Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:31])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH2:14][C:15]2[S:19][C:18]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)=[N:17][C:16]=2[CH3:30])=[CH:9][CH:8]=1)[CH3:2].[CH2:32]=O>O1CCOCC1>[CH2:1]([O:3][C:4](=[O:31])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]([CH3:32])[CH2:14][C:15]2[S:19][C:18]([C:20]3[CH:21]=[CH:22][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:24][CH:25]=3)=[N:17][C:16]=2[CH3:30])=[CH:9][CH:8]=1)[CH3:2]
Reactant: CCOC(=O)COc1ccc(NCc2sc(-c3ccc(C(F)(F)F)cc3)nc2C)cc1
Reactant: C=O
Solvent: C1COCCO1
Product: CCOC(=O)COc1ccc(N(C)Cc2sc(-c3ccc(C(F)(F)F)cc3)nc2C)cc1
Temperature: 60 °C
Yield: 86 %

Procedure:
A solution of (4-{[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-amino}-phenoxy)-acetic acid ethyl ester (0.09 g, 0.2 mmol) in dioxane (1 mL) was treated with 1N NaH2PO3 solution (1 ml) and a 37% aqueous solution of formaldehyde (1 ml). The mixture was heated to 60° C. for 7.5 h. Additional dioxane (1 ml) was added and heated for 11.5 h. The mixture was extracted with aqueous saturated NaHCO3 solution/Et2O (3×). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4) and evaporated to give 0.08 g (86%) of (4-{methyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-amino}-phenoxy)-acetic acid ethyl ester as yellow waxy solid, MS: 465 (MH+).
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:18])=[C:4]([NH:8][C:9](=S)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2F)[CH:5]=[CH:6][CH:7]=1.[NH2:19][NH2:20]>CS(C)=O.C([O-])(O)=O.[Na+]>[Br:1][C:2]1[C:3]([CH3:18])=[C:4]([NH:8][C:9]2[C:10]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:20][N:19]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: NN
Reactant: Cc1c(Br)cccc1NC(=S)c1ccccc1F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CS(C)=O
Product: Cc1c(Br)cccc1Nc1n[nH]c2ccccc12
Temperature: 150 °C

Procedure:
Step 3 A yellow solution of N-(3-bromo-2-methylphenyl)-2-fluorobenzothioamide (500 mg, 1.542 mmol) in DMSO (5 mL) was treated with anhydrous hydrazine (0.484 mL, 15.42 mmol) and heated at 150° C. After 2 h 20 min the solution was cooled to rt, diluted with NaHCO3 (aq) and extracted twice with EtOAc. The combined organic phases were washed twice with water and once with brine, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 85:15 to 50:50 hexane-EtOAc) to provide N-(3-bromo-2-methylphenyl)-1H-indazol-3-amine as a tan waxy solid (162 mg, 35%). 1H NMR (400 MHz, chloroform-d) δ 9.38 (1H, br. s.), 7.49 (1H, d, J=8.1 Hz), 7.45 (1H, d, J=7.9 Hz), 7.40 (2H, d, J=3.5 Hz), 7.19 (1H, dd, J=7.9, 0.9 Hz), 7.10 (1H, dt, J=8.1, 4.0 Hz), 6.98 (1H, t, J=8.1 Hz), 6.10 (1H, s), 2.49 (3H, s). Mass spectrum m/z 302, 304 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:12]2[CH:17]=[CH:16][N:15]([CH2:18][CH3:19])[C:14](=[O:20])[CH:13]=2)=[C:5]([C:7]2[O:8][CH:9]=[CH:10][CH:11]=2)[N:6]=1.[C:21](O)(=[O:28])[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.O>[CH2:18]([N:15]1[CH:16]=[CH:17][C:12]([C:4]2[S:3][C:2]([NH:1][C:21]([C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)=[O:28])=[N:6][C:5]=2[C:7]2[O:8][CH:9]=[CH:10][CH:11]=2)=[CH:13][C:14]1=[O:20])[CH3:19]
Reactant: CCn1ccc(-c2sc(N)nc2-c2ccco2)cc1=O
Reactant: O=C(O)c1ccncc1
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: CCn1ccc(-c2sc(NC(=O)c3ccncc3)nc2-c2ccco2)cc1=O
Temperature: 80 °C
Reaction time: 1 h
Yield: 36.6 %

Procedure:
2-Amino-5-(1-ethyl-2-oxo-1,2-dihydropyridin-4-yl)-4-(2-furyl)thiazole (167 mg, 0.582 mmol) obtained in Step 1 was dissolved in DMF (8 mL), and isonicotinic acid (143 mg, 1.16 mmol), PyBOP (664 mg, 1.28 mmol) and triethylamine (0.356 mL, 2.55 mmol) were added thereto, followed by stirring at 80° C. for 1 hour. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform:methanol=17:1), followed by reslurrying with a mixed solvent of methanol and diethyl ether to afford the entitled Compound 124 (83.5 mg, 37%) as a pale brown solid.
Reaction SMILES: [Li+].[OH-].[C:3]1([CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([O:19]CC3C=CC=CC=3)=[O:18])=[CH:13][C:12]=2[C:27]([O:29]CC2C=CC=CC=2)=[O:28])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl>O.O1CCCC1>[C:3]1([CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([OH:19])=[O:18])=[CH:13][C:12]=2[C:27]([OH:29])=[O:28])[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: O=C(OCc1ccccc1)c1ccc(OCc2ccccc2)c(C(=O)OCc2ccccc2)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1ccc(OCc2ccccc2)c(C(=O)O)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of LiOH (6.12 g, 146 mmol) in water (100 ml) was added to a stirred solution of bis(phenylmethyl) 4-[(phenylmethyl)oxy]-1,3-benzenedicarboxylate (may be prepared as described in Description 47; 6.6 g, 14.59 mmol) in tetrahydrofuran (25 ml) at room temperature. The mixture was stirred at room temperature overnight. The reaction mixture was acidified with concentrated HCl. The white precipitate was collected by filtration, and dried to yield the title compound as a white solid. 3.8 g.
Reaction SMILES: [CH:1]1([C:8]2[S:12][C:11]([N:13]=[C:14]=[O:15])=[N:10][N:9]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:16][NH:17][CH2:18][CH:19]=[O:20]>C1C=CC=CC=1>[CH3:16][N:17]([CH2:18][CH:19]=[O:20])[C:14]([NH:13][C:11]1[S:12][C:8]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]2)=[N:9][N:10]=1)=[O:15]
Reactant: CNCC=O
Reactant: O=C=Nc1nnc(C2CCCCCC2)s1
Solvent: c1ccccc1
Product: CN(CC=O)C(=O)Nc1nnc(C2CCCCCC2)s1

Procedure:
A mixture of 5-cycloheptyl-1,3,4-thiadiazol-2-yl isocyanate dimer (0.05 mole), the dimethyl acetal of 2-methylaminoacetaldehyde (0.1 mole) and benzene (60 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer and reflux condenser. The reaction mixture is heated at reflux for a period of about 15 minutes. After this time to the mixture is stripped of benzene under reduced pressure yield a solid product as the residue. The residue is then recrystallized to yield the desired product the dimethyl acetal of 2-[1-methyl-3-(5-cycloheptyl-1,3,4-thiadiazol-2-yl)ureido]acetaldehyde.
Reaction SMILES: [NH2:1][CH2:2][C:3]1([CH2:6][O:7][C:8]2[C:13]([O:14][CH3:15])=[C:12]([O:16][CH3:17])[CH:11]=[CH:10][C:9]=2[C:18]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:19]=2[CH2:20][CH2:21][C:22]3=[O:27])[CH2:5][CH2:4]1.C(N(CC)CC)C.[C:35](Cl)(=[O:39])[O:36][CH2:37][CH3:38].C(OCC)(=O)C>ClCCl>[CH2:37]([O:36][C:35](=[O:39])[NH:1][CH2:2][C:3]1([CH2:6][O:7][C:8]2[C:9]([C:18]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:19]=3[CH2:20][CH2:21][C:22]4=[O:27])=[CH:10][CH:11]=[C:12]([O:16][CH3:17])[C:13]=2[O:14][CH3:15])[CH2:4][CH2:5]1)[CH3:38]
Reactant: COc1ccc(-c2cccc3c2CCC3=O)c(OCC2(CN)CC2)c1OC
Reactant: CCOC(=O)Cl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCOC(=O)NCC1(COc2c(-c3cccc4c3CCC4=O)ccc(OC)c2OC)CC1

Procedure:
To a stirring solution of 4-[2-(1-Aminomethyl-cyclopropylmethoxy)-3,4-dimethoxy-phenyl]-indan-1-one (Compound 182) (110 mg, 0.272 mmol) in dichloromethane (10 mL), were added triethylamine (0.082 g, 0.811 mmol) and ethyl carbonochloridate (59 mg, 0.544 mmol) and the resultant reaction mixture was subjected to the conditions used in the preparation of Compound 183 and Purification by column chromatography (silica gel, 0-25% ethyl acetate in pet ether) to afford the title compound as a solid.
Reaction SMILES: [CH3:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:13]O)[CH:9]=[CH:10][C:11]=1[F:12].C(N(CC)CC)C.S([Cl:31])(C)(=O)=O>C(Cl)Cl>[Cl:31][CH2:13][C:8]1[CH:9]=[CH:10][C:11]([F:12])=[C:6]([CH:7]=1)[O:5][CH2:4][C:3]1[C:2]([CH3:1])=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:19]
Reactant: CS(=O)(=O)Cl
Reactant: Cc1cccc(C)c1COc1cc(CO)ccc1F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1cccc(C)c1COc1cc(CCl)ccc1F
Reaction time: 6 h

Procedure:
To a stirred solution of (3-(2,6-dimethylbenzyloxy)-4-fluorophenyl)methanol (Step B, 3.7 g, 14.21 mmol), triethylamine (5 g, 50 mmol) in CH2Cl2 (50 ml) was added mesyl chloride (10.34 g, 90.2 mmol) at 0° C. under argon. The reaction mixture was stirred for 6 hours, washed with 10% Na2CO3, dried over Na2SO4, filtered, concentrated and purified by flash chromatography on a silica gel column (hexane:ethyl acetate, 5:1) to give the title compound.
Reaction SMILES: Br[C:2]1[S:3][C:4]2[C:10]([O:11][S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13])=[C:9]([C@H:19]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:8]([CH3:30])=[CH:7][C:5]=2[N:6]=1.[NH:31]1[CH2:34][CH2:33][CH2:32]1.[NH4+].[Cl-]>C1COCC1>[N:31]1([C:2]2[S:3][C:4]3[C:10]([O:11][S:12]([C:15]([F:17])([F:16])[F:18])(=[O:14])=[O:13])=[C:9]([C@H:19]([O:25][C:26]([CH3:28])([CH3:29])[CH3:27])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:8]([CH3:30])=[CH:7][C:5]=3[N:6]=2)[CH2:34][CH2:33][CH2:32]1
Reactant: C1CNC1
Reactant: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(Br)sc2c1OS(=O)(=O)C(F)(F)F
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(N3CCC3)sc2c1OS(=O)(=O)C(F)(F)F
Temperature: 70 °C

Procedure:
To a solution of 32 (50 mg, 0.094 mmol) in THF (1 mL) was added azetidine (20 μL). The reaction mixture was heated at 70° C. for 30 min. A saturated solution of NH4Cl (3 mL) was added, and the layers were separated. The aqueous layer was extracted with EtOAc. The combined organic layer were dried, filtered, and concentrated in vacuo. The crude material was purified by column chromatography (EtOAc/hexanes) to give 38 mg of 33. LCMS-ESI+: calc'd for C20H25F3N2O6S2: 511.1 (M+H+); Found: 511.0 (M+H+).
Reaction SMILES: Br[CH2:2][CH2:3][C@H:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@@H:6]([C:17]([O:19][CH3:20])=[O:18])[CH2:5]1.CS(C)=O.[C-:25]#[N:26].[Na+].O>[Cl-].[Na+].O>[C:25]([CH2:2][CH2:3][C@H:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@@H:6]([C:17]([O:19][CH3:20])=[O:18])[CH2:5]1)#[N:26]
Reactant: [C-]#N
Reactant: COC(=O)[C@H]1C[C@@H](CCBr)CCN1C(=O)OC(C)(C)C
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: COC(=O)[C@H]1C[C@@H](CCC#N)CCN1C(=O)OC(C)(C)C
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 85.4 %

Procedure:
To a solution of 12.95 g (0.031 mol, containing triphenylphosphine oxide) of methyl cis-4-(2-bromoethyl)-N-t-butoxycarbonyl-2-piperidinecarboxylate and 40 ml of DMSO was added 2.30 g (0.047 mol) of sodium cyanide. The mixture was stirred for approximately 30 minutes at 50° C. To the mixture was added 50 ml each of water and brine and the mixture was extracted four times with methylene chloride and once with diethyl ether. The organic extracts were combined, washed twice with water and once with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The resultant residue was dissolved in 100 ml of ethyl acetate:hexane (1:3, v:v) and filtered through a one inch pad of silica gel (230-400 mesh) in a 150 ml medium porosity sintered glass funnel. The silica gel pad was washed with an additional 400 ml of ethyl acetate:hexane (1:3, v:v). The filtrate was concentrated under vacuum to afford 7.85 g of methyl cis-4-(2-cyanoethyl)-N-t-butoxycarbonyl-2-piperidinecarboxylate.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:23][CH:12]3[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH:11]3[CH2:10]2)[C:5]([Cl:24])=[CH:4][N:3]=1.[CH3:25][N:26]1[CH:30]=[C:29]([NH2:31])[N:28]=[CH:27]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:24][C:5]1[C:6]([NH:8][CH:9]2[CH2:23][CH:12]3[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH:11]3[CH2:10]2)=[N:7][C:2]([NH:31][C:29]2[N:28]=[CH:27][N:26]([CH3:25])[CH:30]=2)=[N:3][CH:4]=1
Reactant: CC(C)(C)OC(=O)N1CC2CC(Nc3nc(Cl)ncc3Cl)CC2C1
Reactant: Cn1cnc(N)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: Cn1cnc(Nc2ncc(Cl)c(NC3CC4CN(C(=O)OC(C)(C)C)CC4C3)n2)c1
Temperature: 150 °C
Reaction time: 2 h
Yield: 48.4 %

Procedure:
To a suspension of tert-butyl 5-[(2,5-dichloropyrimidin-4-yl)amino]-hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (373.0 mg, 1.00 mmol) and 1-methylimidazol-4-amine (341.8 mg, 3.52 mmol) in dioxane (10 mL) were added Pd(OAc)2 (52.0 mg, 0.23 mmol), BINAP (125.0 mg, 0.19 mmol) and Cs2CO3 (647.2 mg, 1.99 mmol). The reaction mixture was stirred at 150° C. under microwave for 2 h and concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/DCM (v/v)=1/50) to give the title compound as a pale yellow solid (0.21 g, 48%).
Reaction SMILES: [N+]([O-])(O)=O.[CH:5]12[CH2:14][CH:9]3[CH2:10][CH:11]([CH2:13][CH:7]([CH2:8]3)[C:6]1=[O:15])[CH2:12]2.[OH-:16].[Na+]>OS(O)(=O)=O>[OH:16][C:11]12[CH2:13][CH:7]3[CH2:8][CH:9]([CH2:14][CH:5]([C:6]3=[O:15])[CH2:12]1)[CH2:10]2
Reactant: O=C1C2CC3CC(C2)CC1C3
Reactant: [OH-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O=[N+]([O-])O
Product: O=C1C2CC3CC1CC(O)(C3)C2
Temperature: 0 °C
Reaction time: 5 h

Procedure:
To a mixture of H2SO4 (96%; 150 ml) and HNO3 (70%; 15 ml), cooled to 0° C. is added tricyclo[3.3.1.13,7 ]decan-2-one (10 g; 0.067 mole) and the mixture stirred at room temperature for 5 hrs. The reaction mixture is then poured over ice, basified to pH 8 using 50% NaOH, extracted into ether, dried over MgSO4 and evaporated to dryness. The resultant product is recrystallized from carbon tetrachloride to obtain 5-hydroxytricyclo[3.3.1.13,7 ]decan-2-one [(m. p. 314° C. (dec.)] which is used directly in step B.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@H:11]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@@:10]([CH2:29][O:30][S:31]([CH3:34])(=[O:33])=[O:32])([CH2:20][O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[O:9][CH:6]1OC)(=[O:3])[CH3:2].[C:35]1([S:41][Si](C)(C)C)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O>ClCCl>[C:1]([O:4][C@@H:5]1[C@H:11]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@@:10]([CH2:29][O:30][S:31]([CH3:34])(=[O:33])=[O:32])([CH2:20][O:21][CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[O:9][C@H:6]1[S:41][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)(=[O:3])[CH3:2]
Reactant: C[Si](C)(C)Sc1ccccc1
Reactant: COC1O[C@@](COCc2ccccc2)(COS(C)(=O)=O)[C@@H](OCc2ccccc2)[C@H]1OC(C)=O
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: ClCCl
Product: CC(=O)O[C@H]1[C@H](Sc2ccccc2)O[C@@](COCc2ccccc2)(COS(C)(=O)=O)[C@H]1OCc1ccccc1
Temperature: 0 °C
Reaction time: 4 h
Yield: 66.1 %

Procedure:
Method a. A stirred solution of 209 (738 mg, 1.49 mmol) in anhydrous dichloromethane (6.4 mL) was added phenylthiotrimethylsilane (2.42 mL, 12.8 mmol) and cooled to 0° C. Trimethylsilyl triflate (0.67 mL, 3.67 mmol) was added dropwise and the solution was stirred at room temperature for 4 h. The reaction was quenched with a saturated aqueous solution of sodium hydrogen carbonate (100 mL) and extracted with dichloromethane (2×200 mL). The combined extract was dried (MgSO4) and the solvent removed by distillation under reduced pressure. The residue was purified by chromatography over silica gel with dichloromethane as eluent to give the product 210 as a clear oil (564 mg, 66%) and unreacted starting material (191 mg, 26%); Method b. A stirred solution of 211 (86 mg, 0.165 mmol) in anhydrous dichloromethane (0.49 mL) was added phenylthiotrimethylsilane (0.16 mL, 0.825 mmol) and cooled to 0° C. Trimethylsilyl triflate (0.037 mL, 0.206 mmol) was added and the solution was stirred at room temperature for 2 h. The reaction was quenched with a saturated aqueous solution of sodium hydrogen carbonate (15 mL) and the resulting mixture was extracted with dichloromethane (2×25 mL). The combined extract was dried (MgSO4) and the solvent removed by distillation under reduced pressure. The residue was purified by chromatography over silica gel with dichloromethane as eluent to give the product 210 as a clear oil (75 mg, 79%); 1H NMR (CDCl3): δ 7.47-7.19 (15H, m, Bn, SPh), 5.48 (1H, d, J 3.6 Hz, H-2), 5.34 (1H, dd, J 3.7, 5.2 Hz, H-1), 4.54-4.36 (7H, m, H-3, H-5′, Bn), 3.66 (1H, d, J 9.7 Hz, H-5), 3.48 (1H, d, J 9.5 Hz, H-5), 2.89 (3H, s, SO2CH3), 2.09 (3H, s, OCCH3); 13C NMR (CDCl3): δ 169.93 (C═O), 137.69, 137.08, 132.65, 132.45, 129.15, 128.53, 128.52, 128.18, 128.14, 128.08, 127.91, 127.85 (Bn, SPh), 87.99, 84.35, 80.34, 75.33, 74.20, 73.67, 70.83, 69.34 (C-1, C-2, C-3, C-4, C-5, C-5′, Bn), 37.27 (SO2CH3), 20.68 (OCCH3); MS FAB: 463 (M-SPh, 100%), 595 (M+Na, 24%); Found: C, 61.17; H, 5.55; C29H32O8S2 requires C, 60.82; H, 5.63%.
Reaction SMILES: Br[C:2]1[N:3]([CH2:21][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2.[C:31](=[O:34])([O-])O.[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([O:26][C:24]([NH:23][CH2:22][CH2:21][N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2)[C:10]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[C:2]1[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:31]=[O:34])=[O:25])([CH3:30])([CH3:29])[CH3:28]
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c(Br)n(CCNC(=O)OC(C)(C)C)c2c1
Reactant: O=C([O-])O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: COC(=O)c1ccc2c(C3CCCCC3)c(-c3ccccc3C=O)n(CCNC(=O)OC(C)(C)C)c2c1
Temperature: 90 °C
Reaction time: 2 h
Yield: 171.5 %

Procedure:
To a suspension of methyl 2-bromo-1-(2-tert-butoxycarbonylaminoethyl)-3-cyclohexyl-1H-indole-6-carboxylate (500 mg, 1.04 mmol), 2-formylphenylbononic acid (187 mg, 1.24 mmol) and sodium hydrogen carbonate (345 mg, 4.15 mmol) in 1,2-dimethoxyethane (5 ml) and water (2.5 ml) was added tetrakis(triphenylphosphine)palladium (60.0 mg, 0.05 mmol), and the mixture was stirred at 90° C. for 2 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was successively washed with water and saturated brine and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (hexane:ethyl acetate=5:1-3:1) to give methyl 1-(2-tert-butoxycarbonylaminoethyl)-3-cyclohexyl-2-(2-formylphenyl)-1H-indole-6-carboxylate (450 mg, yield 85%).
Reaction SMILES: O.Cl.[NH:3]1[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]1.C(=O)(O)[O-].[K+].C(OCC)(=O)C.Cl[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23]>O>[CH2:25]([O:24][C:22]([N:3]1[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]1)=[O:23])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=C1CCNCC1
Reactant: O=C(Cl)OCc1ccccc1
Agent: Cl
Agent: O=C([O-])O
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Product: O=C1CCN(C(=O)OCc2ccccc2)CC1
Reaction time: 2.5 h

Procedure:
4-Piperidone hydrochloride hydrate (50.0 g, 325 mmol) and potassium bicarbonate (181.9 g, 1.82 mol) were combined in a two phase mixture of ethyl acetate (750 mL) and water (75 mL). Benzyl chloroformate (49 mL, 343 mmol) was added dropwise to the stirred mixture over 10 minutes. The mixture was stirred 2.5 hours, then it was diluted with water (700 mL) and the phases were separated. The aqueous layer was extracted with ethyl acetate and the combined organic phase was washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated to a light yellow oil (76.75 g, 100%). The material was found to be analytically pure and suitable for further transformation without further workup. Analysis calculated for C13H15NO3 : C, 66.94; H, 6.48; N, 6.00. Found: C, 66.67; H, 6.48; N, 5.90.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][NH:10][CH2:11][CH2:12][CH2:13][NH:14][CH2:15][CH2:16][CH2:17][CH2:18][NH:19][CH2:20][CH2:21][CH2:22][NH2:23])[CH:6]=[CH:5][C:4]=1[OH:24].[Cl:25][C:26]1[N:31]=[C:30]([NH:32][CH:33]([CH2:41][CH3:42])[C:34]2[CH:39]=[CH:38][C:37]([OH:40])=[CH:36][CH:35]=2)[CH:29]=[C:28]([CH2:43][CH3:44])[N:27]=1.[CH:45]1([CH2:48]Cl)[CH2:47][CH2:46]1.O.C1(C)C=CC=CC=1>CN(C)C=O.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][NH:10][CH2:11][CH2:12][CH2:13][NH:14][CH2:15][CH2:16][CH2:17][CH2:18][NH:19][CH2:20][CH2:21][CH2:22][NH2:23])[CH:6]=[CH:5][C:4]=1[OH:24].[Cl:25][C:26]1[N:31]=[C:30]([NH:32][CH:33]([CH2:41][CH3:42])[C:34]2[CH:39]=[CH:38][C:37]([O:40][CH2:48][CH:45]3[CH2:47][CH2:46]3)=[CH:36][CH:35]=2)[CH:29]=[C:28]([CH2:43][CH3:44])[N:27]=1
Reactant: ClCC1CC1
Reactant: CCc1cc(NC(CC)c2ccc(O)cc2)nc(Cl)n1
Agent: COc1cc(CNCCCNCCCCNCCCN)ccc1O
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CCc1cc(NC(CC)c2ccc(OCC3CC3)cc2)nc(Cl)n1
Reaction time: 8 h
Yield: 41.9 %

Procedure:
To a solution of 1.1 g of dl-5-chloro-6-ethyl-4-(α-ethyl-4-hydroxybenzyl)aminopyrimidine dissolved in 30 ml of N,N-dimethylformamide was added 0.4 g of cyclopropylmethyl chloride, and the mixture was stirred at 90° to 100° C. for 8 hours. After completion of the reaction, the reaction mixture was charged into water and the separated oily product was extracted with ethyl acetate. The extract was washed with water, dried with anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The oil product obtained was isolated by column chromatography (Wako Gel C-200, trade name, eluted with toluene: ethyl acetate=7:1) to give 0.5 g of the desired product as pale yellow liquid.
Reaction SMILES: [C:1]1([CH3:31])[CH:6]=[C:5]([CH3:7])[CH:4]=[C:3]([CH3:8])[C:2]=1[C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:16]=2[OH:22])[N:12]=[C:11]([C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][C:24]=2[OH:30])[N:10]=1.[CH2:32]([O:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH:33]1[O:35][CH2:34]1>[Br-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C.C1(C)C=C(C)C=C(C)C=1.C(OCC)(=O)C>[C:1]1([CH3:31])[CH:6]=[C:5]([CH3:7])[CH:4]=[C:3]([CH3:8])[C:2]=1[C:9]1[N:10]=[C:11]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:34][CH:33]([OH:35])[CH2:32][O:36][CH2:37][CH2:38][CH2:39][CH3:40])=[CH:25][C:24]=2[OH:30])[N:12]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:34][CH:33]([OH:35])[CH2:32][O:36][CH2:37][CH2:38][CH2:39][CH3:40])=[CH:17][C:16]=2[OH:22])[N:14]=1
Reactant: CCCCOCC1CO1
Reactant: Cc1cc(C)c(-c2nc(-c3ccc(O)cc3O)nc(-c3ccc(O)cc3O)n2)c(C)c1
Agent: CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: Cc1cc(C)cc(C)c1
Solvent: CCOC(C)=O
Product: CCCCOCC(O)COc1ccc(-c2nc(-c3ccc(OCC(O)COCCCC)cc3O)nc(-c3c(C)cc(C)cc3C)n2)c(O)c1
Temperature: 140 °C
Reaction time: 21 h
Yield: 104.8 %

Procedure:
A mixture of 20.0 g (0.048 mol) of 2-mesityl-4,6-bis(2,4-dihydroxyphenyl)-1,3,5-triazine (compound 1b), 13.8 g (0.105 mol) of n-butyl glycidyl ether (purity 95%) and 1.8 g (4.8 mmol) of ethyltriphenylphosphonium bromide (purity 97%) in 100 ml of mesitylene (purity 99%) is stirred at 140° C. under nitrogen for 21 hours. Decantation and evaporation of the remaining solvent gives 41.2 g of crude product. This is dissolved in 100 ml of ethyl acetate and filtered through a 10.5 cm layer of silica gel 60 (230-400 mesh) of diameter 7.5 cm, with elution with 3 l of ethyl acetate/hexane (1:1 mixture). The 34.0 g of solid obtained after removal of the solvent are re-dissolved in 25 ml of ethyl acetate. 250 ml of hexane are added to the viscous solution. The mixture is stirred at 0° C. for 2 hours and filtered, and the solid is dried for 24 hours at 80° C. and a pressure of 60 mmHg (8000 Pa), giving 23.0 g of the title product (compound 2) of the formula ##STR105## of m.p. 125°-131° C.