Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:12])[CH3:11])[N:7]([CH3:13])[C:6]=2[C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1.Cl[C:22]1[N:30]=[CH:29][N:28]=[C:27]2[C:23]=1[N:24]=[CH:25][N:26]2C1CCCCO1.CCN(C(C)C)C(C)C>CC(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH:12][C:22]3[N:30]=[CH:29][N:28]=[C:27]4[C:23]=3[N:24]=[CH:25][NH:26]4)[CH3:11])[N:7]([CH3:13])[C:6]=2[C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1
Reactant: Clc1ncnc2c1ncn2C1CCCCO1
Reactant: C[C@H](N)c1nc2ccc(F)c(-c3ccccn3)c2n1C
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: C[C@H](Nc1ncnc2[nH]cnc12)c1nc2ccc(F)c(-c3ccccn3)c2n1C
Temperature: 90 °C
Yield: 46.6 %

Procedure:
A mixture of (S)-1-(6-fluoro-1-methyl-7-pyridin-2-yl-1H-benzoimidazol-2-yl)ethylamine (100 mg, 0.37 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (88 mg, 0.37 mmol) and DIPEA (340 μL, 1.85 mmol) in IPA (5 mL) were added and the reaction mixture heated at 90° C. for 16 h. The reaction mixture was loaded onto an SCX column to remove the THP group. The column was washed with MeOH and the product was eluted with 2M NH3 in MeOH. The product fractions were collected, concentrated in vacuo and the resultant residue was subjected to flash chromatography (Si—PPC, gradient 0-5% MeOH in DCM) to give 413 as a white solid (67 mg, 47%). LCMS (Method K): RT 2.53 min [M+H]+ 389. 1H NMR (DMSO-d6, 400 MHz): δ 12.7 (1H, br s), 8.68 (1H, ddd, J=4.8, 1.7, 0.8 Hz), 8.13 (2H, d, J=21.9 Hz), 7.91 (1H, br s), 7.90 (1H, td, J=7.8, 1.8 Hz), 7.65 (1H, dd, J=8.8, 4.8 Hz), 7.60 (1H, tq, J=7.7, 1.1 Hz), 7.44 (1H, ddd, J=7.5, 4.8, 1.1 Hz), 7.10 (1H, dd, J=10.4, 8.8 Hz), 5.82-5.67 (1H, m), 3.15 (3H, s), 1.61 (3H, d, J=6.7 Hz)
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([OH:12])=O.Cl.CN.[CH2:16]([N:18](CC)CC)C.C1C=CC2N(O)N=NC=2C=1.O.C(Cl)CCl>CN(C=O)C>[CH3:16][NH:18][C:10]([C:2]1[O:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=1)=[O:12]
Reactant: CCN(CC)CC
Reactant: O=C(O)c1cc2ccccc2o1
Agent: CN
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: O
Solvent: CN(C)C=O
Product: CNC(=O)c1cc2ccccc2o1
Reaction time: 8 h
Yield: 99.9 %

Procedure:
To a solution of 2-benzofurancarboxylic acid (1.62 g, 10 mmole), methylamine hydrochloride (0.79 g, 11 mmole), triethylamine (3.1 mL, 22 mmole), and HOBt.H2O (1.5 g, 11 mmole) in DMF (30 mL) was added EDC (2.1 g, 11 mmole). The reaction was stirred overnight then was concentrated in vacuo. The residue was diluted with 5% NaHCO3 and extracted with CH2Cl2. The combined organic extracts were washed with brine, dried over MgSO4, and concentrated. Flash chromatography on silica gel (3% MeOH/CH2Cl2) gave the title compound (1.75 g, 100%) as white solid: MS (ES) m/e 176 (M+H)+.
Reaction SMILES: C([Li])CCC.C(OP([CH:14]1[S:18][CH2:17][CH2:16][S:15]1)(OCC)=O)C.[CH3:19][C:20]([C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)=O>CCCCCC.O1CCCC1>[S:18]1[CH2:17][CH2:16][S:15][C:14]1=[C:20]([C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)[CH3:19]
Reactant: CC(=O)c1ccc(F)cc1
Reactant: CCOP(=O)(OCC)C1SCCS1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC(=C1SCCS1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A 1.3M solution of n-butyllithium in hexane (28 ml) is added at -78° to a solution of 2-diethoxyphosphoryl-1,3-dithiolane (8.1 g) in dry tetrahydrofuran (70 ml). The mixture is stirred for one hour at -78° and 4-fluoroacetophenone is added (4.3 g). The mixture is stirred for one more hour at the same temperature and slowly warmed to room temperature. After removal of the solvents, the residue is dissolved in dichloromethane (200 ml). The solution is washed with a 10% aqueous solution of ammonium chloride (3×100 ml) and with water (2×100 ml), dried over magnesium sulphate and evaporated in vacuo. The oily residue is purified by column chromatography on silica gel using hexane/toluene 1:1 as eluant. The product is dried in vacuo to constant weight to yield 1-(1,3-dithiolan-2-ylidene)-1-(4-fluorophenyl)-ethane, m.p. 27°-31°.
Reaction SMILES: [C:1]([C:4]1[CH:16]=[CH:15][C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH2:7][C:6]=2[CH:5]=1)(=O)[CH3:2].[CH:17]1([NH2:24])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C(O)C.[BH4-].[Na+]>O>[CH:17]1([NH:24][CH:1]([C:4]2[CH:16]=[CH:15][C:14]3[C:13]4[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=4)[CH2:7][C:6]=3[CH:5]=2)[CH3:2])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: CC(=O)c1ccc2c(c1)Cc1ccccc1-2
Reactant: NC1CCCCCC1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CC(NC1CCCCCC1)c1ccc2c(c1)Cc1ccccc1-2
Temperature: 25 °C
Reaction time: 8 h
Yield: 25.9 %

Procedure:
2-Acetylfluorene (4.17 g, 20 mmol) and cycloheptylamine (2.38 g, 21 mmol) were heated together at 130° C. for 14 hrs and, then, distilled under reduced pressure. To the residue were added ethanol (20 ml) and sodium borohydride (0.76 g, 20 mmol) and the mixture was stirred at room temperature overnight. The mixture was then diluted with water (100 ml) and extracted with chloroform (80 ml×2 times). The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was then purified by silica gel column chromatography to give 1.58 g of the amine compound.
Reaction SMILES: CCN(C(C)C)C(C)C.[C:10]1([CH2:16][CH2:17][C:18]([OH:20])=O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH2:42]([O:49][C:50]([CH:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1)=[O:51])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>CN(C=O)C.O>[CH2:42]([O:49][C:50]([CH:52]1[CH2:57][CH2:56][N:55]([C:18](=[O:20])[CH2:17][CH2:16][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:54][CH2:53]1)=[O:51])[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1
Reactant: O=C(O)CCc1ccccc1
Reactant: O=C(OCc1ccccc1)C1CCNCC1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(OCc1ccccc1)C1CCN(C(=O)CCc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 0.03 h
Yield: 41.3 %

Procedure:
DIPEA (7 g, 9.44 mL, 54.6 mmol) was added to a stirred solution of 3-phenyl-propionic acid (3.27 g, 21.8 mmol) in DMF (15 mL). HOBT (2.94 g, 21.8 mmol) and EDCI (4.16 g, 21.8 mmol) were then added at room temperature. After 2 minutes, piperidine-4-carboxylic acid benzyl ester (4 g, 18.2 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to get the residue. The obtained residue was purified by column chromatography (using 60-120 silica gel and EtOAc in hexane as eluent) to afford 2.64 g (41.25% yield) of 1-(3-phenyl-propionyl)-piperidine-4-carboxylic acid benzyl ester. LCMS Purity: 86.15%.
Reaction SMILES: [CH3:1][C:2]1[NH:16][CH2:15][CH2:14][C:4]2=[C:5]3[C:10](=[N:11][C:3]=12)[CH:9]=[CH:8][C:7]([O:12][CH3:13])=[CH:6]3.[C:17](OC(=O)C)(=[O:19])[CH3:18].C(OCC)(=O)C>N1C=CC=CC=1>[CH2:1]=[C:2]1[C:3]2[NH:11][C:10]3[C:5](=[CH:6][C:7]([O:12][CH3:13])=[CH:8][CH:9]=3)[C:4]=2[CH2:14][CH2:15][N:16]1[C:17](=[O:19])[CH3:18]
Reactant: COc1ccc2c(c1)=C1CCNC(C)=C1N=2
Reactant: CC(=O)OC(C)=O
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: C=C1c2[nH]c3ccc(OC)cc3c2CCN1C(C)=O

Procedure:
To a solution of 10-methoxyharmalan (1 mmol) in pyridine (2 ml) is added acetic anhydride (1.1 eq) . After acid hydrolysis and extraction with ethyl acetate, the crude product is flash-chromatographed (eluent: EtOAc/pet. ether; 50/50). The 1-methylene-2-acetyl-6-methoxy-1,2,3,4-tetrahydro-β-carboline elutes off first.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)([C:14]([NH2:16])=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:25]OC(OC)N(C)C>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2([N:17]([C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)[CH:25]=[N:16][C:14]2=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NC(=O)C1(Nc2ccc(F)cc2)CCN(Cc2ccccc2)CC1
Reactant: COC(OC)N(C)C
Solvent: Cc1ccccc1
Product: O=C1N=CN(c2ccc(F)cc2)C12CCN(Cc1ccccc1)CC2

Procedure:
Mix 1-benzyl-4-(4-fluoro-phenylamino)-piperidine-4-carboxylic acid amide (20 mmol) and hot toluene (240 mL). Add dimethoxy-N,N-dimethylmethanamine (20 mL) and heat at reflux for 48 h. Concentrate in vacuo to obtain a residue. Purify to obtain the title compound.
Reaction SMILES: Cl[CH:2]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)[C:3]1[CH:4]=[C:5]([C:11]2[CH:12]=[CH:13][C:14]([O:17][CH3:18])=[N:15][CH:16]=2)[O:6][C:7]=1[CH2:8][O:9][CH3:10].[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]([NH:34][CH2:35][CH2:36][C:37]([O:39]CC)=[O:38])=[O:33])=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+]>CN(C)C(=O)C.O>[CH:19]1([CH:2]([NH:25][C:26]2[CH:27]=[CH:28][C:29]([C:32]([NH:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:33])=[CH:30][CH:31]=2)[C:3]2[CH:4]=[C:5]([C:11]3[CH:16]=[N:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[O:6][C:7]=2[CH2:8][O:9][CH3:10])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: COCc1oc(-c2ccc(OC)nc2)cc1C(Cl)C1CCCCC1
Reactant: CCOC(=O)CCNC(=O)c1ccc(N)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: COCc1oc(-c2ccc(OC)nc2)cc1C(Nc1ccc(C(=O)NCCC(=O)O)cc1)C1CCCCC1
Temperature: 80 °C
Reaction time: 8 h
Yield: 17.4 %

Procedure:
A mixture of 5-{4-[chloro(cyclohexyl)methyl]-5-(methoxymethyl)furan-2-yl}-2-methoxypyridine (0.4 g), ethyl 3-{[(4-aminophenyl)carbonyl]amino}propanoate (0.3 g), sodium carbonate (0.2 g) and sodium iodide (0.2 g) in N,N-dimethylacetamide (10 mL) was stirred overnight at 80° C. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (25% ethyl acetate/hexane to 70% ethyl acetate/hexane). To the residue were added ethanol (2 mL), tetrahydrofuran (2 mL) and 1N lithium hydroxide (0.45 mL), and the mixture was stirred at room temperature for 1 hr. The solvent was evaporated under reduced pressure, and water (10 mL) was added. The mixture was neutralized with 1N hydrochloric acid under ice-cooling, and stirred for 1 hr. The resulting precipitate was collected by filtration and dried to give the title compound (104 mg, 16%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]([C:13]3[N:17]4[CH:18]=[CH:19][C:20]([CH2:22][OH:23])=[CH:21][C:16]4=[N:15][CH:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH:2]=1>ClCCCl.[O-2].[Mn+4].[O-2]>[NH3:1].[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]([C:13]3[N:17]4[CH:18]=[CH:19][C:20]([CH:22]=[O:23])=[CH:21][C:16]4=[N:15][CH:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH:2]=1
Reactant: OCc1ccn2c(-c3cccc(-c4cccnc4)c3)cnc2c1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCCl
Product: N
Product: O=Cc1ccn2c(-c3cccc(-c4cccnc4)c3)cnc2c1
Temperature: 50 °C
Yield: 115.4 %

Procedure:
A suspension of 3-[3-(pyridin-3-yl)phenyl]imidazo[1,2-α]pyridin-7-ylmethanol (67 mg, 0.22 mmol) in 1,2-dichloroethane (5 ml) was treated with manganese(IV) oxide (0.19 g, 2.2 mmol) and the mixture heated at 50° C. for 18 h. The reaction was cooled to ambient temperature, diluted with 1,2-dichloroethane and pre-adsorbed onto silica. Purification by silica gel chromatography eluting with dichloromethane/methanol/conc. ammonia (95:5:0.5) gave the title compound (38 mg, 58%) as a yellow solid. 1H NMR (360 MHz, CDCl3) δH 7.36-7.45 (2H, m), 7.60-7.73 (3H, m), 7.76-7.78 (1H, m), 7.90-7.95 (1H, m), 7.97 (1H, s), 8.20 (1H, s), 8.40 (1H, d, J 7), 8.65 (1H, d, J 5), 8.90 (1H, s), 10.00 (1H, s); m/z (ES+) 300 (M++H).
Reaction SMILES: [CH3:1][C:2]([C@@H:4]1[C@@:8]2([CH3:24])[CH2:9][CH2:10][C@@H:11]3[C@:21]4([CH2:22]O)[C:15](=[CH:16][C:17]([CH2:19][CH2:20]4)=[O:18])[CH2:14][CH2:13][C@H:12]3[C@@H:7]2[CH2:6][CH2:5]1)=[O:3].CCOC([S-])=[S:29].[K+]>>[SH:29][CH2:22][C@@:21]12[C@@H:11]3[C@H:12]([C@H:7]4[C@:8]([CH3:24])([CH2:9][CH2:10]3)[C@@H:4]([C:2](=[O:3])[CH3:1])[CH2:5][CH2:6]4)[CH2:13][CH2:14][C:15]1=[CH:16][C:17](=[O:18])[CH2:19][CH2:20]2
Reactant: CCOC(=S)[S-]
Reactant: CC(=O)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(CO)[C@H]3CC[C@]12C
Agent: [K+]
Product: CC(=O)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(CS)[C@H]3CC[C@]12C

Procedure:
19-Hydroxyprogesterone is converted to the trifluoromethanesulfonate ester, the sulfonate is displaced with potassium ethyl xanthogenate and the resulting steroid xanthogenate is hydrolyzed to give 19-mercaptopregn-4-ene-3,20-dione, all according to the procedure described by P. J. Bednarski, D. J. Porubek and S. D. Nelson, J. Med. Chem., 28, 775-779 (1985).
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([C:10]([F:13])([F:12])[F:11])[CH:4]=1.[C-:14]#[N:15].[Na+]>CS(C)=O>[Cl:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][C:14]#[N:15])=[CH:4][C:5]=1[C:10]([F:13])([F:12])[F:11]
Reactant: FC(F)(F)c1cc(CBr)ccc1Cl
Reactant: [C-]#N
Agent: [Na+]
Solvent: CS(C)=O
Product: N#CCc1ccc(Cl)c(C(F)(F)F)c1
Temperature: 50 °C

Procedure:
3.94 g of 4-bromomethyl-1-chloro-2-trifluoromethyl-benzene (14.4 mmol) and 1.06 g sodium cyanide (21.6 mmol) were suspended in 12 ml DMSO under argon and stirring and heated to 50° C. for 1 h. The reaction mixture was then poured on water/ice and extracted four times with DCM. The combined organic phases were washed with water, dried with magnesium sulfate, filtered and concentrated in vacuo, leading to 3.188 g of (4-chloro-3-trifluoromethyl-phenyl)-acetonitrile as a dark red oil, which was directly used in the next step.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])[CH:15]=3)[C:10]([S:25]([CH3:27])=[O:26])=[CH:9]2)=[N:6][CH:7]=1.[O:28]1[C:32]2[CH:33]=[CH:34][C:35](B(O)O)=[CH:36][C:31]=2[O:30][CH2:29]1>>[O:28]1[C:32]2[CH:33]=[CH:34][C:35]([C:2]3[CH:3]=[N:4][C:5]([N:8]4[C:16]5[C:11](=[CH:12][CH:13]=[C:14]([C:17]([N:19]6[CH2:24][CH2:23][O:22][CH2:21][CH2:20]6)=[O:18])[CH:15]=5)[C:10]([S:25]([CH3:27])=[O:26])=[CH:9]4)=[N:6][CH:7]=3)=[CH:36][C:31]=2[O:30][CH2:29]1
Reactant: CS(=O)c1cn(-c2ncc(Br)cn2)c2cc(C(=O)N3CCOCC3)ccc12
Reactant: OB(O)c1ccc2c(c1)OCO2
Product: CS(=O)c1cn(-c2ncc(-c3ccc4c(c3)OCO4)cn2)c2cc(C(=O)N3CCOCC3)ccc12

Procedure:
Prepared from (1-(5-bromopyrimidin-2-yl)-3-(methylsulfinyl)-1H-indol-6-yl)(morpholino)-methanone (0.3 g, 0.67 mmol) and benzo[1,3]dioxole-5-boronic acid (0.22 g, 1.33 mmol) analogously to synthesis example 261. White solid. Yield: 0.145 g (44% of theory)
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]1[CH2:13][CH2:12][O:11][C:9](=[O:10])[CH2:8][CH2:7]1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([S:21]([NH2:24])(=[O:23])=[O:22])=[CH:17][CH:16]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl.O1CCCC1>[Cl:14][C:15]1[CH:16]=[CH:17][C:18]([S:21]([NH:24][CH2:2][CH2:3][CH2:4][CH2:5][CH:6]2[CH2:13][CH2:12][O:11][C:9](=[O:10])[CH2:8][CH2:7]2)(=[O:22])=[O:23])=[CH:19][CH:20]=1
Reactant: NS(=O)(=O)c1ccc(Cl)cc1
Reactant: O=C1CCC(CCCCO)CCO1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: ClCCl
Product: O=C1CCC(CCCCNS(=O)(=O)c2ccc(Cl)cc2)CCO1
Temperature: 25 °C

Procedure:
To a solution of 3.53 g of 4-(4-hydroxybutyl)-epsilon-caprolactone in 14 mL methylene chloride and 14 mL tetrahydrofuran is added 4.24 g p-chlorophenylsulfonamide followed by 7.44 g triphenylphosphine. The reaction mixture is stirred at room temperature for one half hour and then 6.1 mL diethyl azodicarboxylate is added slowly with cooling. After the addition, the cooling bath is removed and the solution is stirred at room temperature overnight. The reaction mixture is evaporated to dryness to yield 4-[4-(p-chlorophenylsulfonamido)butyl]-epsilon-caprolactone.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:20]([CH:21]=[O:22])=[C:11]3[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.[C:23]([Mg]Br)#[CH:24].O.Cl>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:20]([CH:21]([OH:22])[C:23]#[CH:24])=[C:11]3[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:15][N:10]3[N:9]=2)=[CH:6][CH:7]=1
Reactant: O=Cc1c(-c2ccc(F)cc2)nn2cc(C(F)(F)F)ccc12
Reactant: C#C[Mg]Br
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Product: C#CC(O)c1c(-c2ccc(F)cc2)nn2cc(C(F)(F)F)ccc12
Temperature: 25 °C
Reaction time: 14 h
Yield: 96.2 %

Procedure:
To a cold (−78° C.) suspension of 2-(4-fluorophenyl)-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine-3-carbaldehyde (11.4 g, 37.0 mmol) in tetrahydrofuran (100 mL) was added ethynylmagnesium bromide (111 mL, 0.5 M in tetrahydrofuran, 56 mmol). The reaction mixture was warmed to room temperature and stirred for 14 hours. The reaction mixture was poured into water and adjusted to neutral pH with 1N aqueous hydrochloric acid. The aqueous mixture was extracted with ethyl acetate. The combined extracts were washed with water and brine. The organic layer was dried over magnesium sulfate. Filtration and concentration provided 1-[2-(4-fluorophenyl)-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl]-2-propyn-1-ol (11.9 g, 96%) as a tan solid. Rf 0.18 (4:1 hexanes:ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 8.81 (s, 1H), 8.15 (d, 1H), 7.75 (m, 2H), 7.35 (d, 1H), 7.19 (t, 2H), 5.76 (s, 1H), 2.71 (d, 1H), 2.60 (d, 1H); MS m/z 335 (M+1).
Reaction SMILES: N1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.C(Br)Br.[CH:16]12CC(CC1)C=[CH:17]2.C=CC1C=CC=CC=1>C1(C)C=CC=CC=1>[CH:10]1[C:9]2[NH:8][C:7]3[C:2](=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:17]=2[CH:16]=[CH:12][CH:11]=1
Reactant: c1ccc(-c2ccccn2)nc1
Reactant: C1=CC2CCC1C2
Solvent: C=Cc1ccccc1
Solvent: BrCBr
Solvent: Cc1ccccc1
Product: c1ccc2c(c1)[nH]c1ccccc12
Temperature: 100 °C
Reaction time: 12 h

Procedure:
To an ampoule, Cu(I)Br (1 mmol), 2,2′-bipyridine (1 mmol), norbornene methylene bromide (NBMBr)(1 mmol) and styrene (St) (100 mmol) were added in 10 mL toluene. The heterogeneous mixture was placed under vacuum and degassed via a freeze-pump-thaw cycle thrice. After degassing, the reaction mixture in ampoule was stirred at 100° C. for 12 hrs. The macromonomer containing polystyrene segments (NBMPStBr) was precipitated from methanol. Polymer was dissolved in THF and reprecipitated from methanol three times. Number average molecular weight of (NBMPStBr) is 160000 and PDI is 1.28(by GPC).
Reaction SMILES: C[C@H]1OC(=O)C2C(O)=CC(O)=C(Cl)C=2CC(=O)C=CC=C[C@H]2O[C@H]2C1.[C:26]([CH2:28][CH2:29][CH2:30][CH2:31]CCCCCCC(Cl)=O)#[N:27].C(Cl)Cl.[N:44]1[CH:49]=CC=C[CH:45]=1>>[CH3:45][N:44]([C:31]1[CH:30]=[CH:29][CH:28]=[CH:26][N:27]=1)[CH3:49]
Reactant: N#CCCCCCCCCCCC(=O)Cl
Reactant: c1ccncc1
Agent: C[C@@H]1C[C@@H]2O[C@@H]2/C=C\C=C\C(=O)Cc2c(Cl)c(O)cc(O)c2C(=O)O1
Agent: C[C@@H]1C[C@@H]2O[C@@H]2C=CC=CC(=O)Cc2c(Cl)c(O)cc(O)c2C(=O)O1
Solvent: ClCCl
Product: CN(C)c1ccccn1

Procedure:
Following a procedure similar to that described in Example 1, but using 365 mg of radicicol, 11-cyanoundecanoyl chloride (prepared from 1.055 g of 11-cyanoundecanoic acid), 7 ml of dry methylene chloride, 1.21 ml of pyridine and a catalytic amount of dimethylaminopyridine, 707 mg of the title compound were obtained.
Reaction SMILES: [CH3:1][N:2]([CH3:12])[CH:3]([C:7]1[CH:11]=[CH:10][S:9][CH:8]=1)[C:4]([OH:6])=O.C(Cl)CCl.[NH2:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([NH2:24])=[O:23])=[C:20]([CH3:27])[CH:19]=1.C([O-])(O)=O.[Na+]>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[CH3:12][N:2]([CH3:1])[CH:3]([C:7]1[CH:11]=[CH:10][S:9][CH:8]=1)[C:4]([NH:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([NH2:24])=[O:23])=[C:20]([CH3:27])[CH:19]=1)=[O:6]
Reactant: CN(C)C(C(=O)O)c1ccsc1
Reactant: Cc1cc(N)ccc1C(N)=O
Agent: CN(C)c1ccncc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Solvent: c1ccncc1
Product: Cc1cc(NC(=O)C(c2ccsc2)N(C)C)ccc1C(N)=O
Temperature: 25 °C
Reaction time: 10 h

Procedure:
To 2-(dimethylamino)-2-(thiophen-3-yl)acetic acid in pyridine was added EDC, DMAP and 4-amino-2-methylbenzamide (E112) and the solution was stirred for 10 hours at room temperature. The mixture was poured into NaHCO3 (sat) and extracted with EtOAc. The extracts were dried (MgSO4), filtered and evaporated. Column chromatography (SiO2, 0-100% EtOAc/Hex) gave pure 4-(2-(dimethylamino)-2-(thiophen-3-yl)acetamido)-2-methylbenzamide (E113).
Reaction SMILES: [BH4-].[Na+].[C:3]1([S:9]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([C:21](=O)[CH3:22])=[CH:18][CH:19]=3)[CH2:14][CH2:13]2)(=[O:11])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.O.[OH-].[Na+]>C(O)(C(F)(F)F)=O>[CH2:21]([C:17]1[CH:16]=[C:15]2[C:20](=[CH:19][CH:18]=1)[N:12]([S:9]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)(=[O:11])=[O:10])[CH2:13][CH2:14]2)[CH3:22]
Reactant: CC(=O)c1ccc2c(c1)CCN2S(=O)(=O)c1ccccc1
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: CCc1ccc2c(c1)CCN2S(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 42.4 %

Procedure:
To TFA (1600 mL) at 0° C. was added sodium borohydride (64.0 g, 1.69 mol) over 1 h. To this mixture was added dropwise a solution of 1-(1-(phenylsulfonyl)indolin-5-yl)ethanone (40.0 g, 0.133 mol) in TFA (700 mL) over 1 h. The mixture was then stirred overnight at 25° C. After dilution with H2O (1600 mL), the mixture was made basic by the addition of sodium hydroxide pellets at 0° C. The organic layer was separated and the aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica column to give 5-ethyl-1-(phenylsulfonyl)indoline (16.2 g, 47% over two steps).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([C:16]2[NH:20][CH:19]=[N:18][CH:17]=2)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl[C:29]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CN(C=O)C.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([C:16]2[N:20]=[CH:19][N:18]([C:29]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)([C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)[C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH:17]=2)[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Oc1ccc(OCc2ccccc2)cc1-c1cnc[nH]1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Oc1ccc(OCc2ccccc2)cc1-c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Reaction time: 0.17 h
Yield: 92.7 %

Procedure:
To a solution of 4-(benzyloxy)-2-(1H-imidazol-5-yl)phenol (0.488 mmol) in DMF (5 mL) was added triethylamine (0.585 mmol). After stirring for 10 min, chlorotriphenylmethane (0.512 mmol) was added and continued stirring for 16 h. The reaction mixture was diluted with water (25 mL) and the precipitated product was filtered and washed with water (3×10 mL). The solid cake was dissolved in CH2Cl2, washed with water, brine and dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. The crude was purified by column chromatography to afford the final product (0.230 g, 47%).