([O:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH3:53])[C:41]([CH3:44])([CH3:43])[CH2:42]3)[N:3]=[C:2]([NH:56][CH2:57][C:58]([OH:60])=[O:59])[N:7]=2)[CH2:14][C:15]1([CH3:30])[CH3:31])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]
Reactant: CCCCCCCCON1C(C)(C)CC(CCCCNc2nc(Cl)nc(NCCCCC3CC(C)(C)N(OCCCCCCCC)C(C)(C)C3)n2)CC1(C)C
Reactant: NCC(=O)O
Product: CCCCCCCCON1C(C)(C)CC(CCCCNc2nc(NCCCCC3CC(C)(C)N(OCCCCCCCC)C(C)(C)C3)nc(NCC(=O)O)n2)CC1(C)C

Procedure:
The title compound is prepared from the reaction of 2-chloro-4,6-bis[N-(1-octyloxy-2,2,6,6-tetramethylpiperidin-4-yl)butylamino]-1,3,5-triazine and glycine according to the procedure of Example 15.
Reaction SMILES: [C:1]1([C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)[CH:6]=[CH:5][C:4]([N:7]([C:43]2[CH:55]=[CH:54][C:53]3[C:52]4[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=4)[C:46]([CH3:57])([CH3:56])[C:45]=3[CH:44]=2)[C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:15]=[C:16]4[C:24](=[CH:25][CH:26]=3)[N:23](C(OC(C)(C)C)=O)[C:22]3[CH:21]=[C:20]5[C:34]([CH3:42])([CH3:41])[C:35]6[C:40]([C:19]5=[CH:18][C:17]4=3)=[CH:39][CH:38]=[CH:37][CH:36]=6)=[CH:10][CH:9]=2)=[CH:3][CH:2]=1.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O.[OH-].[Na+]>ClCCl>[C:1]1([C:58]2[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=2)[CH:2]=[CH:3][C:4]([N:7]([C:8]2[CH:9]=[CH:10][C:11]([C:14]3[CH:15]=[C:16]4[C:24](=[CH:25][CH:26]=3)[NH:23][C:22]3[CH:21]=[C:20]5[C:34]([CH3:41])([CH3:42])[C:35]6[C:40]([C:19]5=[CH:18][C:17]4=3)=[CH:39][CH:38]=[CH:37][CH:36]=6)=[CH:12][CH:13]=2)[C:43]2[CH:55]=[CH:54][C:53]3[C:52]4[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=4)[C:46]([CH3:56])([CH3:57])[C:45]=3[CH:44]=2)=[CH:5][CH:6]=1
Reactant: CC(C)(C)OC(=O)n1c2ccc(-c3ccc(N(c4ccc(-c5ccccc5)cc4)c4ccc5c(c4)C(C)(C)c4ccccc4-5)cc3)cc2c2cc3c(cc21)C(C)(C)c1ccccc1-3
Agent: [Na+]
Agent: [OH-]
Solvent: COc1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC1(C)c2ccccc2-c2ccc(N(c3ccc(-c4ccccc4)cc3)c3ccc(-c4ccc5[nH]c6cc7c(cc6c5c4)-c4ccccc4C7(C)C)cc3)cc21
Temperature: 40 °C
Reaction time: 3 h
Yield: 89.5 %

Procedure:
20.0 g (24.4 mmol) of tert-butyl 7-{4-[biphenyl-4-yl-(9,9-dimethyl-9H-fluoren-2-yl)amino]phenyl}-12,12-dimethyl-12H-10-azaindeno[2,1-b]fluorene-10-carboxylate are dissolved in 250 ml of dichloromethane and 2.65 ml (24.4 mmol) of anisole, and 5.4 ml of trifluoroacetic acid are subsequently added. The mixture is stirred at 40° C. for 3 h and, when the reaction is complete, neutralised by means of ice-water and 20% NaOH solution. The mixture is extracted with dichloromethane, dried and purified by recrystallisation from toluene/heptane, giving 15.7 g (89%) of the product as a white solid.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[C:13]([CH3:15])[CH:12]=[CH:11][N:10]=2)=[CH:5][C:3]=1[NH2:4].[C:16]([O:20][C:21]([NH:23][C:24]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=S)=[O:22])([CH3:19])([CH3:18])[CH3:17].C(N(C(C)C)CC)(C)C.[I-].C[N+]1C=CC=CC=1Cl>ClCCl>[C:30]([O:29][C:27]([NH:26][C:24]([NH:23][C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:22])=[N:4][C:3]1[CH:5]=[C:6]([C:9]2[CH:14]=[C:13]([CH3:15])[CH:12]=[CH:11][N:10]=2)[CH:7]=[CH:8][C:2]=1[CH3:1])=[O:28])([CH3:33])([CH3:32])[CH3:31]
Reactant: CC(C)(C)OC(=O)NC(=S)NC(=O)OC(C)(C)C
Reactant: Cc1ccnc(-c2ccc(C)c(N)c2)c1
Agent: C[n+]1ccccc1Cl
Agent: [I-]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1ccnc(-c2ccc(C)c(N=C(NC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)c2)c1
Reaction time: 2 h
Yield: 83.2 %

Procedure:
To a suspension of 2-methyl-5-(4-methylpyridin-2-yl)aniline (285 mg), N,N′-bis(tert-butoxycarbonyl)thiourea (475 mg) and diisopropylethylamine (0.577 ml) in dichloromethane (15 ml) was added 1-methyl-2-chloropyridinium iodide (478 mg), and the mixture was stirred for 2 hours. The mixture was diluted with dichloromethane, washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. To the residue was added 2-propanol, and the mixture was stirred. The precipitate was collected by filtration and dried to give N,N′-bis(tert-butoxycarbonyl)-N″-(2-methyl-5-(4-methylpyridin-2-yl)phenyl)guanidine (527 mg).
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([NH:7][C:8](=[O:23])[N:9]([C@H:16]2[CH2:21][CH2:20][C@H:19](C)[CH2:18][CH2:17]2)[CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:4][CH:3]=1.[C:24](O)(=[O:33])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30]([OH:32])=[O:31]>>[Cl:1][C:2]1[S:6][C:5]([NH:7][C:8](=[O:23])[N:9]([CH:10]2[CH2:11][CH2:12][N:13]([C:24](=[O:33])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30]([OH:32])=[O:31])[CH2:14][CH2:15]2)[CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)=[N:4][CH:3]=1
Reactant: O=C(O)CCCCCC(=O)O
Reactant: C[C@H]1CC[C@H](N(C(=O)Nc2ncc(Cl)s2)C2CCNCC2)CC1
Product: O=C(O)CCCCCC(=O)N1CCC(N(C(=O)Nc2ncc(Cl)s2)C2CCCCC2)CC1

Procedure:
Prepared as described in general procedure (G) using 3-(5-chloro-thiazol-2-yl)-1-(trans-4-methyl-cyclohexyl)-1-piperidin-4-yl-urea and pimelic acid.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:26]=[CH:25][C:8]2[C:9]3[N:10]=[C:11]([C:17]4[N:21](C(C)C)[CH:20]=[N:19][N:18]=4)[S:12][C:13]=3[CH2:14][CH2:15][O:16][C:7]=2[CH:6]=1)=[O:4].Br[C:28]1[CH:49]=CC2C3N=C(C4N(C(C)C)N=CN=4)SC=3CCOC=2[CH:29]=1>>[CH3:1][O:2][C:3]([C:5]1[CH:26]=[CH:25][C:8]2[C:9]3[N:10]=[C:11]([C:17]4[N:18]([CH:28]([CH3:49])[CH3:29])[N:19]=[CH:20][N:21]=4)[S:12][C:13]=3[CH2:14][CH2:15][O:16][C:7]=2[CH:6]=1)=[O:4]
Reactant: COC(=O)c1ccc2c(c1)OCCc1sc(-c3nncn3C(C)C)nc1-2
Reactant: CC(C)n1ncnc1-c1nc2c(s1)CCOc1cc(Br)ccc1-2
Product: COC(=O)c1ccc2c(c1)OCCc1sc(-c3ncnn3C(C)C)nc1-2

Procedure:
The title compound was prepared by a similar procedure to 2-(4-isopropyl-4H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-8-carboxylic acid methyl ester using 8-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene 27 instead of 8-bromo-2-(4-isopropyl-4H[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene. The title compound was isolated as a beige solid (0.61 g, 64%). LCMS: RT=4.71 min, [M+H]+=371
Reaction SMILES: C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:8]2[CH:12]=[C:11]([CH2:13][CH2:14][C:15]#[C:16][CH2:17][CH2:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[N:10]=[CH:9]2)C=CC=CC=1.Cl>C(O)C>[NH:8]1[CH:12]=[C:11]([CH2:13][CH2:14][C:15]#[C:16][CH2:17][CH2:18][CH:19]2[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]2)[N:10]=[CH:9]1
Reactant: C(#CCCC1CCCCC1)CCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Agent: Cl
Solvent: CCO
Product: C(#CCCC1CCCCC1)CCc1c[nH]cn1
Temperature: 90 °C
Yield: 105.1 %

Procedure:
1-[1-Triphenylmethyl-1H-imidazol-4-yl]-6-cyclohexyl-3-hexyne (0.30 gram, 0.64 mmol) was dissolved in ethanol (10 ml). 2N HCl (20 ml) was added, and the mixture heated at 90° C. for 1 hour. The reaction mixture was cooled, filtered, and the filtrate neutralized with 10% NAOH solution and then partitioned between chloroform and water. The chloroform layer was separated, dried over Na2SO4, filtered and evaporated in vacuo to obtain the crude oil. The crude product was purified using column chromatography using MeOH/CHCl3, 10:90 to afford 155 mgs of 1-[1H-imidazol-4-yl]-6-cyclohexyl-3-hexyne (23). ##STR54## 4-(6-Cyclohexylhex-3-ynyl)imidazole (23) 1H-NMR (300 MHz, CDCl3): δ7.05 (s, 1H), 6.83 (s, 1H), 2.80 (m, 2H), 2.45 (m, 2H), 2.15 (m, 2H), 1.68 (m, 5H), 1.4-1.1 (m, 6H), 0.86 (m, 2H); Mass Spectrum: (DCl/NH3): 231 (M+1)+, MW=230.3434, C15H22N2. CHN Analysis: Calc.: C: 78.26, H: 9.56, N: 12.17; Found: C: 77.79, H: 9.51, N: 11.86.