Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1]O.[CH3:3][C:4]1[N:5]([CH2:17][C:18]2C=NC=NC=2)[C:6]2[C:11]([C:12]=1[C:13]([O:15]C)=[O:14])=[CH:10][CH:9]=[CH:8][CH:7]=2.[OH-].[K+].Cl>O>[CH:17]([N:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:12]([C:13]([OH:15])=[O:14])=[C:4]1[CH3:3])([CH3:18])[CH3:1]
Reactant: CO
Reactant: COC(=O)c1c(C)n(Cc2cncnc2)c2ccccc12
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: Cc1c(C(=O)O)c2ccccc2n1C(C)C
Yield: 58 %

Procedure:
To a mixed solution of methanol (10 mL) and water (2 mL), methyl 2-methyl-1-(pyrimidin-5-ylmethyl)-1H-indole-3-carboxylate (110 mg, 0.39 mmol) and potassium hydroxide (50 mg, 0.98 mmol) was added. The mixture was stirred at reflux for 12 hours. Then the reaction mixture was acidified by hydrochloric acid aqueous solution (1N) to adjust pH=6 and extracted with dichloromethane (10 mL*3). The organic layers were combined and concentrated to give 1-isopropyl-2-methyl-1H-indole-3-carboxylic acid (60 mg, 58%).
Reaction SMILES: [CH2:1]([C:5]1[S:6][C:7]2[CH2:13][CH2:12][CH2:11][CH:10]([C:14](OCC)=[O:15])[C:8]=2[N:9]=1)[CH2:2][CH2:3][CH3:4]>CCOCC>[CH2:1]([C:5]1[S:6][C:7]2[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][OH:15])[C:8]=2[N:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc2c(s1)CCCC2C(=O)OCC
Solvent: CCOCC
Product: CCCCc1nc2c(s1)CCCC2CO
Yield: 48 %

Procedure:
The compound is prepared by reduction of the above derivative (III), with AlLiH4 in ether at room temperature. B.p.0.6 =130°-132° C. Yield:48%.
Reaction SMILES: C([N:8]([CH2:33][C@@H:34]([C:36]1[CH:47]=[CH:46][C:39]2[O:40]C(C)(C)[O:42][CH2:43][C:38]=2[CH:37]=1)[OH:35])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][C:18]#[C:19][C:20]1[CH:21]=[C:22]([N:26]2[C:30](=[O:31])[CH2:29][NH:28][C:27]2=[O:32])[CH:23]=[CH:24][CH:25]=1)C1C=CC=CC=1.Cl>C(O)(C)C.CCOC(C)=O.[OH-].[OH-].[Pd+2]>[OH:35][C@H:34]([C:36]1[CH:47]=[CH:46][C:39]([OH:40])=[C:38]([CH2:43][OH:42])[CH:37]=1)[CH2:33][NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]1[CH:21]=[C:22]([N:26]2[C:30](=[O:31])[CH2:29][NH:28][C:27]2=[O:32])[CH:23]=[CH:24][CH:25]=1
Reactant: CC1(C)OCc2cc([C@@H](O)CN(CCCCCCOCCC#Cc3cccc(N4C(=O)CNC4=O)c3)Cc3ccccc3)ccc2O1
Agent: [Pd+2]
Agent: Cl
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CC(C)O
Product: O=C1CNC(=O)N1c1cccc(CCCCOCCCCCCNC[C@H](O)c2ccc(O)c(CO)c2)c1
Reaction time: 2 h
Yield: 38.5 %

Procedure:
A solution of 3-(3-{4-[(6-{benzyl[(2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6yl)-2-hydroxyethyl]amino}hexyl)oxy]but-1-ynyl}phenyl)imidazolidine-2,4-dione (9.05 g) in a mixture of isopropanol-EtOAc (9:1, 200 ml) was hydrogenated over Pearlman's catalyst (1.8 g). After 2 days aqueous 2M HCl (10 ml) was added and the mixture was hydrogenated for a further 2 h. The catalyst was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on Biotage eluting with dichloromethane-isopropanol-880 ammonia (34:7:1) to give the title compound (2.8 g) LCMS RT=2.34 min ES+ve 514 (MH)+.
Reaction SMILES: I[CH2:2][C:3]([NH:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])=[O:4].CCN(C(C)C)C(C)C.[SH:33][C:34]([CH3:52])([CH3:51])[CH2:35][N:36]([CH3:50])[CH2:37][CH2:38][O:39][C:40]1[CH:45]=[C:44]([CH2:46][OH:47])[N:43]=[C:42]([CH2:48][OH:49])[CH:41]=1>CN(C=O)C>[OH:47][CH2:46][C:44]1[CH:45]=[C:40]([O:39][CH2:38][CH2:37][N:36]([CH3:50])[CH2:35][C:34]([S:33][CH2:2][C:3]([NH:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])=[O:4])([CH3:52])[CH3:51])[CH:41]=[C:42]([CH2:48][OH:49])[N:43]=1
Reactant: COC(=O)CCOCCOCCOCCOCCNC(=O)CI
Reactant: CN(CCOc1cc(CO)nc(CO)c1)CC(C)(C)S
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)CCOCCOCCOCCOCCNC(=O)CSC(C)(C)CN(C)CCOc1cc(CO)nc(CO)c1
Reaction time: 24 h
Yield: 57.1 %

Procedure:
73.7 mg of methyl 3-[2-(2-{2-[2-(2-iodoacetylamino)ethoxy]ethoxy}ethoxy)ethoxy]propanoate in solution in 1 ml of DMF and 39 μl of DIPEA are added to 45 mg of 4-{2-[(2-mercapto-2-methylpropyl)(methyl)amino]ethoxy}-2,6-bis(hydroxymethyl)pyridine in solution in 1 ml of DMF. After 24 h at AT, the mixture is concentrated under RP and purified by flash chromatography on silica (Analogix Super Flash SiO2 SF25-8 g), using a gradient from 0 to 10% of methanol in DCM. 53 mg of methyl 3-{2-[2-(2-{2-[2-(2-{[2-(2,6-bis(hydroxymethyl)pyridin-4-yloxy)ethyl](methyl)amino}-1,1-dimethylethylsulphanyl)acetylamino]ethoxy}ethoxy)ethoxy]ethoxy}propanoate are thus obtained.
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([NH2:12])=[CH:7][C:6]=1[N+:13]([O-:15])=[O:14].[CH2:16](Cl)[CH2:17][OH:18].[OH-].[Na+]>O>[OH:1][CH2:2][CH2:3][NH:4][C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([NH:12][CH2:16][CH2:17][OH:18])=[CH:7][C:6]=1[N+:13]([O-:15])=[O:14]
Reactant: OCCCl
Reactant: Nc1cc([N+](=O)[O-])c(NCCO)cc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=[N+]([O-])c1cc(NCCO)c(Cl)cc1NCCO
Temperature: 130 °C
Reaction time: 3 h

Procedure:
79.0 g (0.33 mole) of 1-beta-hydroxyethylamino-2-nitro-4-amino-5-chlorobenzene were dissolved in 150 ml methylglycol and 36 g (0.5 mole) ethylenechlorohydrin. 19.8 g of NaOH dissolved in 180 ml water were then added while stirring over a period of 3 hours at a bath temperature of 130°C. The final product was removed by suction after cooling and was recrystallized from water. Yield: 35 g 1,4-di-(beta-hydroxyethylamino)-2-nitro-5-chlorobenzene; m.p.: 127°-128°C. Analysis: C10H14N3O4Cl
Reaction SMILES: [C:1]([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14]O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I:16]N1C(=O)CCC1=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])O.[Na+]>ClCCl>[C:1]([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][I:16])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(OCCOCCO)c1ccccc1
Reactant: O=C1CCC(=O)N1I
Agent: O=C([O-])O
Agent: [Na+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: O=C(OCCOCCI)c1ccccc1
Reaction time: 14 h
Yield: 64.1 %

Procedure:
To a solution of 2,2′-oxydiethanol (2.12 g) in pyridine (20 mL) was added benzoic anhydride (4.52 g) by small portions under ice-cooling, and the reaction mixture was stirred while warming to room temperature for 18 hrs. Pyridine was evaporated under reduced pressure and the obtained residue was diluted with diethyl ether (20 mL). 5% Aqueous sodium hydrogen carbonate solution (100 mL) was added, and the mixture was extracted with diethyl ether (100 mL×3). The solvent was evaporated under reduced pressure, and the obtained residue was subjected to silica gel chromatography (eluent:hexane/ethyl acetate=95/5→40/60). The object fraction was concentrated under reduced pressure and dried to give 2-(2-hydroxyethoxy)ethyl benzoate (2.21 g). To a solution of the obtained 2-(2-hydroxyethoxy)ethyl benzoate (2.10 g) in dichloromethane (10 mL) were added 1-iodopyrrolidine-2,5-dione (2.70 g) and triphenylphosphine (3.14 g) by small portions under ice-cooling, and the mixture was stirred for 14 hrs. The reaction mixture was poured into 5% aqueous sodium hydrogen carbonate solution (100 mL), and extracted with ethyl acetate (120 mL×3). The organic layer was washed successively with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was subjected to silica gel chromatography (eluent:hexane/ethyl acetate=100/0→60/40). The object fraction was concentrated under reduced pressure and dried to give 2-(2-iodoethoxy)ethyl benzoate (2.05 g) as a colorless transparent oil.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:26][CH3:27])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=2[CH:20]2[O:24][C:23](=[O:25])[NH:22][CH2:21]2)[CH:9]=1)([CH3:3])[CH3:2].[F:28][C:29]([F:43])([F:42])[C:30]1[CH:31]=[C:32]([CH:35]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:37]=1)[CH2:33]Br>>[F:28][C:29]([F:42])([F:43])[C:30]1[CH:31]=[C:32]([CH:35]=[C:36]([C:38]([F:41])([F:39])[F:40])[CH:37]=1)[CH2:33][N:22]1[CH2:21][CH:20]([C:11]2[CH:12]=[C:13]([C:16]([F:17])([F:18])[F:19])[CH:14]=[CH:15][C:10]=2[C:8]2[CH:9]=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:5]=[CH:6][C:7]=2[O:26][CH3:27])[O:24][C:23]1=[O:25]
Reactant: FC(F)(F)c1cc(CBr)cc(C(F)(F)F)c1
Reactant: COc1ccc(C(C)C)cc1-c1ccc(C(F)(F)F)cc1C1CNC(=O)O1
Product: COc1ccc(C(C)C)cc1-c1ccc(C(F)(F)F)cc1C1CN(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)C(=O)O1

Procedure:
Following the procedure described in EXAMPLE 50, 44 mg of 5-[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]-1,3-oxazolidin-2-one, enantiomer B, and 43 mg of 3,5-bis(trifluoromethyl)benzyl bromide gave the title compound. Analytical HPLC on Chiralpak AS 4.6×250 mm, eluting with 5% isopropanol in heptane at 0.5 mL/min: tR=11.0 min
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1([CH3:11])[O:8][C@H:7]([CH2:9][OH:10])[CH2:6][O:5]1.[Br:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15](Br)[N:14]=1>C1(C)C=CC=CC=1.O>[Br:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:10][CH2:9][C@@H:7]2[CH2:6][O:5][C:4]([CH3:11])([CH3:3])[O:8]2)[N:14]=1
Reactant: CC1(C)OC[C@@H](CO)O1
Reactant: Brc1cccc(Br)n1
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: CC1(C)OC[C@@H](COc2cccc(Br)n2)O1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Sodium hydride (1.62 g, 60% dispersion in mineral oil, 40.5 mmol) was added portionwise to an ice-cooled solution of (R)-(−)-1,2-O-isopropylideneglycerol (4.86 g, 36.8 mmol) in toluene (100 ml), and once addition was complete, the solution was allowed to warm to room temperature and stirred for 30 minutes. 2,6-Dibromopyridine (8.72 g, 36.8 mmol) was added, and the reaction heated under reflux for 5 hours. The cooled mixture was diluted with water, the layers separated, and the aqueous phase extracted with ether. The combined organic extracts were dried (MgSO4), filtered and evaporated in vacuo to afford the title compound as a yellow oil (quantitative).
Reaction SMILES: C([O:5][C:6](=[O:39])[CH:7]([C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([N:36]([CH3:38])[CH3:37])[CH:31]=1)[CH2:8][C:9]1[CH:13]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=2)[N:11]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=2[Cl:29])[N:10]=1)(C)(C)C>FC(F)(F)C(O)=O.ClCCl>[Cl:21][C:16]1[CH:15]=[C:14]([C:12]2[N:11]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[Cl:29])[N:10]=[C:9]([CH2:8][CH:7]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([N:36]([CH3:38])[CH3:37])[CH:31]=3)[C:6]([OH:39])=[O:5])[CH:13]=2)[CH:19]=[CH:18][C:17]=1[Cl:20]
Reactant: CN(C)c1cccc(C(Cc2cc(-c3ccc(Cl)c(Cl)c3)n(-c3ccc(Cl)cc3Cl)n2)C(=O)OC(C)(C)C)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CN(C)c1cccc(C(Cc2cc(-c3ccc(Cl)c(Cl)c3)n(-c3ccc(Cl)cc3Cl)n2)C(=O)O)c1
Reaction time: 2 h
Yield: 109.2 %

Procedure:
3-[5-(3,4-Dichloro-phenyl)-1-(2,4-dichloro-phenyl)-1H-pyrazol-3-yl]-2-(3-dimethylamino-phenyl)-propionic acid tert-butyl ester (20 mg, 0.03 mmol) was dissolved in 1:1 trifluoroacetic acid/dichloromethane (1.0 mL) and stirred for 2 h. The reaction mixture was concentrated under reduced pressure, and the crude residue was dissolved in 1:1 acetonitrile/water (2.0 mL). The solution was lyopholized to afford the title compound (18 mg, >99%). HPLC: Rt=2.60 (Method B). MS (ESI): mass calculated for C26H21Cl4N3O2, 547.04; m/z found, 548/550[M+H]+. 1H NMR (500 MHz, DMSO-d6): 7.81 (d, J=1.9 Hz, 1H), 7.60-7.58 (m, 3H), 7.45 (d, J=2.2 Hz, 1H), 7.18 (t, J=7.9 Hz, 1H), 7.02 (dd, J=8.5, 2.2 Hz, 1H), 6.78 (m, 3H), 6.64 (s, 1H), 3.96 (dd, J=8.8, 6.6 Hz, 1H), 3.36 (dd, J=15.1, 9.0 Hz, 1H), 2.93 (dd, J=15.1, 6.6 Hz, 1H), 2.91 (s, 6H).
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][C:9]1[O:10][C:11]2[CH:17]=[CH:16][C:15]([C:18]3[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=3)=[CH:14][C:12]=2[CH:13]=1.[Br:26]Br.[O-]S([O-])=O.[Na+].[Na+]>C(O)(C(F)(F)F)=O>[Br:26][C:13]1[C:12]2[CH:14]=[C:15]([C:18]3[CH:19]=[CH:20][C:21]([C:22]#[N:23])=[CH:24][CH:25]=3)[CH:16]=[CH:17][C:11]=2[O:10][C:9]=1[CH2:8][CH2:7][N:3]1[CH2:4][CH2:5][CH2:6][C@H:2]1[CH3:1]
Reactant: C[C@@H]1CCCN1CCc1cc2cc(-c3ccc(C#N)cc3)ccc2o1
Reactant: BrBr
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Product: C[C@@H]1CCCN1CCc1oc2ccc(-c3ccc(C#N)cc3)cc2c1Br
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 97 %

Procedure:
The product from Example 1D (2.5 g (5.2 mmol) and trifluoroacetic acid (40 mL) (TFA) were combined and stirred at 25° C. for 10 min. The mixture was slowly treated with a solution of Br2 (450 μL, 7.8 mmol) in TFA (10 mL). The mixture was allowed to stir at 25° C. for 1 h and then treated with saturated aqueous Na2SO3. The mixture was concentrated and redissolved in 50 mL ethyl acetate. The organic phase was washed with 1M NaOH, dried, and concentrated under reduced pressure to provide the title compound (2.1 g, 97% yield). 1HNMR (300 MHz, CD3OD) δ 1.16 (d, 3H, J=6.1 Hz), 1.42 (m, 1H), 1.78 (m, 2H), 1.98 (m, 1H), 2.32 (m, 1H), 2.50 (m, 2H), 3.11 (m, 2H), 3.28 (m, 2H), 7.58-7.70 (m, 3H), 7.82 (m, 4H); MS (ESI) m/e 409 (M+H)+.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][N:5]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1)[CH2:6][CH2:7][CH3:8].CS[C:17]1[NH:22][C:21](=[O:23])[C:20]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]3[O:31][CH2:32][O:33][C:27]=3[CH:26]=2)=[CH:19][N:18]=1>>[CH2:6]([N:5]([CH2:4][CH2:3][CH2:2][NH:1][C:17]1[NH:22][C:21](=[O:23])[C:20]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]3[O:31][CH2:32][O:33][C:27]=3[CH:26]=2)=[CH:19][N:18]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1)[CH2:7][CH3:8]
Reactant: CSc1ncc(Cc2ccc3c(c2)OCO3)c(=O)[nH]1
Reactant: CCCN(CCCN)c1ccccn1
Product: CCCN(CCCNc1ncc(Cc2ccc3c(c2)OCO3)c(=O)[nH]1)c1ccccn1

Procedure:
2-[N-(3-aminopropyl)-N-propylamino]pyridine (1.0 g) and 2-methylthio-5-(3,4-methylenedioxybenzyl)pyrimid-4-one (1.14 g) were heated together under reflux for 16 hr. After stripping, the residue was crystallised from ethanol/water to give 2-[3-(N-propyl-N-pyrid-2-ylamino)propylamino]-5-(3,4-methylenedioxybenzyl) pyrimid-4-one 1H2O, 1.47 g (81%) mp 86°-92° C.
Reaction SMILES: [C:1]([NH:20][C@H:21]([C:25]([O:27][CH2:28][CH:29]([CH2:32][CH:33]=[CH2:34])[CH2:30][OH:31])=[O:26])[CH:22]([CH3:24])[CH3:23])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:41](Cl)(=[O:59])[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58]>ClCCl>[C:1]([NH:20][C@H:21]([C:25]([O:27][CH2:28][CH:29]([CH2:32][CH:33]=[CH2:34])[CH:30]([C:41](=[O:59])[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])[OH:31])=[O:26])[CH:22]([CH3:24])[CH3:23])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C=CCC(CO)COC(=O)[C@@H](NC(c1ccccc1)(c1ccccc1)c1ccccc1)C(C)C
Reactant: CCCCCCCCCCCCCCCCCC(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: C=CCC(COC(=O)[C@@H](NC(c1ccccc1)(c1ccccc1)c1ccccc1)C(C)C)C(O)C(=O)CCCCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 1-O-(N-trityl-L-valyl)-2-allyl-1,3-propandiol (1.83 g, 4 mmol) in dichloromethane (40 ml) and pyridine (3.2 ml, 40 mmol) at 0° C. was added dropwise stearoyl chloride (3.62 g, 12 mmol) in dichloromethane. The solution was warmed up to room temperature, and kept for 3 hr. It was then washed with sodium hydrogen carbonate aqueous solution and dried. The product was isolated by silica gel column chromatography. 1.9 g
Reaction SMILES: [Br:1][CH2:2][C:3]1[N:4]=[C:5]([C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)[S:6][C:7]=1[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16]C)=[C:12]([CH3:18])[CH:11]=1.C(=O)=O.CC(C)=O.B(Br)(Br)Br>C(Cl)Cl>[Br:1][CH2:2][C:3]1[N:4]=[C:5]([C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)[S:6][C:7]=1[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([CH3:18])[CH:11]=1
Reactant: COc1ccc(CCc2sc(-c3ccc(C(F)(F)F)cc3)nc2CBr)cc1C
Agent: BrB(Br)Br
Agent: O=C=O
Solvent: ClCCl
Solvent: CC(C)=O
Product: Cc1cc(CCc2sc(-c3ccc(C(F)(F)F)cc3)nc2CBr)ccc1O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a 50 ml round-bottom flask equipped with a magnetic stir-bar, an addition funnel and N2 inlet was added 4-(Bromomethyl)-5-[2-(4-methoxy-3-methylphenyl)ethyl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole (468 mg, 1.0 mmoles, 1 eq) and dry CH2Cl2 (15 ml, 0.1M). The mixture was cooled to −78° C. (dry ice/acetone) after which boron tribromide (1M in CH2Cl2, 3 ml, 3.0 mmoles, 3 eq) was added dropwise over the course of 15 minutes. After the addition was complete, the cold bath was removed and the reaction was allowed to warm to room temperature and stirred for 1 hour. After this time, the reaction was cooled to 0° C. and quenched very carefully with water. Once the reaction was quenched, it was transferred to a separatory funnel where the phases were separated. The aqueous fraction was washed three times with CH2Cl2 and the combined organic fractions were dried over Na2SO4, filtered, concentrated in vacuo to yield a quantitative yield of the titled phenol. The product was used without purification.
Reaction SMILES: [Mg].[CH2:2]([C@H:7]1[CH2:12][CH2:11][C@H:10]([C:13]2[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=2)[CH2:9][CH2:8]1)[CH2:3][CH2:4][CH2:5][CH3:6].[C:20](=[S:22])=[S:21].Cl>C1COCC1>[CH2:2]([C@H:7]1[CH2:12][CH2:11][C@H:10]([C:13]2[CH:18]=[CH:17][C:16]([C:20]([SH:22])=[S:21])=[CH:15][CH:14]=2)[CH2:9][CH2:8]1)[CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: S=C=S
Reactant: CCCCC[C@H]1CC[C@H](c2ccc(Br)cc2)CC1
Agent: Cl
Agent: [Mg]
Solvent: C1CCOC1
Product: CCCCC[C@H]1CC[C@H](c2ccc(C(=S)S)cc2)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a suspension prepared by suspending 0.95 g (39 mmol) of magnesium in 200 ml of THF was added dropwise a solution prepared by dissolving 9.28 g (30 mmol) of 4-(trans-4-n-pentylcyclohexyl)bromobenzene in 80 ml of THF, at room temperature while being stirred in 1 hour, and then heated to reflux for 2 hours to prepare a Grignard reagent. To this solution was added dropwise 5.7 g (75 mmol) of carbon disulfide at room temperature in 30 min and stirred as it was overnight. To this reaction solution was added 150 ml of 1M hydrochloric acid to terminate the reaction and extracted with 350 ml of toluene. The organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under a reduced pressure, and the residue was recrystallized from heptane to obtain 4.74 g of 4-(trans-4-n-pentylcyclohexyl)phenyldithiocarboxylic acid (yield 51.5%).
Reaction SMILES: [NH2:1][CH:2]1[CH2:8][S:7][CH:6]([C:9]2[S:10][CH:11]=[CH:12][CH:13]=2)[CH2:5][N:4]([CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:3]1=[O:22].Br[CH:24]([CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>>[CH2:28]([O:27][C:25]([CH:24]([NH:1][CH:2]1[CH2:8][S:7][CH:6]([C:9]2[S:10][CH:11]=[CH:12][CH:13]=2)[CH2:5][N:4]([CH2:14][C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[C:3]1=[O:22])[CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:26])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1
Reactant: CC(C)(C)OC(=O)CN1CC(c2cccs2)SCC(N)C1=O
Reactant: O=C(OCc1ccccc1)C(Br)CCc1ccccc1
Product: CC(C)(C)OC(=O)CN1CC(c2cccs2)SCC(NC(CCc2ccccc2)C(=O)OCc2ccccc2)C1=O

Procedure:
Following the same procedure described in Example 42(h), 0.4 g of t-butyl α-[6-amino-5-oxo-2-(2-thienyl)perhydro-1,4-thiazepin-4-yl]acetate [prepared as described in Example 49(g)] was N-alkylated using 0.80 g of benzyl 2-bromo-4-phenylbutyrate. The resulting product was subjected to silica gel column chromatography eluted with a 1:40 by volume mixture of ethyl acetate and methylene chloride to separate it into two isomers, A and B, (ascribed to the asymmetric carbon atom to which the phenethyl group is attached).
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1[O:9][C:10]2[CH:17]=[CH:16][CH:15]=[C:14](OS(C(F)(F)F)(=O)=O)[C:11]=2[C:12]=1[CH3:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[N+:32]([C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=1)([O-:34])=[O:33].COCCOC>O>[C:1]([O:5][C:6]([C:8]1[O:9][C:10]2[CH:17]=[CH:16][CH:15]=[C:14]([C:39]3[CH:38]=[CH:37][CH:36]=[C:35]([N+:32]([O-:34])=[O:33])[CH:40]=3)[C:11]=2[C:12]=1[CH3:13])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: O=[N+]([O-])c1cccc(B(O)O)c1
Reactant: Cc1c(C(=O)OC(C)(C)C)oc2cccc(OS(=O)(=O)C(F)(F)F)c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: COCCOC
Product: Cc1c(C(=O)OC(C)(C)C)oc2cccc(-c3cccc([N+](=O)[O-])c3)c12
Temperature: 85 °C
Reaction time: 3 h
Yield: 87.7 %

Procedure:
3-Methyl-4-trifluoromethanesulfonyloxy-benzofuran-2-carboxylic acid tert-butyl ester (380 mg, 1 mmol) was mixed with K2CO3 (280 mg, 2 mmol), 3-nitro-phenylboronic acid (334 mg, 2 mmol), Pd(Ph3)4 (115 mg, 0.1 mmol), 4 mL of 1,2-dimethoxyethane and 5 drops of water. The mixture was heated and stirred in an 85° C. oil bath for 3 h. The reaction mixture was poured into water and was extracted with ethyl acetate. The organic extract was washed with water and dried over sodium sulfate. Removal of solvent gave the crude product, which was purified by column chromatography to give 310 mg (88% yield) of 3-methyl-4-(3-nitro-phenyl)-benzofuran-2-carboxylic acid tert-butyl ester, obtained as white solid.
Reaction SMILES: [Li+].[O-][Al:3]=O.[O-2].[Al+3].[O-2].[O-2].[Al+3].[N+:10]([O-:13])([OH:12])=[O:11]>>[N+:10]([O-:13])([O-:12])=[O:11].[Al+3:3].[N+:10]([O-:13])([O-:12])=[O:11].[N+:10]([O-:13])([O-:12])=[O:11]
Reactant: O=[N+]([O-])O
Reactant: O=[Al][O-]
Agent: [Al+3]
Agent: [Li+]
Agent: [O-2]
Product: O=[N+]([O-])[O-]

Procedure:
A preferred method of preparing the composition of the present invention is to first prepare lithium aluminate powder. This powder may be advantageously prepared using sol-gel techniques so that uniformly sized particles with known properties are achieved. Briefly, aluminium oxide is dissolved in nitric acid to form an aluminum nitrate solution. The aluminum nitrate solution is then reacted with ammonia to return aluminum oxide, now in the form of an alumina sol. At this point, a stoichiometric amount of a soluble lithium compound is added to the solution. Depending upon the neutronic characteristics of the reactor, it may be desirable to use lithium fully enriched in the lithium isotope. The alumina sol-lithium mixture is then added dropwise into a bath of solvent which is at least partially immiscible in the alumina sol. As part of the moisture present in the sol is extracted into the solvent, the sol is converted into perfect spheres of a gel. Through appropriate sizing of the drop-forming means, such as a vibrating nozzle, the resulting particles will be sized between 100 and 500 micrometers. The microspheres may then be heated to drive off remaining moisture and then heated to a high temperature to form the compound lithium aluminate.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([CH2:7][CH2:8][NH:9][CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.Cl[C:25]([O:27][CH3:28])=[O:26]>C(OCC)C>[CH:10]1([N:9]([CH2:8][CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:16][CH:15]=2)[C:25](=[O:26])[O:27][CH3:28])[CH2:11][CH2:12][CH2:13][CH2:14]1
Reactant: COC(=O)Cl
Reactant: COc1ccc(CCNC2CCCC2)cc1
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: COC(=O)N(CCc1ccc(OC)cc1)C1CCCC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 85.9 %

Procedure:
To a solution of N-(4-methoxyphenethyl)cyclopentanamine (0.827 g, 3.77 mmol) in diethyl ether was added triethylamine (0.83 mL, 5.66 mmol) and methyl chloroformate (0.44 mL, 5.66 mmol) at 0° C. The reaction mixture was gradually warmed to room temperature and stirred for 30 min. Filtration and concentration of mixture under reduced pressure gave the crude product which was purified by silica gel column chromatography using hexanes/ethyl acetate to provide the product (0.898 g, 86%) as light yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.10 (d, 2H, J=8.6 Hz), 6.81 (d, 211, J=8.6 Hz), 4.32-4.12 (m, 1H), 3.76 (s, 3H), 3.69 (s, 3H), 3.24 (t, 2H, J=7.9 Hz), 2.76 (t, 2H, J=7.9 Hz), 1.79-1.76 (m, 2H), 1.67-1.66 (m, 2H), 1.54-1.47 (m, 4H). LC-MS (ESI) Calcd for C16H23NO3 [M+H]+: 278.17. Found: 278.00.