Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([N:19]4[CH2:22][CH:21]([N:23]5[CH2:28][CH2:27][N:26]([C:29]([C:31]6[S:32][CH:33]=[CH:34][N:35]=6)=[O:30])[CH2:25][CH2:24]5)[CH2:20]4)=[O:18])=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)=[CH:4][CH:3]=1.C1C(=O)N([Cl:43])C(=O)C1>C(Cl)(Cl)(Cl)Cl.C(Cl)Cl>[Cl:43][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[C:13]([C:17]([N:19]3[CH2:20][CH:21]([N:23]4[CH2:28][CH2:27][N:26]([C:29]([C:31]5[S:32][CH:33]=[CH:34][N:35]=5)=[O:30])[CH2:25][CH2:24]4)[CH2:22]3)=[O:18])[CH:12]=2)[N:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH:9]=1
Reactant: O=C(c1ccc2c(ccn2-c2ccc(F)cc2)c1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
Reactant: O=C1CCC(=O)N1Cl
Solvent: ClC(Cl)(Cl)Cl
Solvent: ClCCl
Product: O=C(c1ccc2c(c1)c(Cl)cn2-c1ccc(F)cc1)N1CC(N2CCN(C(=O)c3nccs3)CC2)C1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of Cpd 487 (0.2 mmol, 100 mg) in CCl4 (4 mL) and CH2Cl2 (4 mL) was added NCS (0.25 mmol, 33 mg). The reaction mixture was stirred at room temperature for 4 h. It was then diluted with CH2Cl2 and washed with 1N aqueous NaOH and H2O, dried over Na2SO4, and concentrated. Purification by flash column chromatography (silica gel, 3% MeOH/CH2Cl2) gave 51 mg of Cpd 1365. MS m/z (M+H+) 524.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:16])[C:5]([NH:7][CH2:8][C:9]([O:11][CH2:12][CH2:13][CH2:14][CH3:15])=[O:10])=O)[CH3:2].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.O>C(#N)C>[CH2:12]([O:11][C:9]1[O:10][C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:16])=[N:7][CH:8]=1)[CH2:13][CH2:14][CH3:15]
Reactant: CCCCOC(=O)CNC(=O)C(=O)OCC
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Solvent: O
Solvent: CC#N
Product: CCCCOc1cnc(C(=O)OCC)o1
Temperature: 60 °C

Procedure:
To a solution of butyl N-[ethoxy(oxo)acetyl]glycinate (783 g, 3.38 mol) in acetonitrile (8 L) in a 50 L glass reactor with overhead stirrer, phosphorus pentoxide (415 g, 2.92 mol) was added in portions. The reaction was heated at 60° C. for 1 hour. The product mixture was cooled, and water (8 L) was added with the mixture maintained at 20° C. The resultant mixture was extracted with dichloromethane (8 L, and 3 times 2 L). The organic extracts were combined, washed twice with saturated aqueous sodium bicarbonate (8 L total), dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum. The residual oil was subjected to column chromatography on silica gel eluting with O-30% heptane/ethyl acetate gradient. Collection and concentration of appropriate fractions provided the title material.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][CH2:13][NH2:14].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[O:57]=[C:58]1[CH:62]([C:63](O)=[O:64])[CH2:61][CH2:60][N:59]1[C:66]1[CH:71]=[CH:70][C:69]([C:72]([F:75])([F:74])[F:73])=[CH:68][CH:67]=1>CN(C=O)C>[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][CH2:13][NH:14][C:63]([CH:62]1[CH2:61][CH2:60][N:59]([C:66]2[CH:67]=[CH:68][C:69]([C:72]([F:75])([F:73])[F:74])=[CH:70][CH:71]=2)[C:58]1=[O:57])=[O:64]
Reactant: O=C(O)C1CCN(c2ccc(C(F)(F)F)cc2)C1=O
Reactant: NCCc1c[nH]c2ccc(Cl)cc12
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(NCCc1c[nH]c2ccc(Cl)cc12)C1CCN(c2ccc(C(F)(F)F)cc2)C1=O
Yield: 6.4 %

Procedure:
This compound was prepared according to method E with 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.200 g; 0.865 mmol), PyBOP (0.450 g; 0.865 mmol), N,N diisopropylethylamine (0.373 mL; 2.16 mmol) and 2-oxo-1-(4-(trifluoromethyl)phenyl)pyrrolidine-3-carboxylic acid (0.236 g; 0.865 mmol) in DMF (3 mL). The crude mixture was purified flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane and 1 to 7% methanol in dichloromethane) to yield 0.025 g (7%) of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-2-oxo-1-(4-(trifluoromethyl)phenyl)pyrrolidine-3-carboxamide as a white solid.
Reaction SMILES: C([NH:8][CH:9]1[CH2:12][CH:11]([CH2:13][O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:10]1[F:22])C1C=CC=CC=1>CO.[OH-].[OH-].[Pd+2]>[CH2:15]([O:14][CH2:13][CH:11]1[CH2:12][CH:9]([NH2:8])[CH:10]1[F:22])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: FC1C(COCc2ccccc2)CC1NCc1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: NC1CC(COCc2ccccc2)C1F
Reaction time: 22 h

Procedure:
Benzyl-(3-benzyloxymethyl-2-fluoro-cyclobutyl)-amine (0.34 g, 1.21 mmol) was dissolved in 10 mL MeOH and this was treated with 20% Pd(OH)2 on carbon (0.07 g, 0.11 mmol). This was subjected to the hydrogenolysis conditions (50 psi). After 22 hr, the reaction mixture was filtered through celite and the filtrated was concentrated and was purified by silica gel flash chromatography (Hexane: EtOAc=1:1) to give 0.16 g (63%, Rf==0.30 (CH2Cl2: MeOH=15:1)). 1H NMR (CDCl3, 400 MHz): δ 2.08-2.16 (m, 2H), 2.96-3.12 (m, 1H), 3.52-3.64 (m, 2H), 3.88-3.94 (m, 1H), 4.55 (s, 2H), 5.03-5.19 (td, 1H, J=52.8, 6.0), 7.25-7.38 (m, 5H). 13C NMR (CDCl3, 100 MHz): δ 23.12-23.21 (d, J=9.0), 42.13-42.34 (d, J=21), 48.30, 70.07, 74.39, 87.46-89.63 (d, J=217), 128.98, 129.05, 129.61, 139.63. MS (FAB): expected for C12H16FNO (M+H)+ 210.26. Found 210.12885.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[SH:9].Cl.C(C/C=[CH:16]/[C:17]1[C:22]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)=[CH:21][CH:20]=[C:19]([CH2:36]Cl)[N:18]=1)(O)=O.N12CCCN=C1CCCCC2.C[CH2:50][O:51][C:52]([CH3:54])=[O:53]>CC#N>[CH3:35][O:34][C:31]1[CH:30]=[CH:29][C:28]([CH2:27][CH2:26][CH2:25][CH2:24][O:23][C:22]2[C:17](/[CH:16]=[CH:54]/[C:52]([O:51][CH3:50])=[O:53])=[N:18][C:19]([CH2:36][S:9][C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=3[Cl:8])=[CH:20][CH:21]=2)=[CH:33][CH:32]=1
Reactant: CCOC(C)=O
Reactant: Sc1c(Cl)cccc1Cl
Reactant: COc1ccc(CCCCOc2ccc(CCl)nc2/C=C/CC(=O)O)cc1
Agent: Cl
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: COC(=O)/C=C/c1nc(CSc2c(Cl)cccc2Cl)ccc1OCCCCc1ccc(OC)cc1
Temperature: 50 °C
Reaction time: 3 h

Procedure:
2,6-Dichlorothiophenol (53 mg, 0.297 mmol, Aldrich) was dissolved in dry MeCN (0.60 mL,) and treated with 2-(E-2-carboxymethylethenyl)-3-[4-(4-methoxyphenyl)butyloxy]-6-chloromethylpyridine hydrochloride (115 mg, 0.270 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.142 mL, 0.949 mmol). The reaction was stirred under an atmosphere of argon at 50° C. for 3 h. The reaction solution was diluted with EtOAc and washed with H2O and brine and dried (MgSO4). Purification by flash column chromatography (silica, EtOAc: CH2Cl2 : hexane, 10:15:75) gave a colorless waxy solid: 1H NMR (250 MHz, CDCl3) δ7.94 (d, J=15.7 Hz, 1H, vinyl), 7.31 (d, J=7.6 Hz, 2H, aryl), 7.13 (m, 4H, aryl, pyridyl), 7.11 (d, J=8.4 Hz, 1H, pyridyl), 6.86 (d, J=8.7 Hz, 2H, phenyl), 6.69 (d, J=15.7 Hz, 1H, vinyl), 4.14 (s, 2H, CH2 -S), 3.97 (t, J=6.1 Hz, 2H, CH2 -O), 3.80 (s, 3H, OMe), 3.78 (s, 3H, methyl ester), 2.63 (t, J=7.2 Hz, 2H, benzylic), 1.81 (m, 4H, CH2CH2); analysis calcd. for C27H27Cl2NO4S: C, 60.90; H, 5.11; N, 2.63; found: C, 60.61; H, 5.01; N, 2.57; MS (ES+): 532.0 (M+H).
Reaction SMILES: C[C:2]1[O:3][C:4](=[O:14])/[C:5](=[CH:7]/[C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)/[N:6]=1.[CH2:15](N(CC)CC)C.[F:22][B-:23]([F:26])([F:25])[F:24].[H+].C(OC)(C)(C)C.[CH3:34][OH:35]>>[F:22][B-:23]([F:26])([F:25])[F:24].[C:34]([NH:6][C:5]([C:4]([O:3][CH3:2])=[O:14])=[CH:7][C:8]1[CH:9]=[NH+:10][CH:11]=[CH:12][CH:13]=1)(=[O:35])[CH3:15]
Reactant: CCN(CC)CC
Reactant: CC1=N/C(=C\c2cccnc2)C(=O)O1
Reactant: CO
Agent: F[B-](F)(F)F
Agent: [H+]
Solvent: COC(C)(C)C
Product: COC(=O)C(=Cc1ccc[nH+]c1)NC(C)=O
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
Under nitrogen, a suspension of 2-methyl-4-[pyridin-3-yl-(Z)-methylene]-4H-oxazol-5-one (12.0 kg, 63.83 mol) in methanol (120.0 l) was heated at 60° C. Triethylamine (0.5 l) was pumped in, and the apparatus was rinsed with methanol (0.5 l) (the pH of a sample taken, measured using a glass electrode, was pH 8.15). Within a period of 30 min, the reaction solution was cooled to 30° C. Tetrafluoroboric acid solution (48% strength in water, 11.8 kg, 64.5 mol) was added over a period of 30 min. Within 1 h, the mixture was cooled to an internal temperature of 10° C. and (if required after seeding) the suspension was then stirred at 10° C. for a further 3 h. Methyl tert-butyl ether (40.0 l) was added, and the mixture was stirred at 10° C. for 1 h. The suspension was introduced into a centrifuge which had been inertized with nitrogen, centrifuged, and the the product washed with methyl tert-butyl ether (20.0 l) and dried at 40° C. under reduced pressure. Yield: 18.7 kg (60.71 mol, 95.1% of theory). M.p.: 179.4° C.; MS (ESI+): m/z (%)=221 ([M+H+] of the free base, 100); 1H-NMR (200 MHz, DMSO-d6): δ=2.01 (s, 3H), 3.77 (s, 3H), 7.21 (s, 1H), 7.89 (dd, 1H), 8.48 (d, 1H), 8.76 (d, 1H), 8.98 (s, 1H), 9.92 (s, 1H); IR (KBr): ν=1726.9, 1670.1, 1091.5 cm−1.
Reaction SMILES: [NH2:1][C:2]([CH3:6])([CH3:5])[CH2:3][OH:4].[C:7]([C:13]([O:15][CH3:16])=[O:14])#[C:8][C:9]([O:11][CH3:12])=[O:10]>C(O)C>[CH3:5][C:2]1([CH3:6])[CH2:3][O:4][C:13](=[O:14])[C:7](=[CH:8][C:9]([O:11][CH3:12])=[O:10])[NH:1]1.[O:15]1[CH:16]=[CH:2][N:1]=[CH:7][C:13]1=[O:14]
Reactant: COC(=O)C#CC(=O)OC
Reactant: CC(C)(N)CO
Solvent: CCO
Product: COC(=O)C=C1NC(C)(C)COC1=O
Product: O=c1cncco1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
5,5-Dimethyl-3-(methoxycarbonyl)methylene-3,4,5,6-tetrahydro-1,4-oxazin-2-one was prepared as follows: 2-amino-2-methyl-1-propanol (5.35 ml, 0.056 mol) was dissolved in 100 ml of anhydrous ethanol. Dimethyl acetylenedicarboxylate (7.20 ml, 0.056 mol) was added dropwise at a rate which caused the solution to mildly reflux. Then, the reaction mixture was stirred at ambient temperature for 2 hours, and the solvent was evaporated to yield the desired 1,4-oxazinone derivative. After recrystallization from ethanol, 5.79 g of pure product was obtained melting at 94°-97° C.
Reaction SMILES: C(O[C:6]([N:8](C)[CH2:9][C:10]([N:12]([CH3:35])[CH2:13][CH2:14][CH2:15][P+:16]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:11])=O)(C)(C)C.[Br-].[F:38][C:39]([F:44])([F:43])[C:40]([OH:42])=[O:41]>>[F:38][C:39]([F:44])([F:43])[C:40]([O-:42])=[O:41].[CH3:35][N:12]([CH2:13][CH2:14][CH2:15][P+:16]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:10](=[O:11])[CH2:9][NH:8][CH3:6]
Reactant: O=C(O)C(F)(F)F
Reactant: CN(CCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1)C(=O)CN(C)C(=O)OC(C)(C)C
Agent: [Br-]
Product: CNCC(=O)N(C)CCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: O=C([O-])C(F)(F)F
Reaction time: 0.5 h

Procedure:
N2-(tert-butoxycarbonyl)-N,N2-dimethyl-N-[3-(triphenylphosphonio)propyl]glycinamide bromide (280 mg, 0.48 mmol) was dissolved in trifluoroacetic acid (1.9 mL, 25 mol) at room temperature. After 30 minutes, the volatiles were removed under high vacuum and the crude product taken up in methylene chloride and washed with aqueous NaHCO3. The organic layer was then washed with water and concentrated to give the title compound in quantitative yield.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[C:5]([CH3:13])[N:4]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][NH2:22])=[CH:16][CH:15]=2)[N:3]=1.ClCCl.C(N(CC)CC)C.[C:33](Cl)(=[O:41])[O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>O>[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[C:5]([CH3:13])[N:4]([C:14]2[CH:15]=[CH:16][C:17]([CH2:20][CH2:21][NH:22][C:33](=[O:41])[O:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[CH:18][CH:19]=2)[N:3]=1
Reactant: Cc1nn(-c2ccc(CCN)cc2)c(C)c1-c1ccccc1
Reactant: O=C(Cl)Oc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: Cc1nn(-c2ccc(CCNC(=O)Oc3ccccc3)cc2)c(C)c1-c1ccccc1
Reaction time: 1 h
Yield: 81.9 %

Procedure:
To a stirred solution of 2-[4-(3,5-dimethyl-4-phenyl-1H-pyrazol-1-yl)phenyl]ethylamine (step 3 of Example 14, 1.36 g, 4.66 mmol), dichloromethane (30 m]L) and triethylamine (0.78 mL, 5.60 mmol) was added phenyl chlorocarbonate (0.64 mL, 5.13 mmol) slowly at room temperature. After 1 h, the mixture was poured into water and extracted with dichloromethane. The organic fraction was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with hexane/ethyl acetate (2:1) to afford 1.57 g (82%) of the title compound as white solids: MS (ESI) m/z 412 [M+H]+, 1H-NMR (CDCl3) δ 7.48-7.10 (14H, m), 5.06 (1H, br.s), 3.60-3.53 (2H, m), 2.96 (2H, t, J=6.8 Hz), 2.34 (3H, s), 2.31 (3H, s).
Reaction SMILES: [CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[NH:4][N:3]=1.[H-].[Na+].[H][H].[Br:17][CH2:18][CH2:19]Br>CN(C)C=O>[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[N:4]([CH2:19][CH2:18][Br:17])[N:3]=1
Reactant: BrCCBr
Reactant: Cc1n[nH]c(=O)c2ccccc12
Reactant: [H][H]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1nn(CCBr)c(=O)c2ccccc12
Reaction time: 2 h

Procedure:
4-Methyl-(2H)-phthalazin-1-one (6 g) and sodium hydride (1.5 g, 60% in oil) in dimethylformamide (DMF) were stirred at room temperature until hydrogen evolution ceased. To this suspension was added a five fold excess of 1,2-dibromoethane (25 ml) and stirring was continued for a further 2 hours. The solvent was removed and the residue taken up in ethyl acetate, washed twice with brine, dried (MgSO4) and evaporated. Chromatography on silica [Merck `Kieselgel 60` (Trade Mark)] eluting with methylene chloride containing methanol (0% up to 5%) gave, after collection and evaporation of appropriate fractions, a solid which was recrystallised from ethanol to give the title compound, yield 6.25 g, m.p. 102°-103°, used in the next stage.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:3][NH:4][C:5]1[N:10]([CH3:11])[C:9](=[O:12])[C:8]([N+:13]([O-])=O)=[C:7]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)[N:6]=1.[H][H]>[Pd]>[NH2:1][C@@H:2]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:3][NH:4][C:5]1[N:10]([CH3:11])[C:9](=[O:12])[C:8]([NH2:13])=[C:7]([C:16]2[CH:17]=[CH:18][N:19]=[CH:20][CH:21]=2)[N:6]=1
Reactant: Cn1c(NC[C@@H](N)Cc2ccccc2)nc(-c2ccncc2)c([N+](=O)[O-])c1=O
Reactant: [H][H]
Agent: [Pd]
Product: Cn1c(NC[C@@H](N)Cc2ccccc2)nc(-c2ccncc2)c(N)c1=O

Procedure:
A suspension of 2-(2 (S)-amino-3-phenyl-propylamino)-3-methyl-5-nitro-6-pyridin-4-yl-3H-pyrimidin-4-one (0.2 mmol) and Pd/C was stirred over a hydrogen filled balloon for 1 h at room temperature. The product was filtered through a bed of celite, and the solvents removed under vacuum. The product was purified on reverse phase HPLC M+1=351.
Reaction SMILES: [CH2:1]([N:3]([CH2:28][CH3:29])[C:4](=[O:27])[C:5]1[CH:10]=[CH:9][C:8]([CH:11](Cl)[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH:13]=2)=[CH:7][CH:6]=1)[CH3:2].[CH3:30][C@H:31]1[CH2:36][NH:35][C@@H:34]([CH3:37])[CH2:33][NH:32]1.N[C@H](C(N[C@H](C(O)=O)C)=O)C.O=C1NCCNC1=O>C1(C)C=CC=CC=1>[CH2:1]([N:3]([CH2:28][CH3:29])[C:4](=[O:27])[C:5]1[CH:10]=[CH:9][C:8]([CH:11]([N:32]2[CH2:33][C@H:34]([CH3:37])[NH:35][CH2:36][C@@H:31]2[CH3:30])[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH:13]=2)=[CH:7][CH:6]=1)[CH3:2]
Reactant: C[C@H]1CN[C@@H](C)CN1
Reactant: CCN(CC)C(=O)c1ccc(C(Cl)c2cccc(O[Si](C)(C)C(C)(C)C)c2)cc1
Agent: C[C@H](N)C(=O)N[C@@H](C)C(=O)O
Agent: O=C1NCCNC1=O
Solvent: Cc1ccccc1
Product: CCN(CC)C(=O)c1ccc(C(c2cccc(O[Si](C)(C)C(C)(C)C)c2)N2C[C@H](C)NC[C@@H]2C)cc1
Yield: 22.1 %

Procedure:
A mixture of 15.65 g (36 mmol) of N,N-diethyl-4-(3-(t-butyldimethylsilyloxy)-α-chlorobenzyl)benzamide, prepared as described in Example 11, 7.22 g (65 mmol) of (+)-(2S,5S)-2,5-dimethylpiperazine, prepared from L-Ala-L-Ala-diketopiperazine (Bachem Chemicals, Philadelphia, Pa.) as described by Jung and Rohloff (J. Org. Chem. 50, 4909-13 (1985)), and 3 mL of toluene was heated as in Example 1. The product was purified by chromatography on silica gel (Waters Prep 500 with dichloromethane containing 1% ethanol and 0.1% triethylamine) to give 4.06 g (22%) of N,N-diethyl-4-(3-(tert-butyldimethylsilyloxy)-α-((2S,5S)-2.5-dimethyl-1-piperazinyl)benzyl)benzamide as a beige foam.
Reaction SMILES: BrBr.Cl[CH2:4][CH2:5][CH2:6][C:7](=[O:9])[CH3:8].C(=O)([O-])[O-].[K+].[K+].[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[OH:23]>C(Cl)Cl.CN(C)C=O.O>[C:7]([C:6]1([O:23][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[Cl:16])[CH2:4][CH2:5]1)(=[O:9])[CH3:8]
Reactant: Oc1ccccc1Cl
Reactant: CC(=O)CCCCl
Agent: BrBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: O
Solvent: CN(C)C=O
Product: CC(=O)C1(Oc2ccccc2Cl)CC1
Reaction time: 0.25 h
Yield: 52.9 %

Procedure:
A solution of 134 g (0.84 mol) of bromine in 130 ml of methylene chloride is added dropwise at 10° C. with stirring to a mixture of 100 g (0.83 mol) of 5-chloropentan-2-one and 400 ml of methylene chloride. After completion of the addition, the reaction mixture is stirred for a further 15 minutes and then poured into 500 ml of water. The organic phase is separated off, washed successively with 5% strength aqueous sodium carbonate solution and with water, then dried over sodium sulphate and concentrated by stripping off the solvent under reduced pressure. The residue is taken up in 200 ml of dimethylformamide, and the resulting solution is added dropwise at 60° C. to a mixture of 230 g of potassium carbonate, 106 g (0.83 mol) of 2-chlorophenol and 400 ml of dimethylformamide. The reaction mixture is initially stirred for 4 hours at 60° C. and then for 4 hours at 90° C. The mixture is then filtered from the solid residue with suction, the solvent is stripped off under reduced pressure and the remaining residue is taken up in a mixture of ethyl acetate and toluene. The organic phase is washed with water, dried over sodium sulphate and concentrated by stripping off the solvent under reduced pressure. The remaining residue is subjected to a vacuum distillation. In this manner, 92.5 g (53% of theory) of 1-acetyl-1-(2-chlorophenoxy)-cyclopropane are obtained in the form of a liquid of boiling point 81° C./0.2 mbar.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C:6]2=[O:13].P(Cl)(Cl)(Cl)(Cl)[Cl:17]>>[Cl-:17].[F:15][C:2]([F:1])([F:14])[C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C:6]2=[O:13]
Reactant: ClP(Cl)(Cl)(Cl)Cl
Agent: O=C1Nc2ccc(C(F)(F)F)cc2C1=O
Product: [Cl-]

Procedure:
By reacting 5-trifluoromethylisatin with phosphorus pentachloride, there is obtained 5-trifluoromethylisatin chloride which, on reation with 3(2H)-thianaphthenone, yields 5'-trifluoromethyl-2'-indole-2-thianap indigo, which also is useful as a dyestuff.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.Br[CH:16]1[CH2:21][CH2:20][S:19](=[O:23])(=[O:22])[CH2:18][CH2:17]1.CC1(C)C(C)(C)OB(C2C=NN(C3CS(=O)(=O)C3)C=2)O1>>[CH3:1][C:2]1([CH3:14])[C:6]([CH3:7])([CH3:8])[O:5][B:4]([C:9]2[CH:13]=[N:12][N:11]([CH:17]3[CH2:16][CH2:21][CH2:20][S:19](=[O:23])(=[O:22])[CH2:18]3)[CH:10]=2)[O:3]1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: O=S1(=O)CCC(Br)CC1
Agent: CC1(C)OB(c2cnn(C3CS(=O)(=O)C3)c2)OC1(C)C
Product: CC1(C)OB(c2cnn(C3CCCS(=O)(=O)C3)c2)OC1(C)C

Procedure:
3-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide was synthesized from 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 4-bromotetrahydro-2H-thiopyran 1,1-dioxide according to the procedure outlined above for 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)thietane 1,1-dioxide (Intermediate 7). 13C NMR (400 MHz, CDCl3) δ ppm 20.85 (s, 1C), 24.75 (s, 1C), 24.77 (s, 4C), 31.38 (s, 1C), 50.50 (s, 1C), 56.62 (s, 1C), 57.33 (s, 1C), 83.50 (s, 2C), 134.95 (s, 1C), 146.21 (s, 1C). MS (ESI, pos. ion) m/z 327 [M+H]+.
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:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.[CH2:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:26][CH2:25][N:24]1[C:33]([N:35]=[C:36]=[S:37])=[O:34]>C1(C)C=CC=CC=1.C(O)C>[CH2:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:26][CH2:25][N:24]1[C:33]([N:35]=[C:36]=[S:37])=[O:34].[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:22]=[CH:21][C:19]([NH:20][C:36]([NH:35][C:33]([N:24]2[CH2:25][CH2:26][C:27]3[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:23]2)=[O:34])=[S:37])=[CH:18][CH:17]=1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Agent: O=C(N=C=S)N1CCc2ccccc2C1
Solvent: Cc1ccccc1
Solvent: CCO
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)N4CCc5ccccc5C4)cc3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 94 %

Procedure:
Commercially available 1,2,3,4-tetrahydroisoquinoline (50 mg) was dissolved in chloroform (10 ml), and triphosgene (111 mg) was added to the solution. The mixture was stirred at room temperature for 2 hr. The solvent was removed by distillation to give 1,2,3,4-tetrahydro-2-isoquinolinecarbonyl chloride. 1,2,3,4-Tetrahydro-2-isoquinolinecarbonyl isothiocyanate was prepared using this compound as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 1,2,3,4-tetrahydro-2-isoquinolinecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (78 mg, yield 94%).
Reaction SMILES: [C:1]([N:5]([C:7](=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[NH2:6])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[C:17]1([CH3:26])[CH:22]=[CH:21][CH:20]=[C:19]([C:23](Cl)=[O:24])[CH:18]=1>C1(C)C=CC=CC=1>[C:1]([N:5]([C:7](=[O:14])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[NH:6][C:23]([C:19]1[CH:18]=[C:17]([CH3:26])[CH:22]=[CH:21][CH:20]=1)=[O:24])([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1cccc(C(=O)Cl)c1
Reactant: CC(C)(C)N(N)C(=O)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: Cc1cccc(C(=O)NN(C(=O)c2ccccc2)C(C)(C)C)c1
Reaction time: 2 h

Procedure:
To a stirred mixture of N'-t-butyl-N'-benzoylhydrazine (1.0 g) in 15 ml toluene and aqueous sodium hydroxide (0.5 g of 50% NaOH) was added 3-toluoyl-chloride (0.9 g). After stirring for 2 hours, the product was isolated by filtration to give N'-t-butyl-N-(3-toluoyl)-N'-benzoylhydrazine in good yield: m.p. 111°-114° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:13]([C:17](=[O:31])[CH2:18][C:19]2[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=2)[CH2:14][CH2:15]O)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[H][H]>[Pd].C(O)C>[CH3:12][O:11][C:7]1[CH:6]=[C:5]([CH:13]2[CH2:14][CH2:15][CH:18]([C:19]3[CH:20]=[C:21]([O:29][CH3:30])[C:22]([O:27][CH3:28])=[C:23]([O:25][CH3:26])[CH:24]=3)[C:17]2=[O:31])[CH:4]=[C:3]([O:2][CH3:1])[C:8]=1[O:9][CH3:10]
Reactant: COc1cc(CC(=O)C(CCO)c2cc(OC)c(OC)c(OC)c2)cc(OC)c1OC
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: COc1cc(C2CCC(c3cc(OC)c(OC)c(OC)c3)C2=O)cc(OC)c1OC

Procedure:
A mixture of 2.38 g of the compound of Example 1 as a 0.1M ethanol solution and 900 mg of 10% palladium on carbon was stirred, under a 50 psi. atmosphere of hydrogen gas, for 17 hours. The mixture was then filtered through Celite and the crude residue was flash chromatographed on silica gel employing ethyl acetate as the eluent to yield the title compound.