Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F-].[Cs+].Br[C:4]1[N:9]=[C:8]2[N:10]([CH2:13][C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[N:20]=[CH:19][CH:18]=[CH:17]4)[N:11]=[N:12][C:7]2=[N:6][CH:5]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[N:34][N:35](C(OC(C)(C)C)=O)[CH:36]=2)O1.C(Cl)Cl>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.COCCOC>[NH:34]1[CH:33]=[C:32]([C:4]2[N:9]=[C:8]3[N:10]([CH2:13][C:14]4[CH:15]=[C:16]5[C:21](=[CH:22][CH:23]=4)[N:20]=[CH:19][CH:18]=[CH:17]5)[N:11]=[N:12][C:7]3=[N:6][CH:5]=2)[CH:36]=[N:35]1
Reactant: CC(C)(C)OC(=O)n1cc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: Brc1cnc2nnn(Cc3ccc4ncccc4c3)c2n1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: [Cs+]
Solvent: O
Solvent: COCCOC
Solvent: ClCCl
Product: c1cnc2ccc(Cn3nnc4ncc(-c5cn[nH]c5)nc43)cc2c1
Temperature: 80 °C
Yield: 63 %

Procedure:
A mixture of DME (3.0 mL) and 1 M aqueous CsF (0.88 mL) was degassed by bubbling in Argon for 10 minutes. The mixture was transferred via syringe to a vial containing 6-((6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)quinoline (100 mg, 0.29 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (95 mg, 0.32 mmol) and Pd(dppf)2Cl2.CH2Cl2 (6.1 mg, 0.01 mmol). The vial was capped and heated to 80° C. for 16 hours. Water (5 mL) was added to the crude reaction mixture and the resulting suspension was filtered. The precipitate was washed with water and air dried. The precipitate was purified by column chromatography using gradient elution with methanol and dichloromethane to afford 6-((6-(1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)quinoline (60 mg, 62%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[S:12]1[CH:16]=[CH:15][CH:14]=[C:13]1B(O)O>>[F:9][C:8]([F:11])([F:10])[C:5]1[CH:6]=[CH:7][C:2]([C:13]2[S:12][CH:16]=[CH:15][CH:14]=2)=[CH:3][CH:4]=1
Reactant: OB(O)c1cccs1
Reactant: FC(F)(F)c1ccc(Br)cc1
Product: FC(F)(F)c1ccc(-c2cccs2)cc1

Procedure:
4-Bromobenzotrifluoride and thiophene-2-boronic acid were treated in a manner similar to Reference Example 20-(1) to give 2-(4-trifluoromethylphenyl)thiophene as colorless crystals.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]([OH:10])=[O:9].Cl.[CH3:12]O>>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]([O:10][CH3:12])=[O:9]
Reactant: COCCCCCC(=O)O
Reactant: CO
Agent: Cl
Product: COCCCCCC(=O)OC
Reaction time: 8 h

Procedure:
6-Methoxy-caproic acid (6.17 g) was dissolved in dry methanol (90 ml) containing hydrogen chloride (catalytic amount) and held overnight at room temperature. The solvent was distilled off from the reaction solution under reduced pressure to give methyl 6-methoxy-caproate. Yield; 5.68 g
Reaction SMILES: [C:1]1([CH:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[O:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:28][C:29]#[N:30]>CN(C)C=O>[C:29]([CH2:28][N:12]1[CH2:13][CH2:14][CH:9]([O:8][CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:10][CH2:11]1)#[N:30]
Reactant: c1ccc(C(OC2CCNCC2)c2ccccc2)cc1
Reactant: N#CCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: N#CCN1CCC(OC(c2ccccc2)c2ccccc2)CC1

Procedure:
To the solution of 55.0 g of 4-diphenylmethoxy-piperidine in 250 ml of dimethylformamide, 32.0 g of anhydrous potassium carbonate are added while stirring, followed by the dropwise addition of the solution of 17.2 g of chloroacetonitrile in 25 ml of dimethylformamide and the suspension is stirred overnight at room temperature. It is concentrated, partitioned between water and diethyl ether, the organic phase washed with saturated aqueous sodium chloride, dried and evaporated. The residue is recrystallized from ethanol, to yield the 1-cyanomethyl-4-diphenylmethoxypiperidine melting at 78°-80°.
Reaction SMILES: [CH2:1]([O:3][P:4]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2([CH2:22][CH:23]3[C:36]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[O:30][C:29]4[C:24]3=[CH:25][CH:26]=[CH:27][CH:28]=4)[NH:19]C(=O)N[C:16]2=[O:21])=[CH:11][CH:10]=1)([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].[OH-:37].[Na+]>O>[NH2:19][C:15]([C:12]1[CH:13]=[CH:14][C:9]([P:4]([O:3][CH2:1][CH3:2])([O:6][CH2:7][CH3:8])=[O:5])=[CH:10][CH:11]=1)([CH2:22][CH:23]1[C:36]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[O:30][C:29]2[C:24]1=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:16]([OH:37])=[O:21]
Reactant: CCOP(=O)(OCC)c1ccc(C2(CC3c4ccccc4Oc4ccccc43)NC(=O)NC2=O)cc1
Reactant: [OH-]
Agent: [Na+]
Solvent: O
Product: CCOP(=O)(OCC)c1ccc(C(N)(CC2c3ccccc3Oc3ccccc32)C(=O)O)cc1

Procedure:
5-(4-Diethylphosphonophenyl)-5-(9H-xanthen-9-ylmethyl)hydantoin (1.0 g), 2.0 mmol) was reacted with aqueous sodium hydroxide (2M, 6 ml) in water (4 ml) following the procedure described in Example 1 (vi) to give 2-amino-3-(9H-xanthen-9-yl)-2-(4-diethylphosphonophenyl)propanoic acid as a white powder.
Reaction SMILES: [N:1]([C@H:4]1[C@@H:9]([CH3:10])[CH2:8][N:7]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[NH:17][C:18](=[O:34])[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]3[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=3[F:33])[N:20]=2)[CH2:6][C@H:5]1[NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[N+:2]=[N-:3].C.[CH3:44][O:45][CH2:46][C:47]#[CH:48].C(N(CC)CC)C>O1CCOCC1.[Cu]>[F:32][C:31]1[CH:30]=[CH:29][CH:28]=[C:27]([F:33])[C:26]=1[C:21]1[N:20]=[C:19]([C:18]([NH:17][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][C:11]=2[N:7]2[CH2:8][C@H:9]([CH3:10])[C@H:4]([N:1]3[CH:48]=[C:47]([CH2:46][O:45][CH3:44])[N:3]=[N:2]3)[C@H:5]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:6]2)=[O:34])[CH:24]=[CH:23][C:22]=1[F:25]
Reactant: C#CCOC
Reactant: C[C@H]1CN(c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C[C@@H](NC(=O)OC(C)(C)C)[C@H]1N=[N+]=[N-]
Agent: [Cu]
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: COCc1cn([C@H]2[C@@H](C)CN(c3ccncc3NC(=O)c3ccc(F)c(-c4c(F)cccc4F)n3)C[C@H]2NC(=O)OC(C)(C)C)nn1
Temperature: 70 °C
Yield: 95 %

Procedure:
In a high pressure vial was added tert-butyl (3R,4S,5S)-4-azido-1-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-5-methylpiperidin-3-ylcarbamate (1.0 equiv.), copper in charcoal (0.2 equiv.), 3-methoxyprop-1-yne (1.5 equiv.) and triethylamine (1.5 equiv.), in dioxane (0.20 M) to give a black suspension. The pressure tube was sealed and the mixture was stirred with heating to 70° C. for 16 hrs. The reaction was cooled to RT, filtered through celite, concentrated to yield tert-butyl (3R,4S,5S)-1-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-4-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)-5-methylpiperidin-3-ylcarbamate in 95% yield. LC/MS (m/z)=653.2 (MH+), Rt=0.86 min.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([O:12][CH3:13])=[O:11].C(=O)([O-])[O-].[K+].[K+].[OH:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1>CS(C)=O.[Cu]I>[F:1][C:2]1[CH:7]=[C:6]([N:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]2=[O:20])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([O:12][CH3:13])=[O:11]
Reactant: Oc1ccccn1
Reactant: COC(=O)Cc1ccc(I)cc1F
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: COC(=O)Cc1ccc(-n2ccccc2=O)cc1F
Temperature: 125 °C
Reaction time: 14 h
Yield: 38.3 %

Procedure:
Part G. To methyl (2-fluoro-4-iodophenyl)acetate (1.0 g, 3.4 mmol) in dimethylsulfoxide (68 mL) was added potassium carbonate (1.9 g, 14 mmol) and 2-hydroxypyridine (650 mg, 6.8 mmol). The resulting mixture was degassed (alternate vacuum/nitrogen three times), and copper(I) iodide (650 mg, 3.4 mmol) was added in one portion. The light green mixture was again degassed (vac/N2) and warmed to 125° C. After 14 h, the brown-black mixture was cooled and poured into saturated aqueous ammonium hydroxide (50 mL) and ethyl acetate (100 mL). The layers were separated, and the organic layers were washed with water (2×50 mL) and saturated aqueous sodium chloride. The organic layers were concentrated, and the resulting residue was purified by radial chromatography (20-100% ethyl acetate in hexanes) to afford methyl [2-fluoro-4-(2-oxo-1(2H)-pyridinyl)-phenyl]acetate (340 mg, 39%) as a green-brown solid. LC/MS (ESI+): 262.2 (M+H)+. 1H NMR (CDCl3) δ 7.22-7.36 (m, 3H), 7.08 (t, 2H), 6.54 (d, 1H), 6.18 (t, 1H), 3.63 (s, 5H).
Reaction SMILES: [Cl:1][C:2]1[CH:31]=[CH:30][C:5]([CH:6]=[CH:7][CH2:8][N:9]2[C:14](=[O:15])[C:13]([NH:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:12][C:11]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)=[N:10]2)=[CH:4][CH:3]=1.[C:32]1([CH2:38][CH2:39][CH2:40]Br)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:6]=[CH:7][CH2:8][N:9]2[C:14](=[O:15])[C:13]([N:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:40][CH2:39][CH2:38][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[CH:12][C:11]([C:22]3[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=3)=[N:10]2)=[CH:30][CH:31]=1
Reactant: BrCCCc1ccccc1
Reactant: CCOC(=O)Nc1cc(-c2ccc(OC)cc2)nn(CC=Cc2ccc(Cl)cc2)c1=O
Product: CCOC(=O)N(CCCc1ccccc1)c1cc(-c2ccc(OC)cc2)nn(CC=Cc2ccc(Cl)cc2)c1=O
Yield: 68.7 %

Procedure:
Using 2-(4-chlorocinnamyl)-4-ethoxycarbonylamino-6-(4-methoxyphenyl)-2H-pyridazin-3-one (70 mg) and 3-phenylpropyl bromide as starting materials, the procedures of Example 116 were repeated likewise, whereby the title compound (61 mg, 68.7%) was obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([C:10]([CH3:13])([CH3:12])[CH3:11])[CH:7]=[C:6]([N+:14]([O-:16])=[O:15])[C:5]=1Cl)([O-:3])=[O:2].[CH3:18][NH:19][CH3:20].C(O)C>O>[CH3:18][N:19]([CH3:20])[C:5]1[C:4]([N+:1]([O-:3])=[O:2])=[CH:9][C:8]([C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:7][C:6]=1[N+:14]([O-:16])=[O:15]
Reactant: CC(C)(C)c1cc([N+](=O)[O-])c(Cl)c([N+](=O)[O-])c1
Reactant: CNC
Solvent: CCO
Solvent: O
Product: CN(C)c1c([N+](=O)[O-])cc(C(C)(C)C)cc1[N+](=O)[O-]
Reaction time: 1 h

Procedure:
Two and six-tenths grams (.01 mole) of 2,6-dinitro-4-t-butylchlorobenzene was reacted with 3.1 grams of 40% aqueous solution of dimethylamine in 50 ml. ethanol. The temperature was slowly increased as follows: 30° C. for 1 hour, 40° C. for 1 hour, 50° C. for one hour, then 80° C. for five hours. When the reaction was complete, about 100 ml. H2O was added, precipitating the product. This was filtered, washed with portions of H2O and upon recrystallization from ethanol yielded 2.5 grams of N,N-dimethyl-2,6-dinitro-4-t-butylaniline in the form of orange-yellow needles melting at 101-102° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:16]2[C:15](=[O:17])[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][C:13]=3[O:18][CH3:19])[C:8](=[O:20])[C:7]=2[CH:6]=[C:5]([CH3:21])[CH:4]=1.[Br:22]N1C(C)(C)C(=O)N(Br)C1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:22][CH2:21][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[C:16]2[C:15](=[O:17])[C:14]3[C:9]([C:8](=[O:20])[C:7]=2[CH:6]=1)=[CH:10][CH:11]=[CH:12][C:13]=3[O:18][CH3:19]
Reactant: CC1(C)C(=O)N(Br)C(=O)N1Br
Reactant: COc1cccc2c1C(=O)c1c(OC)cc(C)cc1C2=O
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: COc1cccc2c1C(=O)c1c(OC)cc(CBr)cc1C2=O
Temperature: 25 °C
Yield: 95 %

Procedure:
To a hot solution of 1,8-dimethoxy-3-methyl-9,10-anthraquinone (4.5 g, 16 mM) and 1,3-dibromo-5,5-dimethylhydantoin (2.75 g, 19.2 mM) in carbon tetrachloride (500 mL) is added benzoyl peroxide (0.7 g), and the mixture is heated under reflux for 5 hours. The mixture is allowed to cool to room temperature. Insoluble hydantoin is removed by filtration, the filtrate is concentrated to dryness, and the residue recrystallized twice from ethyl acetate to give 3-bromomethyl-1,8-dimethoxy-9,10-anthraquinone (3.3 g, 57%), mp 176-178° C. 1H NMR (CDCl3) δ: 4.01 (3H, s, OMe), 4.03 (3H, s, OMe), 4.52 (2H, s, CH2Br), 7.26-7.84 (5H, m, aromatic H). Analyses (C17H13BrO4). Calculated: C, 56.53; H, 3.63; Br, 22.12. Found: C, 56.48; H, 3.67; Br, 21.93.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:22]1([CH:28]2[C:32]3[S:33][CH:34]=[CH:35][C:31]=3[C:30](=O)[O:29]2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.Cl>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[C:30]1[O:29][CH:28]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:32]2[S:33][CH:34]=[CH:35][C:31]1=2
Reactant: O=C1Cc2cc(F)ccc2N1
Reactant: O=C1OC(c2ccccc2)c2sccc21
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C1Nc2ccc(F)cc2C1=C1OC(c2ccccc2)c2sccc21
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 2.9 %

Procedure:
A solution of 5-fluoro-1,3-dihydro-indol-2-one (340 mg, 2.25 mmol.) in THF (3 mL) is cooled to 0° C. under an Argon atmosphere and treated with a solution of lithium bis(trimethylsilyl)amide (4.5 mL of a 1 M solution in THF, 4.5 mmol) dropwise. The resulting solution is stirred at 0° C. for 10 min and then warmed to room temperature. A solution of 6-phenyl-6H-thieno[2,3-c]furan-4-one, (320 mg, 1.5 mmol) in THF (6 mL) is added dropwise to the reaction mixture. The resulting solution is stirred for 4 h. and then poured into aqueous 10% HCl solution (50 mL). The resulting mixture is heated to 90° C. for 45 min and stirred at room temperature for 36 h. The precipitate which formed is collected by filtration and dried. The solid obtained is purified by chromatography (silica gel, ethyl acetate/hexane) to give the title compound as a yellow solid (15 mg, 3%).
Reaction SMILES: Cl[CH:2]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH:11]([CH3:13])[CH3:12])=[CH:6][CH:5]=1)[CH3:3].[Na].O>CN(C)C=O>[CH2:10]([C:7]1[CH:6]=[CH:5][C:4]([CH:2]=[CH2:3])=[CH:9][CH:8]=1)[CH:11]([CH3:13])[CH3:12]
Reactant: CC(C)Cc1ccc(C(C)Cl)cc1
Agent: [Na]
Solvent: O
Solvent: CN(C)C=O
Product: C=Cc1ccc(CC(C)C)cc1
Yield: 93.8 %

Procedure:
A flat bottomed vial was charged with a mixture of 1-chloro-1-(4-isobutylphenyl)ethane (500 mg; 2.54 mmol), 250 mg (11 mmol) of sodium spheres in 5 mL of dry dimethylformamide. The vial was immersed in an ultrasound cleaner filled with water, and sonicated at room temperature for 2 hours. The reaction mixture was carefully treated with 30 mL of water and extracted with ether (3×30 mL). The ether extract was washed with water (3 ×15 mL) and dried over anhydrous MgSO4. It was filtered and stripped off the solvent to obtain 382 mg (94% yield) of pure 4-isobutylstyrene.
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][C:3]=1[CH:4]=[C:5]([CH3:8])[CH2:6]Cl.[OH2:16]>O1CCCC1>[CH2:10]([NH:13][C:6](=[O:16])[C:5]([CH3:8])=[CH:4][C:3]1[CH:9]=[C:10]([N+:13]([O-:15])=[O:14])[CH:11]=[CH:12][C:2]=1[Cl:1])[CH:9]=[CH2:3]
Reactant: CC(=Cc1cc([N+](=O)[O-])ccc1Cl)CCl
Reactant: O
Solvent: C1CCOC1
Product: C=CCNC(=O)C(C)=Cc1cc([N+](=O)[O-])ccc1Cl
Reaction time: 2 h
Yield: 81 %

Procedure:
At 5° to 10° C., 10.4 g (0.04 mol) of 2-chloro-5-nitro-α-methylcinnamyl chloride in 100 ml of tetrahydrofuran was added to 4.6 g (0.08 mol) of alkylamine in 50 ml of tetrahydrofuran. After 2 hours the solvent was stripped off, and the remaining mixture was stirred into water. The solid which formed was isolated. Drying of the solid gave 8.1 g (81% of theory) of 2-chloro-5-nitro-α-methylcinnamic acid-N-allylamide of m.p. 111°-112° C.
Reaction SMILES: Cl.[Si:2]([O:19][C@H:20]([C:27]1[S:28][CH:29]=[CH:30][N:31]=1)[C@H:21]1[CH2:26][CH2:25][CH2:24][NH2+:23][CH2:22]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[OH-].[Na+].C(OCC)(=O)C>CO.O>[Si:2]([O:19][C@H:20]([C:27]1[S:28][CH:29]=[CH:30][N:31]=1)[C@H:21]1[CH2:26][CH2:25][CH2:24][NH:23][CH2:22]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CC(C)(C)[Si](O[C@H](c1nccs1)[C@H]1CCC[NH2+]C1)(c1ccccc1)c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: O
Product: CC(C)(C)[Si](O[C@H](c1nccs1)[C@H]1CCCNC1)(c1ccccc1)c1ccccc1

Procedure:
30 ml of hydrogen chloride (4 M in 1,4-dioxane) were added dropwise at +5° C. to a solution of 1.08 g (2.0 mmol) of tert-butyl (S)-3-[(S)-(tert-butyldiphenylsilanyloxy)thiazol-2-ylmethyl]-piperidine-1-carboxylate in 30 ml of dichloromethane. The reaction mixture was stirred at room temperature for 2 hours. Evaporation gave 1.03 g of (S)-3-[(S)-(tert-butyldiphenylsilanyloxy)thiazol-2-yl-methyl]piperidinium hydrochloride; HPLC/MS (M+H)+=437; rotation value in methanol [α]20D=−18.1°. The hydrochloride was dissolved in 10 ml of water, cooled in an ice bath, and 1 ml of sodium hydroxide solution (2 M) was added dropwise. The precipitate was taken up with ethyl acetate, washed with saturated sodium chloride solution, dried over sodium sufate, filtered and evaporated, giving 0.8 g of (S)-3-[(S)-(tert-butyldiphenylsilanyloxy)thiazol-2-ylmethyl]piperidine as amorphous resin; HPLC/MS (M+H)+=437; rotation value in methanol [α]20D=−22.1°. 1H NMR (400 MHz, DMSO) δ 7.69-7.56 (m, 4H), 7.52-7.38 (m, 6H), 7.38-7.26 (m, 2H), 4.84 (d, J=6.6, 1H), 4.03 (q, J=7.1, 1H), 2.94 (d, J=11.2, 1H), 2.73 (d, J=11.8, 1H), 2.25-2.10 (m, 2H), 1.78 (dtd, J=10.5, 6.9, 3.3, 1H), 1.49-1.30 (m, 2H), 1.19-1.10 (m, 2H), 1.04-0.93 (m, 9H).
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[C:6]1[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=1.[C:12]1([CH3:22])[CH:17]=[CH:16][C:15]([S:18](Cl)(=[O:20])=[O:19])=[CH:14][CH:13]=1>>[C:12]1([CH3:22])[CH:17]=[CH:16][C:15]([S:18]([N:1]2[CH2:5][CH2:4][CH2:3][CH:2]2[C:6]2[CH:7]=[CH:8][N:9]=[CH:10][CH:11]=2)(=[O:20])=[O:19])=[CH:14][CH:13]=1
Reactant: c1cc(C2CCCN2)ccn1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Product: Cc1ccc(S(=O)(=O)N2CCCC2c2ccncc2)cc1

Procedure:
The title compound, pale brown solid, m.p. 158° C. and MS: m/e=302 (M+) was prepared in accordance with the general method of example 1e from (RS)-4-(2-pyrrolidinyl)-pyridine and toluene-4-sulfonyl chloride.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[CH:7]=[C:6]([N+:13]([O-:15])=[O:14])[C:5]=1[CH3:16])([O-:3])=[O:2].CO[CH:19](OC)[N:20]([CH3:22])[CH3:21]>>[CH3:19][N:20]([CH:22]=[CH:16][C:5]1[C:4]([N+:1]([O-:3])=[O:2])=[CH:9][C:8]([N+:10]([O-:12])=[O:11])=[CH:7][C:6]=1[N+:13]([O-:15])=[O:14])[CH3:21]
Reactant: Cc1c([N+](=O)[O-])cc([N+](=O)[O-])cc1[N+](=O)[O-]
Reactant: COC(OC)N(C)C
Product: CN(C)C=Cc1c([N+](=O)[O-])cc([N+](=O)[O-])cc1[N+](=O)[O-]
Yield: 90 %

Procedure:
A mixture of 2,4,6-trinitrotoluene (0.5 g, 2.2 mmol) and N,N-dimethylformamide dimethyl acetal (2.7 ml) was refluxed for 2 h under nitrogen atmosphere. A dark purple red product was separated. N,N-dimethylformamide dimethyl acetal was removed under reduced pressure to give the title compound (0.56 g, 90% yield). m.p.: 155-157° C.; IR (KBr): 1635, 1585, 1530 cm-1; 1H NMR (CDCl3): δ 3.05 (s, 6H, 2×CH3); 5.65 (d, J=13.17 Hz, 1H, α-CH); 6.87 (d, J=13.2 Hz, 1H, β-CH); 8.55 (s, 2H, Ar--H); UV: Imax: 474 nm (CH3CN).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:30])[C:5]([O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([CH3:22])[CH:6]([C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:10][CH:9]=1)O)[CH3:2].B(F)(F)F.CCOCC.C([SiH](CC)CC)C.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:30])[C:5]([O:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)([CH3:22])[CH2:6][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[CH:10][CH:9]=1)[CH3:2]
Reactant: CCOC(=O)C(C)(Oc1ccccc1)C(O)c1ccc(OCc2ccccc2)cc1
Agent: CC[SiH](CC)CC
Agent: FB(F)F
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: CCOCC
Product: CCOC(=O)C(C)(Cc1ccc(OCc2ccccc2)cc1)Oc1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
2-Phenoxy-3-(4-benzyloxyphenyl)-3-hydroxy-2-methylpropionic acid ethyl ester (3.84 g, 9.5 mmol) in anhydrous CH2Cl2 (30 mL) was cooled to 0° C. and treated with BF3-Et2O (1.16 mL, 9.5 mmol) and triethylsilane (1.51 mL, 9.5 mmol). The mixture was stirred for 2 h and gradually warmed to ambient temperature. Saturated aqueous Na2CO3 (15 mL) was added and the mixture was stirred vigorously. The solution was partitioned and the organic layer was washed twice with water and brine, dried over Na2SO4, and concentrated in vacuo to produce 2-phenoxy-3-(4-benzyloxyphenyl)-2-methyl-propionic acid ethyl ester, shown above, as a colorless oil (1.34 g, 36%). Rf=0.90 (9:1 hexanes:ethyl acetate). 1H NMR (300 MHz, CDCl3): δ 7.36-7.42 (m, 3H), 7.34 (t, 1H), 7.17-7.24 (m, 5H), 6.98 (t, 1H), 6.91 (d, 2H), 6.83 (d, 2H), 5.05 (s, 2H), 4.22 (q, 1H, J=7.1), 3.26 (d, 1H, J=13.7), 3.13 (d, 1H, J=13.7), 1.40 (s, 3H), 1.22 (t, 3H, J=7.1). MS [EI+] 408 (M+NH4)+.
Reaction SMILES: [CH3:1][N:2]1[CH:7]2[CH2:8][C:9]3[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][C:16]=4[CH:6]2[CH2:5][CH:4]([C:18]([OH:20])=[O:19])[CH2:3]1)[NH:11][CH:10]=3.[OH-].[K+].C1(C)C=CC(S(O[CH:33]2[CH2:37][CH2:36][CH2:35][CH2:34]2)(=O)=O)=CC=1>CS(C)=O>[CH:33]1([N:11]2[C:12]3[C:17]4[C:9]([CH2:8][C@@H:7]5[C@@H:6]([C:16]=4[CH:15]=[CH:14][CH:13]=3)[CH2:5][CH:4]([C:18]([OH:20])=[O:19])[CH2:3][N:2]5[CH3:1])=[CH:10]2)[CH2:37][CH2:36][CH2:35][CH2:34]1
Reactant: CN1CC(C(=O)O)CC2c3cccc4[nH]cc(c34)CC21
Reactant: Cc1ccc(S(=O)(=O)OC2CCCC2)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Product: CN1CC(C(=O)O)C[C@@H]2c3cccc4c3c(cn4C3CCCC3)C[C@H]21
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 87.6 %

Procedure:
To a 500 ml, three-neck round bottom flask was added 10.0 g (33.9 mmol) of 92% pure 9,10-dihydrolysergic acid, 11.72 g (180.0 mmol) of 86% pure powdered potassium hydroxide and 150 ml of DMSO. The mixture was stirred for 15 minutes and 10.22 g (42.6 mmol) of p-toluenesulfonic acid, cyclopentyl ester was added. The mixture was stirred at room temperature for about 20 hours and an additional 3.11 g (13.0 mmol) of p-toluenesulfonic acid, cyclopentyl ester was added. The mixture was stirred for an additional two hours and was poured into 750 ml of ice water. The mixture was washed twice with 200 ml portions of ethyl acetate and the pH of the aqueous phase was lowered to about 5 with glacial acetic acid. The mixture was cooled and the precipitated solid was collected by vacuum filtration. The solid was washed with water and dried under vacuum to provide 10.05 g of the title compound having a purity of 96.3 %. Yield 85.2%. Exact mass: theory 339.20725; found 339.20633.
Reaction SMILES: [Mg].[CH:2]1([C:5]([CH2:7][CH2:8][CH2:9][CH3:10])=[O:6])[CH2:4][CH2:3]1.[CH2:11](Br)[C:12]#[CH:13].[Cl-].[NH4+]>CCOCC>[CH:2]1([C:5]([OH:6])([CH2:7][CH2:8][CH2:9][CH3:10])[CH2:13][C:12]#[CH:11])[CH2:4][CH2:3]1
Reactant: C#CCBr
Reactant: CCCCC(=O)C1CC1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: CCOCC
Product: C#CCC(O)(CCCC)C1CC1

Procedure:
To a stirred, refluxing suspension of amalgam prepared from 6.2 g of magnesium and 50 mg of mercuric chloride suspended in 60 ml of ether is added a solution of a mixture of 30.4 g of n-butyl cyclopropyl ketone (Example 8) and 29.8 g of propargyl bromide in 65 ml of ether during 60 minutes. After reaction at reflux temperature for an additional 30 minutes, the mixture is cooled to 0° and treated with 35 ml of saturated ammonium chloride. The mixture is diluted with ether and filtered through Celite. The filtrate is washed with brine, dried over potassium carbonate, and concentrated. The residue is distilled to provide a liquid, b.p. 93°-94° C (12 mm), pmr spectrums (CDCl3): δ 0.43 (cyclopropyl hydrogens), 2.07 (triplet, HC≡C), and 2.44 (doublet, C≡CCH2).
Reaction SMILES: [Br:1][C:2]1[C:10]2[N:9]=[CH:8][NH:7][C:6]=2[CH:5]=[C:4]([Cl:11])[CH:3]=1.[C:12](=O)([O-])[O-].[K+].[K+].IC.O>CN(C)C=O>[Br:1][C:2]1[C:10]2[N:9]=[CH:8][N:7]([CH3:12])[C:6]=2[CH:5]=[C:4]([Cl:11])[CH:3]=1
Reactant: Clc1cc(Br)c2nc[nH]c2c1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Solvent: O
Product: Cn1cnc2c(Br)cc(Cl)cc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 38 %

Procedure:
To a solution of 109c (3.5 g, 15 mmol) in N,N-dimethylformamide (30 mL) was added potassium carbonate (4.14 g, 30 mmol) and iodomethane (1.4 mL, 22.7 mmol). The reaction was stirred at room temperature for overnight. Water (50 mL) was added to quench the reaction and the resulting mixture was extracted with ethyl acetate (5 mL×3). The combined organic phase was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by column chromatography eluting with petroleum ether/ethyl acetate (from 4:1 to 1:2) to afford 109d as a white solid (1.4 g, 38%). LCMS: [M+H]+ 245/247. 1H NMR (500 MHz, CDCl3) δ 7.89 (s, 1H), 7.46 (d, J=2.0 Hz, 1H), 7.32 (d, J=2.0 Hz, 1H), 3.81 (s, 3H).