Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[C:2]([S:21][CH2:22][CH2:23][NH2:24])([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:25][C:26]1[CH:27]=[C:28]2[C:32](=[C:33]([NH:35][S:36]([C:39]3[S:40][CH:41]=[CH:42][CH:43]=3)(=[O:38])=[O:37])[CH:34]=1)[NH:31][C:30]([C:44](O)=[O:45])=[CH:29]2.N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>C(OCC)(=O)C.CN(C)C=O.C(N(CC)CC)C>[CH3:25][C:26]1[CH:27]=[C:28]2[C:32](=[C:33]([NH:35][S:36]([C:39]3[S:40][CH:41]=[CH:42][CH:43]=3)(=[O:38])=[O:37])[CH:34]=1)[NH:31][C:30]([C:44]([NH:24][CH2:23][CH2:22][S:21][C:2]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)=[O:45])=[CH:29]2
Reactant: NCCSC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cc1cc(NS(=O)(=O)c2cccs2)c2[nH]c(C(=O)O)cc2c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1cc(NS(=O)(=O)c2cccs2)c2[nH]c(C(=O)NCCSC(c3ccccc3)(c3ccccc3)c3ccccc3)cc2c1
Temperature: 25 °C
Reaction time: 15 h
Yield: 94.1 %

Procedure:
To a mixture of 2-(tritylthio)ethylamine hydrochloride (0.77 g), triethylamine (0.31 mL) and N,N-dimethylformamide (20 mL) were added 5-methyl-7-[(2-thienylsulfonyl)amino]-1H-indole-2-carboxylic acid (0.60 g), 1H-1,2,3-benzotriazol-1-ol (0.36 g) and N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (0.45 g) under ice-cooling, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with ethyl acetate, washed with aqueous citric acid solution, aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained oil was crystallized from ethyl acetate-hexane to give the title compound (1.07 g, yield 95%) as pale-yellow crystals. melting point 214-215° C.
Reaction SMILES: [CH2:1]([N:6]1[C:15]2[C:10](=[N:11][C:12]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:14]=2)[CH2:9][CH2:8][CH2:7]1)[CH2:2][CH2:3][CH:4]=[CH2:5].[C:28]([O:33][CH3:34])(=[O:32])[CH2:29]C=C>C(Cl)Cl.Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1>[C:22]1([C:12]2[N:11]=[C:10]3[CH2:9][CH2:8][CH2:7][N:6]([CH2:1][CH2:2][CH2:3]/[CH:4]=[CH:5]/[CH2:29][C:28]([O:33][CH3:34])=[O:32])[C:15]3=[N:14][C:13]=2[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: C=CCCCN1CCCc2nc(-c3ccccc3)c(-c3ccccc3)nc21
Reactant: C=CCC(=O)OC
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)(=Cc2ccccc2)[P](C2CCCCC2)(C2CCCCC2)C2CCCCC2)c(C)c1
Solvent: ClCCl
Product: COC(=O)C/C=C/CCCN1CCCc2nc(-c3ccccc3)c(-c3ccccc3)nc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 5-(pent-4-enyl)-2,3-diphenyl-5,6,7,8-tetrahydropyrido[3,2-b]pyrazine (step 1) (200 mg, 0.563 mmol) and methyl but-3-enoate (225 mg, 2.251 mmol) in DCM (300 ml) was added Grubbs Catalyst second generation (5 mol %, 23.88 mg, 0.028 mmol). The reaction was stirred at RT under an atmosphere of nitrogen overnight. An additional portion of Grubbs Catalyst second generation (5 mol %, 23.88 mg, 0.028 mmol) was added and stirring continued for 2.5 h. The solvent was removed in vacuo and the resulting crude was purified by chromatography on silica eluting with EtOAc/iso-hexane to afford the title compound;
Reaction SMILES: [CH:1]([CH2:3][C:4]([CH3:12])([CH3:11])[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])=[O:2].[CH2:13](O)[CH2:14][OH:15].O>C1(C)C=CC=CC=1>[O:8]1[CH2:9][CH2:10][O:7][CH:6]1[CH2:5][C:4]([CH3:11])([CH3:12])[CH2:3][C:1]([O:15][CH2:14][CH3:13])=[O:2]
Reactant: OCCO
Reactant: CCOC(=O)CC(C)(C)CC=O
Solvent: Cc1ccccc1
Solvent: O
Product: CCOC(=O)CC(C)(C)CC1OCCO1
Yield: 93.3 %

Procedure:
74 g of ethyl 4-formyl-3,3-dimethylbutanoate, prepared in Example 91, are dissolved in 450 ml of anhydrous toluene in the presence of 0.5 g of paratoluenesulfonic acid and 26.7 g of ethylene glycol. The mixture is heated to the reflux temperature and the water formed during the reaction is removed by means of a Dean-Stark apparatus. After refluxing for two hours, the solvent is evaporated off under vacuum and the residue is distilled to give 86.7 g of ethyl 4-(dioxolan-2-yl)-3,3-dimethylbutanoate in the form of a liquid with a boiling point b.p. of 138°-140° C.
Reaction SMILES: Br[C:2]1[C:3](=[O:19])[CH2:4][C:5]2([CH2:17][CH3:18])[CH2:14][CH2:13][C:12]3[C:7](=[CH:8][CH:9]=[C:10]([O:15][CH3:16])[CH:11]=3)[C:6]=12.[C:20]1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:21]=1.O.C([O-])([O-])=O.[Cs+].[Cs+].C(B(CC)CC)C>CN(C=O)C.O1CCCC1>[CH2:20]([C:2]1[C:3](=[O:19])[CH2:4][C:5]2([CH2:17][CH3:18])[CH2:14][CH2:13][C:12]3[C:7](=[CH:8][CH:9]=[C:10]([O:15][CH3:16])[CH:11]=3)[C:6]=12)[CH3:21]
Reactant: CCC12CCc3cc(OC)ccc3C1=C(Br)C(=O)C2
Reactant: c1ccc([As](c2ccccc2)c2ccccc2)cc1
Agent: CCB(CC)CC
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CCC1=C2c3ccc(OC)cc3CCC2(CC)CC1=O
Temperature: 60 °C

Procedure:
A solution of 1-bromo-3a-ethyl-7-methoxy-3,3a,4,5-tetrahydro-2H-cyclopenta[a]naphthalen-2-one (120 mg, 0.37 mmol) in DMF (3 mL) was treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (61 mg, 0.075 mmol), triphenylarsine (23 mg, 0.075 mmol), water (0.22 mL, 12.2 mmol), Cs2CO3 (244 mg, 0.75 mmol), and triethylborane (0.75 mL of a 1.0M solution in tetrahydrofuran, 0.75 mmol). The resulting mixture was placed under a N2 atmosphere, stirred, and heated in an oil bath at 55-65° C. for 100 minutes. After cooling, the mixture was quenched with saturated aqueous NH4Cl and diluted with CH2Cl2. The organic phase was dried over MgSO4 and filtered through a pad of silica gel, washing through with EtOAc. The filtrate was evaporated under vacuum to remove the solvents. The residue was purified by preparative layer chromatography on two 0.1×20×20 cm silica gel GF plates (Analtech, Newark, Del.), developing with 4:1 hexane-EtOAc. The UV visible product band was extracted with 5% MeOH in CH2Cl2 and the extracts evaporated under vacuum to provide 1,3a-diethyl-7-methoxy-3,3a,4,5-tetrahydro-2H-cyclopenta[a]naphthalen-2-one as a crystalline solid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH3:16])[CH3:15])[C:11]([Cl:17])=[CH:10][C:9]=1[NH2:18])([CH3:4])([CH3:3])[CH3:2].C([O:24][C:25](=O)[CH2:26][C:27]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]2[O:39][N:38]=[C:37]([CH3:40])[CH:36]=2)[CH:30]=1)=[O:28])(C)(C)C>>[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH3:16])[CH3:15])[C:11]([Cl:17])=[CH:10][C:9]=1[NH:18][C:25](=[O:24])[CH2:26][C:27]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]2[O:39][N:38]=[C:37]([CH3:40])[CH:36]=2)[CH:30]=1)=[O:28])([CH3:4])([CH3:2])[CH3:3]
Reactant: CN(C)c1cc(NC(=O)OC(C)(C)C)c(N)cc1Cl
Reactant: Cc1cc(-c2cccc(C(=O)CC(=O)OC(C)(C)C)c2)on1
Product: Cc1cc(-c2cccc(C(=O)CC(=O)Nc3cc(Cl)c(N(C)C)cc3NC(=O)OC(C)(C)C)c2)on1

Procedure:
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example J1) (143 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (450 mg, 0.75 mmol) according to the general procedure M. Obtained as a white solid (136 mg).
Reaction SMILES: [CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C:3]1=O.[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]=[N:17][C:18](=[O:21])[S:19][CH:20]=2)=[CH:11][CH:10]=1.C(N(CC)CC)C.Cl.ClC1C=CN=CC=1>CC(C)=O.CCOCC>[N:2]1[CH:1]=[CH:6][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH2:20][S:19][C:18](=[O:21])[NH:17][N:16]=3)=[CH:13][CH:14]=2)=[CH:4][CH:3]=1
Reactant: Nc1ccc(-c2csc(=O)nn2)cc1
Reactant: CN1CCCC1=O
Agent: Cl
Agent: Clc1ccncc1
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: O=C1NN=C(c2ccc(Nc3ccncc3)cc2)CS1
Temperature: 100 °C
Yield: 70.3 %

Procedure:
To a N-methyl-2-pyrrolidone solution (3 mL) containing 5-(4-aminophenyl)-2H-1,3,4-thiadiazine-2-one (0.27 g), triethylamine (90 μL) and 4-chloropyridine hydrochloride (0.20 g) were added in this order by heating at 100° C. with stirring, followed by further stirring with the temperature maintained for four hours. The reacted mixture was cooled and diluted with acetone (10 mL) and ether (15 mL). The precipitated crystal was separated by filtration, air-dried, dissolved in warm water (50 mL), and adjusted to pH8 with saturated potassium carbonate. The precipitated solid was separated by filtration, and purified by a silica gel column chromatography to obtain the captioned compound (0.26 g). Yield was 70.3%. melting point: 222° to 225° C. (decomposition)
Reaction SMILES: Br[C:2]1[CH:7]=[N:6][C:5]([O:8][CH3:9])=[C:4]2[O:10][C:11]([C:13]([O:17][CH3:18])([O:15][CH3:16])[CH3:14])=[CH:12][C:3]=12.C1(P(C(P(C2C=CC=CC=2)C2C=CC=CC=2)(C)C)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[O:55]1[CH2:59]CCC1.[OH2:60]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:16][O:15][C:13]([C:11]1[O:10][C:4]2[C:5]([O:8][CH3:9])=[N:6][CH:7]=[C:2]([C:59]([OH:55])=[O:60])[C:3]=2[CH:12]=1)([O:17][CH3:18])[CH3:14]
Reactant: O
Reactant: COc1ncc(Br)c2cc(C(C)(OC)OC)oc12
Reactant: C1CCOC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(P(c1ccccc1)c1ccccc1)P(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Product: COc1ncc(C(=O)O)c2cc(C(C)(OC)OC)oc12
Temperature: 90 °C
Yield: 30 %

Procedure:
4-Bromo-2-(1,1-dimethoxyethyl)-7-methoxyfuro[2,3-c]pyridine (1.0 g), palladium acetate (71 mg), bis-diphenylphosphinopropane (0.26 g), triethylamine (4.4 ml), tetrahydrofuran (60 ml) and water (30 ml) were combined in a Parr pressure reactor. The vessel was purged with carbon monoxide 3 times before being charged with carbon monoxide at 965 kPa (140 psi). The vessel was then heated at 90° C. for 3 days before cooling and release of the pressure. The reaction mixture was concentrated in vacuo and the residue taken up in 1N sodium hydroxide solution (100 ml). The mixture was washed with ethyl acetate (2×100 ml) then acidified to pH4 with glacial acetic acid. The resulting mixture was extracted with dichloromethane (2×100 ml), the combined organic extracts dried over magnesium sulfate, filtered and the solvent removed in vacuo. Co-evaporation from toluene to remove excess acetic acid gave the title compound (contaminated with 30% 2-acetyl-7-methoxyfuro[2,3-c]pyridine-4-carboxylic acid) as a white solid (0.66 g).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][CH:3]=1.C([Li])CCC.[C:14]1([CH:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:22](=O)[O:21]2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl>C1COCC1.CCCCCC>[Br:8][C:5]1([C:22]2[O:21][C:20]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[C:29]3[C:24]=2[CH:25]=[CH:26][CH:27]=[CH:28]3)[CH:6]=[CH:7][CH:2]=[CH:3][CH2:4]1
Reactant: O=C1OC(c2ccccc2)c2ccccc21
Reactant: Brc1ccc(Br)cc1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: BrC1(c2oc(-c3ccccc3)c3ccccc23)C=CC=CC1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 69.7 %

Procedure:
Into a 200-cm3 Schlenk tube filled with argon, 5.0 g (2.12×10−2 mol) of 1,4-dibromobenzene was weighed. Into the Schlenk tube, 100 cm3 of dehydrated THF was poured, whereby a THF solution was prepared. After the THF solution was cooled to −50° C., 12.7 cm3 (1.9×10−2 mol) of a 1.5 mol/L hexane solution of n-butyllithium was added to the THF solution. The solution mixture was agitated for 1.5 hours while being cooled. To the resulting solution mixture, 4 g (1.9×10−2 mol) of 3-phenylphthalide was added. This mixture was cooled for two hours and then warmed to room temperature. To this mixture, 30 cm3 of a 35% aqueous solution of hydrochloric acid was added. This mixture was allowed to stand for one hour, transferred to a separatory funnel, and then subjected to extraction using toluene. The toluene layer in the separatory funnel was sufficiently washed with distilled water and then concentrated. The resulting toluene layer was fractionated by silica gel chromatography using a mixture containing toluene and hexane at a ratio of 1:4, whereby 4.65 g of 1-bromophenyl-3-phenylisobenzofuran was obtained as shown in FIG. 10. The yield of 1-bromophenyl-3-phenylisobenzofuran was 70%.
Reaction SMILES: [ClH:1].C([O:4][CH:5](OCC)[CH2:6][N:7]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=2)[CH:10]=[CH:9][C:8]1=[O:18])C>CC(=O)CC>[OH2:4].[ClH:1].[F:17][C:14]1[CH:15]=[C:16]2[C:11]([CH:10]=[CH:9][C:8](=[O:18])[N:7]2[CH2:6][CH:5]=[O:4])=[N:12][CH:13]=1
Reactant: CCOC(Cn1c(=O)ccc2ncc(F)cc21)OCC
Agent: Cl
Solvent: CCC(C)=O
Product: O
Product: O=CCn1c(=O)ccc2ncc(F)cc21
Temperature: 70 °C

Procedure:
To 480 mL of 2-butanone, 30 mL of 12 mol/L hydrochloric acid was added, the mixture was heated to 70° C. and a solution of 60 g of 1-(2,2-diethoxyethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one in 60 mL of 2-butanone was added dropwise, followed by reflux for 2 hours. After cooling the reaction mixture to 25° C., the solid product was obtained by filtration and washed with 2-butanone to give 50.3 g of (7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde hydrochloride monohydrate as a light yellow solid.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]([C:12]([NH:17][CH3:18])=[CH:13][N+:14]([O-:16])=[O:15])[CH2:10][CH3:11])=[CH:4][CH:3]=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([SH:26])=[CH:22][CH:21]=1.[CH2:27]=O>C(O)C>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([S:26][CH2:27][C:13]([N+:14]([O-:16])=[O:15])=[C:12]([N:9]([CH2:8][C:5]2[CH:6]=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH2:10][CH3:11])[NH:17][CH3:18])=[CH:22][CH:21]=1
Reactant: Sc1ccc(Cl)cc1
Reactant: C=O
Reactant: CCN(Cc1ccc(Cl)nc1)C(=C[N+](=O)[O-])NC
Solvent: CCO
Product: CCN(Cc1ccc(Cl)nc1)C(NC)=C(CSc1ccc(Cl)cc1)[N+](=O)[O-]
Temperature: 20 °C
Reaction time: 2 h
Yield: 77.1 %

Procedure:
A mixture of 1-[N-(6-chloro-3-pyridylmethyl)-N-ethylamino]-1-methylamino-2-nitroethylene (2.71 g), p-chlorothiophenol (1.45 g), 37% aqueous solution of formaldehyde (0.97 g) and ethanol (30 ml) was stirred at 20° C. for 2 hours and under refluxing for 5 hours. The reaction mixture was concentrated and the residue was purified by column chromatography (eluting solvent:dichloromethane-methanol (6:1) to give 3-(4-chlorophenylthio)-1-[N-(6-chloro-3-pyridylmethyl)-N-ethylamino]-1-methylamino-2-nitro-1-propene (Compound No. 31) (3.30 g) as a yellow amorphous.
Reaction SMILES: [F:1][C:2]1[C:3]([OH:13])=[C:4]([C:9](=[O:12])[CH2:10][CH3:11])[CH:5]=[CH:6][C:7]=1[F:8].[C:14](=O)([O-])[O-].[K+].[K+].CI>CC(C)=O>[F:1][C:2]1[C:3]([O:13][CH3:14])=[C:4]([C:9](=[O:12])[CH2:10][CH3:11])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: CCC(=O)c1ccc(F)c(F)c1O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Product: CCC(=O)c1ccc(F)c(F)c1OC
Temperature: 25 °C
Reaction time: 12 h
Yield: 92.1 %

Procedure:
30.1 g (161 mmol) of 2,3-difluorophenyl propionate in 16 ml of 1,2-dichlorobenzene are added dropwise to 21.5 g (161 mmol) of aluminum trichloride in 16 ml of 1,2-dichlorobenzene and the mixture is subsequently stirred at 100° C. for 6 hours. It is cooled, diluted with dichloromethane and poured cautiously onto a mixture of 2 M hydrochloric acid and ice. The phases are separated, extraction is carried out with dichloromethane and the extracts are washed with saturated sodium chloride solution and dried over sodium sulphate. The crude product is purified by column chromatography on silica gel (hexane/ethyl acetate 10-20%) to give 21.5 g of 1-(3,4-difluoro-2-hydroxyphenyl)propan-1-one. 21.4 g (115 mmol) of 1-(3,4-difluoro-2-hydroxyphenyl)propan-1-one are dissolved in 170 ml of acetone, and the solution is admixed with 29.5 g of potassium carbonate and 13 ml (209 mmol) of methyl iodide. The mixture is boiled under reflux for 4 hours and stirred at room temperature for 12 hours and then the solvent is largely removed. The residue is poured into water and subjected to extraction with diethyl ether. The extracts are washed with water, dried over sodium sulphate and, following the removal of the solvent in vacuo, give 21.2 g of 1-(3,4-difluoro-2-methoxyphenyl)propan-1-one.
Reaction SMILES: [NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5](I)=[CH:4][N:3]=1.[CH:33]([C:35]1[O:39][C:38](B(O)O)=[CH:37][CH:36]=1)=[O:34]>>[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5]([C:38]2[O:39][C:35]([CH:33]=[O:34])=[CH:36][CH:37]=2)=[CH:4][N:3]=1
Reactant: COc1cc(-c2csc3c(I)cnc(N)c23)ccc1NC(=O)c1cc2ccccc2n1C
Reactant: O=Cc1ccc(B(O)O)o1
Product: COc1cc(-c2csc3c(-c4ccc(C=O)o4)cnc(N)c23)ccc1NC(=O)c1cc2ccccc2n1C

Procedure:
The title compound was prepared using N-[4-(4-amino-7-iodothieno[3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-indole-2-carboxamide (0.120 g, 0.217 mmol), 5-formyl-2-furylboronic acid (0.247 mmol) and the procedure described in General Procedure A.
Reaction SMILES: C1C=CC=CC=1.[C:7]([OH:30])(=[O:29])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].[Ag:31]>O>[C:7]([O-:30])(=[O:29])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].[Ag+:31]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Reactant: [Ag]
Solvent: c1ccccc1
Solvent: O
Product: CCCCCCCCCCCCCCCCCCCCCC(=O)[O-]
Product: [Ag+]

Procedure:
Into 100 ml benzene at 60° C, 3.4 g of behenic acid was dissolved and further 100 ml of water was added to the solution at 60° C with stirring to produce an emulsion. To the emulsion, 100 ml of an aqueous solution silver ammine complex salt at 10° C was added to form fine particles of silver behenate. The aqueous silver ammine complex salt solution was prepared by adding an aqueous ammonia solution to about 80 ml of an aqueous solution containing 1.7 g of silver nitrate and then adding water to make the total volume 100 ml.
Reaction SMILES: [F:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([OH:11])=[C:4]([CH3:12])[CH:3]=1.[CH3:13][CH:14](O)[CH3:15].C1(P(C2C=CC=CC=2)C2C=CC=CN=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.Cl>O1CCCC1.CCOCC>[CH3:13][CH:14]([O:11][C:5]1[CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]([F:1])=[CH:3][C:4]=1[CH3:12])[CH3:15]
Reactant: Cc1cc(F)c([N+](=O)[O-])cc1O
Reactant: CC(C)O
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccn2)cc1
Solvent: CCOCC
Solvent: C1CCOC1
Product: Cc1cc(F)c([N+](=O)[O-])cc1OC(C)C
Reaction time: 3 h
Yield: 62.4 %

Procedure:
A solution of 4-fluoro-2-methyl-5-nitrophenol (D16) (0.85 mmol, 145 mg) in tetrahydrofuran (5 mL) was treated with 2-propanol (0.85 mmol, 51.1 mg, 1 eq), diphenyl-2-pyridylphosphine (1.28 mmol, 335.7 mg, 1.5 eq) and di-tert-butyl azodicarboxylate (1.28 mmol, 293.5 mg, 1.5 eq) under argon at room temperature. The mixture was stirred for 3 h then a solution of hydrogen chloride in ether (1M) was added and the mixture was stirred for 1 h. A gummy precipitate appeared. The mixture was concentrated under reduced pressure and the residue was dissolved in ether, washed twice with 5M aqueous hydrogen chloride solution for 30 min then washed twice with 10% aqueous sodium carbonate solution. The organic (ether) phase was dried and concentrated under reduced pressure to give a residue which was purified by chromatography on silica (ethyl acetate/petrol ether) to give the title compound as a pale yellow solid (0.53 mmol, 115 mg, 63% yield).
Reaction SMILES: [O:1]=[C:2]([CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])/[CH:3]=[CH:4]/[C:5]1[O:6][C:7]([CH2:23][O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:8][C:9](=[O:22])[C:10]=1[O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18].C([BH-](CC)CC)C.[Li+]>O1CCCC1>[OH:1][CH:2]([CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])/[CH:3]=[CH:4]/[C:5]1[O:6][C:7]([CH2:23][O:24][C:25](=[O:30])[C:26]([CH3:27])([CH3:28])[CH3:29])=[CH:8][C:9](=[O:22])[C:10]=1[O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18]
Reactant: CCCCCC(=O)/C=C/c1oc(COC(=O)C(C)(C)C)cc(=O)c1OCCCCCC(=O)OCC
Agent: CC[BH-](CC)CC
Agent: [Li+]
Solvent: C1CCOC1
Product: CCCCCC(O)/C=C/c1oc(COC(=O)C(C)(C)C)cc(=O)c1OCCCCCC(=O)OCC
Reaction time: 0.5 h
Yield: 40.4 %

Procedure:
To a solution, cooled under nitrogen to -78°, of 0.715 g (1.45 mmol) of 2-(3-oxo-trans-1-octenyl)-3-(5-carboethoxypentyloxy)-6-(trimethylacetoxymethyl)-4-pyrone in 10 ml of tetrahydrofuran was added dropwise keeping the internal temperature at -70° to -75°, 1.7 ml (1.7 mmole) of lithium triethylborohydride. After being stirred for an additional 30 min the cold reaction was quenched by the addition of 5 drops of 40% aqueous acetic acid and then partially concentrated under reduced pressure. The residue was dissolved in methylene chloride and washed successively with aqueous sodium bicarbonate and brine solution. The organic solution was dried over magnesium sulfate and evaporated to give an oil. Chromatographic purification on silica gel eluting with ether furnished 0.290 g (40%) of 2-[(3RS)-3-hydroxy-trans-1-octenyl]-3-(5-carboethoxypentyloxy)-6-(trimethylacetoxymethyl)-4-pyrone. NMR (CDCl3): δ0.90 (3H, t, J = 4.5 Hz), 2.31 (2H, t, J = 6 Hz), 4.88 (2H, s).
Reaction SMILES: C[O:2][C:3]([CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][C:9]([O:17][CH3:18])=[C:10]([O:15][CH3:16])[CH:11]=2)[C:6]1=[O:19])=[O:4].[BH4-].[Na+].O>C(Cl)Cl.CO>[CH3:16][O:15][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][C:9]=1[O:17][CH3:18])[CH:6]([OH:19])[CH:5]([C:3]([OH:4])=[O:2])[CH2:14][CH2:13]2
Reactant: COC(=O)C1CCc2cc(OC)c(OC)cc2C1=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Solvent: ClCCl
Product: COc1cc2c(cc1OC)C(O)C(C(=O)O)CC2
Temperature: 25 °C

Procedure:
6,7-Dimethoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthoic acid methyl ester [Hashem et al., J. Med. Chem., 19, 229 (1976)] (14 g) is dissolved in a mixture of methylene chloride (200 ml) and methanol (200 ml). Sodium borohydride (1 g) is added to the solution with stirring at room temperature, and the mixture is then stirred for one hour. The resulting mixture is supplemented with sodium borohydride (1 g) and the mixture is stirred for 30 minutes. To the resultant is then further added sodium borohydride (0.5 g) and the mixture is stirred for 30 minutes. After addition of water (500 ml) to the mixture, the methylene chloride layer is separated. The aqueous layer is extracted with methylene chloride (200 ml). The extracts are combined and concentrated under reduced pressure to give the methyl ester of 6,7-dimethoxy-1-hydroxy-1,2,3,4-tetrahydro-2-naphthoic acid. This product is dissolved in methanol (10 ml), and an aqueous solution (100 ml) of sodium hydroxide (14 g) is added dropwise to the solution at room temperature with stirring. After finishing the dropwise addition, the mixture is allowed to stand at room temperature for 30 minutes. Water (200 ml) is added to the mixture, and the mixture is extracted with a mixture of ethyl ether (100 ml) and petroleum ether (100 ml). The aqueous layer is made acid with concentrated hydrochloric acid and extracted with methylene chloride (300 ml). The extract is washed with water, dried and concentrated under reduced pressure. To the residue are added dioxane (100 ml) and concentrated hydrochloric acid (10 ml), and the mixture is heated at 80° C. for 5 minutes. The reaction mixture is concentrated under reduced pressure to half of its original volume. To the concentrate is added an aqueous solution (200 ml) of sodium hydroxide (10 g). The mixture is extracted with a mixture of ether (50 ml) and petroleum (50 ml). The aqueous layer is made acid with concentrated hydrochloric acid, and then precipitating colorless prisms are collected by filtration to give 1,2-dihydro-6,7-dimethoxy-3-naphthoic acid (6.2 g), m.p. 191°-194° C.