Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([NH:8][C:9]([C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])=[C:28]([C:41]([F:44])([F:43])[F:42])[CH:27]=2)=[CH:22][N:21]=1)(C(OCC)=O)[C:10](OCC)=[O:11])=O)(C)(C)C.[Li+].[BH4-].C(O)C>C1COCC1>[NH2:8][CH:9]([C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])=[C:28]([C:41]([F:44])([F:42])[F:43])[CH:27]=2)=[CH:22][N:21]=1)[CH2:10][OH:11]
Reactant: CCCCCCCCOc1ccc(-c2ccc(C(NC(=O)OC(C)(C)C)(C(=O)OCC)C(=O)OCC)nc2)cc1C(F)(F)F
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCO
Product: CCCCCCCCOc1ccc(-c2ccc(C(N)CO)nc2)cc1C(F)(F)F
Temperature: 25 °C

Procedure:
Diethyl 2-(tert-butoxycarbonylamino)-2-(5-(4-(octyloxy)-3-(trifluoromethyl)-phenyl)-pyridin-2-yl)malonate 5a (110 mg, 0.176 mmol, 1.0 equiv) in THF (2.0 mL) was added LiBH4 (57 mg, 2.64 mmol, 15.0 equiv) at 0° C., followed by addition of ethanol (0.8 mL) carefully. The resultant was warmed up to room temperature for 10 minutes. LC-MS indicated the completion of the reaction. The reaction was terminated by addition of water. Extraction with ethyl acetate and the organic layer was washed with brine and dried over sodium sulfate and condensed. The residue (crude reduction product with significant decarboxylation) was treated with 2M HCl in THF to afford the title compound after preparative HPLC purification. MS (ESI, M+H+)=411.1; 1H NMR (400 MHz, DMSO-d6) δ 8.95 (d, 1H, J=2.4 Hz), 8.39 (s, 3H), 8.22 (dd, 1H, J=8.4 Hz, J=2.4 Hz), 8.01 (dd, 1H, J=8.4 Hz, J=2.0 Hz), 7.93 (d, 1H, J=2.0 Hz), 7.60 (d, 1H, J=8.4 Hz), 7.39 (d, 1H, J=9.2 Hz), 5.48 (br, 1H), 4.48 (br, 1H), 4.17 (t, 2H, J=6.0 Hz), 3.86-3.72 (m, 2H), 1.75 (m, 2H), 1.44 (m, 2H), 1.29 (m, 8H), 0.86 (t, 3H, J=6.8 Hz).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.[OH-].[Na+].O.[Cl:9][CH2:10][C:11]([N:13]([CH2:22]Cl)[C:14]1[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:21])=[O:12]>C1(C)C=CC=CC=1>[Cl:9][CH2:10][C:11]([N:13]([CH2:22][N:1]1[CH:5]=[CH:4][CH:3]=[N:2]1)[C:14]1[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:21])=[O:12]
Reactant: c1cn[nH]c1
Reactant: Cc1cccc(C)c1N(CCl)C(=O)CCl
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: O
Product: Cc1cccc(C)c1N(Cn1cccn1)C(=O)CCl
Reaction time: 4 h

Procedure:
A solution of 7.5 parts by weight of pyrazole and 4.0 parts by weight of sodium hydroxide in 20 parts by volume of water was added dropwise at 20°-25° C., with vigorous stirring, to a solution of 24.6 parts by weight of 2-chloro-N-chloromethyl-2',6'-dimethylacetanilide and M parts by weight of phase transfer catalyst in 70 parts by volume of toluene, and stirring was continued for 3-5 hours at the same temperature. After complete conversion (checked by thin layer chromatography), the organic phase was washed three times with water, dried and concentrated under reduced pressure at 70° to give G parts by weight of 2-chloro-2',6'-dimethyl-N-(pyrazol-1-yl-methyl)-acetanilide, as shown in the Table which follows.
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[S:6][C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[C:9](=S)[NH:10][C:4]=2[CH:3]=1.[NH2:18][CH2:19][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1>C(OCCO)C>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[S:6][C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[C:9]([NH:18][CH2:19][C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)=[N:10][C:4]=2[CH:3]=1
Reactant: S=C1Nc2cc(Cl)ccc2Sc2ccccc21
Reactant: NCc1cccnc1
Solvent: CCOCCO
Product: Clc1ccc2c(c1)N=C(NCc1cccnc1)c1ccccc1S2
Yield: 68.2 %

Procedure:
A solution of 682 mg (2.5 mmol) of 8-chlorodibenzo[b,f]-1,4-thiazepin-11(10H)-thione (Polivka Z., et al., Coll. Czech. Chem. Comm., 48:1465 (1983)) in 15 mL of 2-ethoxyethanol was treated with 0.5 mL (5.0 mmol) of 3-(aminomethyl)pyridine and heated at reflux overnight. The solvent was removed under reduced pressure and the residue taken up in EtOAc and washed three times with H2O, then saturated NaHCO3 solution and saturated NaCl solution. Drying over MgSO4 and removal of the solvent under reduced pressure left the crude product. Chromatography on silica gel, eluting with CHCl3 /MeOH (98/2) following by recrystallization from CHCl3 /hexane gave 600 mg (69.8% yield) of the product as a white solid, mp 152-153° C. The structure was confirmed by NMR and mass spectroscopy. (m+H)+ =352.
Reaction SMILES: F[C:2]1[C:7]([C:8]2[C:9]3[CH:16]=[CH:15][NH:14][C:10]=3[N:11]=[CH:12][N:13]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:17][C:18]1[C:27]([CH3:28])=[CH:26][CH:25]=[C:24]2[C:19]=1[CH:20]=[CH:21][NH:22][C:23]2=[O:29].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[N:11]1[C:10]2[NH:14][CH:15]=[CH:16][C:9]=2[C:8]([C:7]2[C:2]([NH:17][C:18]3[C:27]([CH3:28])=[CH:26][CH:25]=[C:24]4[C:19]=3[CH:20]=[CH:21][NH:22][C:23]4=[O:29])=[N:3][CH:4]=[CH:5][CH:6]=2)=[N:13][CH:12]=1
Reactant: Cc1ccc2c(=O)[nH]ccc2c1N
Reactant: Fc1ncccc1-c1ncnc2[nH]ccc12
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1ccc2c(=O)[nH]ccc2c1Nc1ncccc1-c1ncnc2[nH]ccc12
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 69.1 %

Procedure:
A mixture of 4-(2-fluoropyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (463 mg, 2162 μmol) and 5-amino-6-methylisoquinolin-1(2H)-one (377 mg, 2162 μmol) in THF (1.5 mL) was sonicated for 5 min until all the solid was mixed well. Lithium bis(trimethylsilyl)amide (9.7 mL, 9.72 mmol; 1 M in THF) was added via a syringe and the reaction tube was sonicated and stirred at RT for 5 min. The reaction was heated to 120° C. in a microwave for 20 min. The reaction mixture was cooled to rt and partitioned between DCM and NaHCO3. The aqueous layer was washed with DCM three times. The combined organic layers were washed with brine and dried over Na2SO4, then concentrated in vacuo. The residue was purified via flash column on silica (MeOH-DCM=0.5-6%) to give a light brown solid 5-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1(2H)-one (550 mg, 69% yield). MS (ESI, pos. ion) m/z: 369
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]([CH2:17][OH:18])=[C:5]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])[N:6]=1.C(OCC)(=O)C.CCCCCCC>ClCCl>[CH3:1][C:2]1[S:3][C:4]([CH:17]=[O:18])=[C:5]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])[N:6]=1
Reactant: COC(=O)CCCCCCc1nc(C)sc1CO
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCCCCCC
Product: COC(=O)CCCCCCc1nc(C)sc1C=O
Reaction time: 0.5 h
Yield: 77.4 %

Procedure:
The solution of 2.8 g of crude 2-methyl-4-(6-carbomethoxyhexyl)-5-hydroxymethyl thiazole (XII, R1 = CH3) in 25 ml of dichloromethane was dropwise added to the solution of 16 g of chromium trioxide-dipyiridine complex in 320 ml of dichloromethane. Stirring of the reaction mixture was continued for 30 minutes, then the reaction mixture was filtered and the filtrate was evaporated in vacuo. After purifying the crude product obtained as evaporation residue, by preparative thin layer chromatography using a silica gel layer as adsorbent and a mixture of 50 % ethyl acetate and 50 % of n-heptane as running solvent, 2.15 g of 2-methyl-4-(6-carbomethoxyhexyl)-thiazole-5-carbaldehyde (XIII, R1 = CH3) were obtained.
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]([CH3:38])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C@@:17]3([OH:35])[CH2:21][N:20]([C:22]([O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])=[O:23])[C@H:19]([C:31]([O:33][CH3:34])=[O:32])[CH2:18]3)=[CH:13][CH:12]=2)=[C:7]([CH:36]=[CH2:37])[CH:6]=1.[CH3:39]I>CN(C=O)C>[CH3:38][N:4]([CH3:3])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14]([C@@:17]3([O:35][CH3:39])[CH2:21][N:20]([C:22]([O:24][CH2:25][CH2:26][Si:27]([CH3:29])([CH3:30])[CH3:28])=[O:23])[C@H:19]([C:31]([O:33][CH3:34])=[O:32])[CH2:18]3)=[CH:15][CH:16]=2)=[C:7]([CH:36]=[CH2:37])[CH:6]=1
Reactant: CI
Reactant: C=Cc1cc(N(C)C)ccc1-c1ccc([C@]2(O)C[C@@H](C(=O)OC)N(C(=O)OCC[Si](C)(C)C)C2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=Cc1cc(N(C)C)ccc1-c1ccc([C@]2(OC)C[C@@H](C(=O)OC)N(C(=O)OCC[Si](C)(C)C)C2)cc1
Temperature: 25 °C
Yield: 68.1 %

Procedure:
NaH (60% in oil) (46 mg, 1.163 mmol) was added to a solution of (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(4′-(dimethylamino)-2′-vinylbiphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate (330 mg, 0.646 mmol) and methyl iodide (0.073 mL, 1.163 mmol) at 0° C. in DMF and stirred at this temperature and allowed to warm up to r.t. overnight. The reaction was then quenched with saturated NH4Cl solution and ether. The ether layer was washed with brine, dried, filtered and evaporated to give crude material. The crude material was purified by flash chromatography on the Biotage (5-45% EtOAc in hexanes) to give the semi purified (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(4′-(dimethylamino)-2′-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-1,2-dicarboxylate (231 mg, 0.440 mmol, 68% yield) as a clear oil. LCMS: rt=1.86 min. [M+H]+=525; Phenomenex-Luna C-18 (5μ) (3.0×50 mm); Solvent A=10% acetonitrile—90% water—0.1% TFA, Solvent B=90% acetonitrile—10% water—0.1% TFA; gradient 0% to 100% solvent B over 2 min. and then hold for 1 min.; 4 mL/min; inj. vol.=5 uL; wavelength=220.
Reaction SMILES: [I-].[CH3:2][S+](C)(C)=O.[OH-].[Na+].[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[C:11]=1[CH:17]=[CH:18][C:19](=[O:21])[CH3:20]>CS(C)=O>[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[C:11]=1[C@@H:17]1[CH2:2][C@H:18]1[C:19](=[O:21])[CH3:20]
Reactant: C[S+](C)(C)=O
Reactant: CC(=O)C=Cc1c(Cl)cccc1Cl
Agent: [I-]
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Product: CC(=O)[C@@H]1C[C@H]1c1c(Cl)cccc1Cl
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A round bottom flask equipped with magnetic stirrer, nitrogen inlet and additional funnel was charged with trimethylsulfoxonium iodide (1.1 g, 5.02 mmol), DMSO (10 ml) and powdered sodium hydroxide (0.175 g, 4.39 mmol). The suspension was stirred for 1.5 hours at ambient temperature to yield a solution. So prepared solution was added drop wise at ambient temperature to a solution of 4-(2,6-dichloro-phenyl)-but-3-en-2-one (0.90 g, 4.18 mmol) prepared as described in example P31 in DMSO (5 ml). The reaction mixture was stirred for 0.5 hours, poured onto ice and extracted with ether (3×25 ml). Combined organic layers were washed with water, brine and dried over anhydrous sodium sulfate. The solvent was removed in vacuo and the residue was purified by flash chromatography over silica gel (25 g) (eluent: n-hexane/ethyl acetate 20:1) to afford 0.30 g (31% of theory) of trans 1-[2-(2,6-dichloro-phenyl)-cyclopropyl]-ethyanone in form of a pale yellow liquid.
Reaction SMILES: P(N)([O-])[O-].[CH2:5]=[CH:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH3:11][C@@:12]12[C@H:22]3[CH2:23][CH2:24][C@:25]4([CH3:35])[C@@:29]5([O:34]C(=O)CC5)[CH2:28][CH2:27][C@H:26]4[C@@H:21]3[CH:20]=[CH:19][C:18]1=[CH:17][C:15](=[O:16])[CH2:14][CH2:13]2.C[Si](Cl)(C)C>CCOCC.C(Cl)Cl.[Cu].C1C=CC=CC=1>[CH2:5]([C@@H:13]1[C@@:12]2([CH3:11])[C:18]([CH2:19][CH2:20][C@@H:21]3[C@@H:22]2[CH2:23][CH2:24][C@@:25]2([CH3:35])[C@H:26]3[CH2:27][CH2:28][C:29]2=[O:34])=[CH:17][C:15](=[O:16])[CH2:14]1)[CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: C[C@]12CCC(=O)C=C1C=C[C@@H]1[C@@H]2CC[C@@]2(C)[C@H]1CC[C@@]21CCC(=O)O1
Reactant: C=CCCCC
Agent: [Cu]
Agent: C[Si](C)(C)Cl
Agent: NP([O-])[O-]
Solvent: ClCCl
Solvent: CCOCC
Solvent: c1ccccc1
Product: CCCCCC[C@H]1CC(=O)C=C2CC[C@@H]3[C@H](CC[C@]4(C)C(=O)CC[C@@H]34)[C@]21C
Temperature: 25 °C
Reaction time: 1 h
Yield: 21 %

Procedure:
(C6H6) (10.1 mg, 0.02 mmol, 0.05 eq.) and the phosphoramidite ligand (21.6 mg, 0.040 mmol, 0.10 eq.) were dissolved in Et2O (2.0 mL) under an argon atmosphere and allowed to stir for 1 h at room temperature. In another flask, Cp2ZrHCl (206.0 mg, 0.80 mmol, 2.0 eq.) was added to a stirred, room temperature, solution of 1-hexene (0.13 mL, 1.0 mmol, 2.5 eq.) in CH2Cl2 (0.40 mL) under an argon atmosphere. After stirring for 40 min, the resulting clear yellow solution was transferred via syringe over about 1 min to the stirred solution containing the copper and ligand under an argon atmosphere. The resulting dark mixture was allowed to stir for an additional 10 min before Canrenone (136.0 mg, 0.40 mmol, 1.0 eq.) and TMSCl (0.26 mL, 2.00 mmol, 5.0 eq.) were added sequentially dropwise via syringe. Stirring at room temperature was continued arbitrarily for 15 h before the reaction was quenched by the addition of Et2O (ca 3 mL) and NH4Cl (1 M aq., ca 1.5 mL). The mixture was partitioned between the aqueous and Et2O layers and the former phase was extracted with Et2O (3×10 mL). The combined organic phase was washed with NaHCO3 (sat. aq., ca 10 mL), dried (Na2SO4), filtered and concentrated in vacuo to give an oil. Flash column chromatography of the yellow residue (30:70 EtOAc/petrol; SiO2) gave major diastereomer (2) (+)-7α-hexyl-17α-hydroxy-3-oxo-pregn-4-ene-21-carboxylic acid γ-lactone (101 mg, 0.24 mmol, 59%) and minor diastereomer (2a) (+)-1α-hexyl-4-androstene-3,17-dione (35 mg, 0.082 mmol, 21%). Diastereomeric ratio (4.8:1) was determined by integration of 1H NMR spectra.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7](Cl)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[F:15][CH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:27]=[CH:26][C:23]([CH:24]=[O:25])=[CH:22][C:21]=1[OH:28].Cl>C(O)C.O.C(OCC)(=O)C>[CH2:7]([O:28][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][C:20]=1[O:19][CH2:18][CH2:17][CH2:16][F:15])[CH:24]=[O:25])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: O=Cc1ccc(OCCCF)c(O)c1
Reactant: ClCc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCO
Product: O=Cc1ccc(OCCCF)c(OCc2ccccc2)c1
Temperature: 90 °C
Reaction time: 1.5 h
Yield: 91 %

Procedure:
Potassium carbonate (3.87 g, 28.0 mmol) and benzyl chloride (3.2 mL, 27.8 mmol) were added to a suspension of 4-(3-fluoropropoxy)-3-hydroxybenzaldehyde described in Production Example 33-1 (4.62 g, 23.3 mmol) in ethanol (46 mL) under nitrogen atmosphere at mom temperature, and the mixture was stirred at 90° C. for 1.5 hours. The reaction mixture was cooled to 0° C., then 2 M hydrochloric acid, ethyl acetate, and water were added for partition. The organic layer was washed with a saturated saline solution, dried over anhydrous magnesium sulfate, and then filtered. The solvent was evaporated and the resultant residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=9:1-3:2-1:1). The target fraction was concentrated under vacuum to obtain the title compound (6.14 g, 91%).
Reaction SMILES: C([O:3][C:4](OCC)([N:13]1[C:18](=[O:19])[C:17]([NH:20][C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])=[CH:16][N:15]=[CH:14]1)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1)C.C(=O)(O)[O-].[Na+]>O1CCCC1.Cl>[CH2:24]([O:23][C:21]([NH:20][C:17]1[C:18](=[O:19])[N:13]([C:4](=[O:3])[CH2:5][C:6]2[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=2)[CH:14]=[N:15][CH:16]=1)=[O:22])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: CCOC(Cc1ccc(F)cc1)(OCC)n1cncc(NC(=O)OCc2ccccc2)c1=O
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C(Nc1cncn(C(=O)Cc2ccc(F)cc2)c1=O)OCc1ccccc1

Procedure:
A solution of 5-benzyloxycarbonylamino-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-1-pyrimidinylacetaldehyde diethylacetal in tetrahydrofuran (7 mL) and 1N hydrochloric acid (5 mL) was heated at 60° C. for 18 h. The solution was cooled and neutralized with saturated aqueous sodium bicarbonate solution (pH 6). The solution was extracted with ethyl acetate and the organic extracts were dried and evaporated to give 5-benzyloxycarbonylamino-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-1-pyrimidinylacetaldehyde as a white solid; NMR: 9.51 (s,1), 9.03 (s,1), 8.47 (s,1), 7.43 (m,9), 5.19 (s,2), 4.76 (s,2).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:39])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]([CH:21]=[C:22]([O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35](=[O:38])[O:36][CH3:37])[CH:23]=1)[C:18]([OH:20])=O.S(Cl)(Cl)=O.[NH:44]([CH2:51][C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47]>>[CH2:49]([O:48][C:46](=[O:47])[CH2:45][N:44]([CH2:51][C:52]([O:54][CH2:55][CH3:56])=[O:53])[C:18](=[O:20])[C:17]1[CH:21]=[C:22]([O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35](=[O:38])[O:36][CH3:37])[CH:23]=[C:15]([O:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C:3]([O:2][CH3:1])=[O:39])[CH:16]=1)[CH3:50]
Reactant: CCOC(=O)CNCC(=O)OCC
Reactant: COC(=O)CCCCCCCCCCOc1cc(OCCCCCCCCCCC(=O)OC)cc(C(=O)O)c1
Solvent: O=S(Cl)Cl
Product: CCOC(=O)CN(CC(=O)OCC)C(=O)c1cc(OCCCCCCCCCCC(=O)OC)cc(OCCCCCCCCCCC(=O)OC)c1

Procedure:
Conversion of 3,5-bis[(11-methoxy-11-oxoundecyl)oxy]benzoic acid to the acid chloride with thionyl chloride followed by treatment with diethyl iminodiacetate as in Example 21 gave N-(2-ethoxy-2-oxoethyl)-N-[3,5-bis[(11-methoxy-11-oxoundecyl)oxy]-benzoyl]glycine ethyl ester as an oil after chromatography on 125 g of silica gel using 20% ethyl acetate-hexane.
Reaction SMILES: C(OC([NH:8][C@@H:9]([CH:40]([CH3:42])[CH3:41])[C:10]([O:12][C@@H:13]1[CH2:29][C@@H:28]2[C@@:16]([CH3:39])([C@@H:17]3[C@@H:25]([CH2:26][CH2:27]2)[C@:24]2(O)[C@@:20]([CH3:38])([C@@H:21]([C:31]4[CH:32]=[CH:33][C:34](=[O:37])[O:35][CH:36]=4)[CH2:22][CH2:23]2)[CH2:19][CH2:18]3)[CH2:15][CH2:14]1)=[O:11])=O)(C)(C)C.Cl>CCOC(C)=O>[NH2:8][C@@H:9]([CH:40]([CH3:42])[CH3:41])[C:10]([O:12][C@@H:13]1[CH2:29][C@@H:28]2[C@@:16]([CH3:39])([C@@H:17]3[C@@H:25]([CH2:26][CH2:27]2)[C:24]2[C@@:20]([CH3:38])([C@@H:21]([C:31]4[CH:32]=[CH:33][C:34](=[O:37])[O:35][CH:36]=4)[CH2:22][CH:23]=2)[CH2:19][CH2:18]3)[CH2:15][CH2:14]1)=[O:11]
Reactant: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)O[C@H]1CC[C@@]2(C)[C@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H](c4ccc(=O)oc4)CC[C@]32O)C1
Agent: Cl
Solvent: CCOC(C)=O
Product: CC(C)[C@H](N)C(=O)O[C@H]1CC[C@@]2(C)[C@H](CC[C@H]3C4=CC[C@H](c5ccc(=O)oc5)[C@@]4(C)CC[C@@H]32)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 53.3 %

Procedure:
To a solution of (S)-((3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl) 2-(tert-butoxy carbonylamino)-3-methylbutanoate (38 mg, 0.065 mmol, 1 eq) in EtOAc (3 mL) was added HCl (4 M in EtOAc, 3 mL) in drops at 0° C. The resulting mixture was warmed to room temperature after 30 min and stirred for 2 h. The mixture was quenched with saturated NaHCO3 solution and extracted with EtOAc (20 mL×3). The organic layer was washed with H2O (10 mL×4) and then dried over anhydrous Na2SO4, concentrated under reduced pressure. The crude product was then purified via Prep-TLC(CH2Cl2:MeOH=10:1) to afford the (S)-((3S,5R,8R,9S,10S,13R,17S)-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)-2,3,4,5,6,7,8,9,10,11,12,13,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl) 2-amino-3-methylbutanoate (16.2 mg, 8.2%). LCMS (M+H+) m/z 468.5.
Reaction SMILES: [CH:1]1[C:14]2[C:5](=C[C:7]3[C:12]([CH:13]=2)=CC=CC=3)C=CC=1.CI.[Mg].C1[C:31]2[C:22](=C[C:24]3[C:29]([CH:30]=2)=CC=CC=3)C=CC=1.[Mg].[CH3:33]C1CC=CC=1.[Co+3:39].C/C(/[O-])=C/C(C)=O>C1COCC1>[CH3:5][C:14]1[CH2:13][CH:12]=[CH:7][CH:1]=1.[CH3:33][Co:39][CH:24]1[CH:29]=[CH:30][CH:31]=[CH:22]1
Reactant: [Co+3]
Reactant: c1ccc2cc3ccccc3cc2c1
Agent: CC(=O)/C=C(/C)[O-]
Agent: CC1=CC=CC1
Agent: [Mg]
Solvent: C1CCOC1
Solvent: CI
Product: C[Co]C1C=CC=C1
Temperature: 25 °C

Procedure:
1.1 g (6.2 mMoles) of anthracene, 300 ml of THF and 0.1 ml of methyliodide are added in an inert gas atmosphere to 7.2 g (300 mMoles) of magnesium powder (particle size <0.15 mm). A yellow-green solution is formed while stirring at room temperature, orange colored magnesium anthracene precipitating therefrom after about 2 hours. The reaction mixture is treated for about 3 hours in an ultrasonic bath (as in Example 1) and then heated while stirring to 60° C. After the addition of 32.0 g (400 mMoles) of monomeric methyl cyclopentadiene, the heat source is removed and 35.6 g (100 mMoles) of solid cobalt-(III)-acetylacetonate are added over a period of 30 minutes, the reaction mixture changing color to deep red-brown with a reflux-producing heat effect (65° C.). After cooling to 23° C., the reaction mixture is filtered off from any undissolved fractions through a G-3-glass frit and the deep red-brown filtrate is concentrated to dryness (max. bath temperature 30° C.) in vacuo (10-1Torr). The residue is taken up in 500 ml of pentane and any undissolved fractions are eliminated by filtration. The clear, deep red filtrate is concentrated to dryness (max. bath temperature 30° C.) in vacuo (10-1Torr) and the residue distilled at 10-3Torr (bath temperature 80°-140° C.). 13.6 g (62.4 mMoles=62.4% of the theoretical) of η5 -methylcyclopentadienyl cobalt methylcyclopentadiene are obtained in the form of a dark red oil which solidifies at around -5° C.
Reaction SMILES: [C:1]([O:9][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([S:20](O)(=[O:22])=[O:21])=[CH:12][C:11]=1[N:24]=[N:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:34])=O>CN(C)C=O>[C:1]([O:9][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([S:20]([Cl:34])(=[O:22])=[O:21])=[CH:12][C:11]=1[N:24]=[N:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(Oc1c(N=Nc2ccccn2)cc(S(=O)(=O)O)c2ccccc12)c1ccccc1
Solvent: CN(C)C=O
Product: O=C(Oc1c(N=Nc2ccccn2)cc(S(=O)(=O)Cl)c2ccccc12)c1ccccc1
Reaction time: 1 h

Procedure:
4-Benzoyloxy-3-(2-pyridylazo)-1-naphthalenesulfonic acid (70 g) was added to thionyl chloride (300 ml). Dimethylformamide (30 ml) was added in portions while the reaction mixture was being stirred. After 1 hour the starting material was all in solution. The reaction mixture was poured into a large quantity of ice after a further 4 hours' stirring. The product was filtered off and dissolved in chloroform. The chloroform layer was shaken with water to destroy any remaining thionyl chloride and dried over magnesium sulfate.
Reaction SMILES: [NH2:1][C:2]1[C:3](=[S:17])[NH:4][C:5]([C:8]2([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:10][CH2:9]2)=[CH:6][CH:7]=1.[NH:18]1[C:26]2[C:21](=[CH:22][C:23]([C:27](O)=[O:28])=[CH:24][CH:25]=2)[CH:20]=[CH:19]1.O.N1(O)C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C.CCOC(C)=O>[SH:17][C:3]1[C:2]([NH:1][C:27]([C:23]2[CH:22]=[C:21]3[C:26](=[CH:25][CH:24]=2)[NH:18][CH:19]=[CH:20]3)=[O:28])=[CH:7][CH:6]=[C:5]([C:8]2([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:10][CH2:9]2)[N:4]=1
Reactant: O=C(O)c1ccc2[nH]ccc2c1
Reactant: Nc1ccc(C2(c3ccccc3)CC2)[nH]c1=S
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: O=C(Nc1ccc(C2(c3ccccc3)CC2)nc1S)c1ccc2[nH]ccc2c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of 3-amino-6-(1-phenylcyclopropyl)pyridine-2(1H)-thione (750 mg, 3.10 mmol), 1H-indole-5-carboxylic acid (499 mg, 3.10 mmol), 1H-benzo[d][1,2,3]triazol-1-ol hydrate (474 mg, 3.10 mmol), and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (593 mg, 3.10 mmol) in DMF (3.1 mL) was stirred at ambient temperature for 16 h. The reaction mixture was diluted with 100 mL of EtOAc, added to a separatory funnel, partitioned with water, washed 2 times with 50 mL of water, separated, dried over sodium sulfate, and concentrated via rotovap to give N-(2-mercapto-6-(1-phenylcyclopropyl)pyridin-3-yl)-1H-indole-5-carboxamide. MS (ESI) m/z: Calculated: 385.1; Observed: 386.4 (M++H).