Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[C:9](/[C:14]([C:16]2[S:17][C:18]([C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)=[CH:19][CH:20]=2)=[O:15])\[C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.ClCCCl.[Cl-].[Cl-].[Cl-].[Al+3]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[C:20]3[CH:19]=[C:18]([C:21]4[CH:22]=[CH:23][N:24]=[CH:25][CH:26]=4)[S:17][C:16]=3[C:14](=[O:15])[C@H:9]2[C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1
Reactant: COC(=O)/C(=C\c1ccc(Cl)cc1)C(=O)c1ccc(-c2ccncc2)s1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCCl
Product: COC(=O)[C@@H]1C(=O)c2sc(-c3ccncc3)cc2[C@H]1c1ccc(Cl)cc1
Temperature: 80 °C
Reaction time: 48 h
Yield: 44.8 %

Procedure:
To a 20 mL vial was added a solution of methyl (2Z)-3-(4-chlorophenyl)-2-[(5-pyridin-4-yl-2-thienyl)carbonyl]acrylate (0.049 g, 0.128 mmol), in 1,2-dichloroethane (4.000 mL, 50.77 mmol). Aluminum trichloride (0.0340 g, 0.255 mmol) was added and the reaction mixture was heated to 80° C. and allowed to stir for 2 days. The reaction was cooled to ambient temperature and quenched by the addition of a saturated aqueous solution of sodium bicarbonate (5.00 mL) and extracted with EtOAc (10.00 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was dry loaded onto silica gel and then purified using ISCO (12 g cartridge, gradient hexanes to 100% EtOAc over 30 min) to afford the title compound (0.022 g, 43%) as a yellow oil. LC/MS (AA) ES+ 384, 386. 1H NMR (dmso-d6, 400 MHz): δ 8.66-8.65 (m, 2H), 7.81-7.78 (m, 3H), 7.45-7.34 (m, 4H), 4.96 (d, 1H), 4.13 (d, 1H), 3.72 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[Cl:14])[C:5]([CH2:7][CH2:8][CH:9]=O)=O.C([O-])(=O)C.[NH4+:19]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[NH:19][CH:9]=[CH:8][CH:7]=2)[CH:11]=[CH:12][C:13]=1[Cl:14]
Reactant: [NH4+]
Reactant: O=CCCC(=O)c1ccc(Cl)c(Cl)c1
Agent: CC(=O)[O-]
Solvent: CCO
Product: Clc1ccc(-c2ccc[nH]2)cc1Cl
Yield: 83.4 %

Procedure:
To a suspension of 3-(3,4-dichlorobenzoyl) propionaldehyde (6 g, 26 mmol) in 60 mL of absolute ethanol is added ammonium acetate (4 g, 52 mmol). The reaction is refluxed for 20 minutes and allowed to cool. Most of the ethanol is rotary evaporated and 200 mL of 1:1 dichloromethane-diethyl ether along with 50 mL of water is added. The layers are separated and the organic phase is dried over sodium sulfate. Rotary evaporation yields a dark brown oil which is chromatographed over silica gel using 3:1 hexane-ethyl acetate as eluent to give the pyrrole (4.6 g, 83%) as a light brown solid, m.p. 49°-51° C.
Reaction SMILES: [C:1]1([OH:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[CH3:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([Br:22])=[C:18]([CH:21]=1)[CH2:19]O>>[Br:22][C:17]1[CH:16]=[CH:15][C:14]([O:13][CH3:12])=[CH:21][C:18]=1[CH2:19][O:11][C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: Oc1cccc2ccccc12
Reactant: COc1ccc(Br)c(CO)c1
Product: COc1ccc(Br)c(COc2cccc3ccccc23)c1

Procedure:
The title compound was prepared by reacting 1-naphthol (5.7 g, 39.6 mmol) with 5-methoxy-2-bromobenzyl alcohol as described for intermediate 5 to yield 5.94 g (44%) of a white solid: mp 74-75° C.; 1H NMR (CDCl3): δ 3.78 (3H, s), 5.28 (2H, s), 6.77 (1H, dd, J=2.93 Hz, J=8.79 Hz), 6.88 (1H, d, J=7.69 Hz), 7.27 (1H, d, J=3.30 Hz), 7.36-7.39 (1H, m), 7.47-7.53 (4H, m), 7.81-7.83 (1H, m), 8.37-8.39 (1H, m); MS (ESI) m/z 343/345 ([M+H]+);
Reaction SMILES: N1C=CC=C1[C:6]1[CH:7]=[C:8]([NH:12][C:13]2[C:14]3[CH:21]=[C:20]([C:22]4[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:26][CH:27]=4)[NH:19][C:15]=3[N:16]=[CH:17][N:18]=2)[CH:9]=[CH:10][CH:11]=1.[S:35]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36]1>>[S:35]1[CH:39]=[CH:38][C:37]([C:6]2[CH:7]=[C:8]([NH:12][C:13]3[C:14]4[CH:21]=[C:20]([C:22]5[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[CH2:26][CH:27]=5)[NH:19][C:15]=4[N:16]=[CH:17][N:18]=3)[CH:9]=[CH:10][CH:11]=2)=[CH:36]1
Reactant: CC(C)(C)OC(=O)N1CC=C(c2cc3c(Nc4cccc(-c5ccc[nH]5)c4)ncnc3[nH]2)CC1
Reactant: OB(O)c1ccsc1
Product: CC(C)(C)OC(=O)N1CC=C(c2cc3c(Nc4cccc(-c5ccsc5)c4)ncnc3[nH]2)CC1

Procedure:
The title compound was prepared following the procedure for tert-butyl 4-{4-[3-(1H-pyrrol-2-yl)phenylamino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl}-3,6-dihydro-2H-pyridine-1-carboxylate, but using 3-thienylboronic acid. 1H-NMR (CD3OD, 400 MHz): δ=1.50 (s, 9H), 2.56 (m, 2H), 3.67 (m, 2H), 4.13 (m, 2H), 6.30 (s, br, 1H), 6.66 (s, 1H), 7.37-7.42 (m, 2H), 7.47-7.50 (m, 2H), 7.63-7.66 (m, 2H), 8.01-8.02 (m, 1H), 8.23 (s, 1H). MS (ES+): m/z 474.04 [MH+]. HPLC: tR=3.58 min (ZQ2000, polar—5 min).
Reaction SMILES: [Se](=O)=[O:2].[CH:4]1([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[CH3:16])[CH2:6][CH2:5]1>O1CCOCC1>[CH:4]1([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[CH:16]=[O:2])[CH2:6][CH2:5]1
Reactant: O=[Se]=O
Reactant: Cc1nc2ccccc2n1C1CC1
Solvent: C1COCCO1
Product: O=Cc1nc2ccccc2n1C1CC1
Yield: 57.6 %

Procedure:
Selenium dioxide (1.2 g, 0.011 mole) was added to 60 ml of dioxane containing 1.87 g .(0.011 mole) of 1-cyclopropyl-2-methylbenzimidazole and the reaction heated to reflux for 2.5 hours. The reaction was filtered and the filtrate concentrated to a dark oil, 3.0 g. Chromatographing of the residue on silica gel gave 1.18 g of the desired compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]2[N:8]=[CH:9][N:10]([CH3:11])[CH:6]2[N:5]=[C:4]2[N:12]([S:24]([CH:27]3[CH2:29][CH2:28]3)(=[O:26])=[O:25])C(=O)[N:14]([C:15]3[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=3[F:22])[C:3]=12.C[Si](C)(C)[O-].[K+]>C1COCC1>[Cl:1][C:2]1[CH:7]2[N:8]=[CH:9][N:10]([CH3:11])[CH:6]2[N:5]=[C:4]([NH:12][S:24]([CH:27]2[CH2:29][CH2:28]2)(=[O:26])=[O:25])[C:3]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=1[F:22]
Reactant: CN1C=NC2C(Cl)=c3c(n(S(=O)(=O)C4CC4)c(=O)n3-c3ccc(I)cc3F)=NC21
Agent: C[Si](C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CN1C=NC2C(Cl)=C(Nc3ccc(I)cc3F)C(NS(=O)(=O)C3CC3)=NC21
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 8-chloro-3-(cyclopropylsulfonyl)-1-(2-fluoro-4-iodophenyl)-5-methyl-3,4a,5,7a-tetrahydrodiimidazo[4,5-b:4′,5′-e]pyridin-2(1H)-one (79 mg, 0.144 mmol) in THF (5 ml) is added potassium trimethylsilanolate (55 mg, 0.43 mmol). The reaction is stirred at room temperature for 16 h, quenched with saturated aqueous NH4Cl solution (10 ml) and extracted with EtOAc (2×10 ml). The combined organic solution is washed with brine (10 ml), dried over MgSO4 and concentrated. Silica gel chromatography yields the title compound.
Reaction SMILES: [Cl:1][C:2]1[C:7](=[O:8])[NH:6][C:5]([C:9]([OH:11])=O)=[CH:4][CH:3]=1.[CH3:12][O:13][C:14]1[CH:24]=[CH:23][C:17]([CH2:18][NH:19][CH2:20][CH2:21]O)=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(#N)C.O>[Cl:1][C:2]1[C:7](=[O:8])[N:6]2[CH2:21][CH2:20][N:19]([CH2:18][C:17]3[CH:16]=[CH:15][C:14]([O:13][CH3:12])=[CH:24][CH:23]=3)[C:9](=[O:11])[C:5]2=[CH:4][CH:3]=1
Reactant: COc1ccc(CNCCO)cc1
Reactant: O=C(O)c1ccc(Cl)c(=O)[nH]1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CC#N
Product: COc1ccc(CN2CCn3c(ccc(Cl)c3=O)C2=O)cc1
Temperature: 50 °C
Reaction time: 16 h

Procedure:
To a solution of 5-chloro-6-oxo-1,6-dihydropyridine-2-carboxylic acid (1, 0.25 g, 1.44 mmol) in acetonitrile (10 mL), 2-((4-methoxybenzyl)amino)ethanol (2, 0.31 g, 1.73 mmol) followed by cesium carbonate (1.18 g, 3.61 mmol) and HATU (1.26 g, 3.32 mmol) were added and the reaction mixture was stirred at 50° C. for 16 h. The reaction mixture was diluted with water and the compound was extracted in ethyl acetate. The organic layer was washed with brine, separated, dried over sodium sulphate and concentrated under reduced pressure. The residue obtained was purified via column chromatography (silica, ethyl acetate/hexanes=60%) to afford 7-chloro-2-(4-methoxybenzyl)-3,4-dihydro-1H-pyrido[1,2-a]pyrazine-1,6-(2H)-dione (3). Yield: 0.24 g, 52%; MS (ESI) m/z 319 [M+1]+.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][N:15]2C(=O)C3=CC=CC=C3C2=O)[CH2:8][CH2:7]1)=[O:5])[CH3:2].O.NN>C(O)C>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][NH2:15])[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)N1CCN(CCCN2C(=O)c3ccccc3C2=O)CC1
Agent: NN
Solvent: O
Solvent: CCO
Product: CCOC(=O)N1CCN(CCCN)CC1
Reaction time: 4 h
Yield: 60.5 %

Procedure:
To a solution of N-[3-(4-ethoxycarbonyl-1-piperazinyl)propyl]phthalimide (28.9 g) in ethanol (300 ml) was added 10% hydrazine hydrate (8.4 g). The resulting mixture was refluxed with stirring for 4 hours. The reaction mixture was cooled and then filtered. The filter cake was washed with ethanol. The filtrate and washing were combined and evaporated under reduced pressure. After the addition of an aqueous solution of sodium hydroxide to the residue, the mixture was extracted with chloroform The extract was washed with water, dried over magnesium sulfate and then evaporated under reduced pressure to give an oil of 3-(4-ethoxycarbonyl-1-piperazinyl)propylamine (10.9 g).
Reaction SMILES: C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:9][CH:8]=1.[CH2:19]([Si:22](Cl)([CH3:24])[CH3:23])[CH:20]=[CH2:21].[Cl-].[NH4+]>C1COCC1.CCCCCC>[CH2:19]([Si:22]([CH3:24])([CH3:23])[C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:9][CH:8]=1)[CH:20]=[CH2:21]
Reactant: C[Si](C)(C)C#Cc1ccc(Br)cc1
Reactant: C=CC[Si](C)(C)Cl
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: C=CC[Si](C)(C)c1ccc(C#C[Si](C)(C)C)cc1
Reaction time: 0.17 h
Yield: 93.3 %

Procedure:
6.4 mL (10 mmol) of a 1.6 M hexane solution of butyl lithium was added to 60 mL of THF solution containing 2.54 g (10 mmol) of (4-bromo-phenylethynyl)trimethyl silane under an argon atmosphere at a temperature of −78° C. and the resultant mixture was stirred for 30 minutes. Then, 1.5 mL (10 mmol) of allylchlorodimethyl silane was added to the mixture and stirred for 10 minutes, after which the temperature of the mixture was gradually returned to room temperature and additionally stirred for two hours. After an aqueous solution of ammonium chloride was added to the mixture, the resultant solution was subjected to extraction using ether. The organic layer thus created was then washed with saturated brine and dried using magnesium sulfate as a desiccating agent. After the desiccating agent was removed by filtration, the solvent was removed by a rotary evaporator to obtain a crude product, which was then purified by silica gel column chromatography (developing solvent: hexane) to obtain 2.54 g (9.33 mmol) of 1-(allyldimethylsilanyl)-4-trimethylsilanylethynyl benzene. The yield was 93%.
Reaction SMILES: Br[C:2]1[C:6]([N+:7]([O-])=O)=[C:5]([NH:10][CH2:11][CH2:12][OH:13])[N:4]([CH2:14][CH2:15][OH:16])[N:3]=1.S(=O)(=O)(O)O>>[NH2:7][C:6]1[CH:2]=[N:3][N:4]([CH2:14][CH2:15][OH:16])[C:5]=1[NH:10][CH2:11][CH2:12][OH:13]
Reactant: O=[N+]([O-])c1c(Br)nn(CCO)c1NCCO
Agent: O=S(=O)(O)O
Product: Nc1cnn(CCO)c1NCCO
Temperature: -30 °C
Yield: 125.3 %

Procedure:
0.8 g (2.7 mmoles) of 3-bromo-1-(2'-hydroxyethyl)-5-(2'-hydroxyethyl)amino-4-nitropyrazole are hydrogenated over a period of 4 hours according to method (1). After filtering the catalyst, 0.27 g (2.7 mmoles) sulfuric acid (97-percent) is added. After cooling to -30° C., 630 mg (82 percent of theory) of 4-amino-1-(2'-hydroxyethyl)-5-(2'-hydroxyethyl)aminopyrazole hydrosulfate are obtained in the form of colorless crystals with a melting point of 140° to 142° C.
Reaction SMILES: [CH2:1]1[CH2:6][C@H:5]([C:7]([OH:9])=[O:8])[CH2:4][CH2:3][C@H:2]1[CH2:10][NH2:11].[CH3:12][CH:13]([CH3:32])[C:14]([O:16][CH:17]([O:21][C:22](ON1C(=O)CCC1=O)=[O:23])[CH2:18][CH2:19][CH3:20])=[O:15]>CC(OC)(C)C.CC(C)=O.O>[CH3:32][CH:13]([CH3:12])[C:14]([O:16][CH:17]([O:21][C:22]([NH:11][CH2:10][C@H:2]1[CH2:3][CH2:4][C@H:5]([C:7]([OH:9])=[O:8])[CH2:6][CH2:1]1)=[O:23])[CH2:18][CH2:19][CH3:20])=[O:15]
Reactant: CCCC(OC(=O)ON1C(=O)CCC1=O)OC(=O)C(C)C
Reactant: NC[C@H]1CC[C@H](C(=O)O)CC1
Solvent: CC(C)=O
Solvent: O
Solvent: COC(C)(C)C
Product: CCCC(OC(=O)NC[C@H]1CC[C@H](C(=O)O)CC1)OC(=O)C(C)C

Procedure:
Following the general nucleophilic carbamoylation procedure, tranexamic acid (800 mg, 5 mmol) and 1-[(2,5-dioxopyrrolidinyl)oxycarbonyloxy]butyl 2-methylpropanoate (700 mg, 2.3 mmol) were reacted in the MTBE/acetone/water mixture (16 mL) to yield the title compound 36 (100 mg, 13% yield) as a white powder after work-up and mass-guided preparative HPLC purification. 1H NMR (400 MHz, DMSO-d6): δ=0.87-0.95 (m, 8H), 1.08 (d, J=4.0 Hz, 3H), 1.10 (d, J=4.0 Hz, 3H), 1.21-1.41 (br. m, 5H), 1.68-1.73 (m, 4H), 1.89-1.91 (m, 2H), 2.13 (tt, J=12, 3.2 Hz, 1H), 2.79-2.88 (m, 3H), 6.65 (t, J=5.6 Hz, 1H), 7.45 (t, J=(t, J=6.0 Hz, 1H), 12.04 (s, 1H). MS (ESI) m/z 366.21 (M+Na)+; 342.16 (M−H)−.
Reaction SMILES: [OH:1][CH:2]([CH3:10])[CH:3](C)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[C-:11]#[N:12].[Na+]>>[C:11]([CH2:10][CH:2]([OH:1])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:12]
Reactant: CCOC(=O)C(C)C(C)O
Reactant: [C-]#N
Agent: [Na+]
Product: CCOC(=O)CC(O)CC#N

Procedure:
The recombinant E. coli HB101 (pNTS1G) obtained in Example 10 was inoculated in 100 ml of a 2×YT medium sterilized in a 500 ml Sakaguchi flask, and cultured with agitation at 37° C. for 13 hours. Glucose, 7.5 g, 3.2 mg of NADP, and then 4 g of ethyl 2-methyl-3-oxoacetate were added to 50 ml of the resultant culture. The culture was stirred at 30° C. while being adjusted at pH 6.5 with a 5 M sodium hydroxide solution to allow for reaction for 18 hours. After the reaction, the reaction solution was subjected to extraction using ethyl acetate, the solvent was removed under decompression, and the concentrate was purified by silica gel column chromatography, to obtain 3.5 g of ethyl 3-hydroxy-2-methylbutyrate. The optical purity of the ethyl 3-hydroxy-2-methylbutyrate was analyzed as follows and found to be 91.6% e.e. The analysis was performed in the following manner. The sample was reacted with sodium cyanide in demethyl sulfoxide at room temperature to obtain ethyl 4-cyano-3-hydroxybutyrate, which was then changed to a benzoic ester using benzoyl chloride under the presence of pyridine. The optical purity of the benzoic ester was measured by the HPLC method. 1H-NMR(CDCl3) δ (ppm): 1.17(3H,t), 1.22(2H,t), 1.28(3H,t), 2.46(1H,m), 2.82(1H,br), 3.90(1H,m), 4.18(2H,q).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1)[CH3:2].[CH:12]([C:14](=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH3:15])=[O:13].C(OCC)C>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[C:14]([CH3:15])[CH:12]=[O:13])=[CH:6][CH:5]=1)[CH3:2]
Reactant: CC(C=O)=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CCOc1ccc(C=O)cc1
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: CCOc1ccc(C=C(C)C=O)cc1

Procedure:
A suspension of 4-ethoxybenzaldehyde (20 g, 0.133 mol) and α-formylethylidenetriphenylphosphorane (46.6 g, 0.146 mol) in dried toluene (400 ml) was heated with stirring at reflux under an atmosphere of nitrogen for 40 h. The mixture was cooled, diethyl ether added and filtered through a pad of celite. The filtrate was evaporated and the residue taken up in diethyl e;her and the resulting suspension purified on flash silica eluting with hexane-diethyl ether (4:1). The resulting oil was crystallised from hexane-diethyl ether to give 3-(4-ethoxyphenyl)-2-methylpropenaldehyde as yellow crystals.
Reaction SMILES: [CH2:1]([C:17]1([CH3:34])[CH2:26][CH2:25][C:24]2[C:19](=[C:20]([CH3:33])[C:21]([CH3:32])=[C:22]([O:28][CH2:29][CH2:30][OH:31])[C:23]=2[CH3:27])[O:18]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[C:35](=O)([O:44]N1C(=O)CCC1=O)[O:36][N:37]1[C:41](=[O:42])[CH2:40][CH2:39][C:38]1=[O:43].C(N(CC)CC)C.C(#N)C>ClCCl>[CH2:1]([C:17]1([CH3:34])[CH2:26][CH2:25][C:24]2[C:19](=[C:20]([CH3:33])[C:21]([CH3:32])=[C:22]([O:28][CH2:29][CH2:30][O:31][C:35](=[O:44])[O:36][N:37]3[C:41](=[O:42])[CH2:40][CH2:39][C:38]3=[O:43])[C:23]=2[CH3:27])[O:18]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCCC1(C)CCc2c(C)c(OCCO)c(C)c(C)c2O1
Reactant: O=C(ON1C(=O)CCC1=O)ON1C(=O)CCC1=O
Solvent: CC#N
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCCCCCC1(C)CCc2c(C)c(OCCOC(=O)ON3C(=O)CCC3=O)c(C)c(C)c2O1
Temperature: 25 °C
Yield: 76.8 %

Procedure:
Compound 17 (10.5 g, 22 mmol) was dissolved in anhydrous dichloromethane (150 mL) To the solution were added disuccinimidyl carbonate (8.45 g, 33 mmol), triethylamine (20 mL) and acetonitrile (50 mL). The reaction mixture was stirred at room temperature under argon for over night and then evaporated dryness. The residue was dissolved in dichloromethane (300 mL). It was washed with saturated NaHCO3 aqueous solution (3×100 mL). The organic layer was dried over Na2SO4, filtered and evaporated to dryness. Compound 18 (10.4 g, 77%) was obtained as colorless powder after drying in high vacuum, which was directly used for the next step without further purification.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:11].[C:12](OC(=O)C)(=[O:14])[CH3:13]>N1C=CC=CC=1>[C:12]([O:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:11])(=[O:14])[CH3:13]
Reactant: Cc1cc(C(=O)O)ccc1O
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)Oc1ccc(C(=O)O)cc1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 52.7 %

Procedure:
A solution of 5.42 g (35.6 mmol) of the 4-hydroxy-3-methylbenzoic acid in 50 ml of pyridine was added to 16.8 ml (178 mmol) of acetic anhydride. The resulting mixture was stirred overnight at room temperature, and the reaction mixture was distilled off under reduced pressure. The residue was dissolved in ethyl acetate. The resulting solution was washed with 2N hydrochloric acid and a saturated aqueous solution of sodium chloride and was then dried over Na2SO4. The solvent was distilled off under reduced pressure. The residue was recrystallized from ethyl acetate-hexane, whereby 3.64 g of 4-acetoxy-3-methylbenzoic acid were obtained as white powder (yield: 52.6%).
Reaction SMILES: [NH2:1][C:2]1[S:10][C:5]2[CH2:6][NH:7][CH2:8][CH2:9][C:4]=2[C:3]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12].[C:16]1([CH2:22][CH2:23][CH2:24]Br)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[NH2:1][C:2]1[S:10][C:5]2[CH2:6][N:7]([CH2:24][CH2:23][CH2:22][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:8][CH2:9][C:4]=2[C:3]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12]
Reactant: BrCCCc1ccccc1
Reactant: CCOC(=O)c1c(N)sc2c1CCNC2
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: CCOC(=O)c1c(N)sc2c1CCN(CCCc1ccccc1)C2
Yield: 51.2 %

Procedure:
10.0 g (44.2 mmol) of 2-amino-3-carboethoxy-4,5,6,7-tetra-hydrothieno[2,3-c)pyridine [sic] in 100 ml of toluene were mixed with 9.0 g (45 mM) of 1-phenyl-3-bromopropane, 400 mg of potassium iodide and 6.1 g (44.2 mmol) of finely powdered potassium carbonate and refluxed for 6 h. The residue after concentration in a rotary evaporator was taken up in water, adjusted to pH=10 and extracted twice with methylene chloride. The crude product after drying and concentration of the organic phase was extracted by stirring in 50 ml of isopropanol. The pale solid was filtered off with suction and washed with isopropanol. 7.8 g (51%) of product with melting point 108-110° C. were isolated.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[C:11](=[O:25])[CH2:12][C:13]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=1[O:23][CH3:24])=[O:14].[BH4-].[Na+].C(O)(=O)C>C(O)CC>[CH3:24][O:23][C:16]1[CH:17]=[C:18]([O:21][CH3:22])[CH:19]=[CH:20][C:15]=1[CH:13]([OH:14])[CH2:12][CH:11]([C:4]1[CH:5]=[CH:6][C:7]([O:9][CH3:10])=[CH:8][C:3]=1[O:2][CH3:1])[OH:25]
Reactant: COc1ccc(C(=O)CC(=O)c2ccc(OC)cc2OC)c(OC)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCCO
Solvent: CC(=O)O
Product: COc1ccc(C(O)CC(O)c2ccc(OC)cc2OC)c(OC)c1

Procedure:
1,3-Bis(2,4-dimethoxyphenyl)-propan-1,3-dione (8) (5 mg) was dissolved in 1-propanol (1 ml), followed by the addition of sodium borohydride (3 mg) and the mixture was allowed to react at room temperature for 3 hours. Upon completion of the reaction, 20% acetic acid (0.2 ml) was added to neutralize the excess sodium borohydride. The mixture was then separated on a pre-packed C18 column eluting with a MeOH/H2O gradient to provide 1,3-bis(2,4-dimethoxyphenyl)-propan-1,3-diol (9).
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:9])[C@H:5]([CH2:7][OH:8])[NH2:6].Cl[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12].[OH-].[Na+]>O>[OH:8][CH2:7][C@H:5]([NH:6][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[C:4]([O:3][CH3:2])=[O:9]
Reactant: COC(=O)[C@@H](N)CO
Reactant: O=C(Cl)OCc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: COC(=O)[C@H](CO)NC(=O)OCc1ccccc1
Yield: 95 %

Procedure:
To a solution of 24.01 g L-serine-methylester hydrochloride in 130 ml of water were added at 0° C. 29.8 g of benzyl chloroformate. The pH was kept at 6-7 by adding a 40% aqueous solution of sodium hydroxide. After 3 h at 0° C. the mixture was extracted with 5 portions of ethyl acetate, the combined extracts were dried and evaporated to give 37.12 g (95%) of pure methyl 3-hydroxy-(S)-2-benzyloxycarbonylamino-propionate. IR (neat): 3380 m (NH, OH), 1720 s, br. (C=O), 1540 s (amide II).
Reaction SMILES: OC1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)([CH3:10])[CH3:9])=CC=1.S(=O)(=O)(O)O.[CH3:23]C(=C)C>C1(C)C=CC=CC=1>[OH:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[C:8]([CH3:9])([CH3:10])[CH2:5][C:6]2([CH3:7])[CH3:23]
Reactant: C=C(C)C
Reactant: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Agent: O=S(=O)(O)O
Solvent: Cc1ccccc1
Product: CC1(C)CC(C)(C)c2cc(O)ccc21

Procedure:
114 g (0.5 mol) of 2,2-bis-(4-hydroxyphenyl)-propane, 6 ml of concentrated sulphuric acid and 90 g (1.6 mol) of isobutylene are stirred in an autoclave for 6 hours at 180° C. After cooling, the reaction product is taken up in 150 ml of toluene and washed with 10 % by weight aqueous sodium hydrogen carbonate solution to remove the catalyst. The toluene solution is then distilled to remove the solvent and the residue of 176.9 g is subsequently subjected to fractional distillation, giving 20.6 g (22 % of the theoretical) of 5-hydroxy-1,1,3,3-tetramethyl indane.