Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [BH4-].[Li+].[C:3]([N:6]1[CH2:11][CH2:10][CH:9]([O:12][CH:13]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:14](OCC)=[O:15])[CH2:8][CH2:7]1)(=[O:5])[CH3:4].[H][H].O>O1CCCC1>[C:3]([N:6]1[CH2:11][CH2:10][CH:9]([O:12][CH:13]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:14][OH:15])[CH2:8][CH2:7]1)(=[O:5])[CH3:4]
Reactant: CCOC(=O)C(OC1CCN(C(C)=O)CC1)c1ccccc1
Reactant: [H][H]
Agent: [BH4-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CC(=O)N1CCC(OC(CO)c2ccccc2)CC1
Yield: 98.4 %

Procedure:
Lithium borohydride (3.24 g.) was added portionwise to a solution of α-(N-acetyl-4-piperidinoxy) phenylacetic acid, ethyl ester (11.2 g.) in dry tetrahydrofuran (200 ml.). When the hydrogen evolution had subsided the reaction mixture was heated under reflux for 4 hours. Water was added to the cooled solution, the solvent evaporated in vacuo, then the residue taken up in chloroform (200 ml.) and washed with dilute hydrochloric acid, water and brine. The chloroform extract was dried (MgSO4) and the solvent evaporated in vacuo. Thin layer chromatography analysis of the product indicated that reduction was incomplete, therefore the product in tetrahydrofuran (100 ml.) was treated with a further quantity of lithium borohydride (3.24 g.) and heated under reflux for 4 hours. The reaction mixture was treated as above to give N-acetyl-4-(2-hydroxy-1-phenyl-ethoxy) piperidine (9.5 g.) as an oil which solidified on standing. A sample crystallized from ether and had an m.p. of 92°-94° C.
Reaction SMILES: [CH:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[O:10][CH:11]([O:14]C)OC.[CH3:16]N(C=O)C>C(Cl)(Cl)Cl.NCC(O)=O.C(N(CC)CC)C>[C:11]1(=[O:14])[O:10][C:1](=[O:8])[C:2]2=[CH:7][CH:6]=[CH:5][CH:4]=[C:3]2[CH2:16]1
Reactant: COC(OC)OC
Reactant: CN(C)C=O
Reactant: O=Cc1ccccc1
Agent: NCC(=O)O
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: O=C1Cc2ccccc2C(=O)O1
Reaction time: 3 h

Procedure:
Placed in a 20 ml bottle were one of the small (0.241 g of mixed amino acid resin) tea-bags and one of the control (18 micromoles of glycine) tea-bags. The two tea-bags were treated with a solution of benzaldehyde (0.508 ml, 5 mmoles) and anhydrous trimethylorthoformate (1.094 ml, 10 mmoles) in anhydrous DMF (9 ml). After shaking for 3 hrs the packet was washed with anhydrous DMF (3×8 ml). A solution of homophthalic anhydride (801 mg, 5 mmoles) and triethylamine (0.044 ml, 0.3 mmoles) was prepared in chloroform (10 ml) and added to the tea-bag. After shaking at room temperature for 15.5 hrs the packet was washed with DMF (6×30 ml) and DCM (4×30 ml) and dried at room temperature. The remaining 37 tea-bags of mixed resin were each paired with one glycine control tea-bag and reacted as above in 37 separate reactions with the following aldehydes: 1,4-benzodioxan-6-carboxaldehyde, 1-methylindole-3-carboxaldehyde, 2,3-difluorobenzaldehyde, 2-bromobenzaldehyde, 2-chloro-5-nitrobenzaldehyde, 2-furaldehyde, 2-imidazolecarboxaldehyde, 2-naphthaldehyde, 2-pyridinecarboxaldehyde, 2-thiophenecarboxaldehyde, 3,4-dichlorobenzaldehyde, 3,5-bis(trifluoromethyl) benzaldehyde, 3,5-dihydroxybenzaldehyde, 3,5-dimethoxybenzaldehyde, 3,5-dimethyl-4-hydroxybenzaldehyde, 3-(4-methoxyphenoxy) benzaldehyde, 3-furaldehyde, 3-hydroxybenzaldehyde, 3-methyl-4-methoxybenzaldehyde, 3-methylbenzaldehyde, 3-nitrobenzaldehyde, 3-pyridinecarboxaldehyde, 3-thiophenecarboxaldehyde, 4-(3-dimethylaminopropoxy) benzaldehyde, 4-(dimethylamino)benzaldehyde, 4-(methylthio)benzaldehyde, 4-(trifluoromethyl) benzaldehyde, 4-biphenylcarboxaldehyde, 4-bromo-2-thiophenecarboxaldehyde, 4-cyanobenzaldehyde, 4-methoxy-1-naphthaldehyde, 4-nitrobenzaldehyde, 4-pyridinecarboxaldehyde,5-(hydroxymethyl)-2-furaldehyde, 5-bromo-4-hydroxy-3-methoxybenzaldehyde, 5-nitro-2-furaldehyde and 6-methyl-2-pyridinecarboxaldehyde. The large tea-bag containing 1.204 g (900 micromoles total of mixed amino acids) of resin was reacted with 3,5-dimethoxybenzaldehyde in the same manner, but on a five times larger scale of all reagents and solvents and with no control tea-bag.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([O:13][CH2:14][C:15]2[N:16]=[C:17]([C:21]3[O:22][CH:23]=[CH:24][CH:25]=3)[O:18][C:19]=2[CH3:20])=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9].[OH:26][C:27]1[C:31]([CH:32]=[O:33])=[CH:30][N:29]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[N:28]=1.CN(C)C=O.[H-].[Na+]>O>[CH:32]([C:31]1[C:27]([O:26][CH2:2][C:3]2[CH:4]=[CH:5][C:6]([O:13][CH2:14][C:15]3[N:16]=[C:17]([C:21]4[O:22][CH:23]=[CH:24][CH:25]=4)[O:18][C:19]=3[CH3:20])=[C:7]([CH:12]=2)[C:8]([O:10][CH3:11])=[O:9])=[N:28][N:29]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:30]=1)=[O:33]
Reactant: O=Cc1cn(-c2ccccc2)nc1O
Reactant: COC(=O)c1cc(CCl)ccc1OCc1nc(-c2ccco2)oc1C
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cc(COc2nn(-c3ccccc3)cc2C=O)ccc1OCc1nc(-c2ccco2)oc1C
Temperature: 90 °C
Reaction time: 2 h
Yield: 78.4 %

Procedure:
To a mixture of methyl 5-(chloromethyl)-2-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}benzoate (1.16 g), 3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde (0.50 g) and N,N-dimethylformamide (30 mL) was added sodium hydride (60% in oil, 0.12 g) at room temperature, and the mixture was stirred at 90° C. for 2 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give methyl 5-{[(4-formyl-1-phenyl-1H-pyrazol-3-yl)oxy]methyl}-2-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}benzoate as colorless crystals (1.07 g, yield 77%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 173-174° C.
Reaction SMILES: [OH-].[K+].CC(O)C.[C:7]([C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1)(=[O:9])[CH3:8].[H][H]>CC(O)C>[C:10]1([C@H:7]([OH:9])[CH3:8])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1
Reactant: [H][H]
Reactant: CC(=O)c1cccc2ccccc12
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)O
Product: C[C@@H](O)c1cccc2ccccc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 97.5 %

Procedure:
A 100 mL autoclave was charged with 11.7 mg (0.010 mmol) of the mixture of RuCl2[(S)-dm-binap][(S,S)-dpen] and RuCl2[(R)-dm-binap][(R)-3,3′-dimethyl-1,1′-binaphthyl-2,2′-diamine] obtained in Example 2. After purging with argon, 2.8 mL of 2-propanol and 50 μL (0.025 mmol) of KOH/2-propanol (0.5M solution) were added. The resulting mixture was stirred at room temperature for 30 minutes. After addition of 0.38 mL (2.5 mmol) of 1′-acetonaphthone, stirring was conducted at room temperature for 4 hours at a hydrogen pressure adjusted to 0.8 Mpa. The reaction mixture was concentrated by distilling off the solvent under reduced pressure. The residue was filtered using silica gel, whereby 420 mg (yield: 98.7%) of (R)-1-(1-naphthyl)ethanol was obtained. The enantio-selectivity was 96.2%ee.
Reaction SMILES: [CH:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C:4](=[O:10])[CH2:3][C:2]2=[O:11].C1(C)C=CC=CC=1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Br:31][C:32]1[CH:33]=[CH:34][C:35]([CH2:39][CH3:40])=[C:36]([Pb+3])[CH:37]=1.Cl>C(Cl)(Cl)Cl.CN(C)C1C=CN=CC=1.ClCCl>[Br:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:39][CH3:40])=[C:34]([CH:3]2[C:2](=[O:11])[CH:1]3[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9]3)[C:4]2=[O:10])[CH:33]=1
Reactant: CCc1ccc(Br)cc1[Pb+3]
Reactant: O=C1CC(=O)C2CCC1CC2
Agent: CC(=O)[O-]
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: CCc1ccc(Br)cc1C1C(=O)C2CCC(CC2)C1=O
Temperature: 80 °C
Reaction time: 8 h
Yield: 49.1 %

Procedure:
A solution of bicyclo[3.2.2]nonane-2,4-dione (0.12 g, 0.79 mmol), prepared by the method of W. Childers et al., US2006/0004108, in dry chloroform (4 ml) is stirred at room temperature then thoroughly flushed with nitrogen. To this mixture is then added 4-dimethylaminopyridine (0.482 g, 3.95 mmol) and anhydrous toluene (1 ml), followed by heating to 80° C. 5-Bromo-2-ethylphenyllead triacetate (0.673 g, 1.18 mmol) is added in one portion, and the mixture is further heated at this temperature for a further 4 hours then left to stand overnight. Dichloromethane (10 ml) and 2M hydrochloric acid (10 ml) are added, and the resulting biphasic mixture is filtered to remove any inorganic salts (washing with additional dichloromethane, 10 ml). The organic phase separated, and the aqueous phase is extracted again with dichloromethane (10 ml×2). All organic fractions are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to give a yellow gum. This crude product is purified by flash column chromatography on silica gel (100% to 40% hexane/ethyl acetate eluant ratio) to afford 3-(5-bromo-2-ethylphenyl)-bicyclo[3.2.2]nonane-2,4-dione (0.130 g, 49%) as a yellow solid.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([NH:15][C:16]([NH2:18])=[O:17])[CH:13]=2)[NH:8][CH:7]=1.[C:19]1([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(#N)C>[ClH:1].[C:19]1([N:25]2[CH2:30][CH2:29][N:28]([CH2:2][CH2:3][CH2:4][CH2:5][C:6]3[C:14]4[C:9](=[CH:10][CH:11]=[C:12]([NH:15][C:16]([NH2:18])=[O:17])[CH:13]=4)[NH:8][CH:7]=3)[CH2:27][CH2:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: c1ccc(N2CCNCC2)cc1
Reactant: NC(=O)Nc1ccc2[nH]cc(CCCCCl)c2c1
Solvent: CC#N
Product: Cl
Product: NC(=O)Nc1ccc2[nH]cc(CCCCN3CCN(c4ccccc4)CC3)c2c1

Procedure:
A solution of 2.6 g of 3-(4-chlorobutyl)-5-indolylurea [obtainable by reacting 5-nitroindole with 4-chlorobutyryl chloride to give 3-(4-chlorobutyryl)-5nitroindole, reduction with diborane to give 3-(4-chlorobutyl)-5-nitroindole hydrogenation to 3-(4-chlorobutyl)-5-aminoindole and reaction with KCNO] and 16.3 g of 1-phenylpiperazine in ("A") in 200 ml of acetonitrile is stirred for 12 hours at 20° and worked up in a conventional manner to give 3-[4-(4-phenylpiperazino)butyl]-5-indolylurea, hydrochloride, m.p. 207° (dec.).
Reaction SMILES: C([Si:3](CC)([Si:13](CC)(CC)[Si:14](CC)(CC)[Si:15](CC)(CC)[Si:16](C)(C)C)[Si:4](C)(C)C1C=CC=CC=1)C.[F:34][C:35]([F:41])([F:40])[S:36]([OH:39])(=[O:38])=[O:37]>ClCCl>[F:34][C:35]([F:41])([F:40])[S:36]([O:39][SiH2:4][SiH2:3][SiH2:13][SiH2:14][SiH2:15][SiH3:16])(=[O:38])=[O:37]
Reactant: CC[Si](CC)([Si](C)(C)C)[Si](CC)(CC)[Si](CC)(CC)[Si](CC)(CC)[Si](C)(C)c1ccccc1
Reactant: O=S(=O)(O)C(F)(F)F
Solvent: ClCCl
Product: O=S(=O)(O[SiH2][SiH2][SiH2][SiH2][SiH2][SiH3])C(F)(F)F

Procedure:
In an argon atmosphere, to a tetrahydrofuran solution (1 ml) of 52 mg (0.15 mmol) of octaethylcyclotetrasilane was added 0.71 ml (0.10 mmol) of a tetrahydrofuran solution (0.14M) of phenyldimethylsilyllithium, and stirred at 0° C. for 15 minutes. Then, tetrahydrofuran was distilled out under vacuum, and hexane (1 ml) was added to give a hexane solution (Solution 1). A dichloromethane solution (1 ml) of 27 mg (0.05 mmol) of 2,2,3,3,4,4,5,5-octaethyl-1,1,6,6,6-pentamethyl-1-phenylhexasilane (2) obtained in Example 2 was treated with 7.5 mg (0.05 mmol) of trifluoromethanesulfonic acid at room temperature for 30 minutes to give 1-(trifluoromethanesulfonyloxy)hexasilane. Then, dichloromethane was distilled out under vacuum, and hexane (1 ml) was added to give a hexane solution (Solution 2). The Solution 1 was added to the Solution 2 at -78° C. and stirred for 15 minutes. Methanol (0.1 ml) and triethylamine (0.1 ml) were added, then saturated aqueous sodium bicarbonate solution (2 ml) was added, stirred, the hexane layer was separated, and dried with magnesium sulfate. The resulting crude product was purified by a silica gel column chromatography (hexane) to afford 41 mg (86% yield) of undecasilane (8) as a colorless crystal.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10](OC(=O)C)[O:11]C(=O)C)=[C:6]([O:19][CH3:20])[CH:5]=1)([O-:3])=[O:2].O1CCOCC1.Cl>O>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[O:11])=[C:6]([O:19][CH3:20])[CH:5]=1)([O-:3])=[O:2]
Reactant: COc1cc([N+](=O)[O-])ccc1C(OC(C)=O)OC(C)=O
Agent: Cl
Solvent: O
Solvent: C1COCCO1
Product: COc1cc([N+](=O)[O-])ccc1C=O
Temperature: 0 °C
Reaction time: 20 h
Yield: 91 %

Procedure:
To a 2 L rounded bottom flask equipped with a condenser and a mechanical stirrer was placed 1A (250.7 g,0.8851 mol), dioxane (300 mL) and concentrated HCl (60 mL). The reaction mixture was heated to reflux and stirred under N2 for 20 hours. Water (250 mL) was added dropwise while maintaining the reaction mixture at reflux. After cooling to 0° C. with an ice/water bath, the resulting slurry was stirred for 30 minutes and then filtered. The cake was washed with water (4×200 mL) and suction dried for 17 hours to give 1B (I146.3 g, 91%) as yellow solid. 1H NMR (CDCl3) d 10.54 (s, 1H), 8.00 (d, J=8.3 Hz, 1H), 7.91 (s, 1H), 7.89 (d, J=8.3 Hz, 1H), 4.08 (s, 3H).
Reaction SMILES: CC(C[AlH]CC(C)C)C.C1(C)C=CC=CC=1.C([O:19][C:20](=O)/[CH:21]=[C:22](/[C:29]1[CH:34]=[CH:33][C:32]([Br:35])=[CH:31][CH:30]=1)\[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)C.O>C1COCC1>[Br:35][C:32]1[CH:31]=[CH:30][C:29](/[C:22](/[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[CH:21]/[CH2:20][OH:19])=[CH:34][CH:33]=1
Reactant: CCOC(=O)/C=C(\c1ccccc1)c1ccc(Br)cc1
Agent: CC(C)C[AlH]CC(C)C
Solvent: C1CCOC1
Solvent: O
Solvent: Cc1ccccc1
Product: OC/C=C(\c1ccccc1)c1ccc(Br)cc1
Reaction time: 0.5 h
Yield: 99.4 %

Procedure:
A 1.2 M solution of DIBAL-H in toluene (45 ml, 42 mmol) was added dropwise, at −15° C. over 20 min, to a stirred solution of (E)-3-(4-bromophenyl)-3-phenylacrylicacid ethyl ester (6.0 g, 18.1 mmol) in dry THF (80 ml), and the mixture stirred for 30 min. Rochelles salt and water was carefully added, and the resulting mixture extracted with ethyl acetate (x2). The combined organic extracts were washed with brine, dried (MgSO4), and evaporated to give 5.2 g of (E)-3-(4-bromo-phenyl)-3-phenyl-prop-2-en-1-ol.
Reaction SMILES: [Cl:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]([S:12](=[O:15])(=[O:14])[NH2:13])[CH:6]=1)=[O:4].[N:16]1[CH2:21][CH2:20][CH2:19][NH:18][C:17]=1[SH:22]>>[ClH:1].[OH:4][C:3]1([C:5]2[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]([S:12](=[O:15])(=[O:14])[NH2:13])[CH:6]=2)[N:18]2[CH2:19][CH2:20][CH2:21][N:16]=[C:17]2[S:22][CH2:2]1
Reactant: SC1=NCCCN1
Reactant: Cc1ccc(C(=O)CCl)cc1S(N)(=O)=O
Product: Cc1ccc(C2(O)CSC3=NCCCN32)cc1S(N)(=O)=O
Product: Cl

Procedure:
5 g of 2-chloro-4'-methyl-3'-sulfamoylacetophenone and 2.35 g of ground 3,4,5,6-tetrahydro-2-pyrimidine-thiol were reacted as prescribed in Example 12 and worked up as prescribed in Example 67(d). Colorless crystals, melting point: 190° C. (decomposition).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]=[O:7].[CH:8]([Mg]Cl)=[CH2:9].[C:12](OC(=O)C)(=[O:14])[CH3:13]>C1COCC1>[C:12]([O:7][CH:6]([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[CH:8]=[CH2:9])(=[O:14])[CH3:13]
Reactant: C=C[Mg]Cl
Reactant: CC(=O)OC(C)=O
Reactant: O=Cc1cccs1
Solvent: C1CCOC1
Product: C=CC(OC(C)=O)c1cccs1
Temperature: 0 °C
Reaction time: 0.33 h

Procedure:
A 1.514-necked glass flask equipped with a mechanical stirrer, a thermometer and an argon inlet was charged with 112.2 g of 2-thiophenecarbaldehyde (1.00 mol) and 100 ml of THF and to the resulting solution was added dropwise at −20° C. within 1.2 h 650 ml of vinylmagnesium chloride 1.7 M solution in THF. The temperature during the addition was kept between −20 and −25° C. with aid of an acetone/dry ice bath, then increased to 0° C. during 35 min and kept at this temperature for 20 min. To the resulting brown suspension was added at ca. 0° within 40 min 132.7 g of acetic anhydride (1.30 mol). The cooling bath was removed and after stirring for 1 h 400 ml of deionized water was added at 10-15° C. within 20 min. The biphasic yellow-brown mixture was stirred for an additional 1 h at room temperature and transferred to a separatory finnel with aid of 500 ml of hexane. The brown aqueous phase was separated and extracted with 400 ml of hexane. The combined organic phases were washed with 3×200 ml deionized water, dried (Na2SO4, 15 min stirring) and rotatory evaporated (Tbath35°, 12 mbar, 1 h). Material of this quality is defined as “crude” and is also suitable for cyclocarbonylation (see Example 2B). The orange-brown oil (199.7 g) was distilled in an apparatus consisting of a 500-ml two-necked round-bottomed flask, a distillation head with water-cooling and a fraction sampler. A forerun containing low-boiling components (yellowish oil) was collected at Thead between room temperature and 55° C. and 0.5-0.6 mbar, the main fraction was collected at Thead of 59-62° C. (Tpot63-67° C.) and 0.4 mbar. Yield: 161.53 g (88.6%) of 1-(2-thienyl)allyl acetate as a slightly yellow oil.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=2)[C:9]([OH:11])=O)=[CH:2]1.C(Cl)(=O)C(Cl)=O.[NH2:21][C:22]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:23]=1[C:24]([O:26][CH3:27])=[O:25].C(=O)([O-])O.[Na+]>C1COCC1.CC(N(C)C)=O.CN(C)C=O>[Cl:32][C:29]1[CH:30]=[CH:31][C:22]([NH:21][C:9]([C:8]2[CH:12]=[CH:13][CH:14]=[C:6]([C:3]3[CH:4]=[CH:5][O:1][CH:2]=3)[CH:7]=2)=[O:11])=[C:23]([CH:28]=1)[C:24]([O:26][CH3:27])=[O:25]
Reactant: O=C(O)c1cccc(-c2ccoc2)c1
Reactant: COC(=O)c1cc(Cl)ccc1N
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)N(C)C
Solvent: CN(C)C=O
Product: COC(=O)c1cc(Cl)ccc1NC(=O)c1cccc(-c2ccoc2)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 65.6 %

Procedure:
0.50 g (2.7 mmol) of 3-(furan-3-yl)benzoic acid, a catalytic amount of N,N-dimethylformamide (DMF), 0.78 g (3.7 mmol) of oxalyl chloride were stirred at 0° C. for 30 minutes in 10 mL of THF. Thereafter, the solvent was distilled off under reduced pressure. 0.49 g (2.7 mmol) of methyl 2-amino-5-chlorobenzoate and 5 mL of DMAc were added to the obtained residue at 0° C., and the mixture was stirred at room temperature for 0.5 hours. After the completion of the reaction, an aqueous sodium hydrogen carbonate solution was added. The precipitated solids were collected by filtration, followed by washing with water and IPE, thereby giving 0.63 g of methyl 5-chloro-2-({[3-(furan-3-yl)phenyl]carbonyl}amino)benzoate (yield: 67%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1[CH3:14].[H-].[Na+].Br[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([CH2:29][CH3:30])(=[O:28])=[O:27])=[CH:22][C:21]=1[Cl:31].[I-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([S:26]([CH2:29][CH3:30])(=[O:27])=[O:28])=[CH:22][C:21]=2[Cl:31])[C:6]=1[CH3:14]
Reactant: CCS(=O)(=O)c1ccc(CBr)c(Cl)c1
Reactant: COC(=O)Cc1c(C)[nH]c2ncccc12
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCS(=O)(=O)c1ccc(Cn2c(C)c(CC(=O)OC)c3cccnc32)c(Cl)c1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To an ice cooled (0° C.) stirred solution of (2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetic acid methyl ester ((2.68 g, 13.1 mmol) in dry DMF (95 ml) is added sodium hydride (577 mg of a 60% dispersion in mineral oil, 14.41 mmol). After stirring at room temperature for 1.5 hours, the reaction mixture is re-cooled to 0° C. and treated with 1-bromomethyl-2-chloro-4-ethanesulfonyl-benzene (6.6 g, 22.2 mmol) and sodium iodide (3.3 g, 22.2 mmol). The resulting mixture is stirred and allowed to warm to room temperature overnight. The reaction mixture is poured onto water (600 ml) and extracted with 1:1 ethyl acetate/diethyl ether (4×300 ml). The organic portions are washed with brine, dried (MgSO4) and concentrated in vacuo and the resulting crude is purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1:8 increasing to 1:2) to yield the titled product. (MH+ 421)
Reaction SMILES: I[C:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[S:4][C:3]=1[CH3:13].[C:14]1(B(O)O)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:13][C:3]1[S:4][C:5]2[C:10]([C:11](=[O:12])[C:2]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: Cc1sc2ccccc2c(=O)c1I
Reactant: OB(O)c1ccccc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1sc2ccccc2c(=O)c1-c1ccccc1
Yield: 93 %

Procedure:
The compound (1.0 mmol, 302 mg) obtained in (1) above, dichlorobis(triphenylphosphine)palladium (0.03 mmol, 21 mg), phenylboronic acid (1.3 mmol, 159 mg) and potassium carbonate (4.0 mmol, 552 mg) were dissolved in degassed dimethylformamide (3.2 mL) and water (0.8 mL), and the solution was stirred under a nitrogen atmosphere at 80° C. for 4 hours. After the disappearance of the starting materials was confirmed by thin-layer chromatography, water was poured into the reaction solution to terminate the reaction. The organic substances were extracted with ethyl acetate, the obtained organic layer was dried over magnesium sulfate, and the solvents were evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (0.93 mmol, 237 mg) was obtained in a 93% yield.
Reaction SMILES: [CH3:1][N:2]1[CH:24]=[C:5]2[CH2:6][CH2:7][N:8]([C:15](=[O:23])[C:16]3[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=3)[C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:4]2=[N:3]1.C(N(CC)CC)C.[CH3:32][C:33]1[CH:41]=[CH:40][CH:39]=[CH:38][C:34]=1[C:35](Cl)=[O:36]>C(Cl)Cl.O1CCOCC1>[CH3:1][N:2]1[CH:24]=[C:5]2[CH2:6][CH2:7][N:8]([C:15]([C:16]3[CH:17]=[CH:18][C:19]([NH:22][C:35](=[O:36])[C:34]4[CH:38]=[CH:39][CH:40]=[CH:41][C:33]=4[CH3:32])=[CH:20][CH:21]=3)=[O:23])[C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:4]2=[N:3]1
Reactant: Cc1ccccc1C(=O)Cl
Reactant: Cn1cc2c(n1)-c1ccccc1N(C(=O)c1ccc(N)cc1)CC2
Solvent: C1COCCO1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2CCc3cn(C)nc3-c3ccccc32)cc1
Reaction time: 4.5 h

Procedure:
To a mixture of 0.420 g of 2,4,5,6-tetrahydro-2-methyl-6-(4-aminobenzoyl)pyrazolo[4,3-d][1]-benzazepine and 275 p1 of triethylamine in 6 ml of methylene chloride and 2 ml of dioxane is added a solution of 215 p1 of 2-methylbenzoyl chloride in 1.5 ml of dioxane. The reactants are stirred under argon for 4.5 hours. The volatiles are evaporated in vacuo to a residue which is dissolved in methylene chloride and washed with 10% NaHCO3 and brine. The organic layer is treated with activated carbon, dried with MgSO4 and evaporated in vacuo to give 660 mg of a tan foam residue. The residue is purified by column chromatography on silica gel by elution with 30% ethyl acetate-methylene chloride to give 590 mg of the desired product as white crystalline solid, m.p. 246°-248° C; HR FABMS: (M+H)=437.1972.
Reaction SMILES: [F:1][C:2]1[CH:18]=[CH:17][C:5]2[S:6][C:7]3[CH:14]=[C:13]([CH2:15][OH:16])[CH:12]=[CH:11][C:8]=3[CH:9]=[CH:10][C:4]=2[CH:3]=1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.C(OCC)(=O)C>C(Cl)Cl.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:18]=[CH:17][C:5]2[S:6][C:7]3[CH:14]=[C:13]([CH:15]=[O:16])[CH:12]=[CH:11][C:8]=3[CH:9]=[CH:10][C:4]=2[CH:3]=1
Reactant: OCc1ccc2c(c1)Sc1ccc(F)cc1C=C2
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: Cc1ccccc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: O=Cc1ccc2c(c1)Sc1ccc(F)cc1C=C2
Yield: 106.4 %

Procedure:
Dissolve 568 mg (2.2 mmole) of 2-fluoro-7-hydroxymethyldibenzo[b,f]thiepin in 30 ml of methylene chloride and add 647 mg of 98% pyridinium chlorochromate. Stir the mixture and follow the reaction by thin layer chromatography (Merck silica gel F254 with 5% ethyl acetate in toluene). When complete, filter the mixture through a bed of Florisil, and wash through with methylene chloride. Evaporate the filtrate to obtain a brown solid (600 mg). Purify the crude product by chromatography on silica gel using totluene as solvent to obtain the title compound as a yellow solid, m.p. 137°-139° C.