Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[O:6][C:5]([C:7]([NH:9][NH2:10])=[O:8])=[CH:4][CH:3]=1.[OH-].[K+].CO.[C:15](=S)=[S:16]>O>[Br:1][C:2]1[O:6][C:5]([C:7]2[O:8][C:15]([SH:16])=[N:10][N:9]=2)=[CH:4][CH:3]=1
Reactant: NNC(=O)c1ccc(Br)o1
Reactant: S=C=S
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: Sc1nnc(-c2ccc(Br)o2)o1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
5-Bromo-furan-2-carboxylic acid hydrazide (20.5 g, 100 mmol) was added to a mixture of potassium hydroxide (6.2 g, 110 mmol) and methanol (125 ml). The mixture was stirred for 30 minutes at room temperature. Carbon disulfide (15.2 g, 200 mmol) was added. The mixture was stirred at reflux for 30 hours. Water (60 ml) was added and the excess of carbon disulfide and methanol was evaporated. The aqueous suspension was acidified by adding concentrated hydrochloric acid (14 ml). The product precipitated and was washed with water (20 ml), dried and evaporated. Yield 8.58 g (35%).
Reaction SMILES: OC1C=C2C(=CC=1)C=C(C(OC)=C1C3CC4CC(CC1C4)C3)C=C2.C1C2C(=CC=CC=2)C=CC=1.[OH:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([O:53][CH3:54])=[C:43]2[CH:50]3[CH2:51][CH:46]4[CH2:47][CH:48]([CH2:52][CH:44]2[CH2:45]4)[CH2:49]3)[CH:37]=1.[P:55](Cl)(Cl)([O:57]C)=[O:56].[CH3:61][O:62][C:63]1[C:70]([O:71][CH3:72])=[CH:69][C:66]([CH2:67][OH:68])=[C:65]([N+:73]([O-:75])=[O:74])[CH:64]=1>N1C=CC=CC=1.C1C=CC=CC=1>[P:55]([O-:57])([O:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([O:53][CH3:54])=[C:43]2[CH:44]3[CH2:52][CH:48]4[CH2:47][CH:46]([CH2:51][CH:50]2[CH2:49]4)[CH2:45]3)[CH:37]=1)([O:68][CH2:67][C:66]1[CH:69]=[C:70]([O:71][CH3:72])[C:63]([O:62][CH3:61])=[CH:64][C:65]=1[N+:73]([O-:75])=[O:74])=[O:56].[NH+:73]1[CH:63]=[CH:70][CH:69]=[CH:66][CH:65]=1
Reactant: COc1cc(CO)c([N+](=O)[O-])cc1OC
Reactant: COC(=C1C2CC3CC(C2)CC1C3)c1cccc(O)c1
Reactant: COP(=O)(Cl)Cl
Agent: COC(=C1C2CC3CC(C2)CC1C3)c1ccc2cc(O)ccc2c1
Solvent: c1ccncc1
Solvent: c1ccc2ccccc2c1
Solvent: c1ccccc1
Product: COC(=C1C2CC3CC(C2)CC1C3)c1cccc(OP(=O)([O-])OCc2cc(OC)c(OC)cc2[N+](=O)[O-])c1
Product: c1cc[nH+]cc1

Procedure:
The procedure for the preparation of 6-hydroxy-2-(methoxytricyclo[3.3.1.13,7 ]dec-2-ylidene-methyl)naphthalene (Edwards, B., Sparks, A., Voyta, J. C., Strong, R., Murphy, O., Bronstein, I., J. Org. Chem., 55, 6225-6229 (1990) and (U.S. Pat. No. 5,538,847, issued Jul. 23, 1996)), was followed to prepare both the naphthalene and benzene derivatives (Scheme 4). Subsequent phosphorylation of 1-hydroxy-3-(methoxytricyclo[3.3.1.13,7 ]dec-2-ylidenemethyl)benzene with methyl dichlorophosphate in pyridine and coupling with 4,5-dimethoxy 2-nitrobenzyl alcohol in pyridine (Rubinstein, M., Patchornik, A., Tetrahedron 31, 2107-2110 (1975)) afforded pyridinium 4,5-dimethoxy-2-nitrobenzyl 3-(methoxytricyclo[3.3.1.13,7 ]dec-2-ylidenemethyl)phenyl phosphate, which, upon ion exchange to the triethylamine salt, provided compound 9a in Scheme 4. Oxidation afforded 4,5-dimethoxy-2-nitrobenzyl (4-methoxyspiro[1,2-dioxetane-3,2'-tricyclo[3.3.1.13,7 ]decan]-3-yl)phenyl phosphate as the triethylamine salt (compound 10a in Scheme 4) [see Edwards et al., J. Org. Chem., 55, 6225-6229 (1990)]. Similarly, phosphorylation of 1-hydroxy-3-(methoxytricyclo[3.3.1.13,7 ]dec-2-ylidenemethyl)benzene with methyl dichlorophosphate in pyridine and coupling with 2-nitrobenzyl alcohol in pyridine followed by ion exchange to TEA salt and subsequent oxidation afforded triethylammonium 2-nitrobenzyl (4-methoxyspiro[1,2-dioxetane-3,2'-tricyclo[3.3.1.13,7 ]decan]-3-yl)phenyl phosphate.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[CH3:9][Si:10]([C:13]#[CH:14])([CH3:12])[CH3:11]>CCN(CC)CC.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([C:14]#[C:13][Si:10]([CH3:12])([CH3:11])[CH3:9])=[N:3][CH:4]=1
Reactant: Cc1ccc(Br)nc1
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Product: Cc1ccc(C#C[Si](C)(C)C)nc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 81 %

Procedure:
To a solution of 2-bromo-5-methylpyridine (17.4 mmol) in 50 mL of degassed Et3N was added trimethylsilylacetylene (19.1 mmol), CuI, (1.74 mmol) and trans-dichlorobis(triphenylphosphine)palladium (1.74 mmol). The resulting solution was stirred at RT overnight under N2 atmosphere. The black solution was then hydrolyzed with 30 mL of H2O and extracted with Et20 (3×30 mL). Purification of the residue by column chromatography (hexane/Et2O 9/1) provided the desired compound in 81% yield as brown oil. 1H NMR (CDCI3) δ ppm: 0.08 (s, 9H, CH3); 2.30 (s, 3H, CH3); 7.41 (d, 1H, J=7.5 Hz, CHAT), 7.59 (d, 1H, J=7.5 Hz, CHAr); 8.41 (s, 1H, CHAr). 13C NMR (CDCl3) δ ppm: 0.0 (3C, CH3); 18.9 (1C, CH3); 94.0 (1C, C═C); 104.7 (1C, C═C); 126.1 (1C, CHAr); 132 (1C, Cq); 135.2 (1C, CHAr); 141.6 (1C, Cq); 150.7 (1C, CHAr).
Reaction SMILES: [NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:19]=[CH:18][C:10]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][CH:8]=2)[CH2:3]1.CCN(CC)CC.Cl[C:28](Cl)([O:30][C:31](=[O:37])OC(Cl)(Cl)Cl)Cl.[F:39][C:40]([F:44])([F:43])CO>ClCCl>[F:39][C:40]([F:44])([F:43])[CH2:28][O:30][C:31]([NH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:19]=[CH:18][C:10]([C:11]([O:13][C:14]([CH3:16])([CH3:15])[CH3:17])=[O:12])=[CH:9][CH:8]=2)[CH2:3]1)=[O:37]
Reactant: OCC(F)(F)F
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: CC(C)(C)OC(=O)c1ccc(N2CC[C@H](N)C2)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)c1ccc(N2CC[C@H](NC(=O)OCC(F)(F)F)C2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 158.3 %

Procedure:
The compound 17 (400 mg, 1.52 mmol) and Et3N (850 ml, 6.10 mmol) were added to a stirring solution of triphosgene (181 mg, 0.61 mmol) in dichloromethane (8 mL) at −60° C. The reaction mixture was allowed to warm to room temperature and stirred for additional 2 h. 2,2,2-Trifluoroethanol (133 μl, 1.82 mmol) was added and the reaction mixture was stirred for 16 h, diluted with dichloromethane, washed with saturated aqueous NH4Cl, NaHCO3 and brine, dried over MgSO4, filtered and concentrated in vacuo. The solid residue was purified by flash chromatography (eluent 0.5-1% MeOH-dichloromethane) to afford the title compound 139 as a white solid (375 mg, 64% yield). 1H NMR: (DMSO) δ (ppm): 8.09 (d, J=6.8 Hz, 1H), 7.70 (d, J=8.8 Hz, 2H), 6.52 (d, J=8.8, 2H), 4.66 (q, J=9.1 Hz, 2H), 4.24-4.20 (m, 1H), 3.57-3.53 (m, 1H), 3.47-3.41 (m, 1H), 3.36-3.30 (m, 1H, overlap with water), 3.19-3.16 (m, 1H), 2.21-2.16 (m, 1H), 1.99-1.93 (m, 1H), 1.50 (s, 9H). LRMS (ESI): (calc.) 388.2; (obt.) 389.2 (M+H)+.
Reaction SMILES: [C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[CH2:13]([N:20]1[CH2:25][CH2:24][CH:23]([NH:26][C:27]2[CH:28]=[N:29][C:30]3[C:35]([C:36]=2[NH2:37])=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O>CN(C=O)C>[CH2:13]([N:20]1[CH2:25][CH2:24][CH:23]([N:26]2[C:27]3[CH:28]=[N:29][C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:35]=4[C:36]=3[NH:37][C:1]2=[O:2])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: Nc1c(NC2CCN(Cc3ccccc3)CC2)cnc2ccccc12
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: O
Solvent: CN(C)C=O
Product: O=c1[nH]c2c3ccccc3ncc2n1C1CCN(Cc2ccccc2)CC1
Temperature: 100 °C
Reaction time: 1.5 h

Procedure:
23 g (0.14 mol) 1,1′-carbonyldiimidazole were added to a solution of 9.0 g (27 mmol) N3-(1-benzylpiperidin-4-yl)-quinoline-3,4-diamine in 100 mL DMF. The mixture was heated to 100° C. and stirred for 1.5 h at this temperature. After the reaction mixture had cooled it was poured onto 300 mL water. The precipitated solid was filtered off, washed with water and dried at 30° C. i. vac. The residue was triturated with diethyl ether, suction filtered and the solid product was dried i. vac.
Reaction SMILES: [CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:11]([F:28])=[C:12]([NH:18][C@H:19]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[CH3:20])[C:13]([F:17])=[CH:14][C:15]=3[NH2:16])[CH:5]=2)[CH2:3][CH2:2]1.[C:29](O)(=O)C.C(N)=N.C(=O)(O)[O-].[Na+].CCOC(C)=O>CCO>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([N:9]3[C:10]4[C:11]([F:28])=[C:12]([NH:18][C@H:19]([C:21]5[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=5)[CH3:20])[C:13]([F:17])=[CH:14][C:15]=4[N:16]=[CH:29]3)[CH:5]=2)[CH2:3][CH2:2]1
Reactant: CC(=O)O
Reactant: C[C@H](Nc1c(F)cc(N)c(Nc2cc(C3CC3)[nH]n2)c1F)c1ccc(F)cc1
Agent: N=CN
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Product: C[C@H](Nc1c(F)cc2ncn(-c3cc(C4CC4)[nH]n3)c2c1F)c1ccc(F)cc1

Procedure:
(S)-N3-(5-Cyclopropyl-1H-pyrazol-3-yl)-2,6-difluoro-N1-(1-(4-fluorophenyl)ethyl)benzene-1,3,4-triamine (Method 101, 0.278 g, 0.718 mmol) and formamidine acetate (0.149 g, 1.44 mmol) in EtOH (10 ml) was heated at reflux for 1 hour. Saturated sodium bicarbonate solution (5 ml) and EtOAc (15 ml) were added. The organic layer was separated, washed with brine (3 ml) and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by chromatography (Hex-EtOAc=1:1) to give the title compound as off white solid (0.120 g, 42%). 1H NMR (400 MHz) 12.83 (s, 1H), 8.20 (s, 1H), 7.36 (m, 2H), 7.31 (d, J=11.2 Hz, 1H), 7.06 (t, J=8.8 Hz, 2H), 6.15 (s, 1H), 5.15 (d, J=10.4 Hz, 1H), 4.67 (m, 1H), 1.98 (m, 1H), 1.46 (d, J=6.8 Hz, 3H), 1.00 (m, 2H), 0.76 (m, 2H). MS: Calcd.: 397; Found: [M+H]+ 398.
Reaction SMILES: [C:1]([OH:6])(=O)[C:2]#[C:3][CH3:4].ClC(OCC(C)C)=O.CN1CCOCC1.[NH2:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[N:29]=[CH:28][C:27]([C:33]#[N:34])=[C:26]2[NH:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([I:42])[CH:37]=1>C1COCC1>[C:33]([C:27]1[CH:28]=[N:29][C:30]2[C:25]([C:26]=1[NH:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([I:42])[CH:37]=1)=[CH:24][C:23]([NH:22][C:1](=[O:6])[C:2]#[C:3][CH3:4])=[CH:32][CH:31]=2)#[N:34]
Reactant: CC#CC(=O)O
Reactant: N#Cc1cnc2ccc(N)cc2c1Nc1cccc(I)c1
Agent: CC(C)COC(=O)Cl
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Product: CC#CC(=O)Nc1ccc2ncc(C#N)c(Nc3cccc(I)c3)c2c1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 38.8 %

Procedure:
Dissolved 275 mg (3.27 mmol) 2-butynoic acid in 20 ml THF under N2 and chilled to 0° C. Added 420 μl (3.23 mmol) isobutyl chloroformate and 355 μl (3.24 mmol) N-methylmorpholine and stirred for 10 minutes. Added dropwise a solution of 500 mg (1.30 mmol) 6-amino-4-[(3-iodophenyl)amino]-3-quinolinecarbonitrile and after 15 minutes, removed ice bath and stirred overnight at 25° C. Stripped solvent, washed with water and collected solids. Boiled in ethyl acetate, collected, and dried in vacuo, giving 228 mg of orange-brown solid: mass spectrum (electrospray m/e): M+H=453.1.
Reaction SMILES: O.NN.[C:4]([N:7]1[C:13]([CH3:14])=[CH:12][C:11]2[CH:15]=[C:16]3[O:21][CH2:20][O:19][C:17]3=[CH:18][C:10]=2[C:9]([C:22]2[CH:27]=[CH:26][C:25]([N+:28]([O-])=O)=[CH:24][CH:23]=2)=[N:8]1)(=[O:6])[CH3:5]>[Ni].CO>[C:4]([N:7]1[C:13]([CH3:14])=[CH:12][C:11]2[CH:15]=[C:16]3[O:21][CH2:20][O:19][C:17]3=[CH:18][C:10]=2[C:9]([C:22]2[CH:23]=[CH:24][C:25]([NH2:28])=[CH:26][CH:27]=2)=[N:8]1)(=[O:6])[CH3:5]
Reactant: CC(=O)N1N=C(c2ccc([N+](=O)[O-])cc2)c2cc3c(cc2C=C1C)OCO3
Agent: [Ni]
Agent: NN
Solvent: CO
Solvent: O
Product: CC(=O)N1N=C(c2ccc(N)cc2)c2cc3c(cc2C=C1C)OCO3
Reaction time: 0.5 h
Yield: 89.1 %

Procedure:
0.1 g of Raney nickel and 0.25 ml (4.93 mmol) of 98% hydrazine hydrate are added to a suspension of 0.6 g (1.64 mmol) of 7-acetyl-5-(4-nitrophenyl)-8-methyl-7H-1,3-dioxolo[4,5-h][2,3]-benzodiazepine in 40 ml of methanol. The mixture is stirred for 0.5 hour. The starting material is dissolved within a few minutes. After the reaction is completed, catalyst is filtered out. The filtrate is concentrated by evaporation in a vacuum. The residue is absorptively precipitated in water, suctioned off and rewashed with water. 0.49 g of 7-acetyl-5-(4-aminophenyl)-8-methyl-7H-1,3-dioxolo[4,5-h][2,3]-benzodiazepine with a melting point of 175°-180° C. is obtained. Recrystallization of this crude product from 50% aqueous ethanol yields 0.46 g (79%) of 7-acetyl-5-(4-amino-phenyl)-8-methyl-7H-1,3-dioxolo[4,5-h][2,3]-benzodiazepine with a melting point of 208°-210° C.
Reaction SMILES: [CH2:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[O:12][C:11](=[O:14])[CH:10]=[CH:9]2)[CH:2]=C.[O:15]1CCOCC1>O.O=[Os](=O)(=O)=O>[O:14]=[C:11]1[CH:10]=[CH:9][C:8]2[C:13](=[C:4]([CH2:1][CH:2]=[O:15])[CH:5]=[CH:6][CH:7]=2)[O:12]1
Reactant: C1COCCO1
Reactant: C=CCc1cccc2ccc(=O)oc12
Agent: O=[Os](=O)(=O)=O
Solvent: O
Product: O=CCc1cccc2ccc(=O)oc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 93 %

Procedure:
To a solution of 8-(2-propen-1-yl)-2H-chromen-2-one (390 mg, 2.0 mmol) in dioxane (10 mL) and water (5 mL) was added OsO4 (4% solution in H2O, 0.5 mL, 10 mol %) and NaIO4 (430 mg, 4.0 mmol). The reaction was stirred at RT for 2 h and NaIO4 (430 mg, 4.0 mmol) was added and the reaction was allowed to stir another 2 h. The reaction was diluted with 20 mL of H2O and was extracted with ethyl acetate (3×50 mL). The combined extracts were dried (Na2SO4), and concentrated to give the title compound (350 mg, 93%) as a dark oil which was used without further purification: MS (ES) m/e 188.9 (M+H)+.
Reaction SMILES: [C:1]([C:3]1[C:4]([NH:11][CH3:12])=[N:5][C:6]([NH:9][NH2:10])=[N:7][CH:8]=1)#[N:2].Cl.[N:14]([O-])=O.[Na+]>O>[N:9]([C:6]1[N:5]=[C:4]([NH:11][CH3:12])[C:3]([C:1]#[N:2])=[CH:8][N:7]=1)=[N+:10]=[N-:14]
Reactant: CNc1nc(NN)ncc1C#N
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CNc1nc(N=[N+]=[N-])ncc1C#N
Temperature: 5 °C
Reaction time: 0.33 h
Yield: 96.8 %

Procedure:
To a cold (5° C.) solution of 5-cyano-2-hydrazino-4-methylamino-pyrimidine (21.7 g) from Example 4 in a mixture of water (260 mL) and concentrated HCl (26.5 mL) was added dropwise a solution of NaNO2 (10.03 g) in water (25 mL) with overhead mechanical stirring. A white precipitate formed and after the addition was completed, the reaction was stirred for an additional 20 minutes at 5° C. The insoluble product was filtered and washed with cold water to give 22.4 g of the title compound after drying at 23° C. under high vacuum overnight. Crystallization from ethanol provided an analytically pure sample of 2-azido-5-cyano-4-methylamino-pyrimidine; mp 225-230° C.
Reaction SMILES: C(OC([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C@H:16]([NH:22][C:23]([NH:25]C(C)(C)C)=[S:24])[C:17](OCC)=O)=O)C1C=CC=CC=1.[ClH:30]>C(OCC)C>[ClH:30].[ClH:30].[NH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C@H:16]1[CH2:17][S:24][C:23]([NH2:25])=[N:22]1
Reactant: CCOC(=O)[C@H](CCCCNC(=O)OCc1ccccc1)NC(=S)NC(C)(C)C
Agent: Cl
Solvent: CCOCC
Product: NCCCC[C@H]1CSC(N)=N1

Procedure:
The process is performed as in Example 9, starting with 0.59 g of ethyl (2S)-6-{[(benzyloxy)-carbonyl]amino}-2-{[(tert-butylamino)carbothioyl]-amino}hexanoate in 6 cm3 of 6N hydrochloric acid. After concentration of the reaction medium under the same conditions, the foam obtained is taken up 3 times in diethyl ether and the phases are separated each time after settling has taken place, and the remaining insoluble material is then taken up in 10 cm3 of acetonitrile. The resulting crystalline product is spin-filtered, washed with hot acetonitrile and then dried under reduced pressure (5 kPa) at a temperature in the region of 20° C. 0.34 g of (−)-(4S)-4-(4-amino-butyl)-4,5-dihydro-1,3-thiazol-2-ylamine dihydro-chloride in the form of cream-colored crystals melting at 170° C. (αD20=−15.5±0.6 at a concentration of 0.5% in methanol).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[CH:9])=[CH:4][CH:3]=1.[C:10]1([N:16]=[N+:17]=[N-:18])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.IN1CCOCC1.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1>>[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([C:9]2[N:16]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[N:17]=[N:18][C:8]=2[C:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=2)=[CH:30][CH:29]=1
Reactant: C#Cc1ccc(C)cc1
Reactant: COc1ccc(B(O)O)cc1
Reactant: [N-]=[N+]=Nc1ccccc1
Agent: IN1CCOCC1
Product: COc1ccc(-c2c(-c3ccc(C)cc3)nnn2-c2ccccc2)cc1

Procedure:
Synthesized from 4-methyl-phenylacetylene, phenylazide, N-iodomorpholine and 4-methoxy-phenylboronic acid using one-pot/three-step general procedure, 1.22 g, 3.55 mmol, 71%; mp=172-174° C. (dec.); IR (υ[cm−1]) 3064, 2922, 1611, 1523, 1499, 1250, 1177, 995, 847, 820, 760, 687; 1H NMR (600 MHz, CDCl3) δ=7.49 (d, J=8.0, 2H), 7.38-7.33 (m, 3H), 7.32-7.27 (m, 2H), 7.10 (dd, J=13.0, 8.2, 4H), 6.85 (d, J=8.5, 2H), 3.80 (s, 3H), 2.32 (s, 3H); 13C NMR (151 MHz, CDCl3) δ=160.4, 144.9, 137.8, 136.9, 133.4, 131.7, 129.4, 129.3, 129.0, 128.3, 127.4, 125.4, 119.9, 114.7, 55.5, 21.5; HRMS (ESI-TOF) (m/z): [M+H]+ calcd for C22H20N3O, 342.1601; found 342.1600.
Reaction SMILES: CS[C:3]1[NH:12][C:11](=[O:13])[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[N:4]=1.[N:14]1([C:20]2[N:25]=[C:24]([OH:26])[CH:23]=[CH:22][CH:21]=2)[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1>C(O)CC(C)C>[OH:26][C:24]1[N:25]=[C:20]([N:14]2[CH2:19][CH2:18][N:17]([C:3]3[NH:12][C:11](=[O:13])[C:10]4[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=4[N:4]=3)[CH2:16][CH2:15]2)[CH:21]=[CH:22][CH:23]=1
Reactant: CSc1nc2c(c(=O)[nH]1)CCCC2
Reactant: Oc1cccc(N2CCNCC2)n1
Solvent: CC(C)CCO
Product: O=c1[nH]c(N2CCN(c3cccc(O)n3)CC2)nc2c1CCCC2

Procedure:
2-Methylsulfanyl-5,6,7,8-tetrahydro-3H-quinazolin-4-one (100 mg; 0.51 mmol) and 6-piperazin-1-ylpyridin-2-ol (91.3 mg; 0.51 mmol) are reacted in isoamyl alcohol (1 ml) in accordance with the procedure for Example 9 and worked up. The crude product obtained after conventional work-up is purified by column chromatography, triturated with diethyl ether, filtered off with suction and dried; yield: 17 mg (10%), crystals;
Reaction SMILES: [CH3:1][N:2]([CH2:12][CH2:13][OH:14])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=1)=[O:4].[C:15](Cl)(=[O:33])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]/[CH:23]=[CH:24]\[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]>>[CH3:1][N:2]([CH2:12][CH2:13][O:14][C:15](=[O:33])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]/[CH:23]=[CH:24]\[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=1)=[O:4]
Reactant: Cc1ccc(C(=O)N(C)CCO)cc1
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)Cl
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OCCN(C)C(=O)c1ccc(C)cc1

Procedure:
N-methyl-N-(2-oleoyloxyethyl)-p-toluamide was prepared by the procedure of example 1 from 19 gms. (0.1 mole) of N-methyl-N-(2-hydroxyethyl)-p-toluamide and 30 gms. (0.1 mole) of oleoyl chloride. The structure of the final product was characterized on the basis of IR and NMR spectral analyses as described in example 1.
Reaction SMILES: [O:1]([C:8]1[C:9]([NH:21][C:22]2[S:26][N:25]=[C:24]([CH:27]3[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]3)[N:23]=2)=[N:10][CH:11]=[C:12]([S:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)[Cl:41].CO>Cl.O1CCOCC1>[ClH:41].[ClH:41].[ClH:41].[O:1]([C:8]1[C:9]([NH:21][C:22]2[S:26][N:25]=[C:24]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[N:23]=2)=[N:10][CH:11]=[C:12]([S:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCC(c2nsc(Nc3ncc(Sc4ccccn4)cc3Oc3ccccc3)n2)CC1
Reactant: ClCCl
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: c1ccc(Oc2cc(Sc3ccccn3)cnc2Nc2nc(C3CCNCC3)ns2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 98 %

Procedure:
Tert-butyl 4-(5-(3-phenoxy-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidine-1-carboxylate (0.587 g, 1.04 mmol) was dissolved in 1:1 CH2Cl2/methanol and 4N HCl in dioxane added. The reaction was stirred at ambient temperature for 1 hour. The reaction was concentrated and dried in a vacuum oven to provide the title compound (0.473 g, 98.0% yield). 1H NMR (d6-DMSO) δ 12.39 (s, 1H), 8.95 (bs, 1H), 8.80 (bs, 1H), 8.39 (d, 1H), 8.37 (m, 1H), 7.67 (dt, 1H), 7.47 (d, 1H), 7.43 (t, 2H), 7.22-7.12 (m, 5H), 3.30 (d, 2H), 3.16-2.99 (m, 3H), 2.17 (d, 2H), 1.98 (m, 2H).
Reaction SMILES: C(OC([N:8]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([NH:19][CH:20]([C:25]3[CH:30]=[CH:29][C:28]([Br:31])=[CH:27][N:26]=3)[C:21]([F:24])([F:23])[F:22])=[CH:15][CH:14]=2)[CH2:9]1)=O)(C)(C)C.Cl>C1COCC1.O1CCOCC1.C(OCC)(=O)C.C1COCC1>[Br:31][C:28]1[CH:29]=[CH:30][C:25]([CH:20]([NH:19][C:16]2[CH:17]=[CH:18][C:13]([CH:10]3[CH2:11][CH2:12][NH:8][CH2:9]3)=[CH:14][CH:15]=2)[C:21]([F:22])([F:24])[F:23])=[N:26][CH:27]=1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(NC(c3ccc(Br)cn3)C(F)(F)F)cc2)C1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: FC(F)(F)C(Nc1ccc(C2CCNC2)cc1)c1ccc(Br)cn1
Temperature: 60 °C
Yield: 55.6 %

Procedure:
To a stirred solution of (RS)-3-{4-[(RS)-1-(5-bromo-pyridin-2-yl)-2,2,2-trifluoro-ethylamino]-phenyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (27 mg) in THF (1 ml) was added dropwise a solution of hydrogen chloride in dioxane (0.20 ml, 4 M solution) and the mixture was heated at 60° C. for 4 hours. The mixture was then cooled to room temperature, diluted with ethyl acetate/THF (1:1), and washed sequentially with 2 N aq. sodium hydroxide solution and with saturated brine. The organic phase was separated, dried over sodium sulphate, and concentrated in vacuo. The reside was purified by flash column chromatography (silical gel; gradient: heptane/dichloromethane/methanol) to give [(RS)-1-(5-bromo-pyridin-2-yl)-2,2,2-trifluoro-ethyl]-((RS)-4-pyrrolidin-3-yl-phenyl)-amine (12 mg, 56%) as a yellow amorphous solid. MS (ISP): 402.1 ([{81Br}M+H]+), 400.1 ([{79Br}M+H]+).
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].C[Sn](C)(C)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1.O.CCOC(C)=O>C1(C)C=CC=C(C)C=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:8][O:7][C:5]([C:4]1[CH:9]=[CH:10][N:11]=[C:2]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH:3]=1)=[O:6]
Reactant: C[Sn](C)(C)c1ccccn1
Reactant: COC(=O)c1ccnc(Cl)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O
Solvent: Cc1cccc(C)c1
Solvent: CCOC(C)=O
Product: COC(=O)c1ccnc(-c2ccccn2)c1
Temperature: 75 °C

Procedure:
A mixture of commercially available methyl 2-chloroisonicotinate (300 mg; 1.74 mmol), 2-(trimethylstannyl)pyridine (422 mg; 1.74 mmol), and PdCl2(PPh3)2 (122 mg; 0.17 mmol) in anh. meta-xylene (7 ml) was heated to 75° C., under nitrogen, for 18 h. After cooling to rt, water and AcOEt were added. The separated aq. layer was further extracted with AcOEt. The mixed organic layers were washed with brine, dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=15/1) afforded methyl[2,2′-bipyridine]-4-carboxylate as a yellow solid. LC-MS (conditions A): tR=0.46 min.; [M+H]+: 215.15 g/mol.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@:31]2([CH3:32])[C:9](=[CH:10][CH:11](Br)[C@@H:12]3[C@@H:30]2[CH2:29][CH2:28][C@@:27]2([CH3:33])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C@H:17]([CH3:26])[CH2:18][CH2:19][C@H:20]([F:25])[C:21]([OH:24])([CH3:23])[CH3:22])[CH2:8][C@@H:7]([O:35][C:36](=[O:38])[CH3:37])[CH2:6]1)(=[O:3])[CH3:2].CC1C=C(C)N=C(C)C=1.C1(C)C(C)=CC=CC=1>C1(C)C=CC=CC=1>[C:1]([O:4][C@@H:5]1[C@@:31]2([CH3:32])[C:9](=[CH:10][CH:11]=[C:12]3[C@@H:30]2[CH2:29][CH2:28][C@@:27]2([CH3:33])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C@H:17]([CH3:26])[CH2:18][CH2:19][C@H:20]([F:25])[C:21]([OH:24])([CH3:22])[CH3:23])[CH2:8][C@@H:7]([O:35][C:36](=[O:38])[CH3:37])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@@H]1CC2=CC(Br)[C@H]3[C@@H]4CC[C@H]([C@H](C)CC[C@H](F)C(C)(C)O)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(C)=O)C1
Solvent: Cc1cc(C)nc(C)c1
Solvent: Cc1ccccc1C
Solvent: Cc1ccccc1
Product: CC(=O)O[C@@H]1CC2=CC=C3[C@@H]4CC[C@H]([C@H](C)CC[C@H](F)C(C)(C)O)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(C)=O)C1
Temperature: 140 °C

Procedure:
A mixture of 0.300 g. (0.0005 mole) of [1α,3β,7ξ,24S]-7-bromo-24-fluorocholest-5-en-1,3,25-triol 1,3-diacetate, 0.3 ml. of s-collidine and 10 ml. of xylene was heated at reflux (140° C.) for 0.5 hr and cooled. The mixture was diluted with 20 ml. of toluene. This solution was washed with 10% aqueous sulfuric acid, and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. The residue was purified by column chromatography on 0.06-0.20 mm silica gel to yield [1α,3β,24S]-24-fluorocholesta-5,7-dien-1,3,25-triol 1,3-diacetate.