Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:3]([Cl:16])=[CH:4][C:5]2[C:6]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11][C:7]=3[NH:8][C:9]=2[CH:10]=1>C(O)(C(F)(F)F)=O.CO>[Cl:1][C:2]1[C:3]([Cl:16])=[CH:4][C:5]2[C@@H:6]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11][C@@H:7]3[NH:8][C:9]=2[CH:10]=1
Reactant: Clc1cc2[nH]c3c(c2cc1Cl)CCNCC3
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Product: Clc1cc2c(cc1Cl)[C@@H]1CCNCC[C@@H]1N2
Reaction time: 2.5 h
Yield: 34 %

Procedure:
A solution of 8,9-dichloro-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.40 g, 1.6 mmol) in TFA (4.0 mL) was cooled to 0° C., then a freshly prepared solution of Na(CN)BH3 (0.49 g, 7.8 mmol) in MeOH (.1.5 mL) was added dropwise. The ice bath was removed after the addition was complete. After 2.5 h, the reaction was diluted with H2O, made basic with 50% aqueous NaOH, and extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, decanted, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography and prep HPLC to give 0.14 g (36%) of the title compound as pale orange solid. 1H NMR (d-CHCl3) δ 7.00, 6.58, 4.22, 3.81, 3.58, 3.14-2.98, 2.79, 2.07-1.87: IR (drift) 3201, 3170, 3149, 3031, 2927, 2852, 2838, 2750, 1608, 1483, 1450, 1365, 1273, 832, 660 cm−1; HRMS (FAB) calcd for C12H14Cl2N2+H 257.0612, found 257.0614.
Reaction SMILES: [CH2:1]([O:3][P:4]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=1)(Cl)=[O:5])[CH3:2].[CH2:18]([OH:21])[CH:19]=[CH2:20].C(N(CC)CC)C>C(Cl)Cl.O>[F:17][C:14]([F:15])([F:16])[C:10]1[CH:9]=[C:8]([CH:13]=[CH:12][CH:11]=1)[CH2:7][P:4](=[O:5])([O:3][CH2:1][CH3:2])[O:21][CH2:18][CH:19]=[CH2:20]
Reactant: CCOP(=O)(Cl)Cc1cccc(C(F)(F)F)c1
Reactant: C=CCO
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: C=CCOP(=O)(Cc1cccc(C(F)(F)F)c1)OCC
Reaction time: 5 h

Procedure:
The 3-trifluoromethylbenzylphosphonochloridic acid ethyl ester of Example 4 (0.2 g, 0.7 mmol) was dissolved in 20 mL of CH2Cl2 and added slowly at 0° C. to a mixture of 1.0 mmol of allyl alcohol and 1.0 of mmol triethylamine in 20 mL of CH2Cl2. The reaction mixture was stirred for 5 hours and then diluted with H2O. The aqueous phase was further extracted 3 times with CH2Cl2. The organic extracts were combined and, after drying with anhydrous Na2SO4, were evaporated to give the crude product as an oil. Purification by column chromatography on silica gel using ethyl acetate/hexane (2.5:1) yielded 0.14 g (63%) of analytically pure product as a colorless oil. D.C.I.M.S.[MH+ 309].
Reaction SMILES: [Br:1]Br.[CH:3]1([C:7]2[N:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:10]=[C:9]([C:17]([O:19]CC)=[O:18])[CH:8]=2)[CH2:6][CH2:5][CH2:4]1.O.[OH-].[Li+].Cl>C(O)(=O)C.O>[Br:1][C:3]1([C:7]2[N:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:10]=[C:9]([C:17]([OH:19])=[O:18])[CH:8]=2)[CH2:6][CH2:5][CH2:4]1
Reactant: CCOC(=O)c1cc(C2CCC2)nc(C(F)(F)F)n1
Reactant: BrBr
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Product: O=C(O)c1cc(C2(Br)CCC2)nc(C(F)(F)F)n1
Temperature: 80 °C
Reaction time: 0.33 h

Procedure:
Bromine (0.13 mL, 2.6 mmol) was added to a solution of ethyl 6-cyclobutyl-2-(trifluoromethyl)pyrimidine-4-carboxylate (0.65 g, 2.4 mmol, from Step B) in acetic acid (2.0 mL) and the reaction was heated to 80° C. for one hour. The mixture was concentrated and the resulting oil was dissolved in THF (8.0 mL) and cooled to 0° C. A solution of lithium hydroxide, monohydrate (0.20 g, 4.7 mmol) in water (2.0 mL) was added. After stirring for 20 minutes, 1N HCl was added to achieve pH 4. Additional water was introduced and the product was extracted with six portions of 10% isopropanol in chloroform. The combined extracts were dried over sodium sulfate, filtered and concentrated to afford product which was used without further purification (0.64 g, 80%). H NMR (400 MHz, dmso) δ 8.27 (s, 1H), 3.17-2.97 (m, 2H), 2.92-2.71 (m, 2H), 2.34 (dtt, J=10.9, 9.1, 6.9 Hz, 1H), 1.84 (dtt, J=11.0, 8.6, 5.6 Hz, 1H); LCMS (M+H)+: 324.9, 326.7.
Reaction SMILES: [C:1]1(C)[CH:6]=[CH:5][CH:4]=[C:3]([NH:7][C:8]([NH2:10])=[O:9])[CH:2]=1.N[C:13]1[CH:20]=[CH:19][C:16]([CH:17]=[CH2:18])=[CH:15][CH:14]=1.[C:21]1(C)C=CC=C(N=C=O)C=1>C(Cl)(Cl)Cl>[CH2:18]=[CH:17][C:16]1[CH:19]=[CH:20][CH:13]=[CH:14][CH:15]=1.[C:2]1([CH3:21])[CH:1]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:7][C:8]([NH2:10])=[O:9]
Reactant: C=Cc1ccc(N)cc1
Reactant: Cc1cccc(NC(N)=O)c1
Reactant: Cc1cccc(N=C=O)c1
Solvent: ClC(Cl)Cl
Product: C=Cc1ccccc1
Product: Cc1ccccc1NC(N)=O

Procedure:
m-Tolyl Urea Styrerie: 1.00 g (8.40 mmol) of p-aminostyrene (99% Tokyo Kasei) was added to a 250 ml round bottom flask containing 10 ml of chloroform. After ten minutes of mixing, 1.12 g (8.41 mmol) of m-tolyl isocyanate (99% Aldrich) was added dropwise. Within seconds, a white, pinkish precipitate formed. Chloroform (20 ml) was added to aid stirring. The precipitate was filtered to remove the reaction liquid, then washed with 20 ml of chloroform resulting in a white powder (166 g, 78% crude yield, mp=203° C.).
Reaction SMILES: [OH:1][CH:2]([C:6]1[CH:7]=[CH:8][C:9]([C:12]([O:14][CH3:15])=[O:13])=[N:10][CH:11]=1)[CH:3]([OH:5])[CH3:4]>N1C=CC=CC=1.C(OC(=O)C)(=O)C>[C:2]([O:1][CH:2]([C:6]1[CH:7]=[CH:8][C:9]([C:12]([O:14][CH3:15])=[O:13])=[N:10][CH:11]=1)[CH:3]([O:5][C:12](=[O:13])[CH3:9])[CH3:4])(=[O:1])[CH3:3]
Reactant: COC(=O)c1ccc(C(O)C(C)O)cn1
Solvent: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: COC(=O)c1ccc(C(OC(C)=O)C(C)OC(C)=O)cn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of methyl 5-(1,2-dihydroxypropyl)-2-pyridinecarboxylate (6 mg) in pyridine (0.1 ml), acetic anhydride (50 μl) was added at room temperature. After stirring for 1 hour at room temperature, the reaction mixture was evaporated under N2 gas. The residue was applied to a silica gel plate (Kiesselgel GF254, 10×10 cm, Merck trademark) and developed with chloroform-methanol (95:5) to give methyl 5-(1,2-diacetoxypropyl)-2-pyridinecarboxylate: white amorphous powder; molecular formula C14H17NO6; LRFAB-MS m/z 296 [M+H]+; 1H-NMR (CDCl3) δ 8.68 (1 H, d, J=2.2 Hz), 8.16 (1H, d, J=8.1 Hz), 8.03 (1 H, dd, J=8.1 and 2.2 Hz), 5.95 (1 H, d, J=4.3 Hz), 5.28 (1H, dq, J=6.5 and 4.3 Hz), 3.97 (3H, s), 2.12 (3H, s), 1.99 (3H, s), 1.18 (3H, d, J=6.5 Hz).
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[C:6]([CH:11]([C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][CH:14]=2)O)=[N:7][CH:8]=[CH:9][CH:10]=1>C(O)C.[Pd]>[NH2:19][C:16]1[CH:15]=[CH:14][C:13]([CH2:11][C:6]2[C:5]([O:4][CH2:3][O:2][CH3:1])=[CH:10][CH:9]=[CH:8][N:7]=2)=[CH:18][CH:17]=1
Reactant: COCOc1cccnc1C(O)c1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Solvent: CCO
Product: COCOc1cccnc1Cc1ccc(N)cc1
Reaction time: 24 h
Yield: 29.5 %

Procedure:
A mixture of (3-methoxymethoxypyridin-2-yl)-(4-nitrophenyl)methanol (11.78 g) and 10% Pd-C (1.2 g) in ethanol (100 ml) was vigorously stirred under hydrogen atmosphere for 24 hours. The catalyst was filtered of, and the filtrate was concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1:1→2:1) to give 2-(4-aminobenzyl)-3-methoxymethoxypyridine (2.92 g) as orange oil.
Reaction SMILES: FC(F)(F)C(O)=O.C(OC([NH:15][O:16][S:17]([C:20]1[C:25]([CH3:26])=[CH:24][C:23]([CH3:27])=[CH:22][C:21]=1[CH3:28])(=[O:19])=[O:18])=O)(C)(C)C.[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH3:35]>C(Cl)(Cl)Cl>[CH3:26][C:25]1[CH:24]=[C:23]([CH3:27])[CH:22]=[C:21]([CH3:28])[C:20]=1[S:17]([O-:19])(=[O:18])=[O:16].[NH2:15][N+:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH3:35]
Reactant: Cc1cc(C)c(S(=O)(=O)ONC(=O)OC(C)(C)C)c(C)c1
Reactant: Cc1ccccn1
Solvent: O=C(O)C(F)(F)F
Solvent: ClC(Cl)Cl
Product: Cc1cc(C)c(S(=O)(=O)[O-])c(C)c1
Product: Cc1cccc[n+]1N
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To cold (0° C.) trifluoroacetic acid (50 mL) was added N-tert-butoxycarbonyl-O-(mesitylsulfonyl)hydroxylamine (16.09 g, 51 mmol) in portions over about 15 minutes. The solution was then stirred for about 15 minutes at room temperature. The solution was poured into ice water (250 mL) and the resulting white precipitate was collected by filtration and air-dried for 5 minutes. The solid was dissolved in chloroform (100 mL) and this solution was dried over anhydrous magnesium sulfate. The magnesium sulfate was removed by filtration and the filtrate was added to a solution of 2-picoline (5.0 g, 54 mmol) in chloroform (5 mL). The mixture was stirred for 45 min and then filtered. To the filtrate was added diethyl ether (225 ml) and the product allowed to precipitate. The solid was collected by filtration, washed with diethyl ether (50 mL) and dried to give the title compound as a white solid, 12.9 g (82%). 1H NMR (CDCl3) δ 9.45 (d, 1H), 8.4 (br s, 2H), 7.84 (t, 1H), 7.55 (t, 1H), 7.50 (d, 1H), 6.80 (s, 2H), 2.81 (s, 3H), 2.62 (s, 6H), 2.25 (s, 3H). MS (+ve electrospray) 109 (100), (M+).
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][C:7](=[O:13])[NH:8]2.[Br:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][CH:16]=1.N1CCCCC1>C(O)C>[Br:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[C:6]2[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][CH2:2][OH:1])[NH:8][C:7]2=[O:13])=[CH:17][CH:16]=1
Reactant: O=Cc1ccc(Br)cc1
Reactant: O=C1Cc2c(CCO)cccc2N1
Solvent: C1CCNCC1
Solvent: CCO
Product: O=C1Nc2cccc(CCO)c2C1=Cc1ccc(Br)cc1
Temperature: 90 °C
Yield: 41 %

Procedure:
A mixture of 4-(2-hydroxy-ethyl)-1,3-dihydro-indol-2-one (3.0 g, 17 mmol), 4-bromobenzaldehyde (3.1 g, 17 mmol) and piperidine (8.4 mL, 85 mmol) in ethanol (113 mL) was heated at 90° C. for overnight. The reaction mixture was concentrated and the residue was chromatographed on a column of silica gel to give 2.4 g (41%) of 3-(4-bromo-benzylidene)-4-(2-hydroxy-ethyl)-1,3-dihydro-indol-2-one as a yellow orange solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH:31]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21](S(C)(=O)=O)[N:20]=2)=[CH:10][CH:9]=1)=[O:6].[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39]>>[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][N:48]([C:21]2[N:20]=[C:19]([O:18][C:11]3[C:12]4[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=4)[C:8]([NH:7][C:5](=[O:6])[C:4]4[CH:29]=[C:30]([N:32]5[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]5)[CH:31]=[C:2]([F:1])[CH:3]=4)=[CH:9][CH:10]=3)[CH:24]=[CH:23][N:22]=2)[CH2:47][CH2:46]1)=[O:44])([CH3:41])([CH3:39])[CH3:40]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: CS(=O)(=O)c1nccc(Oc2ccc(NC(=O)c3cc(F)cc(N4CCCCC4)c3)c3ccccc23)n1
Product: CC(C)(C)OC(=O)N1CCN(c2nccc(Oc3ccc(NC(=O)c4cc(F)cc(N5CCCCC5)c4)c4ccccc34)n2)CC1

Procedure:
Compound is prepared from 3-fluoro-N-[4-(2-methanesulfonyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-5-piperidin-1-yl-benzamide and N-(tert-butoxy carbonyl)piperazine according to conditions described in general procedure C. Mp: 175-177° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.36 (s, 9 H), 1.58-1.59 (m, 6 H), 3.24-3.31 (m, 8 H), 3.47 (s, 4 H), 6.22 (d, J=5.5 Hz, 1 H), 6.96 (d, J=12.4 Hz, 1 H), 7.15 (d, J=9.1 Hz, 1H), 7.41 (d, J=8.0 Hz, 1 H), 7.47 (s, 1 H), 7.50-7.62 (m, 3 H), 7.82-7.84 (m, 1 H), 7.98 (d, J=7.7 Hz, 1 H), 8.27 (d, J=5.5 Hz, 1 H), 10.43 (s, 1 H).
Reaction SMILES: [N:1]1[C:14]2[C:5](=[CH:6][CH:7]=[C:8]3[C:13]=2[N:12]=[CH:11][CH:10]=[CH:9]3)[CH:4]=[CH:3][CH:2]=1.[C:15]1([Li])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1(C)C=CC=CC=1.ClCCl.[O-2].[O-2].[Mn+4]>[C:15]1([C:2]2[CH:3]=[CH:4][C:5]3[C:14](=[C:13]4[C:8](=[CH:7][CH:6]=3)[CH:9]=[CH:10][CH:11]=[N:12]4)[N:1]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: c1cnc2c(c1)ccc1cccnc12
Reactant: [Li]c1ccccc1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: c1ccc(-c2ccc3ccc4cccnc4c3n2)cc1

Procedure:
A compound E-1 was synthesized by the following method. 1,10-phenanthroline (9.64 g) was reacted with phenyl lithium (100 ml) (1.07 M cyclohexane/ether solution) at 0° C. for 1.5 hours in toluene (250 ml) and treated by a conventional method. The resulting product was reacted with manganese dioxide (93.0 g) at room temperature for 56 hours in dichloromethane (300 ml) and treated by a conventional method to obtain 9.44 g of 2-phenyl-1,10-phenanthroline. To 25 ml of a THF solution of 1,3-dibromobenzene (0.34 ml) was added an t-butyl lithium (1.53 M pentane solution) (7.35 mL) at −78° C., and the resulting mixture was stirred for 1 hour, and then its temperature was raised to 0° C. The resulting solution was added to 85 ml of a THF solution of the obtained 2-phenyl-1,10-phenanthroline (1.44 g), and the resulting mixture was stirred at room temperature for 20 hours, and treated by a conventional method. The resulting product was reacted with manganese dioxide (8.50 g) at room temperature for 23 hours in dichloromethane (85 ml) and treated by a conventional method to obtain 1.08 g of a compound E-1.
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:11]=2)[C:6](=[C:18](OCC)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:5]1=[O:28])(=O)C.[CH3:29][N:30]([CH3:42])[CH2:31][CH2:32][N:33]([C:35]1[CH:41]=[CH:40][C:38]([NH2:39])=[CH:37][CH:36]=1)[CH3:34]>>[CH3:29][N:30]([CH3:42])[CH2:31][CH2:32][N:33]([C:35]1[CH:36]=[CH:37][C:38]([NH:39]/[C:18](=[C:6]2\[C:5](=[O:28])[NH:4][C:12]3[C:7]\2=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:11]=3)/[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:40][CH:41]=1)[CH3:34]
Reactant: CCOC(=O)c1ccc2c(c1)N(C(C)=O)C(=O)C2=C(OCC)c1ccccc1
Reactant: CN(C)CCN(C)c1ccc(N)cc1
Product: CCOC(=O)c1ccc2c(c1)NC(=O)/C2=C(\Nc1ccc(N(C)CCN(C)C)cc1)c1ccccc1

Procedure:
Prepared from 1-acetyl-3-(1-ethoxy-1-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl)-N-methyl-amino)-aniline Rf value: 0.5 (aluminium oxide, methylene chloride/ethanol=20:1) C29H32N4O3
Reaction SMILES: Br[C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[C:14]=3[Cl:23])=O)[CH2:10][C:5]2=[N:4][C:3]=1[C:24]([F:27])([F:26])[F:25].[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.COCCOC.[OH2:43]>C(OCC)(=O)C.CCCC(C)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:23][C:14]1[C:15]([C:19]([F:22])([F:21])[F:20])=[CH:16][CH:17]=[CH:18][C:13]=1[C:11]([N:9]1[CH2:8][CH2:7][N:6]2[C:2]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[C:3]([C:24]([F:27])([F:26])[F:25])[N:4]=[C:5]2[CH2:10]1)=[O:43]
Reactant: O=C(c1cccc(C(F)(F)F)c1Cl)N1CCn2c(nc(C(F)(F)F)c2Br)C1
Reactant: OB(O)c1ccccc1
Reactant: O
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: COCCOC
Solvent: CCCC(C)C
Solvent: CCOC(C)=O
Product: O=C(c1cccc(C(F)(F)F)c1Cl)N1CCn2c(nc(C(F)(F)F)c2-c2ccccc2)C1
Yield: 51.3 %

Procedure:
3-bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (0.100 g, 0.210 mmol, Example 19), phenylboronic acid (0.0384 g, 0.315 mmol), bis(triphenylphosphine)palladium(II)chloride (0.0147 g, 0.021 mmol) and 1,2-dimethoxyethane (DME) (5 mL) were heated at 100° C. for 4 h in a 1,2-dimethoxyethane (DME) (5 mL)/water (5.00 mL) mixture. The reaction mixture was diluted with ethyl acetate (50 ml) and extracted with ethyl acetate (2×50 ml). The combined extracts were washed with brine and dried through a hydromatrix cartridge (Varian, 10 g). The filtrate was concentrated to an oil that was purified by mass-directed automated preparative HPLC to afford, after trituration in iso-hexane, 7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-phenyl-2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (0.051 g, 0.108 mmol, 51.3% yield).
Reaction SMILES: [C:1]1([CH2:7][C:8](O)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.CN(C)CCCN=C=NCC.[NH2:23][C:24]1[N:29]=[C:28]2[NH:30][CH:31]=[C:32]([CH:33]=[C:34]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:35]([NH2:37])=[O:36])[C:27]2=[CH:26][CH:25]=1>ClCCl>[C:1]1([CH2:7][C:8]([NH:23][C:24]2[N:29]=[C:28]3[NH:30][CH:31]=[C:32]([CH:33]=[C:34]([C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=4)[C:35]([NH2:37])=[O:36])[C:27]3=[CH:26][CH:25]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NC(=O)C(=Cc1c[nH]c2nc(N)ccc12)c1ccccc1
Reactant: O=C(O)Cc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: NC(=O)C(=Cc1c[nH]c2nc(NC(=O)Cc3ccccc3)ccc12)c1ccccc1
Yield: 64.7 %

Procedure:
500 mg (3.67 mmol) of phenylacetic acid were dissolved in 20 ml of dichloromethane and 705 mg (3.67 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride were added at 0° C. The mixture is maintained at the same temperature for 30 minutes and then a solution of 680 mg (2.44 mmol) of 3-(6-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-phenyl-propenamide in 10 ml of dichloromethane was added dropwise. After 6 hours at room temperature the mixture was washed with aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate and evaporated. The residue was chromatographed on a silica gel column by using a mixture cyclohexane/ethylacetate 4/1 to give 626 mg (65% yield) of the title compound.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:12]O)[CH:8]=2)[N:3]=1.O=S(Cl)[Cl:16]>C(Cl)Cl>[ClH:16].[Cl:16][CH2:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([CH3:1])[CH:11]=[CH:10]2
Reactant: Cc1ccc2cc(CO)ccc2n1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: Cc1ccc2cc(CCl)ccc2n1
Product: Cl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a stirred solution of (2-methylquinolin-6-yl)methanol SLA 47080A (0.973 g, 5.62 mmol) in dry CH2Cl2 (40 mL) in a 100 mL round-bottomed flask equipped with a magnetic stirrer was added dropwise SOCl2 (8.15 mL, 112 mmol). The mixture was stirred for 2 h at RT then concentrated to dryness at 40° C. under vacuum. The residue was then taken up in CH2Cl2 (20 mL) before concentration back to dryness at 40° C. under vacuum (done 3 times) to give 6-(chloromethyl)-2-methylquinoline hydrochloride SLA 47080B as a yellow solid (1.30 g, quant).
Reaction SMILES: C([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]([CH2:41][C:42]([OH:44])=[O:43])[CH2:12][C:13](=[O:40])[O:14][CH2:15][C:16](=[O:39])[C@@H:17]2[C@@:34]34[CH:35]([O:37][C@@H:32]([CH2:33]3)[C@H:31]3[C@@H:21]([CH2:22][CH2:23][C:24]5[C@:29]3([CH3:30])[CH2:28][CH2:27][C:26](=[O:38])[CH:25]=5)[C@@H:20]4[CH2:19][CH2:18]2)[OH:36])=[CH:7][CH:6]=1)(=O)C.C(N(CC)CC)C>CO>[C:42]([CH2:41][CH:11]([C:8]1[CH:7]=[CH:6][C:5]([OH:4])=[CH:10][CH:9]=1)[CH2:12][C:13](=[O:40])[O:14][CH2:15][C:16](=[O:39])[C@@H:17]1[C@@:34]23[CH:35]([O:37][C@@H:32]([CH2:33]2)[C@H:31]2[C@@H:21]([CH2:22][CH2:23][C:24]4[C@:29]2([CH3:30])[CH2:28][CH2:27][C:26](=[O:38])[CH:25]=4)[C@@H:20]3[CH2:19][CH2:18]1)[OH:36])([OH:44])=[O:43]
Reactant: CC(=O)Oc1ccc(C(CC(=O)O)CC(=O)OCC(=O)[C@H]2CC[C@H]3[C@@H]4CCC5=CC(=O)CC[C@]5(C)[C@H]4[C@@H]4C[C@]23C(O)O4)cc1
Solvent: CCN(CC)CC
Solvent: CO
Product: C[C@]12CCC(=O)C=C1CC[C@@H]1[C@@H]2[C@@H]2C[C@]3(C(O)O2)[C@@H](C(=O)COC(=O)CC(CC(=O)O)c2ccc(O)cc2)CC[C@@H]13
Reaction time: 24 h
Yield: 68.6 %

Procedure:
A solution of 21-[3-(4-acetyloxyphenyl)-4-carboxy-1-oxobutoxy]-11β,18-epoxy-18-hydroxypregn-4-ene-3,20-dione (130 mg) in anhydrous methanol (15 ml) containing triethylamine (0.2 ml) is allowed to stand at room temperature for 24 hours. The methanol is then evaporated in vacuo, the residue is diluted with water (5.0 ml), acidified with 10% hydrochloric acid and extracted with ethyl acetate (three 5.0 ml portions). The ethyl acetate solution is washed with brine, dried over anhydrous magnesium sulfate, evaporated and the residue is subjected to preparative thin-layer chromatography on silica gel plates (using chloroform-methanol, 9:1 for development) to isolate 83 mg of the title compound, melting point 145°-152° C., with consistent spectral data.
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[OH:13][C:14]1[CH:30]=[CH:29][C:17]([C:18]([C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)=[O:19])=[CH:16][CH:15]=1.O[CH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[O:35]1[CH2:36][CH2:37][CH:32]([O:13][C:14]2[CH:30]=[CH:29][C:17]([C:18]([C:20]3[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=3)=[O:19])=[CH:16][CH:15]=2)[CH2:33][CH2:34]1
Reactant: O=C(c1ccc(O)cc1)c1ccc([N+](=O)[O-])cc1
Reactant: OC1CCOCC1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=C(c1ccc(OC2CCOCC2)cc1)c1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Yield: 61.1 %

Procedure:
Diethyl azodicarboxylate (1.47 g, 8.4 mmol) was slowly added dropwise to a solution of 4-(4-hydroxybenzoyl)-nitrobenzene (1.7 g, 7mmol) (prepared as described in Example 1, steps), 4-hydroxytetrahydropyran (0,78 g, 7.7 mmol) and triphenylphosphine (2.2 g, 8.4mmol) in dry tetrahydrofuran (20 mL) while stirring at room temperature under inert atmosphere. The reaction mixture was stirred for an additional hour then quenched with water (1 mL) and concentrated in vacuo. The residue was diluted with water and extracted with ethyl acetate The combined organic extracts were washed with water and brine, dried (Na2SO4), and concentrated in vacuo. The crude product was chromatographed on silica gel (25% ethyl acetate/hexanes) and crystallized from hexanes to give 4-(4-tetrahydropyran-4-yloxybenzoyl)-nitrobenzene (1.4 g, 61%) as a white solid, m.p. 105-106 ° C.; Analysis for C18H17NO5: Calc.: C, 66.05; H, 5.23; N, 4.28; Found: C, 65.95; H, 3.14; N, 4.38. MS m/e (%): 283 (M+; 100).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([NH:13][C@@H:14]([CH2:19][CH:20]=[CH2:21])[C:15]([O:17][CH3:18])=[O:16])(=[O:12])=[O:11])([O-:3])=[O:2].[CH2:22]=[C:23]([CH2:27][CH2:28][CH3:29])[CH2:24][CH2:25]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH2:22]=[C:23]([CH2:27][CH2:28][CH3:29])[CH2:24][CH2:25][N:13]([C@@H:14]([CH2:19][CH:20]=[CH2:21])[C:15]([O:17][CH3:18])=[O:16])[S:10]([C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[N+:1]([O-:3])=[O:2])(=[O:12])=[O:11]
Reactant: C=C(CCC)CCO
Reactant: C=CC[C@H](NS(=O)(=O)c1ccccc1[N+](=O)[O-])C(=O)OC
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: C=CC[C@@H](C(=O)OC)N(CCC(=C)CCC)S(=O)(=O)c1ccccc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 81.7 %

Procedure:
Tetrahydrofuran (30.2 ml) was added to 2.27 g (7.22 mmol) of the title compound produced in step (i) of Example 47 and 1.07 g (9.39 mmol) of the title compound produced in step (ii) of Example 47. The mixture was cooled to 0° C., 2.84 g (10.8 mmol) of triphenylphosphine was added thereto, and the mixture was stirred for 10 min. Diisopropyl azodicarboxylate (2.1 ml, 10.8 mmol) was added thereto. The temperature of the mixture was raised over a period of 2 hr before it was stirred for 19 hr. The solvent was removed under the reduced pressure, and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=20:1) to give 2.42 g (yield 82%) of the title compound.