Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[CH2:5][C@@H:6]([CH2:10][CH2:11][C@H:12]([CH2:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[C:13]([OH:15])=[O:14])[C:7]([OH:9])=[O:8].[H][H]>CO.CCOC(C)=O.[Pd]>[CH2:5]([C@@H:6]([CH2:10][CH2:11][C@H:12]([CH2:16][CH:17]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]1)[C:13]([OH:15])=[O:14])[C:7]([OH:9])=[O:8])[C:4]1[CH:23]=[CH:24][CH:25]=[CH:2][CH:3]=1
Reactant: O=C(O)[C@H](CC[C@H](CC1CCCCC1)C(=O)O)Cc1cccc(Cl)c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: O=C(O)[C@H](CC[C@H](CC1CCCCC1)C(=O)O)Cc1ccccc1
Yield: 30 %

Procedure:
To a solution of (2R,5R)-2-(3-chlorobenzyl)-5-(cyclohexylmethyl)hexanedioic acid (37 mg, 0.10 mmol) in MeOH (2 mL) and EtOAc (2 mL) was bubbled through Argon for 5 min. Then 5% Pd/C (40 mg) was added to the solution. The reaction was stirred at 1 atm of hydrogen (balloon) for 2 hr. The reaction was filtered through CELITE® and washed with MeOH. The combined filtrate and MeOH wash was concentrated. The resulting residue was purified using RP prep-HPLC (Method B). The desired fraction was concentrated in vacuum and lyophilized with CH3CN to give (2R,5R)-2-benzyl-5-(cyclohexylmethyl)hexanedioic acid (10 mg, 0.030 mmol, 30% yield) as a white solid.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[C:15]([F:23])[CH:14]=3)[N:11]=[C:10]([C:24]([F:27])([F:26])[F:25])[CH:9]=2)[CH:5]=[CH:4][C:3]=1[OH:28].[Cl-:29].O>C(Cl)Cl>[Cl:29][C:4]1[CH:5]=[C:6]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[C:15]([F:23])[CH:14]=3)[N:11]=[C:10]([C:24]([F:25])([F:26])[F:27])[CH:9]=2)[CH:7]=[C:2]([CH3:1])[C:3]=1[OH:28]
Reactant: [Cl-]
Reactant: Cc1cc(-c2cc(C(F)(F)F)nn2-c2ccc(S(C)(=O)=O)c(F)c2)ccc1O
Solvent: ClCCl
Solvent: O
Product: Cc1cc(-c2cc(C(F)(F)F)nn2-c2ccc(S(C)(=O)=O)c(F)c2)cc(Cl)c1O
Reaction time: 0.5 h
Yield: 88.6 %

Procedure:
To a stirred solution of 2-methyl-4-[1-[3-fluoro-4-(methylsulfonyl)phenyl]-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenol (0.332 g, 0.8 mmol) in CH2Cl2 (10 ml) was added sulfryl chloride (0.113 g, 0.84 mmol) at room temperature, and the mixture was stirred for 30 minutes. The reaction mixture was poured into water, and the whole was extracted with CH2Cl2. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was recystallized with CH2Cl2-hexane to give the subtitle compound (0.318 g, 88.6% yield).
Reaction SMILES: [ClH:1].[F:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[CH2:14][CH2:13][NH:12][CH2:11][C@H:10]2[CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]3[O:23][CH2:24][O:25][C:19]=3[CH:18]=2)=[CH:5][CH:4]=1.Br[CH2:27][CH2:28][C:29]#[N:30].C(=O)([O-])[O-].[K+].[K+].CC(C)=O>C(O)C.C(OCC)C>[ClH:1].[C:29]([CH2:28][CH2:27][N:12]1[CH2:13][CH2:14][C@@H:9]([C:6]2[CH:7]=[CH:8][C:3]([F:2])=[CH:4][CH:5]=2)[C@H:10]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]3[O:23][CH2:24][O:25][C:19]=3[CH:18]=2)[CH2:11]1)#[N:30]
Reactant: Fc1ccc([C@@H]2CCNC[C@H]2COc2ccc3c(c2)OCO3)cc1
Reactant: N#CCCBr
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CC(C)=O
Solvent: CCO
Product: N#CCCN1CC[C@@H](c2ccc(F)cc2)[C@H](COc2ccc3c(c2)OCO3)C1

Procedure:
1 g of (-)-trans-4-(4-fluorophenyl)-3-(3,4-methylene dioxyphenoxymethyl)-piperidine hydrochloride in 50 ml 99.9% ethanol was mixed with 3-bromopropionitrile (7 ml) and 2 g potassium carbonate. The mixture was refluxed for 70 h. After cooling 25 ml acetone and 25 ml diethylether were added, the precipitate filtered off, and the filtrate evaporated in vacuo. The residue was extracted with 1N NaOH/ether, the ether layer dried (MgSO4) and evaporated to dryness. The residue was dissolved in acetone and excess conc. HCl was added. Subsequent evaporation gave a hard glass, which was purified on a silica gel column using 99.5% ethanol as eluent. The title compound was isolated, and its structure confirmed by the IR and NMR data. M.p. 156° C.
Reaction SMILES: [NH2:1][C:2]1[C:7]([Cl:8])=[C:6]([CH3:9])[N:5]=[C:4]([CH3:10])[N:3]=1.[CH2:11]([O:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23]Cl)=[CH:21][C:20]=1[O:27][CH3:28])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[H-].[Na+]>CN1CCCC1=O>[CH2:11]([O:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH:1][C:2]2[C:7]([Cl:8])=[C:6]([CH3:9])[N:5]=[C:4]([CH3:10])[N:3]=2)=[CH:21][C:20]=1[O:27][CH3:28])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: Cc1nc(C)c(Cl)c(N)n1
Reactant: COc1cc(CCl)ccc1OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN1CCCC1=O
Product: COc1cc(CNc2nc(C)nc(C)c2Cl)ccc1OCc1ccccc1

Procedure:
In analogy to the method described in example A1, 3.67 g (22.8 mmol) of 4-amino-5-chloro-2,6-dimethylpyrimidine, 6.0 g (22.8 mmol) of 4-benzyloxy-3-methoxybenzyl chloride and 0.91 g (23 mmol) of sodium hydride (60% suspension in liquid paraffin) are reacted in a total of 190 ml of N-methylpyrrolidone. After chromatography on silica gel (mobile phase: toluene/dioxane=10:1) and crystallization from petroleum ether, the title compound is isolated as a pale beige solid. Yield: 3.42 g (39% of theory). m.p.: 101-105° C.
Reaction SMILES: [OH:1][C:2]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:3]=1[C:4]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=[O:10])=[O:5].C(=O)([O-])[O-].[K+].[K+].Br[CH2:28][CH2:29][CH2:30][CH3:31]>CC(C)=O.O>[CH2:28]([O:1][C:2]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:3]=1[C:4]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=[O:10])=[O:5])[CH2:29][CH2:30][CH3:31]
Reactant: COc1ccc(C(=O)c2cccc(C(=O)O)c2)c(O)c1
Reactant: CCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: CCCCOc1cc(OC)ccc1C(=O)c1cccc(C(=O)O)c1
Temperature: 25 °C
Yield: 41.5 %

Procedure:
A mixture of 3-(2-hydroxy-4-methoxybenzoyl)benzoic acid (1 g) and anhydrous potassium carbonate (1.12 g) is heated under reflux in acetone (30 ml) for 30 minutes. Then, 1-bromobutane (1.1 g) is added and the resulting mixture heated under reflux for 48 hours. The reaction mixture is then cooled to room temperature, diluted with water (100 ml) and extracted with ether (3×30 ml). The ether extracts are dried over magnesium sulfate, filtered and evaporated to dryness. The residue is heated under reflux with 2N sodium hydroxide (2 ml) for 4 hours. The mixture is then acidified with concentrated hydrochloric acid, diluted with water (50 ml) and extracted with ether (3×25 ml). Ether extracts are dried over magnesium sulfate, filtered, and evaporated to dryness. The residue is recrystallized from aqueous ethanol to yield 3-(2-butoxy-4methoxybenzoyl)benzoic acid (0.5 g), m.p. 112°-115° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][C:18]([O:20][CH3:21])=[O:19])=[CH:13][CH:12]=2)=[N:8][CH:9]=1)([O-:3])=[O:2].[H-].[Na+].[CH3:24]I.[Cl-].[NH4+]>CN(C=O)C>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]([CH3:24])[C:18]([O:20][CH3:21])=[O:19])=[CH:13][CH:12]=2)=[N:8][CH:9]=1)([O-:3])=[O:2]
Reactant: CI
Reactant: COC(=O)Cc1ccc(Oc2ccc([N+](=O)[O-])cn2)cc1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: COC(=O)C(C)c1ccc(Oc2ccc([N+](=O)[O-])cn2)cc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of methyl 2-[4-(5-nitropyridin-2-yloxy)phenyl]acetate (0.50 g, 1.7 mmol) in DMF (10 mL) were added 60% sodium hydride (0.153 g, 3.8 mmol) and methyl iodide (0.13 mL, 2.1 mmol), and the resulting reaction solution was stirred for 1 hour at 0° C. To the reaction solution was added saturated aqueous ammonium chloride, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated aqueous sodium chloride. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel chromatography (n-hexane:ethyl acetate=8:1), to thereby yield 0.32 g of the title compound.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[C:15]3[O:14][CH:13]([CH2:16][NH2:17])[CH2:12][C:11]=3[CH:10]=[CH:9][CH:8]=2)[CH:2]=1.C(N(C(C)C)CC)(C)C.Cl[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29]>>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[C:15]3[O:14][CH:13]([CH2:16][NH:17][C:28](=[O:29])[O:30][CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH2:12][C:11]=3[CH:10]=[CH:9][CH:8]=2)[CH:2]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: NCC1Cc2cccc(-c3cccnc3)c2O1
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NCC1Cc2cccc(-c3cccnc3)c2O1)OCc1ccccc1
Yield: 57.3 %

Procedure:
Treatment of (±)-1-(7-pyridin-3-yl-2,3-dihydro-1-benzofuran-2-yl)methanamine (0.770 g, 3.40 mmol) with diisopropylethylamine (0.660 g, 5.1 mmol) and benzyl chloroformate (0.778 g, 4.08 mmol) generally according to the procedure described for Intermediate 12 provided 0.702 g (57%) of (±)-benzyl [(7-pyridin-3-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]carbamate as an amber oil.
Reaction SMILES: [CH:1]1([C:6]([OH:31])([CH2:21][C:22]2[O:23]C(C)(C)O[C:26](=[O:28])[CH:27]=2)[CH2:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([CH3:19])([CH3:18])[C:16]#[N:17])=[C:11]([F:20])[CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(C(O)(CC2OC(C)(C)OC(=O)C=2)CCC2C=CC(C3(C#N)CC3)=C(F)C=2)CCCC1>>[CH:1]1([C:6]2([CH2:7][CH2:8][C:9]3[CH:14]=[CH:13][C:12]([C:15]([CH3:19])([CH3:18])[C:16]#[N:17])=[C:11]([F:20])[CH:10]=3)[CH2:21][C:22](=[O:23])[CH2:27][C:26](=[O:28])[O:31]2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CC1(C)OC(=O)C=C(CC(O)(CCc2ccc(C(C)(C)C#N)c(F)c2)C2CCCC2)O1
Agent: CC1(C)OC(=O)C=C(CC(O)(CCc2ccc(C3(C#N)CC3)c(F)c2)C2CCCC2)O1
Product: CC(C)(C#N)c1ccc(CCC2(C3CCCC3)CC(=O)CC(=O)O2)cc1F

Procedure:
The desired product was prepared analogously to Step 5 of Example A(86), substituting 2-{4-[3-Cyclopentyl-4-(2,2-dimethyl-6-oxo-6H-[1,3]dioxin-4-yl)-3-hydroxy-butyl]-2-fluoro-phenyl}-2-methyl-propionitrile (1.23 g, 2.9 mmol) from Step 3 below in place of 1-{4-[3-Cyclopentyl-4-(2,2-dimethyl-6-oxo-6H-[1,3]dioxin-4-yl)-3-hydroxy-butyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile. Yield: 0.614 g, 56%.
Reaction SMILES: C([Li])CCC.[C:6]1([C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:13]Br)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[B:21]([O-])([O-:27])[O:22]CCCC.Cl>CCCCCC.C1COCC1.O>[C:6]1([C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:13][B:21]([OH:27])[OH:22])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: BrC=C(c1ccccc1)c1ccccc1
Reactant: CCCCOB([O-])[O-]
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: O
Solvent: C1CCOC1
Product: OB(O)C=C(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
n-Butyllithium in hexane (2.5 M, 20 mL) was added slowly under nitrogen to a stirred solution of 2,2-diphenylvinyl bromide (6.50 g, 25.1 mmol) in THF (40 mL) at −78° C. and then the mixture was stirred further for 1 h. n-Butyl borate (15 mL, 55.5 mmol) was added at −78° C. before the mixture was warmed slowly to room temperature and stirred overnight. Water (50 mL) was added, followed by conc. HCl (100 mL) to acidify the mixture, which was then stirred for 3 h. The reaction mixture was extracted with EtOAc and the combined organic phases were dried over MgSO4. Concentration under reduced pressure gave 2,2-diphenylvinyl boronic acid, which, without further purification, was reacted with pinacol (4.25 g, 36.0 mmol) in toluene under reflux for 2 h to effect condensation by the azeotropic removal of the water formed. The mixture was concentrated under reduced pressure and the residue was purified by column chromatography (hexanes/CH2Cl2=1/1) to afford C (4.10 g, 53%) as transparent liquid.
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])[NH:6]2.[CH2:19]([N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)[CH3:20].C(N(CC)CC)C>C(O)C>[Cl:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:5]1[NH:6][C:7]2[C:3]([N:4]=1)=[C:2]([N:24]1[CH2:25][CH2:26][N:21]([CH2:19][CH3:20])[CH2:22][CH2:23]1)[N:10]=[C:9]([CH3:11])[N:8]=2
Reactant: CCN1CCNCC1
Reactant: Cc1nc(Cl)c2nc(-c3ccccc3Cl)[nH]c2n1
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCN1CCN(c2nc(C)nc3[nH]c(-c4ccccc4Cl)nc23)CC1
Yield: 41.2 %

Procedure:
Heat a solution of 6-chloro-8-(2-chloro-phenyl)-2-methyl-9H-purine (0.5 g, 0.0017 mol), N-ethyl piperazine (0.22 g, 0.0019 mol), and triethyl amine (0.22 g, 0.0022 mol) in ethanol (10 mL) at 90° C. for 8 h. Alternatively, heat the reaction with microwave irradiation. Upon reaction completion, concentrate the reaction mixture under reduced pressure. Dissolve the residue in dry dichloromethane and wash with saturated sodium bicarbonate solution, water, and brine. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate under reduced pressure to give a residue. Purify the residue on a silica gel column using MeOH:DCM (2:98) as eluent to give 8-(2-Chlorophenyl)-6-(4-ethylpiperazin-1-yl)-2-methyl-9H-purine (0.25 g). Add HCl (2 M solution in ethanol) (1.0 eq) into the mixture of 8-(2-chlorophenyl)-6-(4-ethylpiperazin-1-yl)-2-methyl-9H-purine (0.25 g, 0.0007 mol) in dry ether (2.5 mL) at 0° C. and stir for one hour at room temperature. Filter the precipitate, wash with ether and DCM. Dry under vacuum to give the title compound (0.275 g) as a white solid. ES/MS m/z 357 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[CH3:8].[N+:10]([O-])([OH:12])=[O:11]>ClCCCl.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[F:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([N+:10]([O-:12])=[O:11])=[C:4]([OH:9])[CH:3]=1
Reactant: Cc1ccc(O)cc1F
Reactant: O=[N+]([O-])O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Solvent: ClCCCl
Solvent: O
Product: Cc1cc([N+](=O)[O-])c(O)cc1F
Temperature: 25 °C
Reaction time: 4 h
Yield: 57 %

Procedure:
3-fluoro-4-methylphenol (3.66 g, 29.0 mmol) was dissolved in DCE (32 mL) and tetrabutylammonium bromide (0.935 g, 2.90 mmol) was added. HNO3 70% (3.7 mL, 58 mmol) was diluted with H2O (33 mL) to make a 7% HNO3 solution. This solution was added to the reaction mixture, which was then stirred at rt for 4 h at which time the reaction was judged complete by TLC. The reaction was poured into H2O and extracted with DCM (3×). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The resulting residue was adsorbed onto silica gel and flash chromatographed to give the title compound of step A (2.83 g, 57%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.10 (s, 1H), 7.89 (d, J=8.1 Hz, 1H), 6.85 (d, J=11.0 Hz, 1H), 2.13 (s, 3H).
Reaction SMILES: [C:1]([NH:5][CH2:6][CH:7]([OH:28])[CH2:8][O:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16]C)=[O:15])=[CH:12][C:11]=1[C:20](=[O:27])[CH2:21][CH2:22][C:23]([O:25]C)=[O:24])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>C(O)(=O)C>[C:1]([NH:5][CH2:6][CH:7]([OH:28])[CH2:8][O:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([OH:16])=[O:15])=[CH:12][C:11]=1[C:20](=[O:27])[CH2:21][CH2:22][C:23]([OH:25])=[O:24])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)CCC(=O)c1cc(C(=O)OC)ccc1OCC(O)CNC(C)(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Product: CC(C)(C)NCC(O)COc1ccc(C(=O)O)cc1C(=O)CCC(=O)O

Procedure:
Methyl 4-(3-t-butylamino-2-hydroxypropoxy)-3-(3-carbomethoxypropionyl)benzoate was heated with dilute sodium hydroxide solution until hydrolysis was complete. The solution was neutralised with acetic acid then evaporated under reduced pressure. Extraction of the residue with ethanol and evaporation of the extracts gave 4-(3-t-butylamino-2-hydroxypropoxy)-3-(3-carboxypropionyl)benzoic acid.
Reaction SMILES: [CH2:1]([N:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[NH:17]C=O)[CH3:2].Cl>CO>[NH2:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[CH2:10][CH2:9][CH:4]1[CH2:5][CH2:6][CH2:7][CH2:8][N:3]1[CH2:1][CH3:2]
Reactant: CCN1CCCCC1CCc1ccccc1NC=O
Agent: Cl
Solvent: CO
Product: CCN1CCCCC1CCc1ccccc1N
Reaction time: 24 h

Procedure:
A solution of 1-ethyl-2-(2-formamidophenethyl)piperidine (27.6 g., 0.11 mole), methanol (450 ml.) and concentrated HCl (100 ml.) allowed to stand for 24 hr. provides 2-(2-aminophenethyl)-1-ethylpiperidine, purified by distillation, yield 17.72 g. (69%), b.p. 107°-128° C./0.1 Torr, nD30° 1.5510.
Reaction SMILES: [OH:1][C:2]1[C:7]2[C:8]3[CH:16]([CH3:17])[CH2:15][S:14][C:9]=3[C:10]([CH3:13])([CH3:12])[O:11][C:6]=2[CH:5]=[C:4]([CH:18]([CH:20]([CH3:26])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH3:19])[CH:3]=1.Cl.[N:28]1([CH2:34][CH2:35][CH2:36][C:37](O)=[O:38])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[CH3:26][CH:20]([CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH:18]([C:4]1[CH:3]=[C:2]([O:1][C:37](=[O:38])[CH2:36][CH2:35][CH2:34][N:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)[C:7]2[C:8]3[CH:16]([CH3:17])[CH2:15][S:14][C:9]=3[C:10]([CH3:13])([CH3:12])[O:11][C:6]=2[CH:5]=1)[CH3:19]
Reactant: CCCCCC(C)C(C)c1cc(O)c2c(c1)OC(C)(C)C1=C2C(C)CS1
Reactant: O=C(O)CCCN1CCCCC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Solvent: ClCCl
Product: CCCCCC(C)C(C)c1cc(OC(=O)CCCN2CCCCC2)c2c(c1)OC(C)(C)C1=C2C(C)CS1

Procedure:
A combination of 2.4 g. (6.4 mmole) of 1,2-dihydro-9-hydroxy-7-(3-methyl-2-octyl)-1,4,4,-trimethyl-4H-thieno[2,3-c][1]benzopyran, 1.33 g. (6.4 mmole) of γ-piperidinobutyric acid hydrochloride, 1.40 g. (6.75 mmole) of dicyclohexylcarbodiimide and 125 ml. of methylene chloride was stirred at room temperature for 18 hours. The reaction mixture was cooled and the byproduct of dicyclohexylurea was removed by filtration. The methylene chloride was distilled off on a rotary evaporator to give a colorless, foamy residue, which was purified on 80 g. of magnesium silicate (60-100 mesh) using a graded methanol/chloroform solvent system. The fractions were monitored by thin layer chromatography, and the appropriate fractions were combined to give 1.23 g. (37%) of the desired material as a golden gum. The infrared and nuclear magnetic resonance spectra were in agreement with the desired product.
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(N(CC)CC)C.Cl[C:25]([O:27][CH2:28][CH3:29])=[O:26]>ClCCl>[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:25]([O:27][CH2:28][CH3:29])=[O:26]
Reactant: CCOC(=O)Cl
Reactant: COc1ccc2c(c1)=C1CCNC(C)=C1N=2
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=C1c2[nH]c3ccc(OC)cc3c2CCN1C(=O)OCC
Temperature: 0 °C

Procedure:
To a solution of 10-methoxyharmalan in dichloro-methane is added triethylamine (1.5 eq) and the mixture is cooled to 0° C. A solution (1/5 v/v) of ethyl chloro-formate in dichloromethane is then added dropwise. The mixture is stirred at 0° C. until the starting material disappears (2 h). After evaporation of the solvent, the crude product is separated out on a chromatography plate (eluent: EtOAc/pet. ether; 50/50).
Reaction SMILES: Br([O-])(=O)=[O:2].[Na+].[CH2:6]([OH:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C(#N)C.O>[C:6]([OH:2])(=[O:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: OCc1ccccc1
Reactant: [O-][Br+2]([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: O=C(O)c1ccccc1
Yield: 90.6 %

Procedure:
The separated catalyst was added to a fresh batch of sodium bromate (0.3 g) and benzyl alcohol (0.216 g, 2 mmol) in acetonitrile:water (5:7, 12 ml). The above procedure was repeated to give benzoic acid as a white solid (0.22 g, 90%).
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[N:11]1[C:14](=[O:15])[C:13]([CH3:17])([CH3:16])[NH:12]1)[CH2:8]2.Br[CH:19]1[CH2:24][CH2:23][CH2:22][CH:21]=[CH:20]1>>[CH:24]1([N:12]2[C:13]([CH3:17])([CH3:16])[C:14](=[O:15])[N:11]2[CH:2]2[CH:3]3[CH2:4][CH:5]4[CH2:6][CH:7]([CH2:8][CH:1]2[CH2:10]4)[CH2:9]3)[CH2:23][CH2:22][CH2:21][CH:20]=[CH:19]1
Reactant: CC1(C)NN(C2C3CC4CC(C3)CC2C4)C1=O
Reactant: BrC1C=CCCC1
Product: CC1(C)C(=O)N(C2C3CC4CC(C3)CC2C4)N1C1C=CCCC1

Procedure:
2-(Adamantan-2-yl)-4,4-dimethyl-1,2-diazetidin-3-one prepared in Process 3 of Example 12, and 3-bromocyclohexene were used for a similar reaction and treatment as Process 6 of Example 1, and the title compound was obtained as a colorless oil.
Reaction SMILES: [CH2:1]([O:5][C:6]1[C:11](I)=[CH:10][C:9]([C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:8][C:7]=1[C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:2][CH2:3][CH3:4].C([Li])(C)(C)C.[B:26](OC)([O:29]C)[O:27]C>COCCOC>[CH2:1]([O:5][C:6]1[C:7]([C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:8][C:9]([C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:10][C:11]=1[B:26]([OH:29])[OH:27])[CH2:2][CH2:3][CH3:4]
Reactant: COB(OC)OC
Reactant: CCCCOc1c(I)cc(C(C)(C)C)cc1C(C)(C)C
Agent: [Li]C(C)(C)C
Solvent: COCCOC
Product: CCCCOc1c(B(O)O)cc(C(C)(C)C)cc1C(C)(C)C
Temperature: -75 °C
Reaction time: 0.75 h
Yield: 98 %

Procedure:
2-Butoxy-1,5-di-tert-butyl-3-iodo-benzene (3.88 g, 10 mmol) was dissolved in anhydrous 1,2-dimethoxy-ethane (55 mL under a nitrogen atmosphere. The solution was cooled to −75° C. and t-butyl lithium (14.7 mL, 25 mmol, 1.7M in pentane) was added dropwise over 20-25 min at −72° C. to −69° C. The reaction was stirred at −72° C. for 45 min and then treated with trimethyl borate (5.7 mL, 50 mmol). The reaction was kept cold for 1 h and then the bath was removed and the reaction allowed to warm to room temperature over 24 h. It was treated with 1N hydrochloric acid (35 mL) and stirred for 30 min. The reaction was then diluted with water (200 mL) and extracted with ethyl acetate (150 mL, 2×100 mL). The combined organic portions were washed with bicarbonate solution (100 mL), water (150 mL), brine (150 mL), dried (Na2SO4), filtered and evaporated in vacuo to provide 3.0 g of an oil. The material was purified by flash chromotography (eluet: (9:1) hexane:ethyl acetate and (4:1) hexane:ethyl acetate) to provide 2.04 g (67%) of a white solid. Mp: 82-91° C. 1H NMR (250 MHz, CDCl3): δ 7.66 (d, 1H, J=2.6), 7.48 (d, 1H, J=2.6), 5.75 (s, 1H), 3.84 (t, 2H, J=7.1), 1.84 (m, 2H), 1.47 (m, 2H), 1.42 (s, 9H), 1.33 (s, 9H), 2.66 (t, 3H, J=7.3). MS [EI+] 307 (M+H)+[EI−] 305 (M−H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH:8](Br)Br)[CH:5]=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1.Cl.[NH2:19][OH:20]>>[Cl:1][C:2]1[CH:7]=[C:6]([CH:8]=[N:19][OH:20])[CH:5]=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1
Reactant: NO
Reactant: Oc1ccc(-c2ccc(C(Br)Br)cc2Cl)cc1
Agent: Cl
Product: ON=Cc1ccc(-c2ccc(O)cc2)c(Cl)c1

Procedure:
The title compound was prepared by reacting 2′-chloro-4′-(dibromomethyl)-1,1′-biphenyl-4-ol (270 mg, 0.722 mmol) with hydroxylamine hydrochloride (185 mg, 2.66 mmol) according to Method C to yield 160 mg (90%) of white solid: mp 178-179° C.; 1H NMR (DMSO-d6): δ 6.85 (2H, d, J=8.54 Hz), 7.28 (2H, d, J=8.51 Hz), 7.39 (1H, d, J=7.98 Hz), 7.60 (1H, dd, J=7.65 Hz, J=1.42 Hz), 7.72 (1H, d, J=1.34 Hz), 8.18 (1H, s), 9.67 (1H, s), 11.45 (1H, s); MS (ESI) m/z 246/248 (M−H)−.
Reaction SMILES: I([O-])(=O)(=O)=O.[Na+].[Si:7]([O:14][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]2[C:24]=1[N:23]=[C:22]([C:25]1[N:29]3[CH:30]=[CH:31][C:32]([CH:34]([OH:37])CO)=[CH:33][C:28]3=[N:27][N:26]=1)[CH:21]=[CH:20]2)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]>C(Cl)Cl>[Si:7]([O:14][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]2[C:24]=1[N:23]=[C:22]([C:25]1[N:29]3[CH:30]=[CH:31][C:32]([CH:34]=[O:37])=[CH:33][C:28]3=[N:27][N:26]=1)[CH:21]=[CH:20]2)([C:10]([CH3:11])([CH3:12])[CH3:13])([CH3:8])[CH3:9]
Reactant: CC(C)(C)[Si](C)(C)Oc1cccc2ccc(-c3nnc4cc(C(O)CO)ccn34)nc12
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)Oc1cccc2ccc(-c3nnc4cc(C=O)ccn34)nc12
Reaction time: 1 h

Procedure:
Sodium periodate (6.060 mL, 3.939 mmol) was added to silica gel (6 g) in DCM (10 mL), affording a slurry. 1-(3-(8-(tert-butyldimethylsilyloxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)ethane-1,2-diol (1.433 g, 3.282 mmol) in DCM (10 mL) was added to the slurry and the reaction was stirred for 1 hour. The silica gel was removed by filtration and washed with DCM. The filtrate was concentrated in vacuo to provide the crude product.