Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[C:5]([O:12][CH3:13])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[Br-].[S:15]1[CH:19]=[CH:18][N:17]=[C:16]1[Zn+].N#N>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:13][O:12][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[N:3]=[C:2]([C:16]1[S:15][CH:19]=[CH:18][N:17]=1)[N:11]=[CH:10]2
Reactant: [Zn+]c1nccs1
Reactant: COc1cccc2cnc(Cl)nc12
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: N#N
Solvent: ClCCl
Product: COc1cccc2cnc(-c3nccs3)nc12
Temperature: 50 °C
Reaction time: 1 h
Yield: 20 %

Procedure:
2-Chloro-8-methoxyquinazoline (1.0 eq), and thiazol-2-ylzinc(II) bromide (1M in THF, 3 eq) was degassed by anhydrous N2 stream for 5 min followed by the addition of Pd(dppf)Cl2-DCM (0.1 eq). The reaction mixture was stirred at 50° C. for 1 hour. Solvents were removed under reduced pressure. The crude product was purified by column (10% methanol in ethyl acetate:hexanes=1:1) to give 2-(8-methoxyquinazolin-2-yl)thiazole (20%). LC/MS (m/z): 243.9 (MH+), Rt=0.68.
Reaction SMILES: C[Si](C)(C)Cl.[CH:6](=[O:14])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13].Br[CH:16]([CH3:21])[C:17]([O:19][CH3:20])=[O:18].Cl>C(OCC)(=O)C.[Zn]>[OH:14][CH:6]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[CH:16]([CH3:21])[C:17]([O:19][CH3:20])=[O:18]
Reactant: CCCCCCCC=O
Reactant: COC(=O)C(C)Br
Agent: C[Si](C)(C)Cl
Agent: Cl
Agent: [Zn]
Solvent: CCOC(C)=O
Product: CCCCCCCC(O)C(C)C(=O)OC
Temperature: 65 °C
Reaction time: 0.08 h

Procedure:
At room temperature, a three-necked flask fitted with reflux condenser, internal thermometer, dropping funnel and stirrer was charged, under nitrogen protective gas, with 5.5 g of zinc powder (84 mmol) in 34 ml of ethyl acetate. After 1.6 ml of trimethylchlorosilane (12.5 mmol) had been added, the mixture was heated at 65° C. Following cooling to 60° C., 7.2 g of octanal (56 mmol) were added, and over the course of 4 min, 11.2 g of methyl 2-bromopropionate (67 mmol) were added dropwise, the temperature being maintained at 65° C. by external cooling. The mixture was then stirred at 60° C. for 5 min and, after cooling to 0° C., acidified with 40 ml of 2 N hydrochloric acid to a pH of 1 and stirred for 30 min. Excess zinc was removed by filtration and the organic phase separated. The organic phase was then stirred at 0° C. with 40 ml of 0.5 N hydrochloric acid and finally washed with 20 ml of saturated sodium hydrogen carbonate solution. Following phase separation and drying over sodium sulfate, the solvent was removed by distillation under reduced pressure. Methyl 3-hydroxy-2-methyldecanoate was obtained in a yield of 10.2 g (85% of theory) with a boiling point of 68° C. (0.04 mbar). The diastereomer ratio was 2:1.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=O)=[CH:4][C:3]=1[C:11]1[C:22](=[O:23])[N:21]([CH3:24])[C:14]2[N:15]=[C:16]([S:19][CH3:20])[N:17]=[CH:18][C:13]=2[CH:12]=1>O=S(Cl)Cl>[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]#[N:8])=[CH:4][C:3]=1[C:11]1[C:22](=[O:23])[N:21]([CH3:24])[C:14]2[N:15]=[C:16]([S:19][CH3:20])[N:17]=[CH:18][C:13]=2[CH:12]=1
Reactant: CSc1ncc2cc(-c3cc(C(N)=O)ccc3C)c(=O)n(C)c2n1
Solvent: O=S(Cl)Cl
Product: CSc1ncc2cc(-c3cc(C#N)ccc3C)c(=O)n(C)c2n1
Temperature: 75 °C

Procedure:
4-Methyl-3-(8-methyl-2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-benzamide (24 mg) was stirred in 3 g of SOCl2 for 100 hours at room temperature. Additional SOCl2 (4.5 g) was then added, and the reaction mixture was heated to 75° C. for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was eluted with 5% MeOH in methylene chloride via preparative TLC plate to give 4-methyl-3-(8-methyl-2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-benzonitrile: MS (M+H)=323.
Reaction SMILES: [C:1]1([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]([S:16]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)(=[O:18])=[O:17])[C:8]=2[CH2:26]O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C(=O)N([Br:54])C(=O)C1>C(Cl)Cl>[Br:54][CH2:26][C:8]1[N:9]([S:16]([C:19]2[CH:20]=[CH:21][C:22]([CH3:25])=[CH:23][CH:24]=2)(=[O:17])=[O:18])[C:10]2[C:15]([C:7]=1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2
Reactant: Cc1ccc(S(=O)(=O)n2c(CO)c(-c3ccccc3)c3ccccc32)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)n2c(CBr)c(-c3ccccc3)c3ccccc32)cc1
Reaction time: 2 h
Yield: 28.8 %

Procedure:
To a solution of [3-phenyl-1-(toluene-4-sulfonyl)-1H-indol-2-yl]methanol (1.31 g, 3.47 mmol) and triphenylphosphine (1.09 g, 4.16 mmol) in DCM (30 mL) at RT under a nitrogen atmosphere was added NBS (240 mg, 4.16 mmol) and stirring was continued for 2 h. Volatiles were removed under reduced pressure and the resulting residue purified by column chromatography (Si—PCC, gradient 30-100% DCM in pentane) affording the title compound as a gum (440 mg, 29%). 1H NMR (CDCl3, 400 MHz): δ 8.16 (1H, dt, J=8.48, 0.84 Hz), 7.92-7.88 (2H, m), 7.60-7.49 (4H, m), 7.48-7.37 (3H, m), 7.28-7.22 (3H, m), 5.05 (2H, s), 2.38 (3H, s)
Reaction SMILES: [CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[N:9]=[C:10]3[C:16]([CH:17]=[O:18])=[CH:15][N:14]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:11]3=[N:12][CH:13]=2)[CH:5]=[N:4]1)[CH3:2].S(=O)(=O)([OH:29])N.[O-]Cl=O.[Na+].OP([O-])(O)=O.[K+]>O1CCOCC1.O>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[N:9]=[C:10]3[C:16]([C:17]([OH:29])=[O:18])=[CH:15][N:14]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:25])([CH3:24])[CH3:26])[C:11]3=[N:12][CH:13]=2)[CH:5]=[N:4]1)[CH3:2]
Reactant: NS(=O)(=O)O
Reactant: CCn1cc(-c2cnc3c(n2)c(C=O)cn3COCC[Si](C)(C)C)cn1
Agent: O=P([O-])(O)O
Agent: [K+]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CCn1cc(-c2cnc3c(n2)c(C(=O)O)cn3COCC[Si](C)(C)C)cn1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 90 %

Procedure:
To a solution of 2-(1-ethyl-1H-pyrazol-4-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (1.12 g, 3.01 mmol) in 1,4-dioxane (50 mL) and H2O (10 mL) at 0° C. was added sulfamic acid (1.76 g, 18.1 mmol). Then added a solution of NaClO2 (0.44 g, 3.92 mmol) and KH2PO4 (4.92 g, 36.2 mmol) in H2O (30 mL) via dropping funnel over 15 min. The ice bath was removed and the yellow cloudy reaction mixture was stirred at room temperature for 2.5 h. The reaction mixture was diluted with H2O and extracted with EtOAc (2×). The combined organic layers were dried over MgSO4 and concentrated to an oily yellow solid which was triturated with 5% EtOAc/hexanes to afford 1.05 g (90%) of 2-(1-ethyl-1H-pyrazol-4-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid as a light yellow solid.
Reaction SMILES: [Li+].[OH-].O.[F:4][C@@:5]1([C:17]([O:19]CC)=[O:18])[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:6]1=[O:16].Cl>C1COCC1.O>[F:4][C@@:5]1([C:17]([OH:19])=[O:18])[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:6]1=[O:16]
Reactant: CCOC(=O)[C@]1(F)CCN(c2ccccc2)C1=O
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)[C@]1(F)CCN(c2ccccc2)C1=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 56.3 %

Procedure:
84 mg of LiOH/H2O are added to a solution of 180 mg of ethyl (S)-3-fluoro-2-oxo-1-phenylpyrrolidine-3-carboxylate in THF/H2O=3:1, and the mixture is stirred at RT for 4 h. When the reaction is complete, the batch is neutralised using 1.5 N HCl. The aqueous phase is extracted with ethyl acetate, and the organic phase is dried over sodium sulfate. Removal of the solvent in vacuo gives 90 mg of (S)-3-fluoro-2-oxo-1-phenylpyrrolidine-3-carboxylic acid;
Reaction SMILES: Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1)=[O:3].C([N:27]1[CH2:30][CH:29]([O:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[F:44])=[CH:34][N:33]=2)[CH2:28]1)(C1C=CC=CC=1)C1C=CC=CC=1>ClCCl>[N+:11]([C:8]1[CH:9]=[CH:10][C:5]([O:4][C:2]([N:27]2[CH2:30][CH:29]([O:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=4[F:44])=[CH:34][N:33]=3)[CH2:28]2)=[O:3])=[CH:6][CH:7]=1)([O-:13])=[O:12]
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: Fc1ccccc1-c1ccc(OC2CN(C(c3ccccc3)c3ccccc3)C2)nc1
Solvent: ClCCl
Product: O=C(Oc1ccc([N+](=O)[O-])cc1)N1CC(Oc2ccc(-c3ccccc3F)cn2)C1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
4-nitrophenyl chloroformate (734 mg g, 3.64 mmol) was added to a stirred solution of 2-(1-Benzhydryl-azetidin-3-yloxy)-5-(2-fluoro-phenyl)-pyridine (996 mg, 2.43 mol) in dichloromethane (25 mL) at ambient temperature. The resulting solution was stirred at ambient temperature for 18 hr, diluted with dichloromethane (150 mL) and washed sequentially with sat. aqueous sodium hydrogen carbonate solution (3×150 mL) then sat. sodium chloride solution (150 mL). The organic phase was dried over magnesium sulphate and filtered. Filtrate solvents were removed in vacuo and the residue was purified by trituration with Methyl tertiary butyl ether (25 mL) to give after filtration a yellow solid (786 mg, 79%).
Reaction SMILES: [CH2:1]([N:3]([C:6]1[CH:7]=[CH:8][C:9]2[CH:13]=[C:12]([CH:14]=O)[O:11][C:10]=2[CH:16]=1)[CH2:4][CH3:5])[CH3:2].[C:17]([CH:19]1[C:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:22][O:21][C:20]1=[O:30])#[N:18].[NH4+].[Cl-]>N1C=CC=CC=1>[C:17]([C:19]1[C:20](=[O:30])[O:21][C:22](=[CH:14][C:12]2[O:11][C:10]3[CH:16]=[C:6]([N:3]([CH:1]=[CH2:2])[CH:4]=[CH2:5])[CH:7]=[CH:8][C:9]=3[CH:13]=2)[C:23]=1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)#[N:18]
Reactant: CCN(CC)c1ccc2cc(C=O)oc2c1
Reactant: N#CC1C(=O)OC=C1c1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: c1ccncc1
Product: C=CN(C=C)c1ccc2cc(C=C3OC(=O)C(C#N)=C3c3ccccc3)oc2c1
Temperature: 80 °C

Procedure:
To 5 mL of pyridine in a 15 mL round bottom flask was added 217 mg (1 mmol) of the compound of Example 2 and 172 mg (1 mmol) of 3-cyano-4-phenyl-2-furanone. The solution was heated at 80° C. for one hour, cooled and poured into 20 mL dilute NH4Cl. The resulting mixture was extracted 2X with 20 mL 3:2 hexanes Et2O and the combined organic extracts were washed once with 10 mL of water, The organic phase was dried (MgSO4) and the solvent removed by rotary evaporation. The resulting solid was purified by flash chromatography (7:2 cyclohexane/EtOA; SiO2, 1×12") to yield 292 mg of dye. Anal. calcd. for C24H20N2O3 : C, 74.2; H, 5.4; N, 7.5. Found: C, 74.0; H, 5.2; N, 6.9.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([Br:19])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.CN(/[CH:24]=[N:25]/[C:26]1[N:27]=[CH:28][NH:29][C:30]=1[C:31](OCC)=[O:32])C.C1(O)C=CC=CC=1>C(Cl)Cl>[Br:19][C:17]1[CH:16]=[C:13]([CH:12]=[C:11]([O:10][C:5]2[C:6]([Cl:9])=[CH:7][CH:8]=[C:3]([CH2:2][N:1]3[C:31](=[O:32])[C:30]4[NH:29][CH:28]=[N:27][C:26]=4[N:25]=[CH:24]3)[C:4]=2[F:20])[CH:18]=1)[C:14]#[N:15]
Reactant: CCOC(=O)c1[nH]cnc1/N=C/N(C)C
Reactant: N#Cc1cc(Br)cc(Oc2c(Cl)ccc(CN)c2F)c1
Solvent: ClCCl
Solvent: Oc1ccccc1
Product: N#Cc1cc(Br)cc(Oc2c(Cl)ccc(Cn3cnc4nc[nH]c4c3=O)c2F)c1
Yield: 38.1 %

Procedure:
The title compound was prepared in a manner similar to that described herein using 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-bromobenzonitrile (0.61 g, 1.715 mmol), ethyl 4-{[(1E)-(dimethylamino)methylidene]amino}-1H-imidazole-5-carboxylate (0.397 g, 1.887 mmol) and phenol (0.484 g, 5.15 mmol) in DCM (3 mL) to give 0.31 g (38%) of the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.58 (br. s., 1H), 8.45 (s, 1H), 8.17 (br. s., 1H), 7.93 (s, 1H), 7.58 (d, 2H), 7.47 (d, 1H), 7.21 (t, 1H), 5.30 (s, 2H). LCMS m/z 474.1 (M−H).
Reaction SMILES: [CH:1]1([C:4]2[N:8]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([C:16]4[C:17]([C:22]([O:24]C(C)(C)C)=[O:23])=[CH:18][CH:19]=[CH:20][CH:21]=4)=[CH:12][CH:11]=3)[C:7]3[CH:29]=[C:30]([C:34]4[N:35]=[CH:36][N:37]([CH2:39][CH2:40][O:41][CH3:42])[CH:38]=4)[CH:31]=[C:32]([CH3:33])[C:6]=3[N:5]=2)[CH2:3][CH2:2]1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH:1]1([C:4]2[N:8]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([C:16]4[C:17]([C:22]([OH:24])=[O:23])=[CH:18][CH:19]=[CH:20][CH:21]=4)=[CH:12][CH:11]=3)[C:7]3[CH:29]=[C:30]([C:34]4[N:35]=[CH:36][N:37]([CH2:39][CH2:40][O:41][CH3:42])[CH:38]=4)[CH:31]=[C:32]([CH3:33])[C:6]=3[N:5]=2)[CH2:3][CH2:2]1
Reactant: COCCn1cnc(-c2cc(C)c3nc(C4CC4)n(Cc4ccc(-c5ccccc5C(=O)OC(C)(C)C)cc4)c3c2)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COCCn1cnc(-c2cc(C)c3nc(C4CC4)n(Cc4ccc(-c5ccccc5C(=O)O)cc4)c3c2)c1

Procedure:
Prepared analogously to Example 88 from tert. butyl 4'-[(2-cyclopropyl-4-methyl-6-(1-(2-methoxyethyl)-imidazol-4-yl)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylate and trifluoroacetic acid in methylene chloride.
Reaction SMILES: [NH2:1][C:2]1[S:6][N:5]=[C:4]([CH:7]([CH3:9])[CH3:8])[C:3]=1[C:10]#[N:11].S(Cl)(Cl)=O.O.[CH3:17][N:18]([CH3:21])[CH:19]=O>>[C:10]([C:3]1[C:4]([CH:7]([CH3:9])[CH3:8])=[N:5][S:6][C:2]=1[N:1]=[CH:17][N:18]([CH3:21])[CH3:19])#[N:11]
Reactant: CN(C)C=O
Reactant: CC(C)c1nsc(N)c1C#N
Solvent: O=S(Cl)Cl
Solvent: O
Product: CC(C)c1nsc(N=CN(C)C)c1C#N

Procedure:
To a solution of 6.7 g of 5-amino-4-cyano-3-isopropylisothiazole in 30 ml of dimethylformamide was slowly added 10.4 ml of thionyl chloride and the mixture was heated under reflux for 3 hours. The mixture was poured into 300 ml of water and the water-dimethylformamide was removed under reduced pressure. The residue was dissolved in ethanol. The solution was treated with decolorizing charcoal, then was diluted with 300 ml of water. The small amount of solid which separated was removed by filtration and was discarded. As the solution stood undisturbed, tan solid separated which was collected and recrystallized from methylcyclohexane to give 3.0 g of N'-(4-cyano-3-isopropyl-5-isothiazolyl)-N,N-dimethylformamidine, m.p. 95°-97°. A small amount was sublimed at 120° under 0.03 mm without change in melting point. The nmr spectrum was consistent with the assigned structure.
Reaction SMILES: C(O[C:6]([N:8](C)[CH2:9][CH2:10][N:11]([CH2:19][C:20]1[S:21][CH:22]=[C:23]([N:25]2[C:29]([C:30](=[O:41])[NH:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[O:39][CH3:40])=[CH:28][C:27]([C:42]([F:45])([F:44])[F:43])=[N:26]2)[CH:24]=1)C(=O)OC(C)(C)C)=O)(C)(C)C.C(O)(C(F)(F)F)=O.N[C@@H](C)C(NCC1SC=C(N2C(C(NCC3C=CC=CC=3OC)=O)=CC(C(F)(F)F)=N2)C=1)=O>>[CH3:40][O:39][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[CH2:32][NH:31][C:30]([C:29]1[N:25]([C:23]2[CH:24]=[C:20]([CH2:19][NH:11][CH2:10][CH2:9][NH:8][CH3:6])[S:21][CH:22]=2)[N:26]=[C:27]([C:42]([F:43])([F:44])[F:45])[CH:28]=1)=[O:41]
Reactant: COc1ccccc1CNC(=O)c1cc(C(F)(F)F)nn1-c1csc(CN(CCN(C)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)c1
Agent: COc1ccccc1CNC(=O)c1cc(C(F)(F)F)nn1-c1csc(CNC(=O)[C@H](C)N)c1
Solvent: O=C(O)C(F)(F)F
Product: CNCCNCc1cc(-n2nc(C(F)(F)F)cc2C(=O)NCc2ccccc2OC)cs1

Procedure:
The title compound 214 (133 mg, bis-TFA salt) was obtained as a white fluffy solid following the procedure described for the synthesis of 9a (scheme 2, example 1c, step 9) using 214 (135 mg, 0.202 mmol) in place of 15a
Reaction SMILES: [CH3:1][NH:2][C@@H:3]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C@H:6]([C:13]2[CH:14]=[CH:15][C:16]([Cl:20])=[C:17]([Cl:19])[CH:18]=2)[CH2:5][CH2:4]1.[C:21]([OH:26])(=[O:25])[C@H:22]([CH3:24])[OH:23]>C(O)(C)C.C(OCC)(=O)C>[CH3:1][NH:2][C@@H:3]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C@H:6]([C:13]2[CH:14]=[CH:15][C:16]([Cl:20])=[C:17]([Cl:19])[CH:18]=2)[CH2:5][CH2:4]1.[C:21]([O-:26])(=[O:25])[C@H:22]([CH3:24])[OH:23]
Reactant: C[C@H](O)C(=O)O
Agent: CN[C@H]1CC[C@@H](c2ccc(Cl)c(Cl)c2)c2ccccc21
Solvent: CC(C)O
Solvent: CCOC(C)=O
Product: C[C@H](O)C(=O)[O-]
Temperature: 40 °C

Procedure:
Sertraline base (10 g)was dissolved in isopropanol (150 mL) in a 500 mL round bottom flask and the solution was heated to 40° C. L-Lactic acid (3.4 g) was separately dissolved in ethyl acetate (25 mL). The L-lactic acid solution was added in small portions to the solution in the round bottom flask which was constantly stirred with a magnetic stirrer. The reaction mixture was stirred at 40° C. for 4 hours after the addition of the L-lactic acid solution was complete. The reaction mixture was then allowed to cool to room temperature and the solids were filtered. The solids were washed with 50 mL of hexane and then dried under vacuum at 40° C. for 48 hours. The dried solid was identified as the L-lactate salt of sertraline. The yield was calculated to be 94%. mp 153° C.
Reaction SMILES: [C:1]([O-:4])(=[O:3])[CH3:2].[K+].Cl[CH2:7][CH:8]=[C:9]([CH3:16])[CH2:10][CH2:11][O:12][CH:13]([CH3:15])[CH3:14]>CN(C)C=O>[C:1]([O:4][CH2:7][CH:8]=[C:9]([CH3:16])[CH2:10][CH2:11][O:12][CH:13]([CH3:15])[CH3:14])(=[O:3])[CH3:2]
Reactant: CC(=CCCl)CCOC(C)C
Reactant: CC(=O)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(=O)OCC=C(C)CCOC(C)C
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of 450 g (4.6 mols) of potassium acetate and 637 g (3.6 mols) of 1-chloro-5-isopropoxy-3-methyl-2-pentene in 3000 cc of dimethylformamide is stirred at room temperature for 24 hours and then at 50°C for 4 hours. The reaction mixture is filtered, and solvent is distilled off at 1.4 mm Hg and the residue is fractionally distilled. A cis/trans mixture of 1-acetoxy-5-isopropoxy-3-methyl-2-pentene is obtained. B.P.: 122°-126° /18 mm Hg.
Reaction SMILES: [C:1]1(SC)C=CC=CC=1.S(OC)(OC)(=O)=O.COS([O-])(=O)=O.C1([S+](C)C)C=CC=CC=1.[CH2:31]([C:35]1[CH:40]=[CH:39][C:38]([C:41](=[O:43])[CH3:42])=[CH:37][CH:36]=1)[CH:32]([CH3:34])[CH3:33].[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:31]([C:35]1[CH:36]=[CH:37][C:38]([C:41]2([CH3:1])[O:43][CH2:42]2)=[CH:39][CH:40]=1)[CH:32]([CH3:34])[CH3:33]
Reactant: CSc1ccccc1
Reactant: CC(=O)c1ccc(CC(C)C)cc1
Agent: COS(=O)(=O)[O-]
Agent: C[S+](C)c1ccccc1
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: COS(=O)(=O)OC
Product: CC(C)Cc1ccc(C2(C)CO2)cc1
Reaction time: 0.5 h
Yield: 86.5 %

Procedure:
24.8 g (0.2 mole) of thioanisole was heated to 90° C. with stirring, 27.8 g (0.22 mole) of dimethyl sulfate was added thereto at 90°-95° C. over a period of 30 minutes and stirred for another 30 minutes at the same temperature. To the reaction mixture, 100 ml of toluene was added portionwise so as to maintain the temperature above 80° C. and then the mixture was cooled gradually with stirring to afford a suspension of phenyldimethylsulfonium methylsulfate in quantititative yield. To the suspension, 26.4 g (0.15 mole) of p-isobutylacetophenone and 16.0 g (0.4 mole) of powdered sodium hydroxide was added and the mixture was stirred for 8 hours at 50° C. The reaction mixture was worked up in the same manner as described in Example 6 to afford 24.7 g of 2-(4-isobutylphenyl)-1,2-epoxypropane in 86.7% yield.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7](B2OC(C)(C)C(C)(C)O2)=[C:6]([CH3:19])[CH:5]=1.FC(F)(F)S(O[C:27]1[CH2:32][CH2:31][CH2:30][CH2:29][C:28]=1[C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([O:39][CH3:40])[CH:34]=1)(=O)=O>>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([C:27]2[CH2:32][CH2:31][CH2:30][CH2:29][C:28]=2[C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([O:39][CH3:40])[CH:34]=2)=[C:6]([CH3:19])[CH:5]=1
Reactant: COC(=O)c1ccc(B2OC(C)(C)C(C)(C)O2)c(C)c1
Reactant: COc1cccc(C2=C(OS(=O)(=O)C(F)(F)F)CCCC2)c1
Product: COC(=O)c1ccc(C2=C(c3cccc(OC)c3)CCCC2)c(C)c1
Yield: 53.4 %

Procedure:
3-Methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester of Example 28, Step A (0.300 g, 1.09 mmol) and 2-(3-methoxy-phenyl)-cyclohex-1-en-1-yl trifluoromethanesulfonate (0.441 g, 1.31 mmol) were reacted in the manner of Example 1, Step F. Purification by flash column chromatography on silica gel, eluting with a solvent gradient of from 0 to 5% ethyl acetate in hexane, afforded the title compound (0.196 g) as a light yellow oil.
Reaction SMILES: [OH:1][C:2]1[CH:6]=[C:5]([CH2:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[N:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:3]=1.Cl[CH2:21][C:22]1[CH:23]=[C:24]([CH:39]=[CH:40][CH:41]=1)[O:25][CH2:26][C:27]1[N:28]=[C:29]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[O:30][C:31]=1[CH3:32].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:32][C:31]1[O:30][C:29]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[N:28][C:27]=1[CH2:26][O:25][C:24]1[CH:23]=[C:22]([CH:41]=[CH:40][CH:39]=1)[CH2:21][O:1][C:2]1[CH:6]=[C:5]([CH2:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[N:4]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:3]=1
Reactant: CCOC(=O)CCc1cc(O)nn1-c1ccccc1
Reactant: Cc1oc(-c2ccccc2)nc1COc1cccc(CCl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCc1cc(OCc2cccc(OCc3nc(-c4ccccc4)oc3C)c2)nn1-c1ccccc1
Temperature: 60 °C
Reaction time: 4 h
Yield: 90.2 %

Procedure:
A mixture of ethyl 3-(3-hydroxy-1-phenyl-1H-pyrazol-5-yl)propionate (460 mg), 4-(3-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (550 mg), potassium carbonate (350 mg) and N,N-dimethylformamide. (10 ml) was stirred at 60° C. for 4 hrs. The reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and ethyl 3-[3-[3-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxy]-1-phenyl-1H-pyrazol-5-yl]propionate (850 mg, yield 90%) was obtained as a colorless oil from a fraction eluted with ethyl acetate-hexane (1:1, volume ratio).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7](=O)[CH2:8][C:9]([O:11]CC)=O)=[CH:3][CH:2]=1.Cl.[NH:16]=[C:17]1[CH:23]([N:24]2[C:32](=[O:33])[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25]2=[O:34])[CH2:22][CH2:21][CH2:20][CH2:19][NH:18]1>>[O:11]=[C:9]1[N:18]2[CH2:19][CH2:20][CH2:21][CH2:22][CH:23]([N:24]3[C:32](=[O:33])[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:25]3=[O:34])[C:17]2=[N:16][C:7]([C:4]2[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=2)=[CH:8]1
Reactant: CCOC(=O)CC(=O)c1ccncc1
Reactant: N=C1NCCCCC1N1C(=O)c2ccccc2C1=O
Agent: Cl
Product: O=C1c2ccccc2C(=O)N1C1CCCCn2c1nc(-c1ccncc1)cc2=O

Procedure:
By analogy with the method described in example 1 (step 1.3), using ethyl 3-(pyridin-4-yl)-3-oxopropionate and using 2-(2-iminoazepan-3-yl)-1H-isoindole-1,3(2H)-dione hydrochloride (1:1), the compound was obtained as a white powder.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[CH:3][C:2]=1[C:11]1[CH:12]=[C:13]([NH2:17])[CH:14]=[CH:15][CH:16]=1.C(N(C(C)C)CC)(C)C.[Cl:27][CH:28]([Cl:32])[C:29](Cl)=[O:30]>C1COCC1.C(OCC)(=O)C>[Cl:27][CH:28]([Cl:32])[C:29]([NH:17][C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([C:2]2[CH:3]=[N:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:1]=2)[CH:12]=1)=[O:30]
Reactant: O=C(Cl)C(Cl)Cl
Reactant: Nc1cccc(-c2cnc3ccccc3n2)c1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: O=C(Nc1cccc(-c2cnc3ccccc3n2)c1)C(Cl)Cl
Temperature: 25 °C
Reaction time: 24 h
Yield: 40.5 %

Procedure:
To a solution of (3-quinoxalin-2-ylphenyl)amine (135 mg, 0.610 mmol) and diisopropylethylamine (DIEA, 121 μL, 0.732 mmol) in THF (5 mL), dichloroacetyl chloride (65 μL, 0.673 mmol) was added at room temperature. The reaction mixture was stirred at room temperature for 24 hrs and then diluted with ethyl acetate (25 mL). The organic phase was washed with water (25 mL) and then brine (25 mL), dried over MgSO4, and the solvent was evaporated in vacuo to afford 2,2-dichloro-N-[3-(quinoxalin-2-yl)phenyl]acetamide (82 mg, 40% yield). LCMS calculated for C16H11Cl2N3O (M+H): 332.03. found 332.09. 1H-NMR (DMSO-d6, 400, Mhz) δH: 10.60 (1H, br. s), 9.55 (1H, s), 8.53 (1H, s), 8.18-8.05 (3H, m), 7.95-7.85 (3H, m), 7.62 (1H, m), 6.65 (1H, s).