Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH2:2][C:3]([S:6]([CH2:9][CH:10]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])(=[O:8])=[O:7])([CH3:5])[CH3:4].[C:28](O)(=[O:46])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]/[CH:36]=[CH:37]\[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:4][C:3]([S:6]([CH2:9][CH:10]([CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:11]([O:13][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:12])(=[O:8])=[O:7])([CH3:5])[CH2:2][O:1][C:28](=[O:46])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]/[CH:36]=[CH:37]\[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Reactant: CC(C)(CO)S(=O)(=O)CC(Cc1ccccc1)C(=O)OCc1ccccc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: CN(C)c1ccncc1
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OCC(C)(C)S(=O)(=O)CC(Cc1ccccc1)C(=O)OCc1ccccc1
Temperature: 0 °C
Yield: 82 %

Procedure:
A solution of 420 mg (1.08 mmol) of benzyl rac-α-[[(2-hydroxy-1,1-dimethylethyl)sulfonyl]methyl]hydrocinnamate, 610 mg (2.15 mmol) of oleic acid, 710 mg (1.88 mmol) of HBTU and 660 mg (5.38 mmol) of 4-dimethylaminopyridine in 10 ml of methylene chloride was stirred at room temperature for 15 hours. The reaction solution was subsequently poured into 70 ml of ice-cold 2N sodium carbonate solution and extracted three times with 150 ml of ethyl acetate each time. The organic extracts were washed with 70 ml of ammonium chloride solution, then combined, dried over magnesium sulphate and evaporated under reduced pressure. For purification, the crude product (1.25 g) was chromatographed on 50 g of silica gel with a 95:5 mixture of toluene and ethyl acetate as the eluent. There were obtained 580 mg of benzyl rac-α-[[[1,1-dimethyl-2-[[(Z)-9octadecenoyl]oxy]ethyl]sulfonyl]methyl]hydrocinnamate as a colourless oil, MS: 655 (M+H)+.
Reaction SMILES: C([NH:8][C@H:9]([C:18]([NH:20][C@@H:21]([C:26]([NH:28][CH2:29][C:30]([NH:32][C@H:33]([C:41]([CH:43]1[C:50]2([NH2:52])[CH2:51][CH:46]3[CH2:47][CH:48]([CH2:53][C:44]1([C:54]([O:56][CH3:57])=[O:55])[CH2:45]3)[CH2:49]2)=[O:42])[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:31])=[O:27])[CH2:22][CH2:23][CH2:24][CH3:25])=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)(OC(C)(C)C)=O.[ClH:58]>C(OC)(=O)C.O1CCOCC1>[ClH:58].[NH2:8][C@H:9]([C:18]([NH:20][C@@H:21]([C:26]([NH:28][CH2:29][C:30]([NH:32][C@H:33]([C:41]([CH:43]1[C:50]2([NH2:52])[CH2:51][CH:46]3[CH2:47][CH:48]([CH2:53][C:44]1([C:54]([O:56][CH3:57])=[O:55])[CH2:45]3)[CH2:49]2)=[O:42])[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:31])=[O:27])[CH2:22][CH2:23][CH2:24][CH3:25])=[O:19])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1
Reactant: CCCC[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OC(C)(C)C)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)C1C2(N)CC3CC(C2)CC1(C(=O)OC)C3
Agent: Cl
Solvent: C1COCCO1
Solvent: COC(C)=O
Product: CCCC[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)C1C2(N)CC3CC(C2)CC1(C(=O)OC)C3
Reaction time: 1 h

Procedure:
To a solution of 0.896 g of methyl Boc-L-tyrosyl-D-norleucyl-glycyl-phenylalanyl-3-amino-1-adamantanecarboxylate in 10 ml of methyl acetate is added 10 ml of a 6 M solution of hydrogen chloride in dioxane. The reaction mixture is allowed to stand for one hour at room temperature, then the solvent is removed under vacuum. The residue is extracted with ethyl acetate. Removal of the solvent gives methyl L-tyrosyl-D-norleucyl-glycyl-L-phenylalanyl-3-amino-1-adamantanecarboxylate hydrochloride which is represented by the formula ##STR54##
Reaction SMILES: [CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH:27]4CCN[CH2:29][CH2:28]4)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:34][C:35]([N:37]([CH3:39])[CH3:38])=[O:36].C(N(CC)C(C)C)(C)C.C[N:50]([CH:52]=O)[CH3:51]>>[NH2:26][C:24]1[C:25]2=[C:17]([C:12]3[CH:13]=[CH:14][C:15]4[C:10]([CH:11]=3)=[N:9][N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:16]=4)[CH:18]=[C:19]([CH:27]3[CH2:28][CH2:29][CH2:52][N:50]([CH2:34][C:35]([N:37]([CH3:39])[CH3:38])=[O:36])[CH2:51]3)[N:20]2[N:21]=[CH:22][N:23]=1
Reactant: CN(C)C(=O)CCl
Reactant: CN(C)C=O
Reactant: Nc1ncnn2c(C3CCNCC3)cc(-c3ccc4cn(Cc5ccccc5)nc4c3)c12
Solvent: CCN(C(C)C)C(C)C
Product: CN(C)C(=O)CN1CCCC(c2cc(-c3ccc4cn(Cc5ccccc5)nc4c3)c3c(N)ncnn23)C1
Temperature: 60 °C
Reaction time: 17 h
Yield: 19 %

Procedure:
To a solution of 5-(2-benzyl-2H-indazol-6-yl)-7-piperidin-4-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine (100 mg, 0.24 mmol) in DMF (1.5 mL) was added 2-chloro-N,N-dimethylacetamide (32 mg, 0.26 mmol) and N,N-diisopropylethylamine (123 μL, 0.71 mmol). The reaction was stirred at 60° C. for 17 h. The crude mixture was purified via ISCO® chromatography using 9:1 CH2Cl2 to afford 23 mg (19%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1 H), 7.89 (s, 1 H), 7.78 (d, 1 H), 7.57 (s, 1 H), 7.25-7.45 (m, 5 H), 7.09-7.19 (m, 1 H), 6.63 (s, 1 H), 5.65 (s, 2 H), 3.34-3.52 (m, 2 H), 2.97-3.16 (m, 6H), 2.72-2.91 (m, 4 H), 2.09-2.43 (m, 2 H), 1.85-2.06 (m, 1 H), 1.44-1.89 (m, 2 H); ES-MS m/z 509.30 HPLC RT (min) 2.42.
Reaction SMILES: [CH3:1]/[C:2](=[CH:5]\[CH2:6][C@H:7]1[CH2:12][C@H:11]2[C@:9]([CH3:13])([CH2:10]2)[C:8]1([CH3:15])[CH3:14])/[CH2:3][OH:4].[CH3:16][Mg]Cl.O1CCCC1.BrCBr.C([Mg]Cl)(C)(C)C>>[CH3:1][C:2]1([CH2:3][OH:4])[CH2:16][CH:5]1[CH2:6][C@H:7]1[CH2:12][C@H:11]2[C@:9]([CH3:13])([CH2:10]2)[C:8]1([CH3:15])[CH3:14]
Reactant: C[Mg]Cl
Reactant: C/C(=C\C[C@H]1C[C@@H]2C[C@]2(C)C1(C)C)CO
Agent: CC(C)(C)[Mg]Cl
Solvent: BrCBr
Solvent: C1CCOC1
Product: CC1(CO)CC1C[C@H]1C[C@@H]2C[C@]2(C)C1(C)C
Temperature: 25 °C

Procedure:
System B: (E)-2-methyl-4-((1S,3S,5R)-1,2,2-trimethylbicyclo-[3.1.0]hexan-3-yl)but-2-en-1-ol (5 g, 24 mmol) (F. Schröder, WO 2006066436, priority 20.12.2005 to Givaudan) is added undercooling and stirring to methyl magnesium chloride 3M in tetrahydrofuran (8 ml, 24 mmol) under nitrogen. Dibromomethane and tert-butyl magnesium chloride are added at a temperature of 10°-20° C. The dibromomethane and tert-butyl magnesium chloride are each added in 3 portions, one portion of dibromomethane (4.2 g, 24 mmol) followed by a portion of tert-butyl-magnesium chloride (12 ml, 24 mmol). After the addition of each pair of portions (72 mmol) the mixture is stirred for an appropriate time at room temperature. When complete or nearly complete conversion is reached, as checked by GC, the mixture is quenched by addition of conc. NH4Cl. Tert-Butyl methyl ether extraction, washing of the organic phase with H2O until pH 7, drying over MgSO4 and concentration gives 16.6 g of an an oily residue, which is bulb-to bulb-distilled at 120° C./0.07 Ton giving 4.7 g (89%) of Javanol (dr=1:1), whose analytical data are consistent with the ones described for this compound in the literature (J. A. Bajgrowicz, G. Frater, EP 801049, priority 9.4.1997 to Givaudan-Roure).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:11])[CH:10]=1)[C:5]([NH2:7])=O.S(Cl)(Cl)=O.CN(C=O)C.[OH-].[Na+]>C1C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:11])[CH:10]=1)[C:5]#[N:7]
Reactant: Cc1cc(C)cc(C(N)=O)c1
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccccc1
Solvent: CN(C)C=O
Solvent: O=S(Cl)Cl
Product: Cc1cc(C)cc(C#N)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.5 %

Procedure:
3,5-dimethylbenzamide (50 g, 0.3356 M) was suspended in benzene (400 mL). Thionyl chloride (49 mL, 0.671 M) and DMF (2 mL) were added and the mixture was refluxed for 2 hr. After cooling to room temperature, the mixture was poured into a crushed ice. After 1 hr., the solution was neutralized by the addition of 6 N sodium hydroxide solution. The product was then extracted with ether, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo to give a yellow solid. The crude product was then purified by silica gel column chromatography (eluent, EA:hexane (1:4)) to afford 42 g (95%) of 3,5-dimethylbenzonitrile as a yellow solid. m.p. 51-52° C. 1H NMR (300 MHz, CDCl3) δ 2.34 (6H, s), 7.21 (1H, s), 7.26 (2H, s).
Reaction SMILES: C(#N)C.[N+:4]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH:13]([NH:15][CH2:16][C:17]#[N:18])[CH3:14])([O-:6])=[O:5].C([O-])(O)=O.[Na+].Cl[C:25]([O:27][CH2:28][CH3:29])=[O:26]>CCOC(C)=O.C(Cl)Cl>[C:17]([CH2:16][N:15]([CH:13]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[N+:4]([O-:6])=[O:5])[CH3:14])[C:25](=[O:26])[O:27][CH2:28][CH3:29])#[N:18]
Reactant: CC(NCC#N)c1ccccc1[N+](=O)[O-]
Reactant: CCOC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CCOC(=O)N(CC#N)C(C)c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 14 h
Yield: 4 %

Procedure:
To the acetonitrile solution containing 2-(1-(2-nitrophenyl)ethylamino)acetonitrile (18) from the previous step was added saturated NaHCO3 (5 mL) and ethyl chloroformate (1.83 g, 16.86 mmol). The reaction mixture was stirred vigorously at room temperature for 14 hours. The reaction was diluted with EtOAc (50 mL) and washed with brine (40 mL). The separated organic phase was dried over Na2SO4, filtered, and concentrated. Purification (Biotage 40 s, 3:1 CH2Cl2:hexanes, then 100% CH2Cl2) provided 37.1 mg (0.134 mmol, 4% yield) of ethyl cyanomethyl(1-(2-nitrophenyl)ethyl)carbamate (19) as a light yellow oil.
Reaction SMILES: [CH2:1]1[O:3][C@H:2]1[CH2:4][OH:5].[I:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1.C(N(CC)CC)C>C(O)C>[I:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:1][C@@H:2]([OH:3])[CH2:4][OH:5])=[CH:9][CH:8]=1
Reactant: OC[C@H]1CO1
Reactant: Oc1ccc(I)cc1
Solvent: CCO
Solvent: CCN(CC)CC
Product: OC[C@H](O)COc1ccc(I)cc1
Temperature: 25 °C

Procedure:
(S)-Glycidol (0.36 ml, 5.5 mmol) is added to a solution of 4-iodophenol (1 g, 4.5 mmol) and triethylamine (31 ml, 0.2 mmol) in ethanol (5 ml) and the resulting light brown solution is heated at reflux for 15 hours. The reaction is allowed to cool to room temperature and the solvent removed in vacuo. The residue is purified by chromatography (SiO2, EtOAc/iso-hexane) to afford (S)-3-(4-Iodo-phenoxy)-propane-1,2-diol as a colourless oil.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([Cl:17])[CH:10]=2)[N:5]=[C:4]([NH:18][CH:19]([CH2:22][OH:23])[CH2:20][OH:21])[N:3]=1.[CH3:24][N:25]1[CH2:30][CH2:29][CH:28]([NH:31][CH3:32])[CH2:27][CH2:26]1.[OH-].[Na+].O1CCOC[CH2:36]1>>[Cl:17][C:11]1[CH:10]=[C:9]([NH:8][C:6]2[N:7]=[C:2]([N:31]([CH3:32])[CH:28]3[CH2:29][CH2:30][N:25]([CH3:24])[CH2:26][CH2:27]3)[N:3]=[C:4]([NH:18][CH:19]([CH2:22][OH:23])[CH2:20][OH:21])[N:5]=2)[CH:14]=[CH:13][C:12]=1[O:15][CH2:16][CH3:36]
Reactant: COc1ccc(Nc2nc(Cl)nc(NC(CO)CO)n2)cc1Cl
Reactant: C1COCCO1
Reactant: CNC1CCN(C)CC1
Agent: [Na+]
Agent: [OH-]
Product: CCOc1ccc(Nc2nc(NC(CO)CO)nc(N(C)C3CCN(C)CC3)n2)cc1Cl

Procedure:
To 131 (0.979 g, 0.271 mmol) dissolved in 3 mL 1,4-dioxane was added methyl-4-(methylamino)piperidine (0.05 mL, 0.34 mmol) dissolved in 2 mL 1,4-dioxane followed by the addition of 2.5 N NaOH (aq) (0.11 mL, 0.275 mmol). The mixture was heated at reflux for 3 h 45 min, cooled to about room temperature, and then concentrated under reduced pressure. The resulting material was diluted with dichloromethane and filtered. The filtrate was then concentrated affording 56.5 mg of material. The crude material was purified by silica gel pipet column eluting with 100% methanol affording an white solid 132 (21.1 mg, 18%), mp 84° C.; MS (ESI): m/z 454 (34.7), 452 (M+H, 100), 422 (11.3), 248 (25.3), 247 (51.3), 157 (60.3), 129 (27.5).
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[C:4]([CH3:9])[C:3]=1O.[NH3:11]>[Pd].[Mn].[Ag]>[CH3:1][CH:2]1[CH:7]([CH3:8])[CH2:6][CH2:5][CH:4]([CH3:9])[CH:3]1[NH2:11]
Reactant: N
Reactant: Cc1ccc(C)c(O)c1C
Agent: [Ag]
Agent: [Mn]
Agent: [Pd]
Product: CC1CCC(C)C(N)C1C
Yield: 95.7 %

Procedure:
A mixture of 550 g of 2,3,6-trimethylphenol and 510 g of ammonia and 50 g of catalyst which contains 5.0% by weight of palladium, 1.0% by weight of manganese and 5.0% by weight of silver on aluminum oxide in powder form is hydrogenated at 220° C. and under a hydrogen pressure of 200 bar in a 3 l rolling autoclave. The mixture is cooled and filtered and the filtrate is distilled. 546 g of 2,3,6-trimethylcyclohexylamine, boiling point=78°-81° C./22 mbar, are obtained, corresponding to a yield of 96%.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:15])[C:5]1[CH:10]=[C:9]([F:11])[C:8](F)=[C:7]([Cl:13])[C:6]=1[F:14])[CH3:2].C(N(CC)CC)C.[C:23]([O:27][C:28](=[O:35])[NH:29][CH:30]1[CH2:34][CH2:33][NH:32][CH2:31]1)([CH3:26])([CH3:25])[CH3:24]>C(#N)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:15])[C:5]1[CH:10]=[C:9]([F:11])[C:8]([N:32]2[CH2:33][CH2:34][CH:30]([NH:29][C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:35])[CH2:31]2)=[C:7]([Cl:13])[C:6]=1[F:14])[CH3:2]
Reactant: CCOC(=O)c1cc(F)c(F)c(Cl)c1F
Reactant: CC(C)(C)OC(=O)NC1CCNC1
Solvent: CC#N
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(Cl)c1F
Reaction time: 48 h
Yield: 98.6 %

Procedure:
To a solution of 3-chloro-2,4,5-tri-fluorobenzoic acid ethyl ester (Example 1c, 5.50 g, 23.05 mmol) in acetonitrile (25 mL) is added triethylamine (6.43 mL, 46.1 mmol) and pyrrolidin-3-ylcarbamic acid tert-butyl ester (4.72 g, 25.4 mmol). After 48 hours, the mixture is diluted with ethyl acetate and washed with saturated NaHCO3, water, and brine. The organic layer is dried over MgSO4, filtered, and the filtrate is concentrated to afford the title compound (9.2 g). MS CI: m/z 405 (MH+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[Cl:14])[O:5][CH2:6][C:7](=[NH:10])OC.[NH3:15]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[Cl:14])[O:5][CH2:6][C:7]([NH2:15])=[NH:10]
Reactant: N
Reactant: COC(=N)COc1ccc(Cl)c(Cl)c1
Solvent: CCO
Product: N=C(N)COc1ccc(Cl)c(Cl)c1

Procedure:
Obtained using the procedure described in section b of Example 2, starting with 28.2 g (0.12 mole) of methyl 2-(3,4-dichlorophenoxy)acetimidate and 10.2 g (0.60 mole) of ammonia in 480 ml of absolute ethanol. Reaction time: 3 hours. Yld: 26.3 g (quantitative).
Reaction SMILES: [OH-:1].[Na+:2].O[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][N:12]1[C:16](=[O:17])[CH2:15][S:14][CH:13]1[CH2:18][CH2:19][CH2:20][C:21]1[CH:31]=[CH:30][C:24]([C:25]([O:27]CC)=[O:26])=[CH:23][CH:22]=1.C(Cl)(Cl)[Cl:33]>CO.O>[OH:1][CH:9]([CH2:8][CH2:7][CH2:6][CH2:5][CH3:4])[CH2:10][CH2:11][N:12]1[C:16](=[O:17])[CH2:15][S:14][CH:13]1[CH2:18][CH2:19][CH2:20][C:21]1[CH:31]=[CH:30][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1.[Na+:2].[Cl-:33]
Reactant: [OH-]
Reactant: CCOC(=O)c1ccc(CCCC2SCC(=O)N2CCCCCCCCO)cc1
Reactant: ClC(Cl)Cl
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CCCCCC(O)CCN1C(=O)CSC1CCCc1ccc(C(=O)O)cc1
Product: [Cl-]
Temperature: 0 °C
Reaction time: 3 h

Procedure:
Sodium hydroxide solution (5 N, 2.5 ml., 12.5 mmol.) is added dropwise to a stirred mixture of ethyl 4-{3-[3-(hydroxyoctyl)-4-oxo-2-thiazolidinyl]propyl}benzoate (2.80 g., 6.64 mmol.) in aqueous methanol (25 ml. methanol plus 5 ml. water) maintained at 0° C. The resulting mixture is allowed to warm to room temperature and stirred for 3 hours. Then, the reaction mixture is diluted with water, and extracted with ether. The aqueous phase is separated, acidified with 2 N hydrochloric acid (10 ml.), and extracted with ether. This ethereal extract is washed with water, dried over anhydrous magnesium sulfate, concentrated in vacuo to yield an oil residue. The oil residue is then applied to a silica gel column (75 g.) with chloroform. Elution with chloroform-acetic acid (25:1; v:v; 410 ml.) gives impure material. Continued elution with the same eluant (420 ml.) provides the desired title compound as a viscous pale yellow oil, ir (NaCl) 1700, 1665 cm- 1, pmr (CDCl3) δ0.92 (3H, t), 3.60 (2H, s), 4.72 (1H, m), 7.30 (2H, d), 8.08 (2H, d).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:14][C:15](=[O:22])[C:16]2[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=2)[CH:5]=[N:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].[F:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1>>[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[CH:3]=[C:4]([NH:14][C:15](=[O:22])[C:16]3[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=3)[CH:5]=[N:6][C:7]=2[O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[CH:26][CH:25]=1
Reactant: OB(O)c1ccc(F)cc1
Reactant: O=C(Nc1cnc(OCC(F)(F)F)c(Br)c1)c1cccnc1
Product: O=C(Nc1cnc(OCC(F)(F)F)c(-c2ccc(F)cc2)c1)c1cccnc1

Procedure:
The title compound was synthesized in analogy to Example 39, using N-[5-bromo-6-(2,2,2-trifluoro-ethoxy)-pyridin-3-yl]-nicotinamide (example G) and B-(4-fluorophenyl)-boronic acid (CAN 1765-93-1) as starting materials; LC-MS (UV peak area/ESI) 100%, 392.1005 (M+H)+.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[CH:16]=[C:17]([C:25]([S:28]([CH3:31])(=[O:30])=[O:29])([CH3:27])[CH3:26])[CH:18]=[C:19]4[C:24]=3[N:23]=[CH:22][CH:21]=[CH:20]4)[CH:10]=2)=[CH:5][CH:4]=1.[CH3:32][S:33]([O-:35])=[O:34].[Na+]>CN(C=O)C.O>[CH3:32][S:33]([CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[CH:16]=[C:17]([C:25]([S:28]([CH3:31])(=[O:30])=[O:29])([CH3:27])[CH3:26])[CH:18]=[C:19]4[C:24]=3[N:23]=[CH:22][CH:21]=[CH:20]4)[CH:10]=2)=[CH:5][CH:4]=1)(=[O:35])=[O:34]
Reactant: CC(C)(c1cc(-c2cccc(-c3ccc(CBr)cc3)c2)c2ncccc2c1)S(C)(=O)=O
Reactant: CS(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(c1cc(-c2cccc(-c3ccc(CS(C)(=O)=O)cc3)c2)c2ncccc2c1)S(C)(=O)=O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 8-(4′-Bromomethyl-biphenyl-3-yl)-6-(1-methanesulfonyl-1-methyl-ethyl)-quinoline (1.0 eq.) in DMF (0.1M) was added sodium methanesulfinate (1.3 eq.). The mixture was stirred at rt for 2 h, poured in water and extracted with EtOAc (2×). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. Flash chromatography (Hex:EA; 1:4) and stirring in EtOAc:Hex:Et2O (1:7:2) afforded the title compound as a white solid after filtration. 1H NMR (400 MHz, acetone-d6): δ 8.96 (dd, 1H), 8.49 (dd, 1H), 8.32 (d, 1H), 8.25 (d, 1H), 8.08 (t, 1H), 7.81–7.75 (m, 4H), 7.63–7.59 (m, 4H), 4.48 (s, 2H), 2.90 (s, 3H), 2.75 (s, 3H), 2.03 (s, 6H).
Reaction SMILES: [CH3:1][N:2]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25](=[O:59])[NH:26][C:27]2[CH:32]=[CH:31][C:30]([N:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)=[CH:29][C:28]=2[C:39]2[CH:44]=[C:43]([C:45](=[O:58])[NH:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[C:50]([C:54]([F:57])([F:56])[F:55])[CH:49]=3)[CH:42]=[CH:41][N:40]=2)[CH:20]=1)[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11](OC(C)(C)C)=O)[CH2:7][CH2:6]1.ClCCl.C(O)(C(F)(F)F)=O.C(N(CC)CC)C.CS(Cl)(=O)=O>ClCCl>[CH3:1][N:2]([CH2:18][C:19]1[CH:20]=[C:21]([CH:22]=[CH:23][CH:24]=1)[C:25]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]2)=[CH:29][C:28]=1[C:39]1[CH:44]=[C:43]([CH:42]=[CH:41][N:40]=1)[C:45]([NH:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[C:50]([C:54]([F:55])([F:57])[F:56])[CH:49]=1)=[O:58])=[O:59])[CH2:3][CH2:4][N:5]1[CH2:6][CH2:7][N:8]([CH3:11])[CH2:9][CH2:10]1
Reactant: CN(CCN1CCN(C(=O)OC(C)(C)C)CC1)Cc1cccc(C(=O)Nc2ccc(N3CCCCC3)cc2-c2cc(C(=O)NCc3cccc(C(F)(F)F)c3)ccn2)c1
Agent: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(CC)CC
Product: CN1CCN(CCN(C)Cc2cccc(C(=O)Nc3ccc(N4CCCCC4)cc3-c3cc(C(=O)NCc4cccc(C(F)(F)F)c4)ccn3)c2)CC1
Reaction time: 2 h
Yield: 31.5 %

Procedure:
Into a 25-mL round-bottom flask, was placed 160 mg of tert-butyl 4-(2-(methyl(3-((4-(piperidin-1-yl)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)-carbamoyl)benzyl)amino)ethyl)piperazine-1-carboxylate Example 38 and 10 mL of 1:1 dichloromethane/TFA. After stirring for 2 hours, the solvent was evaporated. The residue was partitioned between ethyl acetate and aqueous sodium bicarbonate solution. The organic phase was dried and the solvent was evaporated. The residue was treated with triethylamine (78 mg, 0.77 mmol, 6.00 equiv), and dichloromethane (2 mL). This was followed by dropwise addition of a solution of methanesulfonyl chloride (21.9 mg, 0.19 mmol, 1.50 equiv) in dichloromethane (1 mL) with stirring at 0° C. The resulting solution was stirred for 4 h at 25° C. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 45 mg (28%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 12.31 (s, 1H), 9.55-9.59 (t, J=6.6 Hz, 1H), 8.93-8.94 (d, J=3 Hz, 1H), 8.35 (s, 1H), 8.27-8.30 (d, J=9 Hz, 1H), 8.09 (s, 1H), 7.96-7.98 (d, J=6 Hz, 1H), 7.85-7.86 (d, J=3 Hz, 1H), 7.56-7.76 (m, 7H), 7.31-7.34 (d, J=9 Hz, 1H), 4.62-4.64 (d, J=6 Hz, 2H), 4.39 (s, 2H), 3.34 (s, 4H), 3.22-3.24 (d, J=6 Hz, 6H), 2.90 (s, 5H), 2.74 (s, 3H), 2.69 (s, 4H), 1.75 (s, 4H), 1.60-1.61 (d, J=3 Hz, 2H). MS (ES, m/z): 792 [M+H]+.
Reaction SMILES: C1(/C=C/C2C=CC=CC=2)C=CC=CC=1.[CH3:15][CH2:16][C@@H:17]1[CH:22]2[CH2:23][C@H:24]([C@@H:25]([O:38]C(C3C=CC(Cl)=CC=3)=O)[C:26]3C=CN=[C:32]4[C:27]=3[CH:28]=[C:29](OC)[CH:30]=[CH:31]4)N(CC2)C1.CC[OH:50]>>[C:27]1([C@@H:26]([OH:50])[C@@H:25]([C:24]2[CH:15]=[CH:16][CH:17]=[CH:22][CH:23]=2)[OH:38])[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: CC[C@H]1CN2CCC1C[C@@H]2[C@@H](OC(=O)c1ccc(Cl)cc1)c1ccnc2ccc(OC)cc12
Reactant: CCO
Agent: C(=C/c1ccccc1)\c1ccccc1
Product: O[C@H](c1ccccc1)[C@H](O)c1ccccc1
Yield: 92 %

Procedure:
Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa The reaction was performed by using an identical process as in Example 9 except the cinchona alkaloid is DHQD-CLB. (R,R)-(+)-1,2-diphenyl-1,2-ethandiol of more than 98.0% of enantiomeric excess was obtained (yield 92%) [∝]D+91.32 (c 1.0, EtOH): e.e.=98.2%
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:11]=[CH:10][C:7]([CH2:8][NH2:9])=[CH:6][CH:5]=1.[N-:12]([C:15]#[N:16])C#N.[Na+].[C:18](#[N:20])C>>[CH3:2][O:3][C:4]1[CH:11]=[CH:10][C:7]([CH2:8][N:9]([C:18]#[N:20])[C:15]([NH2:16])=[NH:12])=[CH:6][CH:5]=1
Reactant: CC#N
Reactant: N#C[N-]C#N
Reactant: COc1ccc(CN)cc1
Agent: Cl
Agent: [Na+]
Product: COc1ccc(CN(C#N)C(=N)N)cc1

Procedure:
800 ml of acetonitrile was added to 70.0 g (0.40 mol) of 4-methoxybenzylamine hydrochloride and 39.5 g (0.44 mol) of sodium dicyanamide. The mixture was refluxed for 19 hours, and the solvent was distilled off under reduced pressure. The residue was heated and dissolved in methanol, and insolubles were filtered off. The solvent was distilled off under reduced pressure, and the residue was recrystallized from ethyl acetate to obtain 67.0 g of colorless crystals having a melting point of 89 to 92° C.