Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[NH:6][CH:5]=[CH:4]O1.[Li]CCCC.[Mg+2].[Br-].[Br-].CC[O:17]CC.[O:20]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH:33]=[O:34])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1COCC1>[O:20]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH:33]([C:1]1[O:17][C:5]([CH3:4])=[N:6][N:2]=1)[OH:34])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CCOCC
Reactant: CN1NC=CO1
Reactant: O=CCCCCCCOc1ccccc1
Agent: [Br-]
Agent: [Li]CCCC
Agent: [Mg+2]
Solvent: C1CCOC1
Product: Cc1nnc(C(O)CCCCCCOc2ccccc2)o1
Temperature: -50 °C
Reaction time: 0.25 h
Yield: 53.1 %

Procedure:
To a stirred solution of 63 (0.252 g, 3 mmol) in anhydrous THF (5 mL), at −78° C., under a nitrogen atmosphere, was added n-BuLi (1.2 mL, 3 mmol, using a 2.5 M solution in hexanes) dropwise. Stirring was continued for 15 min at −78° C. and then MgBr2.Et2O (0.774 g, 3 mmol) was added. The resulting mixture was warmed to −50° C. over a 2 hours period, and then it was transferred by cannula to a cooled (−78° C.) slurry of 62.1 (0.125 g, 0.6 mmol) and CeCl3, (0.738 g, 3 mmol) in anhydrous THF (6 mL), which was previously stirred at room temperature for 2 hours under nitrogen. Following the addition, the resultant mixture was allowed to warm to room temperature over a 4 hours period. The reaction mixture was quenched with dropwise addition of 5% aqueous AcOH solution (10 mL), diluted with AcOEt (20 mL) and the organic phase was separated. The aqueous layer extracted with AcOEt, the combined organic layer was washed with aqueous saturated NaHCO3 solution and brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue obtained was purified by flash column chromatography on silica gel (75% ethyl acetate-hexane) to give 64.1 (92.5 mg, 53% yield) as a white solid (m p 50-52° C.).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:33]2[CH:38]=[CH:37][C:36]([C:39](O)=[O:40])=[CH:35][CH:34]=2)[CH:5]=[C:6]([Cl:32])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][CH:17]([O:20][Si:21]([CH:28]([CH3:30])[CH3:29])([CH:25]([CH3:27])[CH3:26])[CH:22]([CH3:24])[CH3:23])[CH2:16][CH2:15]2)[C:10]1=[O:31].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[F:55][C:56]([F:64])([F:63])[CH:57]1[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.C(OCC)(=O)C>[Cl:32][C:6]1[CH:5]=[C:4]([C:33]2[CH:34]=[CH:35][C:36]([C:39]([N:60]3[CH2:61][CH2:62][CH:57]([C:56]([F:64])([F:63])[F:55])[CH2:58][CH2:59]3)=[O:40])=[CH:37][CH:38]=2)[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][CH:17]([O:20][Si:21]([CH:28]([CH3:29])[CH3:30])([CH:22]([CH3:24])[CH3:23])[CH:25]([CH3:27])[CH3:26])[CH2:16][CH2:15]2)[C:10]1=[O:31]
Reactant: CC(C)[Si](OC1CCN(N2CC[C@@H](Cc3c(Cl)cc(-c4ccc(C(=O)O)cc4)cc3Cl)C2=O)CC1)(C(C)C)C(C)C
Reactant: FC(F)(F)C1CCNCC1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)[Si](OC1CCN(N2CC[C@@H](Cc3c(Cl)cc(-c4ccc(C(=O)N5CCC(C(F)(F)F)CC5)cc4)cc3Cl)C2=O)CC1)(C(C)C)C(C)C
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 82.6 %

Procedure:
Treat a solution of (R)-3′,5′-dichloro-4′-[2-oxo-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-3-ylmethyl]-biphenyl-4-carboxylic acid (0.337 g, 0.545 mmol) in CH2Cl2 (20 mL) with 1,1′-carbonyldiimidazole (0.177 g, 1.09 mmol) and stir for 45 minutes at room temperature. Treat the reaction with 4-trifluoromethylpiperidine hydrochloride (0.155 g, 0.818 mmol) and diisopropylethylamine (0.106 g, 0.818 mmol) and stir for 12 hours at room temperature. Load the mixture on a silica gel column, flash with 25% to 50% ethyl acetate in hexanes to afford 0.34 g (84%) of the title compound. MS (m/z): 754 (M+).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)#[N:2].[CH2:15]=O>C(O)=O>[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]1)#[N:2]
Reactant: N#Cc1ccccc1N1CCNCC1
Reactant: C=O
Solvent: O=CO
Product: CN1CCN(c2ccccc2C#N)CC1

Procedure:
7.48 g of 1-(2-cyanophenyl)-piperazine are refluxed for one hour with 30 ml of formaldehyde and 30 ml of formic acid. The solvents are evaporated in vacuo and the residue is taken up in ether and mixed with water. The mixture is made alkaline with 20% sodium hydroxide solution, saturated with potassium carbonate and extracted with ether. The organic phase is dried over sodium sulphate and concentrated by evaporation in vacuo. To purify the residue it is chromatographed on silica gel with ethyl acetate/isopropanol (70:30, mixed with 1% of a 25% ammonia solution). Yield: 6.7 g (83% of theory).
Reaction SMILES: [CH3:1]S(C)=O.C(Cl)(=O)C(Cl)=O.[CH2:11]([O:18][C@@H:19]1[C@H:24]2[N:25]=[C:26]([N:28]([CH3:30])[CH3:29])[S:27][C@H:23]2[CH2:22][C@H:21]([CH2:31][OH:32])[C@H:20]1[O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C.C[Mg+].[Br-]>C(Cl)Cl.C1COCC1>[CH2:11]([O:18][C@@H:19]1[C@H:24]2[N:25]=[C:26]([N:28]([CH3:30])[CH3:29])[S:27][C@H:23]2[CH2:22][C@H:21]([CH:31]([OH:32])[CH3:1])[C@H:20]1[O:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CN(C)C1=N[C@@H]2[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@@H](CO)C[C@@H]2S1
Reactant: CS(C)=O
Agent: C[Mg+]
Agent: O=C(Cl)C(=O)Cl
Agent: [Br-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(O)[C@H]1C[C@@H]2SC(N(C)C)=N[C@@H]2[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Temperature: -30 °C
Reaction time: 0.75 h

Procedure:
To a solution of DMSO (0.193 g, 2.46 mmol) in anhydrous DCM (10 mL) at −78° C. under N2 was added oxalyl chloride (0.268 g, 2.11 mmol) slowly, and the mixture was stirred at −30° C. for 45 min. The mixture was then cooled at −78° C., and a solution of ((3aR,4R,5R,6R,7aS)-4,5-bis(benzyloxy)-2-(dimethylamino)-3a,4,5,6,7,7a-hexahydrobenzo[d]thiazol-6-yl)methanol (14) (0.330 g, 0.704 mmol) in anhydrous DCM (5 mL) was added slowly. After stirring at −30° C. for 2 h the reaction mixture was cooled back at −78° C., and triethylamine (0.50 g, 5.0 mmol) was added. The mixture was stirred at −30° C. for another 30 min, and then quenched with water (30 mL). The organic layer was collected, and the aqueous was extracted with DCM (3×20 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure to give a sticky pale yellow foam. Under N2 the pale yellow foam was dissolved in anhydrous THF (15 mL), and MeMgBr (1.4 M in THF/toluene, 1.5 mL, 2.1 mmol) was added. After addition the mixture was stirred at room temperature for 1.5 h. The reaction was quenched with saturated aqueous NaHCO3 (20 mL), and then extracted with DCM (3×15 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by flash column chromatography (EtOAc), affording mixed 15a & 15b as a sticky pale yellow foam (0.23 g, 74%) with a ratio of 15a:15b=1:3 based on 1H NMR.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH3:20])=[NH:10])[CH:3]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25](OB(O)O)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+].C([O-])(=O)C>>[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]([NH:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][CH3:20])=[NH:10])[CH:3]=2)=[CH:24][CH:23]=1
Reactant: OB(O)Oc1ccc(F)cc1
Reactant: COc1ccccc1CNC(=N)Nc1cc(Br)ccn1
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: COc1ccccc1CNC(=N)Nc1cc(-c2ccc(F)cc2)ccn1
Temperature: 110 °C
Yield: 27.7 %

Procedure:
The preparation was carried out analogously to Example 56, using 0.150 g (0.447 mmol) N-(4-bromopyridin-2-yl)-N′-(2-methoxybenzyl)guanidine, 0.093 g (0.671 mmol) (4-fluorophenyl)boric acid, 0.142 g (1.343 mmol) sodium carbonate, and 0.036 g (0.031 mmol) tetrakis-(triphenylphosphine)palladium(0). The mixture was likewise heated in a reaction block for 17.5 hr at 110° C. under a nitrogen atmosphere. After appropriate workup and purification via preparative HPLC, 50.9 mg (0.124 mmol, 27%) pure N-[4-(4-fluorophenyl)pyridin-2-yl]-N′-(2-methoxybenzyl)guanidine was obtained in the form of the acetate salt (base/acetate in a ratio of 1:1).
Reaction SMILES: CC(C)([O-])C.[K+].C(O)(C)(C)C.[CH2:12]([O:14][C:15](=[O:20])[CH2:16][C:17](=[O:19])[CH3:18])[CH3:13].Cl[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1>O1CCCC1.O>[CH2:12]([O:14][C:15](=[O:20])[CH:16]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[C:17](=[O:19])[CH3:18])[CH3:13]
Reactant: CCOC(=O)CC(C)=O
Reactant: Fc1ccc(CCl)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)(C)O
Solvent: C1CCOC1
Product: CCOC(=O)C(Cc1ccc(F)cc1)C(C)=O
Temperature: 15 °C

Procedure:
A suspension of potassium tert-butoxide (11.2 g) in anhydrous tetrahydrofuran (200 mL) at 0° C. was treated with a mixture of tert-butanol (0.2 mL) and 3-oxobutyric acid ethyl ester (12.7 mL). The mixture was warmed to 15° C. over a period of 40 minutes and a solution of 1-chloromethyl-4-fluorobenzene (11.9 mL) in tetrahydrofuran (40 mL) was added and the resulting mixture heated at 70° C. for 20 hours. The mixture was cooled to room temperature, diluted with water and the tetrahydrofuran removed under reduced pressure. The residue was extracted with ethyl acetate and the combined extracts washed with water and saturated aqueous sodium chloride solution and then dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by distillation under reduced pressure (boiling point, 102-104° C. at 0.42 mbar) to afford title compound as a colourless oil, 12.4 g.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([O:13][CH3:14])=[CH:5][C:6]2[Te:10][C:9]([CH3:11])=[N:8][C:7]=2[CH:12]=1.[F:15][C:16]([F:24])([F:23])[S:17]([O:20][CH2:21][CH3:22])(=[O:19])=[O:18].C(OCC)C>C(Cl)(Cl)Cl>[F:15][C:16]([F:24])([F:23])[S:17]([O-:20])(=[O:19])=[O:18].[CH2:21]([N+:8]1[C:7]2[CH:12]=[C:3]([O:2][CH3:1])[C:4]([O:13][CH3:14])=[CH:5][C:6]=2[Te:10][C:9]=1[CH3:11])[CH3:22]
Reactant: CCOS(=O)(=O)C(F)(F)F
Reactant: COc1cc2nc(C)[te]c2cc1OC
Solvent: CCOCC
Solvent: ClC(Cl)Cl
Product: CC[n+]1c(C)[te]c2cc(OC)c(OC)cc21
Product: O=S(=O)([O-])C(F)(F)F

Procedure:
5,6-Dimethoxy-2-methylbenzotellurazole (Example 19) was dissolved in chloroform (150 ml). A stoichiometric amount of ethyl trifluoromethanesulfonate was added, and the solution was refluxed for two hours under a condenser protected with a drying tube. After cooling the solution was poured slowly into cold diethyl ether (700 ml) with rapid stirring. The product crystallized and was collected by filtration. Yield 19.3 g (77.3% of theory).
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9].C([O-])(O)=O.[Na+].Cl[CH2:16][C:17](Cl)=[O:18]>C(Cl)(Cl)Cl.O.CC(C)=O>[CH3:1][N:2]1[C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[O:9][CH2:16][C:17]1=[O:18]
Reactant: CNc1ccccc1O
Reactant: O=C(Cl)CCl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClC(Cl)Cl
Solvent: CC(C)=O
Product: CN1C(=O)COc2ccccc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 109.4 %

Procedure:
1 g of 2-(N-methylamino)-phenol were dissolved in chloroform, followed by the addition of 10 ml of sat. NaHCO3 in water. To this suspension was added slowly under vigorous stirring a solution of 1 g of 2-chloroacetylchloride in acetone. The reaction mixture was stirred for 2 hours at room temperature. The layers were separated. The organic layer was washed with water and dried over Na2SO4. After evaporating the solvent, the red oil was taken up in 30 ml DMF and 1 g of K2CO3 were added and the slurry was heated at 70° C. for additional 2 hours. The cyclization was followed by TLC. 200 ml of EtOAc were added and the organic layer was washed 3× with 0.1N HCl and 5× with brine. The remaining organic layer was dried over MgSO4 and filtrated. EtOAc was removed under reduced pressure affording 1.45 g of pure 4-methyl-4H-benzo[1,4]oxazin-3-one.
Reaction SMILES: C([N:8]1[CH2:31][CH:30]([C:32]([OH:35])([CH3:34])[CH3:33])[O:29][C:10]2([CH2:15][CH2:14][N:13]([C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH3:28])[CH:19]=3)=[O:17])[CH2:12][CH2:11]2)[CH2:9]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>C(O)C.[Pd]>[OH:35][C:32]([CH:30]1[CH2:31][NH:8][CH2:9][C:10]2([CH2:15][CH2:14][N:13]([C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:26])[CH3:27])=[C:20]([CH3:28])[CH:19]=3)=[O:17])[CH2:12][CH2:11]2)[O:29]1)([CH3:34])[CH3:33]
Reactant: Cc1cc(C(=O)N2CCC3(CC2)CN(Cc2ccccc2)CC(C(C)(C)O)O3)ccc1OC(C)C
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Product: Cc1cc(C(=O)N2CCC3(CC2)CNCC(C(C)(C)O)O3)ccc1OC(C)C
Temperature: 75 °C
Yield: 96 %

Procedure:
[8-Benzyl-10-(1-hydroxy-1-methyl-ethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (75 mg, 0.16 mmol) was dissolved in ethanol (3 mL) and Pd (8 mg, 0.008 mmol) and ammonium formate (50 mg, 0.80 mmol) were added and the reaction mixture was heated at 75° C. for 30 minutes. The reaction mixture was filtered, concentrated in vacuo, diluted with ethyl acetate, washed with 3M NaOH, dried over MgSO4, filtered and concentrated in vacuo to give (2-(2-hydroxypropan-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)(4-isopropoxy-3-methylphenyl)methanone (60 mg, 94%). ESI-MS m/z calc. 390.3. Found 391.5 (M+1)+; Retention time: 1.27 minutes (3 min run).
Reaction SMILES: C1(C)C(C)=CC=CC=1.C1([SnH](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:28]([C:31]1[CH:36]=[CH:35][C:34]([N:37]=[N:38][C:39](=[C:43]2[C:52]3[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=3)[CH2:46][C:45]([CH3:54])([CH3:53])[NH:44]2)[C:40]([NH2:42])=[O:41])=[CH:33][CH:32]=1)(=[O:30])[CH3:29]>C(#N)C>[C:28]([C:31]1[CH:32]=[CH:33][C:34]([N:37]=[N:38][CH:39]([CH:43]2[C:52]3[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=3)[CH2:46][C:45]([CH3:54])([CH3:53])[NH:44]2)[C:40]([NH2:42])=[O:41])=[CH:35][CH:36]=1)(=[O:30])[CH3:29]
Reactant: CC(=O)c1ccc(N=NC(C(N)=O)=C2NC(C)(C)Cc3ccccc32)cc1
Agent: c1ccc([SnH](c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Solvent: Cc1ccccc1C
Product: CC(=O)c1ccc(N=NC(C(N)=O)C2NC(C)(C)Cc3ccccc32)cc1
Temperature: 25 °C

Procedure:
In a nitrogen atmosphere, 2-(4-acetyl-phenylazo)-2-(3,3-dimethyl-3,4-dihydro-2H-isoquinoline-1-ylidene)-acetamide (Asinex Corp., Russia) is dissolved in acetonitrile, and the obtained product is added with xylene in which triphenyl tin hydride (Aldrich, Corp., USA) is dissolved, and the mixture is refluxed. The refluxed product is cooled to room temperature and an insoluble matter is separated by filtration. The solvent is removed from the filtrate by reducing the pressure. The residue containing the reaction product is purified by column chromatography to obtain the title compound.
Reaction SMILES: [CH3:1][S-:2].[Na+].Cl[CH2:5][C:6]1[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=[C:8]([F:15])[CH:7]=1>C(O)C.[Cl-].[Na+].O>[F:15][C:8]1[CH:9]=[C:10]([N+:12]([O-:14])=[O:13])[CH:11]=[C:6]([CH2:5][S:2][CH3:1])[CH:7]=1
Reactant: C[S-]
Reactant: O=[N+]([O-])c1cc(F)cc(CCl)c1
Agent: [Cl-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CSCc1cc(F)cc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 106.9 %

Procedure:
Sodium methanethiolate (1.22 g; 17.4 mmol) was added in three portions to a stirred solution of 1-(chloromethyl)-3-fluoro-5-nitrobenzene (3.00 g; 15.8 mmol, HE Chemical) in ethanol (33 mL) at 0° C. The ice bath was removed and the batch was stirred at room temperature for 18 hours. Further sodium methanethiolate (0.33 g; 4.7 mmol) was added and the batch was stirred for 5 additional hours at room temperature. The batch was diluted with brine and extracted with ethyl acetate (2×). The combined organic phases were washed with water, dried (sodium sulfate), filtered and concentrated to give the desired product (3.4 g) that was used without further purification.
Reaction SMILES: [CH:1]1([NH:7][CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:14]=O.[Cl:16][C:17]1[CH:18]=[C:19]([C:29]#[CH:30])[CH:20]=[CH:21][C:22]=1[CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>>[ClH:16].[CH:8]1([N:7]([CH2:14][C:30]#[C:29][C:19]2[CH:20]=[CH:21][C:22]([CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[C:17]([Cl:16])[CH:18]=2)[CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1
Reactant: C#Cc1ccc(C2CCCCC2)c(Cl)c1
Reactant: C=O
Reactant: C1CCC(NC2CCCCC2)CC1
Product: Cl
Product: Clc1cc(C#CCN(C2CCCCC2)C2CCCCC2)ccc1C1CCCCC1

Procedure:
This compound is prepared, following the procedure described in Example I, by reacting dicyclohexylamine and paraformaldehyde with 3-chloro-4-cyclohexyl-1 -ethynylbenzene.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7](C)=[CH:6][CH:5]=1)([O-:3])=[O:2].[N+:11]([O-:14])(O)=[O:12].S(=O)(=O)(O)O.[C:20]1(C)C=CC=CC=1>>[N+:11]([C:9]1[C:4]([N+:1]([O-:3])=[O:2])=[C:5]([CH3:20])[CH:6]=[CH:7][CH:8]=1)([O-:14])=[O:12]
Reactant: Cc1ccc([N+](=O)[O-])cc1
Reactant: O=[N+]([O-])O
Reactant: Cc1ccccc1
Agent: O=S(=O)(O)O
Product: Cc1cccc([N+](=O)[O-])c1[N+](=O)[O-]

Procedure:
This invention relates to an improvement in a process for purifying dinitrotoluene is prepared by first reacting toluene or mononitrotoluene with nitric acid in the presence of sulfuric acid, separating the crude dinitrotoluene from the resulting aqueous phases and then contacting the resultant crude dinitrotoluene with an alkaline material to form a purified dinitrotoluene product and an aqueous by-product phase. The improvement in the process relates to selectively maintaining a significant proportion of 2,4-dinitroorthocresol in the dinitrotoluene product and away from the effluent waste while permitting other nitrophenolic impurities to pass to the aqueous by-product phase or effluent waste. The improvement comprises: monitoring the pH of the aqueous phase formed during said contacting step with a pH sensitive instrument and then terminating said contacting step when the pH of the resultant aqueous phase is within a pH range of about 5.8 to 6.4.
Reaction SMILES: C(O)(C(F)(F)F)=O.[CH2:8]([O:50][CH:51]1[C@H:55]2[C@H:56](OC3CCCCO3)[N:57](C(OC(C)(C)C)=O)[C:58]3[CH:65]=[C:64]([O:66][CH3:67])[CH:63]=[CH:62][C:59]=3[C:60](=[O:61])[N:54]2[CH2:53][CH2:52]1)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][O:18][CH:19]1[C@H:23]2[C@H:24](OC3CCCCO3)[N:25](C(OC(C)(C)C)=O)[C:26]3[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:27]=3[C:28](=[O:29])[N:22]2[CH2:21][CH2:20]1.C([O-])(O)=O.[Na+]>CO.C(Cl)(Cl)Cl>[CH2:17]([O:18][CH:19]1[C@@H:23]2[CH:24]=[N:25][C:26]3[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:27]=3[C:28](=[O:29])[N:22]2[CH2:21][CH2:20]1)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][O:50][CH:51]1[C@@H:55]2[CH:56]=[N:57][C:58]3[CH:65]=[C:64]([O:66][CH3:67])[CH:63]=[CH:62][C:59]=3[C:60](=[O:61])[N:54]2[CH2:53][CH2:52]1
Reactant: COc1ccc2c(c1)N(C(=O)OC(C)(C)C)[C@@H](OC1CCCCO1)[C@@H]1C(OCCCCCCCCCCOC3CCN4C(=O)c5ccc(OC)cc5N(C(=O)OC(C)(C)C)[C@@H](OC5CCCCO5)[C@H]34)CCN1C2=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClC(Cl)Cl
Solvent: CO
Product: COc1ccc2c(c1)N=C[C@H]1C(OCCCCCCCCCCOC3CCN4C(=O)c5ccc(OC)cc5N=C[C@@H]34)CCN1C2=O
Reaction time: 1 h
Yield: 88.9 %

Procedure:
95% TFA (3 mL) was added drop-wise to dimer compound 8h (191 mg, 0.18 mmol) at 0° C. This was then stirred for 1 hr and the mixture was poured into saturated NaHCO3 (30 mL) solution to naturalize the reaction mixture. The mixture was extracted with chloroform (3×20 mL). The organic layer was then washed water (20 mL), brine (20 mL) then dried (MgSO4) and filtrated. The excess solvent was removed under reduced pressure to give the crude product, which was subjected to flash column chromatography (SiO2, 2% methanol-chloroform). Removal of excess eluent under reduced pressure without heating afforded the final product 9h (103 mg, 0.16 mmol, 90%) as a solid: [α]20D=+387° (c=0.17, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 1.25-1.50 (m, 12H, 14-H, 14′-H, 15-H, 15′-H, 16-H, 16′-H), 1.72-1.92 (m, 4H, 13-H, 13′-H), 1.98-2.09 (m, 4H, 2-H, 2′-H), 2.25-2.38 (m, 4H, 1-H, 1′-H), 3.52-3.62 (m, 2H, 3-H, 3′-H), 3.68-3.73 (m, 2H, 11a-H, 11a′-H), 3.76-3.85 (m, 2H, 3-H, 3′-H), 3.90 (s, 6H, 7-OMe, 7′-OMe), 3.95-4.19 (m, 4H, 12-H, 12′-H), 6.79 (s, 2H, 9-H; 9′-H), 7.50 (s, 2H, 6-H, 6′-H), 7.64 (d, 2H, J=4, 11-H, 11′-H); 13C NMR (CDCl3, 400 MHz): δ 24.1, 25.9, 29.0, 29.3, 29.4, 29.6, 46.6, 53.7, 56.0, 69.7, 109.6, 112.5, 120.2, 140.5, 147.1, 151.6, 162.2, 164.6; IR (neat): 3325, 2931, 1600, 1506, 1448, 1388, 1262, 1217, 1092, 1024 cm−1; MS (FAB) m/z (relative intensity) 695 ([M+2×MeOH]+., 14), 663 ([M+MeOH]+., 20), 631 (M+., 100).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12](=O)[CH2:13]Cl)[CH2:7][CH2:6][CH2:5]2.C(=O)([O-])[O-].[K+].[K+].[CH:22]([NH2:25])([CH3:24])[CH3:23]>C(#N)C.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][CH2:13][NH:25][CH:22]([CH3:24])[CH3:23])[CH2:7][CH2:6][CH2:5]2
Reactant: O=C(CCl)N1CCCc2cc(Br)ccc21
Reactant: CC(C)N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: CC(C)NCCN1CCCc2cc(Br)ccc21
Temperature: 75 °C
Reaction time: 8 h
Yield: 83.1 %

Procedure:
A solution of 6-bromo-1-(2-iodoethyl)-1,2,3,4-tetrahydroquinoline (compound 1, 0.400 g, 1.093 mmol) in acetonitrile (19 mL) and water (1 mL) in a 50 mL pressure vessel fitted with a stir-bar was treated with potassium carbonate (0.755 g, 5.46 mmol) and isopropylamine (0.646 g, 10.93 mmol) and the sealed vessel stirred at 75° C. overnight. After 24 hours the mixture was partitioned between CH2Cl2 (50 mL) and water (10 mL) and transferred to a separatory funnel. The organic layer was separated and the aqueous layer (pH=12); extracted further with CH2Cl2. The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to a yellow oil. Purification on silica gel eluting with 5% 2M NH3 in methanol/95% dichloromethane yielded a pale yellow oil, 2 (270 mg, 83%). 1H-NMR (DMSO-d6) δ 7.06 (dd, 1H, J=8.8, 2.5 Hz), 6.99 (d, 1H, J=2.5 Hz), 6.52 (d, 1H, J=8.8), 3.31-3.20 (m, 4H), 2.78-2.67 (m, 1H), 2.67-2.59 (m, 4H), 1.84-1.76 (m, 2H), 0.96 (d, 6H, J=6.2 Hz). MS (ESI+): 297/299 (MH+, 10), 238/240 (20), 159 (100).
Reaction SMILES: [CH3:1][C:2]([CH3:4])=[O:3].C[C:6]([CH3:8])=O.[OH:9][S:10](O)(=O)=[O:11].O=[Cr](=O)=O>C(O)(C)C>[S:10]1(=[O:11])(=[O:9])[CH2:6][CH2:8][CH2:4][C:2](=[O:3])[CH2:1]1
Reactant: CC(C)=O
Reactant: O=S(=O)(O)O
Agent: O=[Cr](=O)=O
Solvent: CC(C)O
Product: O=C1CCCS(=O)(=O)C1

Procedure:
To a solution of tetrahydrothiopyran-3-o1-1,1-dioxide (7.5 g, 0.05 moles) and acetone (150 mL) was slowly added enough Jones reagent to maintain a brown color for at least 10 minutes without need for additional reagent. The excess reagent was reduced by addition of isopropanol (5 mL). The mixture was filtered through anhydrous magnesium sulfate and the chromium salts were washed 3× with acetone. The solvent was removed in vacuo to give a solid which was triturated with ethanol. The resulting crystals were isolated by filtration and rinsed 3× with diethyl ether. After drying, 5.0 g of product was obtained. H' NMR CDCl3 4.0 (singlet, 2H) 3.3 (triplet, 2H) 2.6 (triplet, 2H) 2.3 (multiplet, 2H).