Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[Na+].[CH:3]1[N:7]2[C:8]3[C:13]([N:14]=[CH:15][C:6]2=[N:5][C:4]=1[C:16]([O:18]CC)=[O:17])=[CH:12][CH:11]=[CH:10][CH:9]=3.C(O)C>O>[CH:3]1[N:7]2[C:8]3[C:13]([N:14]=[CH:15][C:6]2=[N:5][C:4]=1[C:16]([OH:18])=[O:17])=[CH:12][CH:11]=[CH:10][CH:9]=3
Reactant: CCOC(=O)c1cn2c(cnc3ccccc32)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)c1cn2c(cnc3ccccc32)n1
Yield: 107.8 %

Procedure:
10 ml of 1N sodium hydroxide solution were added to a suspension of 0.63 g of ethyl imidazo-[1,2-a]-quinoxaline-2-carboxylate, 10 ml of ethanol and 30 ml of water and the mixture was refluxed for one hour. The ethanol was evaporated under reduced pressure from the resulting clear yellow solution and the aqueous phase was acidified with concentrated hydrochloric acid. The mixture was filtered to obtain 0.6 g of imidazo-[1,2-a]-quinoxaline-2-carboxylic acid in the form of a buff crystalline solid melting at 274°-275° C.
Reaction SMILES: C([O:5][C:6]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([NH:18][C:19]([NH:21][C:22]2[CH:27]=[C:26]([C:28]([CH3:31])([CH3:30])[CH3:29])[CH:25]=[C:24]([NH:32][S:33]([CH3:36])(=[O:35])=[O:34])[C:23]=2[O:37][CH3:38])=[O:20])=[CH:10][CH:9]=1)=[O:7])(C)(C)C>[Au].C(O)(C(F)(F)F)=O>[C:28]([C:26]1[CH:25]=[C:24]([NH:32][S:33]([CH3:36])(=[O:35])=[O:34])[C:23]([O:37][CH3:38])=[C:22]([NH:21][C:19](=[O:20])[NH:18][C:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:8]([C:6]([OH:7])=[O:5])=[CH:9][CH:10]=2)[CH:27]=1)([CH3:31])([CH3:29])[CH3:30]
Reactant: COc1c(NC(=O)Nc2ccc(C(=O)OC(C)(C)C)c3ccccc23)cc(C(C)(C)C)cc1NS(C)(=O)=O
Agent: [Au]
Solvent: O=C(O)C(F)(F)F
Product: COc1c(NC(=O)Nc2ccc(C(=O)O)c3ccccc23)cc(C(C)(C)C)cc1NS(C)(=O)=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 73.9 %

Procedure:
To a 0° C. solution of 10 mL of TFA was added 878 mg (1.9 mmol) of 4-[3-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalene-1-carboxylic acid tert-butyl ester. The clear, light gold reaction was allowed to warm to room temperature, and kept there for 1 h. After this time, the reaction was concentrated in vacuo, and then diluted with toluene. The toluene was then removed in vacuo and the pale white solid was triturated with ether to provide 682 mg (89%) of the title compound.
Reaction SMILES: ClC(Cl)(Cl)CO[C:5](=[O:19])[NH:6][C:7]1[N:8]([CH2:16][CH2:17][OH:18])[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:24]=1[C:30]1[N:34]2[CH:35]=[C:36]([O:39][C@H:40]3[C:49]4[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=4)[C@@H:43]([NH2:50])[CH2:42][CH2:41]3)[CH:37]=[CH:38][C:33]2=[N:32][N:31]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:50][C@@H:43]2[C:44]3[C:49](=[CH:48][CH:47]=[CH:46][CH:45]=3)[C@H:40]([O:39][C:36]3[CH:37]=[CH:38][C:33]4[N:34]([C:30]([C:24]5[C:23]([Cl:22])=[CH:28][CH:27]=[CH:26][C:25]=5[Cl:29])=[N:31][N:32]=4)[CH:35]=3)[CH2:41][CH2:42]2)=[O:19])[N:8]([CH2:16][CH2:17][OH:18])[N:9]=1)([CH3:13])([CH3:14])[CH3:15]
Reactant: CC(C)(C)c1cc(NC(=O)OCC(Cl)(Cl)Cl)n(CCO)n1
Reactant: N[C@H]1CC[C@@H](Oc2ccc3nnc(-c4c(Cl)cccc4Cl)n3c2)c2ccccc21
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)c1cc(NC(=O)N[C@H]2CC[C@@H](Oc3ccc4nnc(-c5c(Cl)cccc5Cl)n4c3)c3ccccc32)n(CCO)n1
Temperature: 60 °C
Reaction time: 42 h
Yield: 14.3 %

Procedure:
A mixture of Intermediate 26a (100 mg, 0.279 mmol), Intermediate 26d (108 mg, 0.254 mmol), and DIPEA (73 μL, 0.419 mmol) in dioxane (2.5 mL) was stirred at 60° C. for 42 h and then left standing at RT for 72 h. The volatiles were concentrated in vacuo and the resultant residue was purified by FCC, using 0-10% MeOH in DCM followed by MDAP (Method 7) to afford the title compound (23 mg, 14%) as a white solid. LCMS (Method 5): Rt 4.19 min, m/z 634 [MH+]. 1H NMR (400 MHz, DMSO): 1.21 (9H, s), 1.79-2.16 (4H, m), 3.62-3.70 (2H, m), 3.94 (2H, t, J=6.0 Hz), 4.78-4.88 (1H, m), 4.99 (1H, br s), 5.55 (1H, t, J=4.2 Hz), 6.05 (1H, s), 7.07 (1H, d, J=8.6 Hz), 7.23-7.30 (1H, m), 7.31-7.38 (4H, m), 7.70-7.74 (1H, m), 7.74-7.80 (2H, m), 7.91 (1H, d, J=9.9 Hz), 7.98 (1H, d, J=2.1 Hz), 8.19 (1H, s).
Reaction SMILES: Cl[C:2]1[C:11]2[N:12]=[CH:13][S:14][C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([C:15]([O:17]C)=[O:16])=[CH:5][C:4]=2[N:3]=1.[NH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN1C(=O)CCC1>[C:20]1([NH:19][C:2]2[C:11]3[N:12]=[CH:13][S:14][C:10]=3[C:9]3[CH:8]=[CH:7][C:6]([C:15]([OH:17])=[O:16])=[CH:5][C:4]=3[N:3]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: Nc1ccccc1
Reactant: COC(=O)c1ccc2c(c1)nc(Cl)c1ncsc12
Solvent: CN1CCCC1=O
Product: O=C(O)c1ccc2c(c1)nc(Nc1ccccc1)c1ncsc12
Temperature: 120 °C
Reaction time: 2 h
Yield: 8 %

Procedure:
In a microwave vessel, methyl 4-chlorothiazolo[4,5-c]quinoline-7-carboxylate (1.0 eq, 23 mg, 0.084 mmol) and aniline (13 eq, 0.1 ml, 1.1 mmol) were mixed in NMP (0.1 ml). The mixture was heated in a microwave oven at 120° C. for 10 min. The intermediate ester was purified by preparative HPLC and isolated as a solid after genevac evaporation. The solid was stirred in a (1:1:1, v:v:v) mixture of THF, MeOH and water (0.6 ml) with LiOH (41 mg) at room temperature for 2 hours. HCl and water were added, the organic solvents were evaporated and the solution allowed resting for 2 hours. The precipitate that slowly formed was filtered and dried to afford 4-(phenylamino)thiazolo[4,5-c]quinoline-7-carboxylic acid as a solid (8% yield over 2 steps). LCMS (ES): >95% pure, m/z 322 [M+1]+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[N:11][N:10]([CH3:13])[C:9]=2[CH2:14][O:15][C:16]2[CH:24]=[CH:23][C:19]([C:20]([OH:22])=O)=[CH:18][N:17]=2)=[CH:4][CH:3]=1.CN(C(O[N:33]1N=N[C:35]2C=CC=[CH:39][C:34]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.NC1CCOCC1>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[N:11][N:10]([CH3:13])[C:9]=2[CH2:14][O:15][C:16]2[CH:24]=[CH:23][C:19]([C:20]([NH:33][CH:34]([CH3:39])[CH3:35])=[O:22])=[CH:18][N:17]=2)=[CH:4][CH:3]=1
Reactant: Cn1nnc(-c2ccc(F)cc2)c1COc1ccc(C(=O)O)cn1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: NC1CCOCC1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)NC(=O)c1ccc(OCc2c(-c3ccc(F)cc3)nnn2C)nc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 76.5 %

Procedure:
To a solution of 6-[5-(4-fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-nicotinic acid (94 mg, 0.29 mmol) and TBTU (101 mg, 0.32 mmol) in DMF (1.5 mL) was added DIPEA (245 μL, 1.43 mmol). Then 4-aminotetrahydropyran (56 mg, 0.55 mmol) was added and the mixture was stirred at room temperature under Ar for 1 h. The mixture was then evaporated and purification by chromatography (silica, 50 to 100% ethyl acetate in heptane) afforded the title compound (82 mg, 70%) as a white solid after recrystallisation from methanol/water. MS: m/e=412.2 [M+H]+.
Reaction SMILES: Br[Mg]C.[C:4]1(C)C=CC=CC=1.[Br:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18]C(OCC)=O)=[CH:14][CH:13]=1.CC[O:26][CH2:27][CH3:28]>C1COCC1>[Br:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C:27]([CH3:28])([OH:26])[CH3:4])=[CH:14][CH:13]=1
Reactant: CCOC(=O)Cc1ccc(Br)cc1
Reactant: Cc1ccccc1
Reactant: CCOCC
Agent: C[Mg]Br
Solvent: C1CCOC1
Product: CC(C)(O)Cc1ccc(Br)cc1
Temperature: 40 °C
Reaction time: 1 h
Yield: 73 %

Procedure:
A solution of bromo(methyl)magnesium in diethyl ether (25 mL of 3 M, 74.5 mmol) in THF (8 mL) and toluene (25 mL) was added to a solution of ethyl 2-(4-bromophenyl)acetate (8.23 g, 33.9 mmol) in Et2O (165 mL) and the reaction mixture was stirred at 40° C. for 1 hour. The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (200 mL) and the phases were separated. The organics were dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography eluting with 0-30% EtOAc-hexanes to give 1-(4-bromophenyl)-2-methyl-propan-2-ol (5.68 g, 73%), as a clear oil. ESI-MS m/z calc. 228.1. Found 229.5 (M+1)+; Retention time: 1.45 minutes (3 min run).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[C:7]([N:9]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[N:10]2)[CH:6]=[CH:5][C:4]=1[CH2:18][CH2:19][NH2:20].ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[F:40][C:41]([F:52])([F:51])[C:42]1[C:43]([C:48](O)=[O:49])=[N:44][CH:45]=[CH:46][CH:47]=1>ClCCl>[Cl:2][C:3]1[CH:8]=[C:7]([N:9]2[CH:13]=[CH:12][C:11]([C:14]([F:15])([F:16])[F:17])=[N:10]2)[CH:6]=[CH:5][C:4]=1[CH2:18][CH2:19][NH:20][C:48]([C:43]1[C:42]([C:41]([F:52])([F:40])[F:51])=[CH:47][CH:46]=[CH:45][N:44]=1)=[O:49]
Reactant: NCCc1ccc(-n2ccc(C(F)(F)F)n2)cc1Cl
Reactant: O=C(O)c1ncccc1C(F)(F)F
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(NCCc1ccc(-n2ccc(C(F)(F)F)n2)cc1Cl)c1ncccc1C(F)(F)F
Reaction time: 12 h

Procedure:
To a solution of 2-chloro-4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]benzeneethanamine hydrochloride (1:1) (i.e. the product of Step C; 300 mg, 1.11 mmol), N-(3-dimethyl-aminopropyl)-N′-ethylcarbodiimide (297 mg, 1.66 mmol), 1-hydroxybenzotriazole (212 mg, 1.66 mmol) and N,N-diisopropylethylamine (0.9 mL, 5.55 mmol) in dichloromethane (15 mL) was added 3-(trifluoromethyl)pyridine-2-carboxylic acid (198 mg, 1.21 mmol), and the resulting mixture was stirred for 12 h. The reaction mixture was washed with water and brine, dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluted with 50% ethyl acetate in hexanes to afford the title compound (210 mg) as a brown solid.
Reaction SMILES: [C:1]1([CH:7]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10](O)([C:17]3[CH:18]=[C:19]4[C:24](=[CH:25][C:26]=3[OH:27])[N:23]=[CH:22][CH:21]=[N:20]4)[C:9]2=[O:29])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>[Zn].S(Cl)(Cl)=O>[C:30]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]([C:17]3[CH:18]=[C:19]4[C:24](=[CH:25][C:26]=3[OH:27])[N:23]=[CH:22][CH:21]=[N:20]4)[C:9]2=[O:29])[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: O=C1N(C(c2ccccc2)c2ccccc2)c2ccccc2C1(O)c1cc2nccnc2cc1O
Agent: [Zn]
Solvent: O=S(Cl)Cl
Product: O=C1C(c2cc3nccnc3cc2O)c2ccccc2N1C(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 82.9 %

Procedure:
To thionyl chloride (60 mL) was added 1-(diphenylmethyl)-3-hydroxy-3-(7-hydroxyquinoxalin-6-yl)-1,3-dihydro-2H-indol-2-one (3.0 g, 6.53 mmol) at −10° C. The resulting reaction mixture was stirred at 0° C. for 1 h, and concentrated in vacuo. The residue was dissolved in acetic acid (150 mL), followed by the addition of zinc dust (4.50 g, 68.81 mmol). The resulting mixture was stirred at ambient temperature for 40 min. The solids were filtered out. The filtrate was concentrated in vacuo. The residue was dissolved in ethyl acetate (200 mL), washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo, the residue was purified by column chromatography (dichloromethane/methanol 200/1) to give 1-(diphenylmethyl)-3-(7-hydroxyquinoxalin-6-yl)-1,3-dihydro-2H-indol-2-one (2.40 g, 83%): MS (ES+) m/z 444 (M+1).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[CH3:10][C:11]([CH3:13])=[O:12].[CH3:14][OH:15].CS(O)(=O)=O>O>[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[CH:10][C:11]([CH:13]=[CH:6][C:5]2[CH:8]=[CH:9][C:14]([OH:15])=[CH:3][CH:4]=2)=[O:12])=[CH:4][CH:3]=1
Reactant: CC(C)=O
Reactant: O=Cc1ccc(O)cc1
Reactant: CO
Agent: CS(=O)(=O)O
Solvent: O
Product: O=C(C=Cc1ccc(O)cc1)C=Cc1ccc(O)cc1
Temperature: 70 °C
Reaction time: 4 h
Yield: 54 %

Procedure:
122 g of 4-hydroxybenzaldehyde and 30 g of acetone were added to 300 ml of methanol. To the mixture was then added 10 g of methanesulfonic acid. The reaction mixture was then stirred at a temperature of 70° C. for 4 hours. To the reaction solution was then added gradually 1,000 ml of distilled water to obtain bis(4-hydroxystyryl)ketone in the form of yellow crystal. 50 g of the yellow crystal was then dissolved in 200 ml of methanol. To the solution was then added 100 ml of a 10% aqueous solution of sodium hydroxide. To the reaction solution was then added dropwise 50 ml of a 37% aqueous solution of formalin in 30 minutes in such a manner that the temperature of the reaction solution didn't exceed 40° C. The reaction solution was stirred for 10 hours, and then neutralized with acetic acid. The resulting yellow powder was then recovered by filtration. The crude crystal was then recrystallized from methanol. (Yield: 54%)
Reaction SMILES: [CH3:1][C:2]1([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:7][CH2:6][CH2:5][N:4](CC2C=CC=CC=2)[C:3]1=[O:15].N>C1COCC1>[CH3:1][C:2]1([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:7][CH2:6][CH2:5][NH:4][C:3]1=[O:15]
Reactant: CC1(Cc2ccccc2)CCCN(Cc2ccccc2)C1=O
Agent: N
Solvent: C1CCOC1
Product: CC1(Cc2ccccc2)CCCNC1=O
Yield: 156.4 %

Procedure:
The reaction of 3-methyl-1,3-diphenylmethyl-2-piperidinone (2.93 g, 10 mmol) with Li metal (0.70 g, 100 mmol) in THF (30 mL) and liquid NH3 (200 mL), as described above in the preparation of Example 11, gave 3.18 g of a colorless viscous residue. Flash chromatography over silica gel (1% MeOH in CHCl3 -EtOAc, 1:1) afforded the lactam (1.75 g, 86% ) as a colorless solid: mp 76-78° C. (ether-hexane).
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=[O:4].CN(P(N(C)C)(N(C)C)=O)C.[CH2:22](I)[CH:23]=[CH2:24]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1([CH2:24][CH:23]=[CH2:22])[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=[O:4]
Reactant: C=CCI
Reactant: COC(=O)C1CCOCC1
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: C1CCOC1
Product: C=CCC1(C(=O)OC)CCOCC1
Temperature: -78 °C
Reaction time: 0.75 h
Yield: 95 %

Procedure:
To this was added tetrahydro-pyran-4-carboxylic acid methyl ester (7.2 g, 50 mmol) in THF (10 mL). There was almost no color change (light a little bit). This was stirred at −78° C. for 45 min. Then, a mixture of 5 g of HMPA and 10.92 g of allyl iodide was added via canula. Towards 90% of addition, white precipitate formed suddenly. This mixture was stirred at −78° C. for 20 min, then, the dry ice bath was removed and the stirring was continued to allow the reaction mixture to warm to r.t. over 30 min. When the precipitate was dissolved, the reaction mixture was poured into ice-water (100 mL) and ether (50 mL). The two layers were separated; the aqueous layer was extracted with ether (3×50 mL). The combined organic layers were washed with brine, dried (K2CO3), filtered, and concentrated in vacuo to get 8.75 g (95% yield) of the title compound as a yellow liquid.
Reaction SMILES: [CH3:1][N:2]([CH3:6])[C:3]([NH2:5])=[O:4].[Br:7][C:8]1[CH:14]=[CH:13][C:11](N)=[CH:10][CH:9]=1.ClC1C=CC(Cl)=CC=1Cl.CNC>>[Br:7][C:8]1[CH:14]=[CH:13][C:11]([NH:5][C:3]([N:2]([CH3:6])[CH3:1])=[O:4])=[CH:10][CH:9]=1
Reactant: CN(C)C(N)=O
Reactant: Nc1ccc(Br)cc1
Agent: CNC
Solvent: Clc1ccc(Cl)c(Cl)c1
Product: CN(C)C(=O)Nc1ccc(Br)cc1
Temperature: 205 °C
Reaction time: 5.5 h

Procedure:
3.35 g (0.038 mol) of N,N-dimethylurea and 4.3 g (0.025 mol) of 4-bromoaniline were added with stirring into 28 ml of 1,2,4-trichlorobenzene, after which the mixture was slowly heated to 205° C. Dimethylamine was introduced from 50° C. After 5.5 hours, 11.6 g (0.25 mol) of dimethylamine had been introduced, and the reaction was complete. The reaction mixture was cooled to room temperature whereupon a precipitate deposited, which was filtered off, washed with 1,2,4-trichlorobenzene, dried at 100° C. in vacuo and then boiled in 100 ml of water. The aqueous mixture was cooled, and the precipitate was filtered off with suction and dried. 4.73 g of N-(4-bromophenyl)-N',N'-dimethylurea, i.e. 78% of theory, having a melting point of 168° to 170° C. were obtained in this way.
Reaction SMILES: [Br:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5](I)=[CH:4][C:3]=1[O:11][CH3:12].[S:13]1[CH:17]=[CH:16][CH:15]=[C:14]1B(O)O>>[Br:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:14]2[S:13][CH:17]=[CH:16][CH:15]=2)=[CH:4][C:3]=1[O:11][CH3:12]
Reactant: OB(O)c1cccs1
Reactant: COc1cc(I)cc(OC)c1Br
Product: COc1cc(-c2cccs2)cc(OC)c1Br

Procedure:
2-(4-Bromo-3,5-dimethoxyphenyl)thiophene was prepared from 2-bromo-5-iodo-1,3-dimethoxybenzene and thiophen-2-ylboronic acid according to the procedure used in Example 12. Purification by chromatography (0-10% EtOAc-hexanes) gave a yellow solid (0.624 g, 55% yield).
Reaction SMILES: [C:1]1([S:7][CH:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([O:19][CH2:20][C:21]4[CH:30]=[CH:29][C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[N:22]=4)[CH:15]=3)[O:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[BH4-].[Na+]>CO.O1CCCC1>[C:1]1([S:7][C@H:8]2[C@H:17]([OH:18])[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([O:19][CH2:20][C:21]4[CH:30]=[CH:29][C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[N:22]=4)[CH:15]=3)[O:10][CH2:9]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C1c2cc(OCc3ccc4ccccc4n3)ccc2OCC1Sc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: O[C@@H]1c2cc(OCc3ccc4ccccc4n3)ccc2OC[C@H]1Sc1ccccc1
Temperature: 25 °C
Yield: 59.8 %

Procedure:
To a suspension of the title product of Example 63 (1.85 g, 0.00447 mol) in 70 ml of methanol at 0°-5° C. was added in portions 208 mg (0.00538 mol) of sodium borohydride. The reaction was warmed with stirring to room temperature, then diluted with 20 ml of tetrahydrofuran to obtain a homogeneous mixture, which, after stirring for 1.2 hours was concentrated in vacuo and the residue taken up in 400 ml ethyl acetate, washed with H2O and brine, dried over Na2SO4, and concentrated carried out by silica gel column chromatography eluting with 20% ethyl acetate/CH2Cl2. The less polar cis-title product was isolated as a white solid (1.11 g, 60%). Recrystallization from isopropanol/hexanes gave 1.04 g of white crystals, m.p. 144°-146° C. The more polar trans-title product was obtained as a mixture, contaminated with a small amount of the less polar product. It was re-chromatographed using the same eluant to yield 400 mg (22%) of trans-title product as a white foamy solid. Recrystallization from toluene-hexanes afforded 280 mg of white crystals, m.p. 100°-102° C.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][C:9]#[C:10][CH3:11].[Cl:12][C:13]1[C:18]2[NH:19][C:20](=[O:23])[N:21]([CH3:22])[C:17]=2[CH:16]=[CH:15][N:14]=1.C(OCC)(=O)C>CN(C)C=O.O>[CH2:8]([N:19]1[C:18]2[C:13]([Cl:12])=[N:14][CH:15]=[CH:16][C:17]=2[N:21]([CH3:22])[C:20]1=[O:23])[C:9]#[C:10][CH3:11]
Reactant: CC#CCBr
Reactant: Cn1c(=O)[nH]c2c(Cl)nccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: CC#CCn1c(=O)n(C)c2ccnc(Cl)c21
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Potassium carbonate (1.17 g) and 1-bromo-2-butyne (0.742 mL) were added to a solution of 4-chloro-1-methyl-1,3-dihydroimidazo[4.5-c]pyridin-2-one in N,N-dimethylformamide (50 mL). This was then stirred at room temperature for 16 hours. Ethyl acetate (300 mL) and water (200 mL) were added, and the organic layer was washed twice with 200 mL of water and then once with 200 mL of saturated aqueous sodium chloride solution, then was dried over anhydrous magnesium sulfate. The organic layer was filtered and concentrated under reduced pressure, and the residue was purified by silica gel chromatography. The ethyl acetate:hexane 3:2 fraction gave the title compound (0.980 g).
Reaction SMILES: [CH3:1][CH2:2][C:3]([CH2:5][CH2:6]/[CH:7]=[C:8](/[CH2:10][CH2:11][CH:12]=[C:13]([CH3:15])[CH3:14])\[CH3:9])=[CH2:4].[C:16]([O:25][CH2:26][CH3:27])(=[O:24])/[CH:17]=[CH:18]\[C:19]([O:21][CH2:22][CH3:23])=[O:20]>>[CH2:26]([O:25][C:16]([CH:17]1[CH2:1][CH:2]=[C:3]([CH2:5][CH2:6][CH:7]=[C:8]([CH3:9])[CH2:10][CH2:11][CH:12]=[C:13]([CH3:15])[CH3:14])[CH2:4][CH:18]1[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[O:24])[CH3:27]
Reactant: CCOC(=O)/C=C\C(=O)OCC
Reactant: C=C(CC)CC/C=C(\C)CCC=C(C)C
Product: CCOC(=O)C1CC=C(CCC=C(C)CCC=C(C)C)CC1C(=O)OCC
Temperature: 180 °C
Yield: 75 %

Procedure:
The (E)-β-farnesene-containing product of Example 1 (10 g) and diethyl maleate (5.0 g) are heated together at 180° C. for two hours. The mixture is then distilled under reduced pressure to give 1,2-bis-(ethoxycarbonyl)-4-(4,8 dimethyl-3,7-nonadienyl) cyclohex-4-ene as a pale yellow oil (8.5 g, 75%); b.p. 175°-180° C./0.3τ; nD20 1.4894; M+ (m/z as % of base peak): 376 (6.6); δ(CCl4) 1.24 (t, 6H), 1.70 (m, 9H), 2.08 (m, 8H), 2.36 (m, 4H), 2.80 (m, 2H), 4.14 (q, 4H), 5.20 (m, 2H), 5.40 (br, t, 1H).
Reaction SMILES: B.CSC.[C:5]([NH:8][C:9]1[CH:10]=[C:11]([OH:15])[CH:12]=[CH:13][CH:14]=1)(=O)[CH3:6].CO>C1COCC1>[CH2:5]([NH:8][C:9]1[CH:10]=[C:11]([OH:15])[CH:12]=[CH:13][CH:14]=1)[CH3:6]
Reactant: CC(=O)Nc1cccc(O)c1
Agent: B
Solvent: C1CCOC1
Solvent: CSC
Solvent: CO
Product: CCNc1cccc(O)c1
Yield: 74 %

Procedure:
A 1.0 M solution of borane-methyl sulfide in dichloromehtane (275 ml) was added dropwise to a solution of 3-acetamidophenol (161 g) in THF (800 ml) over about 1 to 2 hours. The mixture was heated to reflux temperature for about 4 hours and was then poured slowly into methanol (1 liter). The solvent was evaporated to a heavy syrup, which deposited crystals on cooling and scratching. The solid was collected by filtration and redissolved in methanol. Evaporation and recrystallization as above gave a 74% yield of the compound.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:19][CH:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]3=[O:25])=[CH:11][C:10]=2[F:26])=[CH:5][CH:4]=1.[N:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]([CH:37]=O)=[CH:29][CH:28]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.CN(C=O)C>[F:26][C:10]1[CH:11]=[C:12]([N:15]2[CH2:19][CH:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]2=[O:25])[CH:13]=[CH:14][C:9]=1[C:6]1[CH:7]=[CH:8][C:3]([CH2:2][NH:1][CH2:37][C:30]2[C:31]3[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=3)[N:27]=[CH:28][CH:29]=2)=[CH:4][CH:5]=1
Reactant: CC(=O)NCC1CN(c2ccc(-c3ccc(CN)cc3)c(F)c2)C(=O)O1
Reactant: O=Cc1ccnc2ccccc12
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CC(=O)NCC1CN(c2ccc(-c3ccc(CNCc4ccnc5ccccc45)cc3)c(F)c2)C(=O)O1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 66 %

Procedure:
A solution of amine 54 (36 mg, 0.1 mmol) in a mixture of THF and DMF (3:1, v/v) was treated with quinoline-4-carboxaldehyde (16 mg, 0.1 mmol, 1.0 equiv) at 25° C. under argon, and the resulting reaction mixture was stirred at 25° C. for 30 min before being treated with sodium triacetoxyborohydride (NaB(OAc)3H, 33 mg, 0.15 mmol, 1.5 equiv) at 25° C. The reaction mixture was subsequently stirred at 25° C. for 6 h. When TLC and HPLC showed the reductive amination reaction was complete, the reaction mixture was concentrated in vacuo. The residue was then directly purified by flash column chromatography (0-7% MeOH—CH2Cl2 gradient elution) to produce the desired N-[3-(2-fluoro-4′-{[(quinolin-4-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 4016 (32.9 mg, 66% yield) as pale-yellow oil, which solidified upon standing at room temperature in vacuo. 1H NMR (300 MHz, DMSO-d6) δ 1.85 (s, 3H, COCH3), 3.44 (t, 2H, J=5.4 Hz), 3.79 (dd, 1H, J=6.4, 9.2 Hz), 3.88 (s, 2H), 4.17 (t, 1H, J=9.1 Hz), 4.30 (s, 2H), 4.77 (m, 1H), 7.41 (dd, 1H, J=2.0, 8.0 Hz), 7.51-7.63 (m, 8H, aromatic-H), 7.74 (t, 1H, J=8.0 Hz), 8.04 (d, 1H, J=8.0 Hz), 8.18 (d, 1H, J=8.0 Hz), 8.27 (t, 1H, J=5.8 Hz, NHCOCH3), 8.87 (d, 1H, J=8.0 Hz). LCMS (ESI) m/e 499 (M+H)+.