Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.C1(S(O[CH2:27][CH2:28][CH2:29][O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[NH:37][C:38](=[O:40])[CH3:39])(=O)=O)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].C(#N)C>O>[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:27][CH2:28][CH2:29][O:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[NH:37][C:38](=[O:40])[CH3:39])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1
Reactant: Fc1ccc2c(C3CCNCC3)noc2c1
Reactant: CC(=O)Nc1ccccc1OCCCOS(=O)(=O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: CC(=O)Nc1ccccc1OCCCN1CCC(c2noc3cc(F)ccc23)CC1
Yield: 45.6 %

Procedure:
A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.4 g, 16 mmol), N-[2-(3-phenylsulfonyloxypropoxy)phenyl]acetamide (5.3 g, 16 mmol), K2CO3 (2.2 g), and acetonitrile (50 ml) was stirred and refluxed for 5 hours. The reaction was poured into water, and the aqueous suspension was extracted with ethyl acetate. The ethyl acetate was washed (water and brine), dried (MgSO) and the solvent was concentrated to afford 6.0 g of a thick, brown oil. The oil was chromatographed on a Waters Prep 500 LC on silica gel. Concentration of the appropriate fractions afforded 3.0 g of a beige solid. This was recrystallized from ethyl acetate to yield (with concentration of the mother liquors) 2.2 g (33%) of N-[2-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)l-piperidinyllpropoxy]phenyl]acetamide as a beige solid, m.p.=118-120° C.
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[O:14])=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(O)C.[BH4-].[Na+].[NH4+].[Cl-]>O>[Si:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13][OH:14])=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(C=O)cc1
Agent: [BH4-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: CC(C)(C)[Si](C)(C)Oc1ccc(CO)cc1
Reaction time: 0.5 h

Procedure:
To a dry 250 ml round bottom flask was added 2.5 mg of 4, to which was added 100 ml of ethanol. NaBH4 (794 mg) was slowly added thereto and the reaction stirred for 30 minutes. NH4Cl (sat'd solution) was carefully added to the reaction to quench excess NaBH4, and the reaction then diluted with 125 ml water. The mixture was extracted with ether and the organic layers combined and washed with brine. The organic layers were again collected and the solvent removed in vacuo to yield the product 6.
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:11]2[C:12]([O:16][CH3:17])=[N:13][CH:14]=[CH:15][C:10]=2[N:9]([C:18]([CH3:21])([CH3:20])[CH3:19])[N:8]=1)(=O)=O.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[C:34]([C:37]([O:39][CH3:40])=[O:38])[S:35][CH:36]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:18]([N:9]1[C:10]2[CH:15]=[CH:14][N:13]=[C:12]([O:16][CH3:17])[C:11]=2[C:7]([C:32]2[CH:33]=[C:34]([C:37]([O:39][CH3:40])=[O:38])[S:35][CH:36]=2)=[N:8]1)([CH3:19])([CH3:20])[CH3:21]
Reactant: COC(=O)c1cc(B2OC(C)(C)C(C)(C)O2)cs1
Reactant: COc1nccc2c1c(OS(=O)(=O)C(F)(F)F)nn2C(C)(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: COC(=O)c1cc(-c2nn(C(C)(C)C)c3ccnc(OC)c23)cs1
Temperature: 100 °C
Reaction time: 8 h
Yield: 120.2 %

Procedure:
To a solution of 1-tert-butyl-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl trifluoromethanesulfonate (1.60 g) obtained in Step C of Example 86 in DME (100 mL) were added methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate (1.46 g) and 2M aqueous sodium carbonate solution (11.3 mL), and then tetrakis(triphenylphosphine)palladium(0) (523 mg) was added thereto under nitrogen atmosphere. The reaction mixture was stirred overnight under nitrogen atmosphere at 100° C. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (1.88 g).
Reaction SMILES: [H-].[Na+].[OH:3][CH2:4][C:5]1[CH:6]=[C:7]([C:16]2[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=2[O:24][C:25]([F:28])([F:27])[F:26])[CH:19]=[O:20])[C:8]2[O:12][CH2:11][C:10]([CH3:14])([CH3:13])[C:9]=2[CH:15]=1.[CH3:29]I.O>O1CCCC1.C(OCC)(=O)C>[CH3:29][O:3][CH2:4][C:5]1[CH:6]=[C:7]([C:16]2[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=2[O:24][C:25]([F:28])([F:26])[F:27])[CH:19]=[O:20])[C:8]2[O:12][CH2:11][C:10]([CH3:13])([CH3:14])[C:9]=2[CH:15]=1
Reactant: CI
Reactant: CC1(C)COc2c(-c3cc(C=O)ccc3OC(F)(F)F)cc(CO)cc21
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: COCc1cc(-c2cc(C=O)ccc2OC(F)(F)F)c2c(c1)C(C)(C)CO2
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 39 %

Procedure:
To a cold solution (0° C.) of sodium hydride in tetrahydrofuran (4 mL), under an atmosphere of argon, was added 3-(5-hydroxymethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde (example 10c) (246 mg, 0.67 mmol) in tetrahydrofuran (6 mL). The mixture was stirred at 0° C. for 15 minutes, then the argon flow was stopped and methyl iodide was added. After 3 hours at room temperature, the mixture was diluted with ethyl acetate. Water was slowly added and the layers separated. The organic layer was further washed with water, brine, dried (MgSO4), filtered and evaporated. The residue was chromatographed on silica gel (20% ethyl acetate in hexane) to afford 99 mg of 3-(5-Methoxymethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde. 39% yield. 1H-NMR (300 MHz, CDCl3): 1.39 (s, 6H), 2.11 (s, 3H), 4.27 (s, 2H), 5.09 (s, 2H), 7.17 (s, 2H), 7.49 (d, J=8.5 Hz, 1H), 7.93 (dd, J1=8.5 Hz, J2=2.1 Hz, 1H), 8.02 (d, J=2.1 Hz, 1H), 10.03 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:11]=[O:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[OH-].[K+].[C:15]1([S:21](Cl)(=[O:23])=[O:22])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.O>ClCCl.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[C:15]1([S:21]([N:8]2[C:5]3=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=[C:4]3[C:10]([CH:11]=[O:12])=[CH:9]2)(=[O:23])=[O:22])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: O=Cc1c[nH]c2ncc(Cl)cc12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: O=Cc1cn(S(=O)(=O)c2ccccc2)c2ncc(Cl)cc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 36 %

Procedure:
To 5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (114, 3.60 g, 19.9 mmol) in 100 mL of dichloromethane, potassium hydroxide (50 mL, 9M aqueous, 0.45 mol), tetrabutylammonium hydrogen sulfate (400 mg, 1.0 mmol) and benzenesulfonyl chloride (11, 2.9 mL, 23.0 mmol) were added. The reaction was stirred at room temperature for 3 hours, then poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was washed with ethyl acetate to provide the desired compound as a white solid (115, 2.3 g).
Reaction SMILES: [CH3:1][C:2]1[C:7]2[O:8][C@:9]3([CH3:49])[O:12][CH:13]=[CH:14][C@H:15]([O:47][CH3:48])[C@@H:16]([CH3:46])[C@@H:17]([O:42][C:43]([CH3:45])=[O:44])[C@H:18]([CH3:41])[C@H:19]([OH:40])[C@H:20]([CH3:39])[C@@H:21]([OH:38])[C@@H:22]([CH3:37])[CH:23]=[CH:24][CH:25]=[C:26]([CH3:36])[C:27]([NH:29][C:30]4[C:34](=[O:35])[C:4](=[C:5]([C:32](=[O:33])[CH:31]=4)[C:6]=2[C:10]3=[O:11])[C:3]=1[OH:50])=[O:28].[N-:51]=[N+]=[N-].[Na+]>CN(C)C=O>[CH3:37][C@@H:22]1[C@H:21]([OH:38])[C@@H:20]([CH3:39])[C@@H:19]([OH:40])[C@@H:18]([CH3:41])[C@H:17]([O:42][C:43]([CH3:45])=[O:44])[C@H:16]([CH3:46])[C@@H:15]([O:47][CH3:48])[CH:14]=[CH:13][O:12][C@:9]2([CH3:49])[C:10](=[O:11])[C:6]3[C:7]([O:8]2)=[C:2]([CH3:1])[C:3]([OH:50])=[C:4]2[C:34](=[O:35])[C:30](=[C:31]([NH2:51])[C:32]([C:5]=32)=[O:33])[NH:29][C:27](=[O:28])[C:26]([CH3:36])=[CH:25][CH:24]=[CH:23]1
Reactant: CO[C@H]1C=CO[C@@]2(C)Oc3c(C)c(O)c4c(c3C2=O)C(=O)C=C(NC(=O)C(C)=CC=C[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C4=O
Reactant: [N-]=[N+]=[N-]
Agent: CO[C@H]1/C=C/O[C@@]2(C)Oc3c(C)c(O)c4c(c3C2=O)C(=O)C(N)=C(NC(=O)/C(C)=C\C=C\[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C4=O
Agent: CO[C@H]1/C=C/O[C@@]2(C)Oc3c(C)c(O)c4c(c3C2=O)C(=O)C=C(NC(=O)/C(C)=C\C=C\[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C4=O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CO[C@H]1C=CO[C@@]2(C)Oc3c(C)c(O)c4c(c3C2=O)C(=O)C(N)=C(NC(=O)C(C)=CC=C[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C4=O
Reaction time: 36 h

Procedure:
50 g rifamycin S were dissolved in 200 ml dimethyl formamide and added with 9 g sodium azide. After 36 hours at a temperature of +5° C, the reaction mixture was treated as in Example 3, to obtain 13 g 3-amino-rifamycin S identical to that described in Example 3.
Reaction SMILES: [CH2:1]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[C:8]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][CH2:23][O:24]C(=O)C)[CH:16]=2)=[C:7]([NH:28][C:29]([NH:31][C:32]2[C:37]([CH:38]([CH3:40])[CH3:39])=[CH:36][CH:35]=[CH:34][C:33]=2[CH:41]([CH3:43])[CH3:42])=[O:30])[C:6]1=[O:44])[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[K+].[K+].O>CO>[CH2:1]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[C:8]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][CH2:23][OH:24])[CH:16]=2)=[C:7]([NH:28][C:29]([NH:31][C:32]2[C:37]([CH:38]([CH3:39])[CH3:40])=[CH:36][CH:35]=[CH:34][C:33]=2[CH:41]([CH3:43])[CH3:42])=[O:30])[C:6]1=[O:44])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCn1c(=O)c(NC(=O)Nc2c(C(C)C)cccc2C(C)C)c(-c2cccc(OCCOC(C)=O)c2)c2cccnc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: CCCCn1c(=O)c(NC(=O)Nc2c(C(C)C)cccc2C(C)C)c(-c2cccc(OCCO)c2)c2cccnc21
Temperature: 25 °C
Reaction time: 4 h
Yield: 78.8 %

Procedure:
To a solution of N-[1-butyl-4-{3-(2-acetoxyethoxy)phenyl}-1,2-dihydro-2-oxo-1,8-naphthyridin-3-yl]-N'-(2,6-diisopropylphenyl)urea (196 mg, 0.33 mmol) in methanol (10 ml) was added potassium carbonate (11 mg), and the mixture was stirred at room temperature for 4 hours. To the mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with water, washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The residue was concentrated under reduced pressure, and crystallized from ether/hexane to give the title compound (145 mg, 0.26 mmol).
Reaction SMILES: [CH3:1][C:2]1([C:12]([O:14][CH3:15])=[O:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][CH2:3]1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>C1(C)C=CC=CC=1>[CH3:1][C:2]1([C:12]([O:14][CH3:15])=[O:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH2:3]1
Reactant: COC(=O)C1(C)CCCc2ccccc21
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: Cc1ccccc1
Product: COC(=O)C1(C)CC=Cc2ccccc21
Yield: 73.6 %

Procedure:
A mixture of 24 g of methyl 3,4-dihydro-1-methylnaphthalenecarboxylate, 30 g of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and 400 ml of toluene was heated at reflux for 18 hours. The reaction mixture was then filtered and concentrated in vacuo. Sodium bisulfite solution (150 ml, 25%) was added to the residue, followed by 150 ml of toluene and 50 ml of ether. The latter mixture was washed twice with each of the following: 25% sodium bisulfite solution, concentrated sodium chloride solution, sodium bicarbonate solution and water. The organic solution was dried over anhydrous sodium sulfate and concentrated in vacuo to give 17.5 g of methyl 1-methylnaphthalenecarboxylate as an oil, which upon further purification gave the product in crystalline form, m.p. 48°-49° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[CH:14][C:13]([CH2:16][S:17]([CH3:20])(=[O:19])=[O:18])=[C:12]([OH:21])[CH:11]=2)=[CH:4][C:3]=1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1.Br[CH2:30][CH:31]([CH3:33])[CH3:32]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:22])[C:10]2[CH:15]=[CH:14][C:13]([CH2:16][S:17]([CH3:20])(=[O:19])=[O:18])=[C:12]([O:21][CH2:30][CH:31]([CH3:33])[CH3:32])[CH:11]=2)=[CH:4][C:3]=1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1
Reactant: CS(=O)(=O)Cc1ccc(C(=O)Nc2ccc(Cl)c(-c3ccccn3)c2)cc1O
Reactant: CC(C)CBr
Product: CC(C)COc1cc(C(=O)Nc2ccc(Cl)c(-c3ccccn3)c2)ccc1CS(C)(=O)=O
Yield: 33.5 %

Procedure:
N-(4-chloro-3-(pyridin-2-yl)phenyl)-3-hydroxy-4-(methylsulfonylmethyl)benzamide (50 mg, 0.12 mmol) was treated with 1-bromo-2-methylpropane (26 μl, 0.24 mmol) via procedure U to yield 19 mg of N-(4-chloro-3-(pyridin-2-yl)phenyl)-3-isobutoxy-4-(methylsulfonylmethyl)benzamide. MS (Q1) 473 (M)+.
Reaction SMILES: [CH3:1][N:2]([CH3:17])[S:3]([C:6]1[O:7][C:8]2[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[CH:11][C:9]=2[CH:10]=1)(=[O:5])=[O:4].[Br:18]N1C(=O)CCC1=O>C(#N)C>[CH3:1][N:2]([CH3:17])[S:3]([C:6]1[O:7][C:8]2[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[C:11]([Br:18])[C:9]=2[CH:10]=1)(=[O:5])=[O:4]
Reactant: O=C1CCC(=O)N1Br
Reactant: COc1cccc2cc(S(=O)(=O)N(C)C)oc12
Solvent: CC#N
Product: COc1ccc(Br)c2cc(S(=O)(=O)N(C)C)oc12
Yield: 93.4 %

Procedure:
Prepared from 7-methoxybenzofuran-2-sulfonic acid dimethylamide (0.82 g) and N-bromosuccinimide (0.57 g) in acetonitrile (50 ml). Purification by column chromatography eluting with 50% ethyl acetate in hexane afforded the desired product as a pale yellow solid (1.0 g).
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]3[C:14](=[N:15][CH:16]=2)[N:13]([CH3:17])[C:12](=[O:18])[C:11]([C:19](=[O:26])[CH2:20][CH2:21][C:22]([O:24]C)=[O:23])=[C:10]3[OH:27])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.C1CCCCC=1.OC1C2C(=NC=C(I)C=2)N(C)C(=O)C=1C(=O)CCC(O)=O>[Pd]>[CH:1]1([C:7]2[CH:8]=[C:9]3[C:14](=[N:15][CH:16]=2)[N:13]([CH3:17])[C:12](=[O:18])[C:11]([C:19](=[O:26])[CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[C:10]3[OH:27])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: COC(=O)CCC(=O)c1c(O)c2cc(C3=CCCCC3)cnc2n(C)c1=O
Agent: [Pd]
Agent: Cn1c(=O)c(C(=O)CCC(=O)O)c(O)c2cc(I)cnc21
Solvent: C1=CCCCC1
Product: Cn1c(=O)c(C(=O)CCC(=O)O)c(O)c2cc(C3CCCCC3)cnc21

Procedure:
Methyl 4-(6-cyclohexenyl-4-hydroxy-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)-4-oxobutanoate. The title compound is prepared by Palladium mediated Heck cross coupling reaction of cyclohexene and methyl 4-(4-hydroxy-6-iodo-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)-4-oxobutanoate (Method 4) according to the procedure set forth in Heck, R. F.; Nolley, J. P. J. Org. Chem., 37, 2320-22 (1971).
Reaction SMILES: C1(C#CC)C=CC=CC=1.C([SiH](CC)CC)C.C([Si](CC)(CC)/C(/C)=C\C1C=CC=CC=1)C.C([Si](CC)(CC)/C(/C)=C/C1C=CC=CC=1)C.[CH2:49]([Si:51]([CH2:63][CH3:64])([CH2:61][CH3:62])/[C:52](/[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[CH:53]\[CH3:54])[CH3:50]>[Rh](Cl)(Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:61]([Si:51]([CH2:49][CH3:50])([CH2:63][CH3:64])/[C:52](/[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[CH:53]/[CH3:54])[CH3:62]
Reactant: C/C=C(/c1ccccc1)[Si](CC)(CC)CC
Agent: Cl[Rh](Cl)Cl
Agent: CC#Cc1ccccc1
Agent: CC[SiH](CC)CC
Product: C/C=C(\c1ccccc1)[Si](CC)(CC)CC
Temperature: 100 °C
Yield: 4 %

Procedure:
A mixture of 0.125 ml (1.0 mmol) of 1-phenylpropyne, 0.192 ml (1.2 mmol) of triethylsilane, and 9.9 mg (0.01 mmol) of chlorodium tris(triphenylphosphine) rhodium chloride was heated in a sealed tube at 100° C. for 16 hours while being stirred. GLC analysis of the reaction mixture revealed that (Z)-β-triethylsilyl-β-methylstyrene, (E)-β-triethylsilyl-β-methylstyrene, (Z)-α-triethylsilyl-β-methylstyrene, and (E)-α-triethylsilyl-β-methylstyrene were produced in a yield of 4%, 33%, 7%, and 56%, respectively.
Reaction SMILES: [N+:1]([C:4]1[C:9]([S:10][C:11]2[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=2)=[CH:8][CH:7]=[CH:6][N:5]=1)([O-])=O>C(O)(=O)C.ClCCl.[Zn]>[NH2:1][C:4]1[C:9]([S:10][C:11]2[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=2)=[CH:8][CH:7]=[CH:6][N:5]=1
Reactant: COC(=O)c1ccc(Sc2cccnc2[N+](=O)[O-])cc1
Agent: [Zn]
Solvent: ClCCl
Solvent: CC(=O)O
Product: COC(=O)c1ccc(Sc2cccnc2N)cc1
Yield: 99.6 %

Procedure:
Added zinc powder (13.88 g, 212.2 mmol) slowly to a solution of methyl 4-(2-nitropyridin-3-ylthio)benzoate (6.16 g, 21.22 mmol) in acetic acid (75 mL) at ambient temperature in an ambient water bath. Stirred for an hour, diluted with dichloromethane, and filtered through celite. Washed the celite pad several times with dichloromethane. Concentrated the filtrate, and partitioned the residue between 2N NaOH and ethyl acetate. The organic layer was washed with water, brine, dried and concentrated to afford the title compound (5.5 g, 99.57% yield).
Reaction SMILES: S([O-])([O-])(=O)=O.[Mg+2].[CH3:7][O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15]1([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[O:19][CH:14]1[CH2:13][CH2:12]2>C1(C)C=CC=CC=1>[CH3:7][O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14](=[O:19])[CH2:13][CH2:12]2
Reactant: COc1ccc2c(c1)CCC1OC21c1ccccc1
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: Cc1ccccc1
Product: COc1ccc2c(c1)CCC(=O)C2c1ccccc1
Temperature: 80 °C

Procedure:
6.0 Grams (0.05 mols) of magnesium sulfate and 500 mL of toluene were added to 50.5 g (0.20 mols) of 5-methoxy-7b-phenyl-1a,2,3,7b-tetrahydro-1-oxacyclopropa[a]naphthalene, and the mixture was heated at 80° C. for 2 hours. After cooled, the reaction product was washed two times each with 250 mL of water, and the organic layer was condensed under reduced pressure to obtain 6-methoxy-1-phenyl-3,4-dihydro-1H-naphthalene-2-one represented by the following formula,
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:5][C:6]2[C:11]([C:12]=1[C:13](O)=[O:14])=[CH:10][CH:9]=[CH:8][CH:7]=2.C(Cl)(=O)C([Cl:25])=O>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:5][C:6]2[C:11]([C:12]=1[C:13]([Cl:25])=[O:14])=[CH:10][CH:9]=[CH:8][CH:7]=2
Reactant: O=C(Cl)C(=O)Cl
Reactant: COc1c(-c2ccccc2)nc2ccccc2c1C(=O)O
Solvent: ClCCl
Product: COc1c(-c2ccccc2)nc2ccccc2c1C(=O)Cl

Procedure:
3-Methyloxy-2-phenylquinoline-4-carboxylic acid (200 mg, 0.72 mmol) [J. Med. Chem. 1999, 42, 1053-1065] was suspended in CH2Cl2 (5 mL) at 0° C. and oxalyl chloride (62 μL, 0.72 mmol) was added with stirring. After stirring at 0° C. for 1 h the cooling bath was removed and the solution allowed to stir at room temperature for 18 h. After this time the solvent was evaporated and the crude acid chloride used in the subsequent reaction without further purification.
Reaction SMILES: [OH:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH:7]([CH3:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:23]1[CH:32]=[N:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]=1>C(#N)C>[N:24]1[C:25]2[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:31]=[CH:32][C:23]=1[O:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH:7]([CH3:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:14][CH:15]=1
Reactant: Clc1cnc2ccccc2n1
Reactant: CCOC(=O)C(C)Oc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)C(C)Oc1ccc(Oc2cnc3ccccc3n2)cc1
Yield: 103.6 %

Procedure:
In 50 ml of acetonitrile, 2.1 g of ethyl 2-(4-hydroxyphenoxy)propionate and 1.66 g of potassium carbonate were added and the mixture was refluxed for 1 hour and then, 1.65 g of 2-chloroquinoxaline was added and the mixture was further refluxed for 30 hours. After cooling, the precipitated inorganic salt was separated by a filtration. Acetone was distilled off from the filtrate under a reduced pressure to obtain 3.5 g of the oily residue. The residue was purified by a silica gel column chromatography (developer solvent: chloroform) to obtain 2.6 g (yield 77%) of the object compound.
Reaction SMILES: [NH2:1][C:2]1[C:7]2[C:8]3[C:9](=[O:23])[NH:10][C:11]([NH:16]C(=O)C(C)(C)C)=[N:12][C:13]=3[CH:14]=[CH:15][C:6]=2[CH:5]=[CH:4][C:3]=1[Br:24].[OH-].[Na+].NC1NC(=O)C2C3C=C(Br)C=CC=3C=CC=2N=1>>[NH2:16][C:11]1[NH:10][C:9](=[O:23])[C:8]2[C:7]3[C:2]([NH2:1])=[C:3]([Br:24])[CH:4]=[CH:5][C:6]=3[CH:15]=[CH:14][C:13]=2[N:12]=1
Reactant: CC(C)(C)C(=O)Nc1nc2ccc3ccc(Br)c(N)c3c2c(=O)[nH]1
Agent: Nc1nc2ccc3ccc(Br)cc3c2c(=O)[nH]1
Agent: [Na+]
Agent: [OH-]
Product: Nc1nc2ccc3ccc(Br)c(N)c3c2c(=O)[nH]1

Procedure:
N-(10-Amino-9-bromo-1,2-dihydro-1-oxobenzo[f]quinazolin-3-yl)pivalamide (0.58 g, 1.5 mmoles) was reacted with aqueous sodium hydroxide as described for the analogous 9-bromo compound (example 2). The product was precipitated from the reaction mixture with acetic acid, filtered and washed with water to give 3,10-diamino-9-bromobenzo[f]quinazolin-1(2H)-one as a yellow solid. (0.36 g, 80%) 1H NMR (DMSO-d6, 200 MHz) δ: 6.49(br s, 2H, NH2); 6.69(br s, 2H, NH2); 7.09(d, J=8.4 Hz, 1H, Ar); 7.22(d, J=8.9 Hz, 1H, Ar); 7.56(d, J=8.4 Hz, 1H, Ar); 7.90(d, J=8.9 Hz, 1H, Ar); 11.47(br s, 1H, NH).
Reaction SMILES: [N:1]1[N:2]([C:10]2[N:31]=[CH:30][CH:29]=[CH:28][C:11]=2[C:12]([NH:14][CH:15]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:16]([OH:20])[C:17]([OH:19])=O)=[O:13])[CH:3]=[C:4]2[C:9]=1[CH2:8][CH2:7][CH2:6][CH2:5]2.Cl.[CH:33]1([NH2:36])[CH2:35][CH2:34]1>>[CH:33]1([NH:36][C:17](=[O:19])[CH:16]([OH:20])[CH:15]([NH:14][C:12](=[O:13])[C:11]2[CH:28]=[CH:29][CH:30]=[N:31][C:10]=2[N:2]2[CH:3]=[C:4]3[C:9]([CH2:8][CH2:7][CH2:6][CH2:5]3)=[N:1]2)[CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:35][CH2:34]1
Reactant: O=C(NC(Cc1ccccc1)C(O)C(=O)O)c1cccnc1-n1cc2c(n1)CCCC2
Reactant: NC1CC1
Agent: Cl
Product: O=C(NC(Cc1ccccc1)C(O)C(=O)NC1CC1)c1cccnc1-n1cc2c(n1)CCCC2

Procedure:
The reaction was carried out in analogy to reaction step 3.1 by reacting 3-[2-(4,5,6,7-tetrahydro-2H-indazol-2-yl)nicotinamido]-2-hydroxy-4-phenylbutanoic acid and cyclopropylamine hydrochloride.