Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.Cl.[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH2:11])[CH2:4]2.[C:12]1(/[C:18](=[CH:22]\[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)/[C:19](O)=[O:20])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH:11][C:19](=[O:20])/[C:18](/[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[CH:22]/[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:4]2
Reactant: N[C@H]1CN2CCC1CC2
Reactant: O=C(O)/C(=C/c1ccccc1)c1ccccc1
Agent: Cl
Product: O=C(N[C@H]1CN2CCC1CC2)/C(=C/c1ccccc1)c1ccccc1

Procedure:
Prepared as free base by a method analogous to that described in Example 1 from (R)-1-azabicyclo[2.2.2]oct-3-ylamine dihydrochloride and E-2,3-diphenylpropenoic acid; MS (ES+) 333 (MH+).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]([C:10]2[NH:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([N+:19]([O-])=O)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.C([O-])=O.[NH4+]>CO.[Pd]>[NH2:19][C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]([C:8]([N:5]1[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]1)=[O:9])=[CH:18]2
Reactant: CN1CCN(C(=O)c2cc3cc([N+](=O)[O-])ccc3[nH]2)CC1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CO
Product: CN1CCN(C(=O)c2cc3cc(N)ccc3[nH]2)CC1

Procedure:
The product of Example 59, (4-Methyl-piperazin-1-yl)-(5-nitro-1H-indol-2-yl)-methanone (1.8 g) was dissolved in CH3OH (50 mL). At room temperature, ammonium formate (3.94 g) was added, followed by 10% palladium on carbon (0.66 g). The reaction mixture was heated to reflux for forty min, cooled and filtered through celite pad. The filtrate was concentrated and the residue was purified via silica gel chromatography (3-10% 2 M ammonia in methanol/dichloromethane) to give the title compound (1.60 g). 1H NMR (400 MHz, CDCl3): δ 10.46 (br s, 1H), 7.12 (d, J=8.80 Hz, 1H), 6.81 (d, J=2.15 Hz, 1H), 6.64 (dd, J=2.15, 6.46 Hz, 1H), 6.54 (d, J=1.37 Hz, 1H), 3.88 (br m, 4H), 3.70 (br s, 2H), 2.40 (t, J=4.70 Hz, 4H), 2.25 (s, 3H). MS (electrospray): exact mass calculated for C14H18N4O, 258.15; m/z found, 259.1 [M+H]+.
Reaction SMILES: [C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[N:11]=[C:12]([NH:15][C:16]3[N:21]=[CH:20][C:19]([S:22][CH2:23][CH2:24][C:25](OC)=[O:26])=[CH:18][C:17]=3[O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[S:13][CH:14]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[OH:26][CH2:25][CH2:24][CH2:23][S:22][C:19]1[CH:18]=[C:17]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:16]([NH:15][C:12]2[S:13][CH:14]=[C:10]([CH:7]3[CH2:6][CH2:5][N:4]([C:1](=[O:3])[CH3:2])[CH2:9][CH2:8]3)[N:11]=2)=[N:21][CH:20]=1
Reactant: COC(=O)CCSc1cnc(Nc2nc(C3CCN(C(C)=O)CC3)cs2)c(Oc2ccccc2)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(=O)N1CCC(c2csc(Nc3ncc(SCCCO)cc3Oc3ccccc3)n2)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 21.2 %

Procedure:
A solution of methyl 3-(6-(4-(1-acetylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate (100 mg, 0.195 mmol) in THF (10 mL) at 0° C. was treated dropwise with LiAlH4 (1M in THF, 195 μL, 0.195 mmol). Once the addition was completed the ice bath was removed and the mixture was stirred at ambient temperature for 30 minutes. The mixture was cooled to 0° C. and quenched with successive addition of water (0.2 mL), 2N NaOH (0.6 mL), and water (0.2 mL). The mixture was stirred at ambient temperature for 30 minutes and the resulting solids were removed by filtration, washing with additional THF. The filtrate was concentrated in vacuo and the residue was purified by reverse phase C-18 chromatography using a gradient of 20%-90% CH3CN/water to provide the title compound (20 mg, 0.0413 mmol, 21.2% yield) as a white solid. 1H NMR (DMSO-d6) δ 10.77 (brs, 1H), 8.11 (s, 1H), 7.42 (m, 2H), 7.86 (s, 1H), 7.18 (m, 1H), 7.06 (d, 2H), 6.66 (s, 1H), 4.49 (t, 1H), 4.42 (d, 1H), 3.85 (d, 1H), 3.44 (q, 2H), 3.12 (t, 1H), 2.88 (t, 2H), 2.80 (m, 1H), 2.62 (t, 1H), 2.00 (s, 3H), 1.92 (t, 2H), 1.66-1.59 (m, 2H), 1.57-1.41 (m, 2H).
Reaction SMILES: CO[C:3]([C@H:5]1[CH2:10][CH2:9][CH2:8][C@@H:7]([CH2:11][OH:12])[CH2:6]1)=[O:4].O[NH:14][C:15](=[NH:22])[C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1>>[N:19]1[CH:20]=[CH:21][C:16]([C:15]2[N:22]=[C:3]([C@@H:5]3[CH2:10][CH2:9][CH2:8][C@H:7]([CH2:11][OH:12])[CH2:6]3)[O:4][N:14]=2)=[CH:17][CH:18]=1
Reactant: COC(=O)[C@H]1CCC[C@@H](CO)C1
Reactant: N=C(NO)c1ccncc1
Product: OC[C@H]1CCC[C@@H](c2nc(-c3ccncc3)no2)C1

Procedure:
cis-Methyl-3-hydroxymethylcyclohexane-1-carboxylate was reacted with N-hydroxy-isonicotinamidine, using the reaction conditions described in Preparation 5, to afford cis-[3-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)cyclohexyl]methanol: RT=2.70 min, m/z (ES+)=246.1 [M+H]+. This was subsequently alkylated with 1-bromobutane, under similar conditions to those described in Example 106, to afford the title compound: RT=4.11 min, m/z (ES+)=316.3 [M+H]+.
Reaction SMILES: [F:1][CH:2]([F:29])[CH2:3][N:4]1[CH2:9][C:8]2([CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]2)[O:7][CH:6]([C:22]2[O:23][C:24]([CH2:27][CH3:28])=[CH:25][N:26]=2)[CH2:5]1.[ClH:30]>C(Cl)Cl>[ClH:30].[F:29][CH:2]([F:1])[CH2:3][N:4]1[CH2:9][C:8]2([CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[O:7][CH:6]([C:22]2[O:23][C:24]([CH2:27][CH3:28])=[CH:25][N:26]=2)[CH2:5]1
Reactant: CCc1cnc(C2CN(CC(F)F)CC3(CCN(C(=O)OC(C)(C)C)CC3)O2)o1
Agent: Cl
Solvent: ClCCl
Product: CCc1cnc(C2CN(CC(F)F)CC3(CCNCC3)O2)o1
Temperature: 25 °C
Reaction time: 1 h
Yield: 106 %

Procedure:
To a solution of tert-butyl 4-(2,2-difluoroethyl)-2-(5-ethyloxazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (154 mg, 0.37 mmol) in DCM (0.4 mL) was added HCl (464 μL of 4 M solution in dioxane, 1.85 mmol) and the reaction mixture was stirred at room temperature for 1 hour. The solvent and excess HCl were removed under reduced pressure and the residue was triturated with Et2O to yield 4-(2,2-difluoroethyl)-2-(5-ethyloxazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane hydrochloride salt (138 mg, 96%) as a white solid. ESI-MS m/z calc. 315.2. found 316.3 (M+1)+; Retention time: 1.07 minutes (3 min run).
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[CH:20][C:19]([CH2:22][C@H:23]2[CH2:25][O:24]2)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:5].[CH3:26][NH2:27].O1CCCC1.Cl>ClCCl>[ClH:1].[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([CH2:22][C@H:23]([OH:24])[CH2:25][NH:27][CH3:26])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:15][CH:14]3[CH2:16][CH:10]([CH2:11][CH:12]([CH2:13]3)[CH2:17]1)[CH2:9]2)=[O:5]
Reactant: O=C(NCC12CC3CC(CC(C3)C1)C2)c1cc(C[C@H]2CO2)ccc1Cl
Reactant: CN
Agent: Cl
Solvent: C1CCOC1
Solvent: ClCCl
Product: CNC[C@@H](O)Cc1ccc(Cl)c(C(=O)NCC23CC4CC(CC(C4)C2)C3)c1

Procedure:
2-Chloro-5-[(2S)-2-oxiranylmethyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (Example 13b) (110 mg), methylamine (40% aqueous solution, 2 mL) and tetrahydrofuran (10 mL) were heated together at 50° C. under nitrogen for 20 hours, cooled and concentrated to give an oil. This was purified by Waters' MCX resin and then by column chromatography eluting with 9:1:0.1 dichloromethane/methanol/ammonia. The oil obtained was dissolved in dichloromethane (5 mL) and 1M ethereal hydrogen chloride (4 mL) was added. The resulting white solid was filtered off to give the titled compound (121 mg).
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([NH:6][C@@H:7]([CH3:19])[CH2:8][N:9]2[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:4][CH:3]=1.N1C=CC=CC=1.Cl[C:27]([O:29][CH3:30])=[O:28]>ClCCCl>[Br:1][C:2]1[CH:11]=[C:10]2[C:5](=[CH:4][CH:3]=1)[N:6]([C:27]([O:29][CH3:30])=[O:28])[C@@H:7]([CH3:19])[CH2:8][N:9]2[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]
Reactant: C[C@H]1CN(C(=O)OC(C)(C)C)c2cc(Br)ccc2N1
Reactant: COC(=O)Cl
Solvent: ClCCCl
Solvent: c1ccncc1
Product: COC(=O)N1c2ccc(Br)cc2N(C(=O)OC(C)(C)C)C[C@@H]1C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 100 %

Procedure:
A 100-mL round bottom flask fitted with nitrogen inlet and magnetic stir bar was charged with (S)-tert-butyl 7-bromo-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate (4.95 g, 15.13 mmol), 1,2-dichloroethane (50 mL), and pyridine (2.45 mL, 30.3 mmol). The reaction was cooled to 0° C. and methyl chloroformate (1.758 ml, 22.69 mmol) was added slowly. The reaction mixture stirred at 0° C. for 30 min and was then warmed to room temperature. After 2 h the reaction was diluted with 1,2-dichloroethane (20 mL) and washed with 1 M aqueous HCl solution (25 mL). The organic was concentrated under reduced pressure to afford (S)-4-tert-butyl 1-methyl 6-bromo-2-methyl-2,3-dihydroquinoxaline-1,4-dicarboxylate (5.83 g, 100%) as an amber oil. The material was used without further purification. MS (ESI, pos. ion) m/z 385 [M+1]+.
Reaction SMILES: [SH:1][C:2]1[NH:3][C:4]2[CH:9]=[CH:8][N:7]=[CH:6][C:5]=2[N:10]=1.[Na].[C:12]([O:20][C:21]1[CH:26]=[C:25]([CH2:27]Br)[CH:24]=[C:23]([O:29][C:30](=[O:37])[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:22]=1)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[C:30]([O:29][C:23]1[CH:24]=[C:25]([CH2:27][S:1][C:2]2[NH:10][C:5]3[CH:6]=[N:7][CH:8]=[CH:9][C:4]=3[N:3]=2)[CH:26]=[C:21]([O:20][C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:22]=1)(=[O:37])[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1
Reactant: O=C(Oc1cc(CBr)cc(OC(=O)c2ccccc2)c1)c1ccccc1
Reactant: Sc1nc2cnccc2[nH]1
Agent: [Na]
Product: O=C(Oc1cc(CSc2nc3ccncc3[nH]2)cc(OC(=O)c2ccccc2)c1)c1ccccc1

Procedure:
The synthesis of this compound proceeded in the same fashion as Example 15 using 1.66 g (0.011 mol) of 2-mercapto-1H-imidazo[4,5-c]pyridine, 0.28 g (0.012 g atom) of sodium and 4.51 g (0.011 mol) of 5-bromomethyl-benzene-1,3-diol dibenzoate. The crude material (4.2 g) when subjected to HPLC gave pure product (m.p. 209°-212° C.).
Reaction SMILES: C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:15][N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.CCN(CC)CC.[CH2:29]([O:31][C:32]([C:34]1[C:39]([O:40][CH2:41][CH3:42])=[C:38]([N:43]2[CH2:48][CH2:47][O:46][CH2:45][CH2:44]2)[N:37]=[C:36]([C:49]2[CH:54]=[CH:53][C:52]([NH:55][C:56]([NH:58][C:59]3[CH:64]=[CH:63][C:62]([C:65]([OH:67])=O)=[CH:61][CH:60]=3)=[O:57])=[CH:51][CH:50]=2)[N:35]=1)=[O:33])[CH3:30]>CN(C=O)C>[CH2:29]([O:31][C:32]([C:34]1[C:39]([O:40][CH2:41][CH3:42])=[C:38]([N:43]2[CH2:48][CH2:47][O:46][CH2:45][CH2:44]2)[N:37]=[C:36]([C:49]2[CH:54]=[CH:53][C:52]([NH:55][C:56]([NH:58][C:59]3[CH:64]=[CH:63][C:62]([C:65]([N:19]4[CH2:20][CH2:21][N:16]([CH3:15])[CH2:17][CH2:18]4)=[O:67])=[CH:61][CH:60]=3)=[O:57])=[CH:51][CH:50]=2)[N:35]=1)=[O:33])[CH3:30]
Reactant: CCOC(=O)c1nc(-c2ccc(NC(=O)Nc3ccc(C(=O)O)cc3)cc2)nc(N2CCOCC2)c1OCC
Reactant: CN1CCNCC1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCOC(=O)c1nc(-c2ccc(NC(=O)Nc3ccc(C(=O)N4CCN(C)CC4)cc3)cc2)nc(N2CCOCC2)c1OCC
Yield: 30 %

Procedure:
EDC (53.7 mg, 1.5 eq.), HOBT (42.9 mg, 1.5 eq.), 1-methyl-piperazine (0.03 ml, 1.5 eq.) and Et3N (0.053 ml, 2.0 eq.) were added to a stirred solution of 2-{4-[3-(4-carboxy-phenyl)-ureido]-phenyl}-5-ethoxy-6-morpholin-4-yl-pyrimidine-4-carboxylic acid ethyl ester (80 mg, 1 eq.) in dry DMF (2 ml) and the mixture reacted overnight at r.t. The mixture was quenched with H2O, extracted with EA, and washed with brine. The crude was purified by chromatography to give a product (34.5 mg, 30%).
Reaction SMILES: [H][H].[BH4-].[Na+].C(N)CN.[OH:9][CH:10]([CH3:23])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]#[C:18][CH2:19][C:20]([OH:22])=[O:21].Cl>C(O)C.[OH-].[Na+].[Cl-].[Na+].O.C([O-])(=O)C.[Ni+2].C([O-])(=O)C>[OH:9][CH:10]([CH3:23])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]/[CH:18]=[CH:19]\[C:20]([OH:22])=[O:21]
Reactant: [H][H]
Reactant: CC(O)CCCCCCC#CCC(=O)O
Agent: [Ni+2]
Agent: CC(=O)[O-]
Agent: Cl
Solvent: O
Solvent: NCCN
Solvent: CCO
Product: CC(O)CCCCCCC/C=C\C(=O)O
Temperature: 23 °C
Reaction time: 1 h
Yield: 96.4 %

Procedure:
To a vigorously stirred mixture of nickel acetate (1 g) and absolute ethanol (25 mL), saturated with hydrogen, was added 5 mL of the filtrate from a solution of sodium borohydride (500 mg) in ethanol (12 mL) and 2N aqueous sodium hydroxide (0.63 mL). After hydrogen evolution had ceased, the black suspension was treated with 0.7 mL of ethylene diamine.6Alkyne 24 (643 mg, 3.0 mmol) was added and the reaction stirred for 1 hr at 23° C. The reaction was diluted with brine (100 mL), acidified with 5% HCl and extracted with ether (4×50 mL). The ether extract was washed with brine (2×50 mL). Product isolation gave 620 mg of 26 (96% yield).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:17])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH2:16])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2].[F:18][C:19]([F:35])([F:34])[O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]#[C:28][CH2:29][CH2:30][C:31](O)=[O:32])=[CH:23][CH:22]=1.Cl.CN(C)CCCN=C=NCC.OS([O-])(=O)=O.[K+].CCOCC>ClCCl>[CH2:1]([O:3][C:4](=[O:17])[C:5]([CH3:7])([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][NH:16][C:31](=[O:32])[CH2:30][CH2:29][C:28]#[C:27][C:24]2[CH:25]=[CH:26][C:21]([O:20][C:19]([F:34])([F:35])[F:18])=[CH:22][CH:23]=2)=[CH:13][CH:14]=1)[CH3:6])[CH3:2]
Reactant: O=C(O)CCC#Cc1ccc(OC(F)(F)F)cc1
Reactant: CCOC(=O)C(C)(C)Oc1ccc(CN)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=S(=O)([O-])O
Solvent: CCOCC
Solvent: ClCCl
Product: CCOC(=O)C(C)(C)Oc1ccc(CNC(=O)CCC#Cc2ccc(OC(F)(F)F)cc2)cc1
Temperature: 0 °C
Reaction time: 28 h
Yield: 47.3 %

Procedure:
0.16 g (0.68 mmol) of 2-(4-aminomethyl-phenoxy)-2-methyl-propionic acid ethyl ester [PCT Int. Appl. WO 2002/096895 A1] and 0.16 g (0.62 mmol) of 5-(4-trifluoromethoxy-phenyl)-pent-4-ynoic acid (example 29D]) were dissolved in 4 ml of dichloromethane. This solution was cooled to 0° C. and then 0.14 g (0.74 mmol) of N-(3-dimethylamino-propyl)-N′-ethyl-carbodiimide-hydrochloride was added and the reaction stirred for 28 hours at ambient temperature. It was subsequently poured into aqueous 10% KHSO4/ether and extracted two fold with ether; the organic layers were washed with aqueous saturated NaHCO3, dried (Na2SO4), filtered and evaporated. The crude product was purified by flash chromatography (SiO2; n-heptane/AcOEt=9:1 to 1:2) to give 0.14 g of the title compound as light brown oil.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]2O[C:10](=[O:18])[C:11]3[CH:17]=[N:16][CH:15]=[CH:14][C:12]=3[N:13]=2)[CH:5]=[C:4]([CH3:19])[C:3]=1[O:20][C:21](=[O:23])[CH3:22].[CH:24]([C:28]1[CH:34]=[CH:33][C:31]([NH2:32])=[CH:30][CH:29]=1)([CH2:26][CH3:27])[CH3:25]>C(O)(=O)C>[CH:24]([C:28]1[CH:29]=[CH:30][C:31]([N:32]2[C:10](=[O:18])[C:11]3[CH:17]=[N:16][CH:15]=[CH:14][C:12]=3[N:13]=[C:8]2[C:6]2[CH:5]=[C:4]([CH3:19])[C:3]([O:20][C:21](=[O:23])[CH3:22])=[C:2]([CH3:1])[CH:7]=2)=[CH:33][CH:34]=1)([CH2:26][CH3:27])[CH3:25]
Reactant: CC(=O)Oc1c(C)cc(-c2nc3ccncc3c(=O)o2)cc1C
Reactant: CCC(C)c1ccc(N)cc1
Solvent: CC(=O)O
Product: CCC(C)c1ccc(-n2c(-c3cc(C)c(OC(C)=O)c(C)c3)nc3ccncc3c2=O)cc1
Temperature: 120 °C
Reaction time: 60 h

Procedure:
To a solution of acetic acid 2,6-dimethyl-4-(4-oxo-4H-pyrido[4,3-d][1,3]oxazin-2-yl)-phenyl ester (1.04 g, 3.35 mmol) in glacial acetic acid (20 mL) was added 4-(sec-butyl)-aniline (B) (0.750 g, 5.02 mmol). The reaction mixture was stirred at 120° C. for 60 hours under nitrogen and cooled to room temperature. Acetic acid was removed under reduced pressure. The residue was diluted with water (100 mL), neutralized to pH 7 with saturated aqueous NaHCO3 solution, and extracted with ethyl acetate (200 mL). The organic phase was washed with water (100 mL), then brine (100 mL), and dried over anhydrous Na2SO4. Solvent was evaporated and the crude compound was purified by column chromatography (silica gel 230-400 mesh; 20-30% ethyl acetate in hexanes as eluent) to give acetic acid 4-[3-(4-sec-butyl-phenyl)-4-oxo-3,4-dihydro-pyrido[4,3,d]pyrimidin-2-yl]-2,6-dimethyl-phenyl ester (7) as a white solid. Yield: 0.580 g (39%).
Reaction SMILES: CS([O:5][CH:6]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7]1)(=O)=O.[OH:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([C:27]2[CH:32]=[CH:31][C:30](O)=[CH:29][CH:28]=2)=[O:26])=[CH:21][CH:20]=1.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>CN(C=O)C>[OH:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]([C:27]2[CH:32]=[CH:31][C:30]([O:5][CH:6]3[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7]3)=[CH:29][CH:28]=2)=[O:26])=[CH:23][CH:24]=1
Reactant: CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)C1
Reactant: O=C(c1ccc(O)cc1)c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccc(C(=O)c3ccc(O)cc3)cc2)C1
Temperature: 100 °C
Yield: 46.2 %

Procedure:
A mixture of tert-butyl 3-(methylsulfonyloxy)pyrrolidine-1-carboxylate (0.6 g, 2.26 mmol), bis(4-hydroxyphenyl)methanone (2.15 g, 10.0 mmol) and K2CO3 (313 mg, 2.26 mmol) in 12 mL DMF was heated at 100° C. for 3.5 h, then quenched with water, and extracted with EtOAc. The extract was washed with water, dried, and concentrated to give a residue, to which was added CH2Cl2 and the white suspension thus formed removed and filtration. The filtrate was concentrated in vacuo and the residue was purified by column chromatography (petroleum ether/CH2Cl2/acetone=4/2/1) to give the desired product (400 mg, 46% yield).
Reaction SMILES: [Cl:1][C:2]([Cl:17])=[CH:3][C:4]1[S:5][C:6]([C:9]2[CH:14]=[CH:13][C:12]([S:15][CH3:16])=[CH:11][CH:10]=2)=[CH:7][CH:8]=1.S([O-])(O[O-])(=O)=[O:19].[K+].[K+]>CO.O.C(O)(C)C>[Cl:17][C:2]([Cl:1])=[CH:3][C:4]1[S:5][C:6]([C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH3:16])=[O:19])=[CH:11][CH:10]=2)=[CH:7][CH:8]=1
Reactant: O=S(=O)([O-])O[O-]
Reactant: CSc1ccc(-c2ccc(C=C(Cl)Cl)s2)cc1
Agent: [K+]
Solvent: O
Solvent: CO
Solvent: CC(C)O
Product: CS(=O)c1ccc(-c2ccc(C=C(Cl)Cl)s2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 126.1 %

Procedure:
To a stirred solution of 2-(2,2-dichloroethenyl)-5-(4-methylthiophenyl)thiophene (1.2 g, 0.0040 mole) in methanol (50 mL) was added a solution of potassium peroxymonosulfate (1.2 g, 0.0020 mole) in water (50 mL). After stirring for one hour at room temperature, an additional 0.3 g of potassium peroxymonosulfate was added, and a second addition of 0.3 g was made after an additional hour. After a total of about four hours of stirring at room temperature the mixture was extracted, first with diethyl ether, followed by methylene chloride. The extracts were combined and dried over anhydrous magnesium sulfate. The dried extract was filtered, and the filtrate was evaporated under reduced pressure leaving a solid residue. This residue was dissolved in isopropyl alcohol (15 mL), and a solution of potassium peroxymonosulfate (0.5 g) dissolved in about 5 mL of water was added. The resultant mixture was heated on a steam bath for approximately one hour. The mixture was diluted with 400 mL of water and cooled to 0° C. for one hour. A solid formed and was collected by filtration. The filter cake was dissolved in methylene chloride, and the solution was dried over anhydrous magnesium sulfate. The dried solution was filtered, and the filtrate was evaporated under reduced pressure, leaving a solid residue. This residue was purified by column chromatography on silica gel, eluting first with petroleum ether, followed by ethyl acetate, to yield 0.8 g of 2-(2,2-dichloroethenyl)-5-(4-methylsulfinylphenyl)thiophene as a solid (mp 124°-126° C.) .
Reaction SMILES: C([O:3][C:4]([C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:16])[NH:8][CH:7]=1)=[O:5])C.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:24][CH2:25][CH2:26][OH:27]>CN(C)C=O>[C:4]([C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:16])[N:8]([CH2:24][CH2:25][CH2:26][OH:27])[CH:7]=1)([OH:3])=[O:5]
Reactant: CCOC(=O)c1c[nH]c(=O)c2ccccc12
Reactant: OCCCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C(O)c1cn(CCCO)c(=O)c2ccccc12
Temperature: 100 °C

Procedure:
A mixture of 21.6 g of 4-ethoxycarbonyl-1(2H)-isoquinolone, 25 g of anhydrous potassium carbonate and 100 ml of dimethylformamide was heated at 100° C. for 2 hours. Then, 14 ml of 3-chloropropanol was added thereto and the mixture was heated at 110° C. for 4 hours. The solvent was distilled off and the residue was extracted with dichloromethane. The extract was washed with water, dried and the solvent was distilled off. 120 ml of an ethanolic solution of 5.5 g of potassium hydroxide was added to the residue, and the mixture was warmed. After cooling, the reaction mixture was poured into ice-water and then filtered. The filtrate was rendered neutral with dilute acetic acid, and the precipitated crystals were filtered and recrystallized from a mixture of ethanol and petroleum ether to obtain 12.5 g of 4-carboxy-2-(3-hydroxypropyl)-1(2H)-isoquinolone having a melting point of 205° C. as colorless prisms.
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.Cl.[CH3:11][N:12]([CH3:17])[CH2:13][CH2:14][CH2:15]Cl.[OH-].[Na+].O>CO>[CH3:11][N:12]([CH3:17])[CH2:13][CH2:14][CH2:15][C:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]=1
Reactant: C1=Cc2ccccc2C1
Reactant: CN(C)CCCCl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CN(C)CCCC1=CCc2ccccc21
Reaction time: 4 h

Procedure:
A mixture of 232 g. (2.0 moles) of indene and the free base prepared from 264 g. (1.6 moles) of 3-dimethylaminopropylchloride-hydrochloride is added in portions over 1 hour to a rapidly stirred mixture of 300 g. (7.5 moles) of sodium hydroxide, 300 g. of water and 300 ml. of 40% Triton B in methanol. The initial temperature is 50° and the rate of addition controlled to keep the temperature between 55°-60° . The green mixture is stirred at 60° for 4 hours, cooled, diluted with 1500 ml. of water and extracted with ether. The ether extract is in turn extracted with a solution of 180 ml. of conc. hydrochloric acid in 600 ml. of water and the aqueous phase separated, basified with 100 g. of sodium hydroxide and extracted with ether. Solvent removal gives 182 g. of brown oil which is distilled to give 102 g. of oil, b.p. 88°- 93° at 0.05 mm. Redistillation gives 19.6 g.; b.p. 87.5°-89.5° at 0.05 mm. and 71.1 g.; b.p. 89.5°-90° at 0.05 mm.
Reaction SMILES: [C:1]1([B:7]([CH:9]([O:16][CH:17]([B:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[OH:25])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[OH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:32]1([NH:38][CH2:39][CH2:40]O)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(O)C>[C:1]1([B:7]([CH:9]([O:16][CH:17]([B:24]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[O:25][CH2:40][CH2:39][NH:38][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[O:8][CH2:40][CH2:39][NH:38][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: OB(c1ccccc1)C(OC(B(O)c1ccccc1)c1ccccc1)c1ccccc1
Reactant: OCCNc1ccccc1
Solvent: CCO
Product: c1ccc(NCCOB(c2ccccc2)C(OC(B(OCCNc2ccccc2)c2ccccc2)c2ccccc2)c2ccccc2)cc1

Procedure:
The entitled compound (43 mg) was obtained by allowing 40.6 mg of bis(4,4′-(phenylhydroxyboryl)benzyl) ether and 14 mg of phenylglycinol to act in 1 mL of ethanol.
Reaction SMILES: [N:1]1[N:2]([C:10]2[CH:15]=[C:14]([C:16]([CH3:23])([CH3:22])[CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:13]=[C:12]([CH:24]([CH2:27][CH2:28][CH3:29])[CH:25]=[CH2:26])[C:11]=2[OH:30])[N:3]=[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12>[Pd].CC([O-])=O.CC([O-])=O.[Pb+2].CCCCCC>[N:1]1[N:2]([C:10]2[CH:15]=[C:14]([C:16]([CH3:22])([CH3:23])[CH2:17][C:18]([CH3:19])([CH3:21])[CH3:20])[CH:13]=[C:12]([CH:24]([CH2:27][CH2:28][CH3:29])[CH2:25][CH3:26])[C:11]=2[OH:30])[N:3]=[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12
Reactant: C=CC(CCC)c1cc(C(C)(C)CC(C)(C)C)cc(-n2nc3ccccc3n2)c1O
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: [Pb+2]
Solvent: CCCCCC
Product: CCCC(CC)c1cc(C(C)(C)CC(C)(C)C)cc(-n2nc3ccccc3n2)c1O
Yield: 99.5 %

Procedure:
2 g of 2-(benzotriazole-2-yl)-4-(1,1,3,3-tetramethylbutyl)-6-(1-hexen-3-yl)-phenol and a trace of “Lindlar catalyst” (Fluka) in 25 ml of hexane was hydrogenated for 5 hours under normal hydrogen pressure. Then the reaction mixture was filtered and concentrated to yield 2 g of 2-(benzotriazole-2-yl)-4-(1,1,3,3-tetramethylbutyl)-6-(3-hexyl)-phenol as an orange liquid.