Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:14](=[O:15])[C@@H:13]2[CH2:16][C@H:9]1[CH2:10][CH2:11][C@@H:12]2[NH:17][C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[BH4-].[Na+]>C1COCC1>[CH2:21]([O:20][C:18]([NH:17][C@H:12]1[CH2:11][CH2:10][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:16][C@H:13]1[CH2:14][OH:15])=[O:19])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: CC(C)(C)OC(=O)N1C(=O)[C@@H]2C[C@H]1CC[C@@H]2NC(=O)OCc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@@H]1CC[C@H](NC(=O)OCc2ccccc2)[C@H](CO)C1
Reaction time: 5 h
Yield: 102.6 %

Procedure:
(1R,2S,5R)-2-Benzyloxycarbonylamino-7-oxo-6-aza-bicyclo[3.2.1]octane-6-carboxylic acid tert-butyl ester (500 mg, 1.3 mmol) was dissolved in THF (10 mL) and water (2.2 mL) prior to the addition of NaBH4 (252.4 mg). After 5 h, the reaction was quenched with saturated NaHCO3 solution and extracted with EtOAc (2×). The organic extracts were combined, dried (MgSO4), filtered, and concentrated in vacuo to afford tert-butyl (1R,3R,4S)-4-benzyloxycarbonylamino-3-(hydroxymethyl)cyclohexylcarbamate (505 mg). MS (ES+)=375.4 (M+H)+.
Reaction SMILES: CC([N:5](C(O)=O)[NH:6][C:7](=[O:25])[CH:8]=[CH:9][C:10]1[CH:15]=[C:14]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:13]([OH:20])=[C:12]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH:11]=1)(C)C.Cl>C(O)C>[CH3:19][C:16]([C:14]1[CH:15]=[C:10]([CH:11]=[C:12]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:13]=1[OH:20])[CH:9]=[CH:8][C:7]([NH:6][NH2:5])=[O:25])([CH3:17])[CH3:18]
Reactant: CC(C)(C)c1cc(C=CC(=O)NN(C(=O)O)C(C)(C)C)cc(C(C)(C)C)c1O
Agent: Cl
Solvent: CCO
Product: CC(C)(C)c1cc(C=CC(=O)NN)cc(C(C)(C)C)c1O
Yield: 93.9 %

Procedure:
1,1-Dimethylethyl 2-[3-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1-oxo-2-propenyl]hydrazinecarboxylic acid (4.3 g, 0.011 mole) in absolute ethanol (20 ml) is treated with aqueous 2M HCl (11.0 ml, 1,0.022 mole). The resulting mixture is heated on a steam-bath for one hour. The mixture is stripped of volatiles under reduced pressure and the residue partitioned between ether and water. The layers are separated and the aqueous phase is treated with saturated aqueous NaHCOa until basic. The product is extracted out with a mixture of 1:1 ethyl acetate/ether. The organic extract is washed with saturated aqueous NaCl and dried over MgSO4. Filtration and concentration provides a solid which is triturated in hot hexane and filtered to yield 3.0 g (3.2 g theor., 94%) of 3,5-bis(1,1-dimethylethyl)-4-hydroxycinnamic acid hydrazide, mp 166° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C@@H:5]([NH:26]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:6][N:7]1[C:11](=[O:12])[C:10]2([CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][CH2:13]2)[NH:9][C:8]1=[O:25])=[O:4].ClCCl.CO.FC(F)(F)[C:53]([OH:55])=[O:54]>>[NH2:26][C@H:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:6][N:7]1[C:11](=[O:12])[C:10]2([CH2:13][CH2:14][NH:15][CH2:16][CH2:17]2)[N:9]([C:53]([O:55][C:10]([CH3:17])([CH3:13])[CH3:11])=[O:54])[C:8]1=[O:25]
Reactant: COC(=O)[C@H](CN1C(=O)NC2(CCN(C(=O)OC(C)(C)C)CC2)C1=O)NC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CO
Product: COC(=O)[C@@H](N)CN1C(=O)N(C(=O)OC(C)(C)C)C2(CCNCC2)C1=O
Yield: 87 %

Procedure:
A solution of 4.6 g (7.5 mmol) of (34.4) in 180 ml of dichloromethane/methanol/trifluoroacetic acid=95.5/3/1.5 is stirred at room temperature for 10 min. The reaction mixture is concentrated and the residue is chromatographed through silica gel. 3.14 g (87%) of (34.5) are obtained after concentrating the product fractions.
Reaction SMILES: C([O:9][C@H:10]1[C@@H:14]([O:15]C(=O)C2C=CC=CC=2)[C@H:13]([CH2:24][O:25]C(=O)C2C=CC=CC=2)[O:12][C@@H:11]1[N:34]1[CH:42]=[N:41][C:40]2[C:35]1=[N:36][C:37]([NH:44]C(=O)C)=[N:38][C:39]=2Cl)(=O)C1C=CC=CC=1.SC([OH:51])C.C[O-].[Na+]>C(O)(=O)C>[C@H:11]1([N:34]2[CH:42]=[N:41][C:40]3[C:39](=[O:51])[NH:38][C:37]([NH2:44])=[N:36][C:35]2=3)[O:12][C@@H:13]([CH2:24][OH:25])[C@H:14]([OH:15])[C@@H:10]1[OH:9]
Reactant: CC(O)S
Reactant: CC(=O)Nc1nc(Cl)c2ncn([C@H]3O[C@@H](COC(=O)c4ccccc4)[C@H](OC(=O)c4ccccc4)[C@@H]3OC(=O)c3ccccc3)c2n1
Agent: C[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: Nc1nc2c(ncn2[C@H]2O[C@@H](CO)[C@H](O)[C@@H]2O)c(=O)[nH]1
Yield: 86.3 %

Procedure:
A mixture of 12 (0.58 g, 0.88 mmol), mercaptoethanol (0.25 ml, 3.53 mmol) and NaOMe (0.76 ml, 3.53 mmol, 35% weight solution in MeOH (10 ml)) was refluxed for six hours. The reaction mixture was cooled, neutralized with glacial acetic acid and evaporated to dryness. The solid obtained was washed with CHCl3 and the residue was crystallized from water to yield pure 13 (0.215 g, 86%) as white crystal: m.p. 248° C. (dec).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.[CH2:23]([C:27]1[CH:32]=[CH:31][C:30]([N:33]=[C:34]=[O:35])=[CH:29][CH:28]=1)[CH2:24][CH2:25][CH3:26]>C1(C)C=CC=CC=1>[CH2:23]([C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34]([NH:22][C:19]2[CH:18]=[CH:17][C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][CH:7]=3)=[CH:21][CH:20]=2)=[O:35])=[CH:29][CH:28]=1)[CH2:24][CH2:25][CH3:26]
Reactant: CCCCc1ccc(N=C=O)cc1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Solvent: Cc1ccccc1
Product: CCCCc1ccc(NC(=O)Nc2ccc(Oc3ccnc4cc(OC)c(OC)cc34)cc2)cc1
Yield: 45 %

Procedure:
6,7-Dimethoxy-4-(4-aminophenoxy)quinoline (50 mg) was dissolved in toluene (3 ml) with heat, 4-butylphenyl isocyanate (0.2 ml) was added, and the admixture was refluxed with heat for 26 minutes. The resulting residue was purified by column chromatography on silica gel eluting with chloroform/acetone (10/1) to obtain 36 mg of the title compound (yield: 45%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.C(Cl)Cl.[C:15](Cl)(=O)[C:16](Cl)=O>CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][CH:7]=1)[CH2:8][C:9](=[O:11])[CH2:16][CH2:15]2
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)Cc1ccc(Br)cc1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C1CCc2cc(Br)ccc2C1
Temperature: 0 °C
Reaction time: 16 h
Yield: 88 %

Procedure:
A single neck 3 liter round bottom flask under an Ar atmosphere was charged with 4-bromo-phenyl acetic acid (250.0 g, 1.15 m), methylene chloride (1.5 L), and dimethylformamide (0.5 mL). This magnetically stirred solution was cooled to 0° C. and treated dropwise with oxalyl chloride (156 mL, 1.74 m). The reaction was allowed to reach room temperature and stirred 16 hrs. The reaction was concentrated on a rotary evaporator to approximately 1 L of volume. A separate dry 5 liter 3 neck round bottom flask under Ar, fitted with gas inlet tube, overhead stirrer, and digital thermometer was charged with methylene chloride (1.5 L) and AlCl3 (312.0 g, 2.34 m). This suspension was cooled to 0° C. and stirred while the above solution of acid chloride was added to it slowly via cannula. When the addition was complete, ethylene gas was introduced for 1-2 hrs to the vigorously stirred suspension while maintaining the internal temperature at 15° C. Upon completion by HPLC, the reaction was warmed to room temperature and stirred for 0.5 hrs. The mixture was recooled to 0° C. and cautiously quenched slowly with water (1.5L). The layers were separated, and the aqueous one washed with 500 mL of methylene chloride. The organic portion was washed with 2N aqueous HCl (2×800 mL), brine (400 mL), and saturated aqueous NaHCO3 (2×800 mL). Each aqueous extract was washed with the same 500 mL methylene chloride extract from above. The methylene chloride extracts were combined, dried (Na2SO4), filtered, and concentrated to approximately 500 mL of volume. This was then added to 5.0L of hexane warmed to 50° C. The methylene chloride was distilled off and the hot solution decanted from an insoluble brown tar. The solution was allowed to cool to 25° C. and placed in the freezer overnight. The precipitate was collected and washed with hexane (200 mL), and dried in vacuo to give 229.0 g of the compound as a pale yellow solid (88%).
Reaction SMILES: [CH2:1]([C:4]1[N:9]=[C:8]([CH3:10])[N:7]=[C:6](Cl)[C:5]=1[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]#[N:26])=[CH:15][CH:14]=1)[CH2:2][CH3:3].O.[NH2:28][NH2:29]>C(O)C>[CH2:1]([C:4]1[N:9]=[C:8]([CH3:10])[N:7]=[C:6]([NH:28][NH2:29])[C:5]=1[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]#[N:26])=[CH:15][CH:14]=1)[CH2:2][CH3:3]
Reactant: CCCc1nc(C)nc(Cl)c1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: NN
Solvent: O
Solvent: CCO
Product: CCCc1nc(C)nc(NN)c1Cc1ccc(-c2ccccc2C#N)cc1

Procedure:
51.7 g of 6-n-propyl-2-methyl-4-chloro-5-[(2'-cyano-4-biphenylyl)methyl]pyrimidine, prepared in Example 10, are dissolved in 150 ml of ethanol and 90 ml of hydrazine hydrate. The mixture is heated to reflux for 6 hours and the solvent is concentrated to one half under vacuum and then treated with water. The crystals formed are drained, washed with water and then with ether and dried to give 46 g of 6-n-propyl-2-methyl-4-hydrazino-5-[(2'-cyano-4-biphenylyl)methyl]pyrimidine in the form of crystals of melting point 156° C.
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:6][S:5](=[O:8])(=[O:7])[NH:4][CH2:3]1.I[C:10]1[CH:15]=[CH:14][C:13]([C:16]([N:18]2[CH2:23][CH2:22][N:21]([C:24]3[C:29]([CH3:30])=[CH:28][C:27]([CH3:31])=[C:26]([CH3:32])[N:25]=3)[CH2:20][CH2:19]2)=[O:17])=[CH:12][CH:11]=1>>[CH3:1][C@@H:2]1[CH2:6][S:5](=[O:8])(=[O:7])[N:4]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([N:18]3[CH2:23][CH2:22][N:21]([C:24]4[C:29]([CH3:30])=[CH:28][C:27]([CH3:31])=[C:26]([CH3:32])[N:25]=4)[CH2:20][CH2:19]3)=[O:17])=[CH:12][CH:11]=2)[CH2:3]1
Reactant: Cc1cc(C)c(N2CCN(C(=O)c3ccc(I)cc3)CC2)nc1C
Reactant: C[C@H]1CNS(=O)(=O)C1
Product: Cc1cc(C)c(N2CCN(C(=O)c3ccc(N4C[C@H](C)CS4(=O)=O)cc3)CC2)nc1C
Yield: 55 %

Procedure:
Using (S)-4-methylisothiazolidine 1,1-dioxide (90 mg) described in Preparation Example 4 and (4-iodophenyl)[4-(3,5,6-trimethylpyridin-2-yl)piperazin-1-yl]methanone (193 mg) described in Preparation Example 120 and by the reaction and treatment in the same manner as in Example 4, the title compound (108 mg) was obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[C:9]([C:11]([N:13]3[CH2:18][CH2:17][N:16]([C:19]4[CH:20]=[C:21]([CH:28]=[CH:29][C:30](OCC)=[O:31])[C:22]([N+:25]([O-])=O)=[CH:23][CH:24]=4)[CH2:15][CH2:14]3)=[O:12])[N:10]=[C:4]2[CH:3]=1.ClCCl.[H][H]>[C].[Pd].CO>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[C:9]([C:11]([N:13]3[CH2:18][CH2:17][N:16]([C:19]4[CH:20]=[C:21]5[C:22](=[CH:23][CH:24]=4)[NH:25][C:30](=[O:31])[CH2:29][CH2:28]5)[CH2:15][CH2:14]3)=[O:12])[N:10]=[C:4]2[CH:3]=1
Reactant: [H][H]
Reactant: CCOC(=O)C=Cc1cc(N2CCN(C(=O)c3cn4ccc(C)cc4n3)CC2)ccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CO
Solvent: ClCCl
Product: Cc1ccn2cc(C(=O)N3CCN(c4ccc5c(c4)CCC(=O)N5)CC3)nc2c1
Yield: 78.7 %

Procedure:
A mixture of ethyl 3-[3-[4-(7-methylimidazo[1,2-a]-pyridine-2-carbonyl)-1-piperazinyl]-6-nitrophenyl]acrylate (926 mg), 10% palladium carbon (139 mg), dichloromethane (50 ml) and methanol (50 ml) was hydrogenated under one atmospheric pressure of hydrogen at ambient temperature for 2.5 hours. After filtration, acetic acid (1 ml) was added to the filtrate containing ethyl 3-[3-[4-(7-methylimidazo[1,2-a]pyridine-2-carbonyl-1-piperazinyl]-6-aminophenyl]propionate and 6-[4-(7-methylimidazo[1,2-a]-pyridine-2-carbonyl)-1-piperazinyl]-3,4-dihydro-2(1H)-quinolinone and evaporated in vacuo. The residue was dissolved in chloroform (30 ml) and washed with saturated aqueous solution of sodium hydrogene carbonate. The extract was dried over magnesium sulfate and concentrated. The residue was crystallized from ethanol to give 6-[4-(7-methylimidazo[1,2-a]pyridine-2-carbonyl)-1-piperazinyl]-3,4-dihydro-2(lH)-quinolinone (612 mg).
Reaction SMILES: C([O:3][C:4](=[O:31])[CH2:5][S:6][C:7]1[S:11][C:10]([NH:12][C:13]([N:15]([CH2:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22](=[O:24])[NH2:23])[CH:17]=2)=[O:14])=[N:9][CH:8]=1)C.C1(CN(C2C=CC(S(C)(=O)=O)=CC=2)C(=O)NC2SC=C(CC(O)=O)N=2)CCCC1.C1(CNC2C=C(C=CC=2)C(N)=O)CCCC1.C(OC(=O)CSC1SC(N)=NC=1)C>>[C:22]([C:18]1[CH:17]=[C:16]([N:15]([CH2:25][CH:26]2[CH2:27][CH2:28][CH2:29][CH2:30]2)[C:13](=[O:14])[NH:12][C:10]2[S:11][C:7]([S:6][CH2:5][C:4]([OH:31])=[O:3])=[CH:8][N:9]=2)[CH:21]=[CH:20][CH:19]=1)(=[O:24])[NH2:23]
Reactant: CCOC(=O)CSc1cnc(NC(=O)N(CC2CCCC2)c2cccc(C(N)=O)c2)s1
Agent: CCOC(=O)CSc1cnc(N)s1
Agent: CS(=O)(=O)c1ccc(N(CC2CCCC2)C(=O)Nc2nc(CC(=O)O)cs2)cc1
Agent: NC(=O)c1cccc(NCC2CCCC2)c1
Product: NC(=O)c1cccc(N(CC2CCCC2)C(=O)Nc2ncc(SCC(=O)O)s2)c1

Procedure:
The title compound was prepared via {2-[3-cyclopentylmethyl-3-(3-carbamoyl-phenyl)ureido]-thiazol-5-ylsulfanyl}-acetic acid ethyl ester in a similar manner as described for the synthesis of {2-[3-cyclopentylmethyl-3-(4-methanesulfonyl-phenyl)-ureido]-thiazol-4-yl}-acetic acid, using 3-(cyclopentylmethyl-amino)-benzamide and (2-amino-thiazol-5-ylsulfanyl)acetic acid ethyl ester
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][OH:8])=[CH:3][CH:2]=1.[H-].[Na+].Cl[C:12]1[N:17]=[CH:16][C:15]([C:18]2[CH:19]=[C:20]([CH:35]=[CH:36][CH:37]=2)[CH2:21][N:22]([CH3:34])[C:23](=[O:33])[CH2:24][NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:14][N:13]=1.O>CN(C=O)C>[C:28]([O:27][C:26](=[O:32])[NH:25][CH2:24][C:23]([N:22]([CH3:34])[CH2:21][C:20]1[CH:35]=[CH:36][CH:37]=[C:18]([C:15]2[CH:16]=[N:17][C:12]([O:8][CH2:7][C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)=[N:13][CH:14]=2)[CH:19]=1)=[O:33])([CH3:31])([CH3:30])[CH3:29]
Reactant: OCc1ccncc1
Reactant: CN(Cc1cccc(-c2cnc(Cl)nc2)c1)C(=O)CNC(=O)OC(C)(C)C
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CN(Cc1cccc(-c2cnc(OCc3ccncc3)nc2)c1)C(=O)CNC(=O)OC(C)(C)C
Reaction time: 0.5 h
Yield: 99.9 %

Procedure:
Pyridin-4-ylmethanol (112 mg) was dissolved in DMF (4 ml), and NaH (45 mg) was added thereto under ice-cooling. After stirring at the same temperature for 30 minutes, tert-butyl (2-{[3-(2-chloropyrimidin-5-yl)benzyl](methyl)amino}-2-oxoethyl)carbamate (200 mg) was added thereto, followed by stirring at room temperature for 2 hours. To the reaction mixture was added water, followed by extraction with EtOAc. The organic layer was dried over MgSO4 and evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (0% to 7% MeOH/CHCl3) to obtain tert-butyl[2-(methyl{3-[2-(pyridin-4-ylmethoxy)pyrimidin-5-yl]benzyl}amino)-2-oxoethyl]carbamate (237 mg).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:12][C:13](=O)[CH3:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].BrBr.BrC(C1C=CC(S(C)(=O)=O)=C(F)C=1)C(=O)C.[C:34]([NH:37][C:38]([NH2:40])=[S:39])(=[O:36])[CH3:35]>O1CCOCC1.C(O)C>[F:1][C:2]1[CH:3]=[C:4]([C:12]2[S:39][C:38]([NH:37][C:34](=[O:36])[CH3:35])=[N:40][C:13]=2[CH3:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]
Reactant: CC(=O)NC(N)=S
Reactant: CC(=O)Cc1ccc(S(C)(=O)=O)c(F)c1
Agent: BrBr
Agent: CC(=O)C(Br)c1ccc(S(C)(=O)=O)c(F)c1
Solvent: CCO
Solvent: C1COCCO1
Product: CC(=O)Nc1nc(C)c(-c2ccc(S(C)(=O)=O)c(F)c2)s1
Temperature: 10 °C
Reaction time: 0.25 h

Procedure:
1-(3-Fluoro-4-methanesulfonyl-phenyl)-propan-2-one (Example 64c) (1.0 g, 4.34 mmol) is dissolved in dioxane (35 ml) and the solution is cooled to 10° C. at which point the mixture is semi frozen. Bromine (0.067 ml, 1.2 mmol, 0.3 eq.) is added slowly and the mixture is stirred for an additional 15 min in a semi frozen state. The mixture is then allowed to warm to room temperature and the solvent is removed to give a brown oil containing starting material and 1-bromo-1-(3-fluoro-4-methanesulfonyl-phenyl)-propan-2-one. This material is dissolved in ethanol (30 ml) and N-acetylthiourea (0.369 g, 3.1 mmol) is added in one portion. The mixture is stirred at 60° C. for 30 minutes then allowed to cool whereupon the product crystallised. Filtration affords the title compound as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.[Cl:27][C:28]1[CH:36]=[CH:35][C:31]([CH:32]([NH2:34])[CH3:33])=[CH:30][CH:29]=1>>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:34][CH:32]([C:31]1[CH:35]=[CH:36][C:28]([Cl:27])=[CH:29][CH:30]=1)[CH3:33]
Reactant: CC(N)c1ccc(Cl)cc1
Reactant: O=C(N1CCc2ccc(Cl)c(OS(=O)(=O)C(F)(F)F)c2CC1)C(F)(F)F
Product: CC(Nc1c(Cl)ccc2c1CCN(C(=O)C(F)(F)F)CC2)c1ccc(Cl)cc1
Yield: 37.8 %

Procedure:
Use a method similar to the General Procedure 5-3 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (852 mg, 2.0 mmol) and (±)-4-chloro-(α-methyl)benzylamine (622 mg, 4.0 mmol). Purify by chromatography on silica gel eluting with hexane/EtOAc (1:0 and 9:1) to obtain (±)-7-chloro-6-[1-(4-chlorophenyl)-ethylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (326 mg, 38%). MS (ES+) m/z: 431 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[C:10]([C:11](=[CH2:22])[C:12]([O:14]CC3C=CC=CC=3)=[O:13])[C:5]2=[N:4][N:3]=1>[Pd].CO>[CH3:1][C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[C:10]([CH:11]([CH3:22])[C:12]([OH:14])=[O:13])[C:5]2=[N:4][N:3]=1
Reactant: C=C(C(=O)OCc1ccccc1)c1cccn2c(C)nnc12
Agent: [Pd]
Solvent: CO
Product: Cc1nnc2c(C(C)C(=O)O)cccn12
Reaction time: 6 h
Yield: 77.6 %

Procedure:
To 0.040 g (0.038 mmol) of 10% palladium on carbon was added a solution of (0.080 g, 0.27 mmol) of benzyl 2-(3-methyl[1,2,4]triazolo[4,3-a]pyridin-8-yl)acrylate prepared in Step C above in 4 mL of methanol. The resulting suspension was stirred under an atmosphere of hydrogen (1 atmosphere) for 6 h. The residue was filtered through a pad of Celite® and the pad was washed with cold methanol. The combined filtrates were evaporated under reduced pressure to give the title compound (0.043 g, 77%). LC-MS: m/z (ES) 206 (MH)+.
Reaction SMILES: Cl[NH:2][C:3]1[N:8]=[C:7]([NH:9]Cl)[N:6]=[C:5]([NH:11]Cl)[N:4]=1.[Cl:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>C(Cl)(Cl)(Cl)Cl.CCCCCC>[Cl:13][CH2:14][CH2:15][C:16]([NH:2][C:3]1[N:8]=[C:7]([NH:9][C:16](=[O:17])[CH2:15][CH2:14][Cl:13])[N:6]=[C:5]([NH:11][C:16](=[O:17])[CH2:15][CH2:14][Cl:13])[N:4]=1)=[O:17]
Reactant: ClNc1nc(NCl)nc(NCl)n1
Reactant: O=C(Cl)CCCl
Solvent: CCCCCC
Solvent: ClC(Cl)(Cl)Cl
Product: O=C(CCCl)Nc1nc(NC(=O)CCCl)nc(NC(=O)CCCl)n1
Yield: 98 %

Procedure:
To a stirring suspension of 2.3 g trichloromelamine in 40 ml CCl4 was added 7.62 g 3-chloropropionyl chloride under Argon. The reaction mixture was heated in an oil bath at 65°-70° C. for 6 hours. The reaction mixture was cooled and then diluted with 50 ml hexane. The precipitates were filtered, washed with hexane and dried under reduced pressure (3.9 g; 98% yield). The product thus obtained was characterized to be N'N',N"-tris (3-chloropropionyl) melamine by 1H NMR, 13C NMR, IR, and mass spectroscopy.
Reaction SMILES: COC1C=CC(N2C[C@H](C[N:15]3[CH2:20][CH2:19][CH:18]([S:21][C:22]4[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=4)[CH2:17][CH2:16]3)OC2=O)=CC=1>CS(C)=O>[CH3:29][O:28][C:25]1[CH:26]=[CH:27][C:22]([S:21][CH:18]2[CH2:19][CH2:20][NH:15][CH2:16][CH2:17]2)=[CH:23][CH:24]=1
Reactant: COc1ccc(SC2CCN(C[C@H]3CN(c4ccc(OC)cc4)C(=O)O3)CC2)cc1
Solvent: CS(C)=O
Product: COc1ccc(SC2CCNCC2)cc1

Procedure:
3-p-methoxyphenyl-5(S)-[(4-p-methoxyphenylthiopiperidino)methyl]-2-oxazolidinone (hydrochloride), m.p. 223°-225°; [α]D =-31.3° (DMSO);
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[NH:13][C:12](=[O:14])[N:11]([C:15]2[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[C:17]([O:24][CH3:25])[CH:16]=2)[N:10]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[F:57][C:58]([F:70])([F:69])[C:59]1[CH:64]=[CH:63][C:62]([C:65]2([NH2:68])[CH2:67][CH2:66]2)=[CH:61][CH:60]=1>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[NH:13][C:12](=[O:14])[N:11]([C:15]2[CH:23]=[CH:22][C:18]([C:19]([NH:68][C:65]3([C:62]4[CH:63]=[CH:64][C:59]([C:58]([F:57])([F:69])[F:70])=[CH:60][CH:61]=4)[CH2:67][CH2:66]3)=[O:20])=[C:17]([O:24][CH3:25])[CH:16]=2)[N:10]=1
Reactant: NC1(c2ccc(C(F)(F)F)cc2)CC1
Reactant: COc1cc(-n2nc(-c3c(F)cccc3Cl)[nH]c2=O)ccc1C(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(-n2nc(-c3c(F)cccc3Cl)[nH]c2=O)ccc1C(=O)NC1(c2ccc(C(F)(F)F)cc2)CC1
Yield: 13.5 %

Procedure:
The title compound was prepared according to the procedure described in Example-17 by using 4-(3-(2-chloro-6-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoic acid (Intermediate-15, 0.100 g, 0.270 mmol), THF (5 mL), di-isopropyl ethyl amine (2.0 mL), TBTU (0.177 g, 0.540 mmol) and 1-[4-(trifluoromethyl)phenyl]cyclopropanamine (Intermediate-13, 0.066 g, 0.320 mmol) to afford 0.020 g of desired product. 1H NMR (300 MHz, DMSO d6): δ 1.37 (s, 4H), 3.95 (s, 3H), 7.42 (d, J=7.8 Hz, 2H), 7.50 (t, J=8.7 Hz, 1H), 7.63 (t, J=7.8 Hz, 4H), 7.73 (t, J=12.3 Hz, 3H), 8.85 (s, 1H), 12.50 (br s, 1H); MS (m/z): 546.99 (M+).
Reaction SMILES: [CH3:1][Li].[CH3:3][C:4]([C:8](=[O:14])[CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])=[CH:5][CH2:6][CH3:7]>>[CH3:3][C:4]([C:8]([CH3:1])([OH:14])[CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])=[CH:5][CH2:6][CH3:7]
Reactant: CCC=C(C)C(=O)CCCCC
Reactant: [Li]C
Product: CCC=C(C)C(C)(O)CCCCC
Reaction time: 2.5 h

Procedure:
To a dry 5 liter multi-neck round bottom flask fitted with an air stirrer, nitrogen inlet condenser and an addition funnel 1.617 g of CH3Li was added and stirred. 336 g of 4-methyl-3-decene-5-one (see example A for preparation of 3-decene-4-methyl-5-one) was added dropwise over 105 minutes. The temperature of the reaction rose to 63° C. The reaction mixture was aged for 150 minutes and a first sample was taken at 37° C. 30 minutes later, a second sample was taken at 30° C. The mixture was quenched with acetic acid, allowed to settle and layers separated. The aqueous layer was washed twice with 100 ml of toluene. The toluene extracts were added to the organic layer and washed with Na2CO3. The NMR spectrum of the 4.5-Dimethyl-3-decene-5-ol is as follows: 0.88 ppm (t, 3H); 0.94 ppm (t, 3H); 1.28 ppm (s, 3H); 1.15-1.35 ppm (m, 6H); 1.50 ppm (s, 1H); 1.55 ppm (s,1H), 2.05 ppm (m, 2H); ; 5.45 ppm (m, 1 H) The IR spectrum of the 4.5-Dimethyl-3-decene-5-ol is as follows: OH-stretch broad at 3416 cm−1, CH-stretch saturated at 2960, 2933, 2872 cm−1, double bond stretch at 1680 cm−1, 1462 and 1372 due to CH stretch.
Reaction SMILES: C([O:4][CH2:5][C:6]1[O:10][N:9]=[C:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[CH:7]=1)(=O)C.[OH-].[Na+].Cl>C(O)C>[F:17][C:14]1[CH:13]=[CH:12][C:11]([C:8]2[CH:7]=[C:6]([CH2:5][OH:4])[O:10][N:9]=2)=[CH:16][CH:15]=1
Reactant: CC(=O)OCc1cc(-c2ccc(F)cc2)no1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: OCc1cc(-c2ccc(F)cc2)no1

Procedure:
[3-(4-fluorophenyl)isoxazol-5-yl]methyl acetate was stirred in a mixture of aqueous 2N sodium hydroxide (1.60 g, 20 mL H2O) and ethanol (10 mL) at room temperature for 2 hours. The reaction mixture was then neutralized with 2N HCl aqueous solution (20 mL), and extracted with ethyl acetate (2×30 mL). The combined organic layers were dried over sodium sulfate and solvent removed under reduced pressure, to provide [3-(4-fluorophenyl)isoxazol-5-yl]methan-1-ol.