Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:27])[CH:7]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:8][C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15]C)=[O:14])=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].O([Si](C)(C)C)[K].[Cl-].[NH4+].Cl>C1COCC1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:27])[CH:7]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:8][C:9]1[CH:18]=[CH:17][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: COC(=O)c1ccc(CC(NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)cc1
Agent: C[Si](C)(C)O[K]
Agent: Cl
Agent: [Cl-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NC(Cc1ccc(C(=O)O)cc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Methyl 4-{3-tert-butoxy-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}benzoate (0.40 g, 1.05 mmol) was dissolved in THF (10 mL). KOSiMe3 (0.27 g, 2.10 mmol) was added to the solution and allowed to stir overnight at room temperature under nitrogen. Saturated ammonium chloride was added and allowed to stir. Hydrochloric acid (2 mL, 1M solution) was added. The reaction was diluted with ethyl acetate and separated. The aqueous layer was extracted three times with ethyl acetate. The combined organic layer was dried with sodium sulfate, filtered, and concentrated. The resulting material was purified by HPLC. MS: cal'd 365 (MH+), exp 388 (MH+).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]2[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.Br[C:20]1[C:21](=[O:28])[N:22]([CH3:27])[CH:23]=[C:24]([Br:26])[CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Br:26][C:24]1[CH:25]=[C:20]([NH:1][C:2]2[N:7]=[CH:6][C:5]([CH:8]3[CH2:9][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:11]3)=[CH:4][CH:3]=2)[C:21](=[O:28])[N:22]([CH3:27])[CH:23]=1
Reactant: Cn1cc(Br)cc(Br)c1=O
Reactant: CC(C)(C)OC(=O)N1CC(c2ccc(N)nc2)C1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: Cn1cc(Br)cc(Nc2ccc(C3CN(C(=O)OC(C)(C)C)C3)cn2)c1=O
Temperature: 105 °C
Yield: 97.6 %

Procedure:
A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (50 mL), tert-butyl 3-(6-aminopyridin-3-yl)azetidine-1-carboxylate (1.8 g, 7.2 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (1.9 g, 7.2 mmol), and cesium carbonate (4.7 g, 14.4 mmol). After bubbling nitrogen through the resulting suspension for 30 minutes, XantPhos (418 mg, 0.72 mmol) and tris(dibenzylideneacetone)dipalladium(0) (661 mg, 0.72 mmol) were added. The reaction mixture was subjected to three cycles of vacuum/argon flush and heated at 105° C. for 0.5 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (120 mL) and water (60 mL). The aqueous layer was separated and extracted with ethyl acetate (3×80 mL). The combined organic layer was washed with brine (30 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:4 ethyl acetate/petroleum ether to afford the 239a as a yellow solid (3.06 g, 98%). MS-ESI: [M+H]+ 435.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][C@@H:13]2[O:18][C:17]3[C:19]([CH:26]=CC)=[C:20]([N+:23]([O-:25])=[O:24])[CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[O:29]=[O+][O-].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([O:11][CH2:12][CH:13]2[O:18][C:17]3[C:19]([CH:26]=[O:29])=[C:20]([N+:23]([O-:25])=[O:24])[CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=[O:10])=[O:9])=[CH:6][CH:7]=1
Reactant: CC=Cc1c([N+](=O)[O-])ccc2c1O[C@@H](COS(=O)(=O)c1ccc(C)cc1)CO2
Reactant: O=[O+][O-]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OCC2COc3ccc([N+](=O)[O-])c(C=O)c3O2)cc1
Reaction time: 8 h

Procedure:
{(2R)-7-Nitro-8-[1-propenyl]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate (10.5 g, 25.9 mmole) dissolved in 400 mL of methylene chloride was treated with excess ozone at −78° C. Diisopropylethylamine (11.5 mL, 66.0 mmole) was then added dropwise over 30 min and the mixture allowed to come to room temperature and stir overnight under a nitrogen atmosphere. The mixture was then diluted to 600 mL with methylene chloride, washed three times with 100 mL portions of 2N HCl (aq), twice with 200 mL portions of saturated aqueous sodium bicarbonate and with 200 mL of saturated brine. The solution was dried over magnesium sulfate, filtered and concentrated in vacuum to a crude brown oil, which was column chromatographed on silica gel with 10% hexane/methylene chloride to give 7.52 g of the (R)-enantiomer of the title compound as a yellow solid. 1H-NMR (CDCl3): doublet 7.8 δ (2H); doublet 7.62 δ (1H); doublet 7.4 δ (2H); doublet 7.0 δ (1H); multiplet 4.4-4.6 δ (2H); multiplet 4.2 δ (3H); singlet 2.4 δ (3H).
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[C:5]([CH3:7])[NH:4][C:3]=1[C:8]([O:10]CC)=O.[CH3:13][O:14][C:15]([NH:17][C:18](=[N:21]C(OC)=O)SC)=[O:16].CC(O)=O.C[O-].[Na+]>CO>[CH3:7][C:5]1[NH:4][C:3]2[C:8](=[O:10])[NH:21][C:18]([NH:17][C:15](=[O:16])[O:14][CH3:13])=[N:1][C:2]=2[CH:6]=1
Reactant: COC(=O)N=C(NC(=O)OC)SC
Reactant: CCOC(=O)c1[nH]c(C)cc1N
Agent: C[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: COC(=O)Nc1nc2cc(C)[nH]c2c(=O)[nH]1
Temperature: 25 °C
Reaction time: 8 h
Yield: 68.6 %

Procedure:
The pyrrole 6 (2.68 g, 16 mmol) was dissolved in MeOH (40 mL), and 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea (3.74 g, 18 mmol) was added followed by AcOH (4.6 mL). The mixture was stirred at room temperature overnight and became a thick paste. To the reaction mixture NaOMe in MeOH (25%) 45 mL was added, and stirring was continued at room temperature for 2 h. The mixture was neutralized with AcOH and the solid collected by filtration and washed well with water. After drying, 7 (2.44 g, 69%) was obtained as an off-white powder: mp 234-236° C.; TLC Rf0.22 (MeOH/CHCl3, 1:5); 1H NMR (DMSO-d6) δ 2.28 (s, 3 H, CH3), 3.73 (s, 3 H, OCH3), 5.95 (s, 1 H), 10.90 (s, 1 H), 11.10 (s, 1 H), 11.76 (1 H). Anal. (C9H10N4O3.0.79C6H6.0.55C7H8O3S) C, H, N.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][C:16](=[O:18])[CH3:17])[C:10]=1[CH2:19][CH2:20][O:21][C:22](=[O:24])[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:25](OCCC(C)C)=O.C([O-])(=O)C.[Na+].C(OC(=O)C)(=O)C>C1(C)C=CC=CC=1>[C:16]([N:15]1[C:11]2[C:10](=[C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:14]=[CH:13][CH:12]=2)[C:19]([CH2:20][O:21][C:22](=[O:24])[CH3:23])=[N:25]1)(=[O:18])[CH3:17]
Reactant: CC(=O)Nc1cccc(OCc2ccccc2)c1CCOC(C)=O
Reactant: CC(C)CCON=O
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Solvent: Cc1ccccc1
Product: CC(=O)OCc1nn(C(C)=O)c2cccc(OCc3ccccc3)c12

Procedure:
This is obtained by nitrosation and subsequent ring closure by treating 2-(2-acetoxyethyl)-3-acetamidophenyl benzyl ether with isoamyl nitrite, sodium acetate and acetic anhydride in toluene at 80° C. It is obtained in the form of colorless crystals; m.p. 99°-100° C.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][C:10]([F:13])([F:12])[F:11])=[CH:5][CH:4]=1.C[O:15][C:16](=[O:37])[CH2:17][O:18][C:19]1[CH:27]=[CH:26][C:25]([S:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=2)=[C:24]2[C:20]=1[CH2:21][CH2:22][CH2:23]2>>[F:11][C:10]([F:13])([F:12])[O:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][O:36][C:33]2[CH:32]=[CH:31][C:30]([CH2:29][S:28][C:25]3[CH:26]=[CH:27][C:19]([O:18][CH2:17][C:16]([OH:37])=[O:15])=[C:20]4[C:24]=3[CH2:23][CH2:22][CH2:21]4)=[CH:35][CH:34]=2)=[CH:4][CH:5]=1
Reactant: COC(=O)COc1ccc(SCc2ccc(O)cc2)c2c1CCC2
Reactant: FC(F)(F)Oc1ccc(CBr)cc1
Product: O=C(O)COc1ccc(SCc2ccc(OCc3ccc(OC(F)(F)F)cc3)cc2)c2c1CCC2

Procedure:
The title compound was prepared in the manner analogous to Example 1F using 1-bromomethyl-4-trifluoromethoxy-benzene and 75C. MS m/z 519 (M+1).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C@H:7]2[CH2:12][CH2:11][CH2:10][C@H:9](O)[CH2:8]2)[CH:2]=1.[C:14]1(=[O:24])[NH:18][C:17](=[O:19])[C:16]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:15]12.CC(OC(/N=N/C(OC(C)C)=O)=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.CCOC(C)=O>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C@@H:7]2[CH2:12][CH2:11][CH2:10][C@H:9]([N:18]3[C:17](=[O:19])[C:16]4=[CH:20][CH:21]=[CH:22][CH:23]=[C:15]4[C:14]3=[O:24])[CH2:8]2)[CH:2]=1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: O[C@H]1CCC[C@H](c2cccnc2)C1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(=O)N1[C@H]1CCC[C@@H](c2cccnc2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 24.1 %

Procedure:
A solution of trans-3-(3-pyridyl)cyclohexanol (3.99 g, 22.5 mmol) in THF (90 mL) was cooled to 4° C. and treated with phthalimide (3.65 g, 24.8 mmol), Diisopropylazodicarboxylate (4.88 mL, 24.8 mmol) and triphenylphosphine (6.50 g, 24.8 mmol). The reaction mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with EtOAc, and washed with H2O and brine. The organic layers was dried over Na2SO4. After concentration under reduced pressure, the residue was purified by column chromatography (Hexane/EtOAc=4/1) to yield cis-N-[3-(3-pyridyl)cyclohexyl]phthalimide (1.66 g, 24%) as colorless powder.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[N:10]=2)[N:5]=[CH:4][C:3]=1C(O)=O>C1(OC2C=CC=CC=2)C=CC=CC=1>[CH3:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][CH:3]=[C:2]2[OH:1]
Reactant: Cc1ccc2ncc(C(=O)O)c(O)c2n1
Solvent: c1ccc(Oc2ccccc2)cc1
Product: Cc1ccc2nccc(O)c2n1
Temperature: 25 °C
Yield: 84.5 %

Procedure:
The suspension of 4-hydroxy-6-methyl-[1,5]naphthyridine-3-carboxylic acid (2.58 g, 12.64 mmol) in diphenylether (100 mL) was heated under refluxing for 4 hrs. After cooling to room temperature, the reaction mixture was poured into a mixture of nHexane (400 mL) and petroleum ether (200 mL). The brown solid was collected by filtration to give 6-methyl-[1,5]naphthyridin-4-ol (1.71 g, 86%). HR-MS-EI (+) m/e calcd for C9H8N2O (M+) 160.0637. found 160.0638
Reaction SMILES: C([NH:5][C:6](=[O:26])[C:7]1[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])=[CH:11][C:10]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[N:9][CH:8]=1)(C)(C)C.CS(O)(=O)=O>>[N:20]1([C:10]2[CH:11]=[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[CH3:19])[C:7]([C:6]([NH2:5])=[O:26])=[CH:8][N:9]=2)[CH2:21][CH2:22][O:23][CH2:24][CH2:25]1
Reactant: Cc1ccccc1-c1cc(N2CCOCC2)ncc1C(=O)NC(C)(C)C
Agent: CS(=O)(=O)O
Product: Cc1ccccc1-c1cc(N2CCOCC2)ncc1C(N)=O
Temperature: 100 °C
Reaction time: 5 h
Yield: 96.8 %

Procedure:
A mixture of 6.0 g (16.5 mMol) N-tert.-butyl-6-morpholin-4-yl-4-o-tolyl-nicotinamide and 12 ml (185 mMol) methanesulfonic acid was stirred at 100° C. for 5 hours, then poured on ice. The aqueous phase was extracted with tert.-butyl-methylether, brought to pH =10 with NaOH aq. 28% and extracted further with tert.-butyl-methylether. The second organic extracts were dried (Na2SO4) and concentrated to yield 4.75 g (96%) 6-morpholin-4-yl-4-o-tolyl-nicotinamide as a light beige crystalline foam.
Reaction SMILES: [CH2:1]([O:4][C:5](=[O:14])[C:6]1[CH:11]=[C:10]([OH:12])[CH:9]=[C:8]([OH:13])[CH:7]=1)[CH:2]=[CH2:3].[Br:15]C1C(O)=CC(C(O)=O)=CC=1O>>[CH2:1]([O:4][C:5](=[O:14])[C:6]1[CH:11]=[C:10]([OH:12])[C:9]([Br:15])=[C:8]([OH:13])[CH:7]=1)[CH:2]=[CH2:3]
Reactant: C=CCOC(=O)c1cc(O)cc(O)c1
Reactant: O=C(O)c1cc(O)c(Br)c(O)c1
Product: C=CCOC(=O)c1cc(O)c(Br)c(O)c1

Procedure:
This compound was prepared analogously to 3,5-Dihydroxy-benzoic acid allyl ester [Example 1(a)], however 4-bromo-3,5-dihydroxybenzoic acid was used instead of 3,5-dihydroxybenzoic acid. 1H NMR (DMSO-d6, 350 MHz): δ=7.04 (s, 2H, aromatic); 5.97-6.06 (m, 1H); 5.25-5.40 (m, 2H); 4.73-4.75(dd, 2H).
Reaction SMILES: Cl.[F:2][CH2:3][CH2:4][N:5]1[N:9]=[N:8][C:7]([CH2:10][CH2:11][NH2:12])=[N:6]1.C(N(CC)CC)C.[F:20][C:21]1[CH:22]=[C:23]([C:31]2[S:35][C:34]([NH:36][C:37](N3C=CN=C3)=[O:38])=[N:33][C:32]=2[CH3:44])[CH:24]=[CH:25][C:26]=1[S:27]([CH3:30])(=[O:29])=[O:28]>CN(C=O)C>[F:2][CH2:3][CH2:4][N:5]1[N:9]=[N:8][C:7]([CH2:10][CH2:11][NH:12][C:37]([NH:36][C:34]2[S:35][C:31]([C:23]3[CH:24]=[CH:25][C:26]([S:27]([CH3:30])(=[O:28])=[O:29])=[C:21]([F:20])[CH:22]=3)=[C:32]([CH3:44])[N:33]=2)=[O:38])=[N:6]1
Reactant: NCCc1nnn(CCF)n1
Reactant: Cc1nc(NC(=O)n2ccnc2)sc1-c1ccc(S(C)(=O)=O)c(F)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cc1nc(NC(=O)NCCc2nnn(CCF)n2)sc1-c1ccc(S(C)(=O)=O)c(F)c1
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
To a stirred solution of 2-[2-(2-Fluoro-ethyl)-2H-tetrazol-5-yl]-ethylamine hydrochloride (0.150 g, 0.0.77 mmol) in DMF (5 ml) was added triethylamine 0.243 ml, 0.1.74 mmol) followed by imidazole-1-carboxylic acid [5-(3-fluoro-4-methanesulfonyl-phenyl)-4-methyl-thiazol-2-yl]-amide (0.265 g, 0.7 mmol). After stirring at room temperature for 3.5 hours, the reaction mixture was filtered and water (3 ml) is added to the filtrate with vigorous stirring. The resulting solid was filtered and dried under high vacuum to yield the titled product as a white solid.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]1[CH:12]=[CH:13][N:14]=[C:7]1[C:6]([NH:15][CH2:16][CH2:17][CH2:18][OH:19])=[N:5]2.[F:20][C:21]([F:32])([F:31])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>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.O.COCCOC>[F:20][C:21]([F:32])([F:31])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]1[CH:12]=[CH:13][N:14]=[C:7]1[C:6]([NH:15][CH2:16][CH2:17][CH2:18][OH:19])=[N:5]2
Reactant: OB(O)c1ccccc1C(F)(F)F
Reactant: OCCCNc1nc2cc(Br)ccc2n2ccnc12
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: [K+]
Solvent: O
Solvent: COCCOC
Product: OCCCNc1nc2cc(-c3ccccc3C(F)(F)F)ccc2n2ccnc12
Yield: 38.7 %

Procedure:
Tetrakis(triphenylphosphine)palladium (11 mg, 0.009 mmol, 0.1 eq), 3-(7-Bromo-imidazo[1,2-a]quinoxalin-4-ylamino)-propan-1-ol (30 mg, 0.093 mmol, 1 eq), 2-(trifluoromethyl)phenylboronic acid (19 mg, 0.102 mmol, 1.1 eq), potassium carbonate (51 mg, 0.372 mmol, 4 eq) are stirred under argon in a mixture of degassed water/1,2-dimethoxyethane (1 mL/1 mL) at 80° C. for 3 days. Evaporation of 1,2-dimethoxyethane, partition (water/ethyl acetate), extraction of the aqueous phase (two times ethyl acetate), reunion of the organic phases, drying over magnesium sulfate and purification over silicagel on prep TLC (eluent: dichloromethane/methanol 90:10) affords the title compound as an off-white solid (14 mg, 0.036 mmol, 39%).
Reaction SMILES: [N+:1]([C:4]1[CH:14]=[CH:13][C:7]2[O:8][CH2:9][C:10](=[O:12])[NH:11][C:6]=2[CH:5]=1)([O-])=O>CO.[Pd]>[NH2:1][C:4]1[CH:14]=[CH:13][C:7]2[O:8][CH2:9][C:10](=[O:12])[NH:11][C:6]=2[CH:5]=1
Reactant: O=C1COc2ccc([N+](=O)[O-])cc2N1
Agent: [Pd]
Solvent: CO
Product: Nc1ccc2c(c1)NC(=O)CO2
Reaction time: 8 h
Yield: 55.6 %

Procedure:
Pd/C (10%) was added to a suspension of 6-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one (1.5 g) in MeOH (20 mL) and the reaction mixture was stirred under an atmosphere of hydrogen overnight. The mixture was filtered through celite and the filtrate was concentrated under vacuum to give the product (0.705 g, 56%) as a beige solid.
Reaction SMILES: [Cl-].[Mg+2].[Cl-].C(CC(OCC1C=CC=CC=1)=O)#N.C(N(CC)CC)C.CS(C1C=C(C(F)(F)F)C=CC=1C(Cl)=O)(=O)=O.Cl.[CH3:42][S:43]([C:46]1[CH:66]=[C:65]([C:67]([F:70])([F:69])[F:68])[CH:64]=[CH:63][C:47]=1[C:48]([CH:50]([C:61]#[N:62])C(OCC1C=CC=CC=1)=O)=[O:49])(=[O:45])=[O:44]>C(#N)C.C1COCC1>[CH3:42][S:43]([C:46]1[CH:66]=[C:65]([C:67]([F:68])([F:70])[F:69])[CH:64]=[CH:63][C:47]=1[C:48]([CH2:50][C:61]#[N:62])=[O:49])(=[O:45])=[O:44]
Reactant: CS(=O)(=O)c1cc(C(F)(F)F)ccc1C(=O)C(C#N)C(=O)OCc1ccccc1
Agent: CS(=O)(=O)c1cc(C(F)(F)F)ccc1C(=O)Cl
Agent: Cl
Agent: N#CCC(=O)OCc1ccccc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: CC#N
Product: CS(=O)(=O)c1cc(C(F)(F)F)ccc1C(=O)CC#N
Temperature: 0 °C
Reaction time: 0.33 h

Procedure:
1.10 g of magnesium chloride (11.5 mmol) in 15 ml of acetonitrile are admixed at 0° C. with 2.0 g (11.4 mmol) of benzyl cyanoacetate and 2.3 g (22.9 mmol) of triethylamine. After stirring for 20 min at 0° C., 3.27 g (11.4 mmol) of 2-(methylsulfonyl)-4-trifluoromethylbenzoyl chloride are added in portions. The mixture is stirred for 16 h at RT, acidified with 2n HCl and extracted with ether. The organic phase is dried and concentrated in a rotary evaporator. Yield 2.74 g (56%; 1H-NMR, CDCl3, 400 MHz: 14.20 (bs, 1H), 8.43 (s, 1H), 8.05 (d, 1H), 7.82 (d, 1H), 5.40 (s, 2H), 3.30 (s, 3H)) of benzyl 2-(2-(methylsulfonyl)-4-trifluoromethylbenzoyl)cyanoacetate, which, after adding 0.65 g (1 eq) of triethylamine in THF, is hydrogenated for 2 h. After filtration, the mixture is diluted with ethyl acetate and washed with 2N HCl, NaHCO3 solution and sodium chloride solution. Yield 1.41 g (75%). 1H NMR, CDCl3, 400 MHz: 8.36 (s, 1H), 8.04 (d, 1H), 7.63 (d, 1H), 4.03 (s, 2H), 3.21 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.Cl[CH2:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16].[I-:19].[Na+]>C(#N)C>[I-:19].[CH3:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N+:6]=1[CH2:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16]
Reactant: C[Si](C)(C)CCCCl
Reactant: Cc1nc2ccccc2s1
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Product: Cc1sc2ccccc2[n+]1CCC[Si](C)(C)C

Procedure:
2-Methylbenzothiazole (14.9 g, 0.10 moles), 3-chloropropyltrimethylsilane (15.0 g, 0.10 moles) and sodium iodide (15.0 g, 0.10 moles) were all suspended in acetonitrile (250 ml) and with stirring the mixture was heated at reflux for four days. The mixture was filtered while hot to remove sodium chloride, the solid was washed with acetonitrile and the filtrate was concentrated to dryness. The residue was stirred with ether and dried. Yield 916 g (25%) mp 203°-205°.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:4]=[CH:5][C:6]2[C:7](=[O:13])[CH2:8][CH2:9][CH2:10][C:11]=2[CH:12]=1.[BH4-].[Na+]>CO>[CH3:1][O:2][C:3]1[N:4]=[CH:5][C:6]2[CH:7]([OH:13])[CH2:8][CH2:9][CH2:10][C:11]=2[CH:12]=1
Reactant: COc1cc2c(cn1)C(=O)CCC2
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1cc2c(cn1)C(O)CCC2
Temperature: 25 °C
Reaction time: 2 h
Yield: 83.3 %

Procedure:
To a stirred 0° C. solution of 3-methoxy-6,7-dihydroisoquinolin-8(5H)-one (1.90 g, 10.72 mmol) in methanol (30 mL) was added sodium borohydride (1.10 g, 29.08 mmol) in small portions. The resulting mixture was allowed to warm to room temperature. After 2 h, the mixture was quenched with water (20 mL) and was extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over sodium sulfate, filtered, and concentrated. Chromatographic purification of the residue (silica gel, 50% ethyl acetate in petroleum ether elute) afforded 1.60 g (85%) of 3-methoxy-5,6,7,8-tetrahydroisoquinolin-8-ol as a light yellow solid.
Reaction SMILES: [CH:1]1([N:4]([CH2:11][CH2:12][OH:13])[S:5]([CH2:8][CH2:9][CH3:10])(=[O:7])=[O:6])[CH2:3][CH2:2]1.[CH2:14]([S:17](Cl)(=[O:19])=[O:18])[CH2:15][CH3:16]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH:1]1([N:4]([S:5]([CH2:8][CH2:9][CH3:10])(=[O:7])=[O:6])[CH2:11][CH2:12][O:13][S:17]([CH2:14][CH2:15][CH3:16])(=[O:19])=[O:18])[CH2:3][CH2:2]1
Reactant: CCCS(=O)(=O)N(CCO)C1CC1
Reactant: CCCS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CCCS(=O)(=O)OCCN(C1CC1)S(=O)(=O)CCC
Temperature: 25 °C
Yield: 78.8 %

Procedure:
To a solution of propane-1-sulfonic acid cyclopropyl-(2-hydroxy-ethyl)-amide (150 mg, 0.8 mmol) in CH2Cl2 and DMAP (97 mg, 0.8 mmol) was added dropwise a solution of propane-1-sulfonyl chloride (97 mg, 0.8 mmol) in CH2Cl2. The resulting mixture was stirred at room temperature over night, diluted with 50 ml of CH2Cl2, extracted subsequently with water, 1 M HCl, and brine, tried over Na2SO4, filtered and the solvent evaporated to obtain 197.5 mg of product which was used in the next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:9](=[N:24][O:25][CH:26]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[CH3:27])[CH2:10][NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:21])[F:20])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.C(C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(#N)C>[Cl:1][C:2]1[C:3](/[C:9](=[N:24]\[O:25][CH:26]([C:28]2[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=2)[CH3:27])/[CH2:10][NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:20])[F:21])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CC(ON=C(CNC(=O)c1ccccc1C(F)(F)F)c1ncc(Cl)cc1Cl)c1ccc(F)cc1
Agent: O=C(c1ccccc1)c1ccccc1
Solvent: CC#N
Product: CC(O/N=C(/CNC(=O)c1ccccc1C(F)(F)F)c1ncc(Cl)cc1Cl)c1ccc(F)cc1
Yield: 57.3 %

Procedure:
To 171 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-[1-(4-fluorophenyl)ethoxyimino]ethyl]-2-(trifluoromethyl)benzamide in 3 ml of acetonitrile, 1 mg of benzophenone was added, and the mixture was irradiated with light for 12 hours in a quartz cell (manufactured by Fine, 4 clear windows for spectroscopy) using a 100 W high-pressure mercury lamp (manufactured by USHIO INC., lamp: UM-102, power supply: UM-103B-B). After completion of the reaction, the solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to obtain 98 mg of the desired product as a pale yellow resinous substance.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([O:16][CH2:17][CH2:18][CH2:19][O:20][CH3:21])[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7]2.[N:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[S:28](Cl)(=[O:30])=[O:29]>N1C=CC=CC=1>[CH3:21][O:20][CH2:19][CH2:18][CH2:17][O:16][C:4]1[CH:5]=[C:6]2[C:10](=[C:2]([NH:1][S:28]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][N:22]=3)(=[O:30])=[O:29])[CH:3]=1)[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7]2
Reactant: O=S(=O)(Cl)c1ccccn1
Reactant: CCOC(=O)c1cc2cc(OCCCOC)cc(N)c2[nH]1
Solvent: c1ccncc1
Product: CCOC(=O)c1cc2cc(OCCCOC)cc(NS(=O)(=O)c3ccccn3)c2[nH]1
Temperature: 25 °C
Reaction time: 15 h
Yield: 90 %

Procedure:
To a mixture of ethyl 7-amino-5-(3-methoxypropoxy)-1H-indole-2-carboxylate (3.00 g) and pyridine (50 mL) was added pyridine-2-sulfonyl chloride (2.0.g) at 0° C., and the mixture was stirred at room temperature for 15 hr. The reaction mixture was concentrated, 1N hydrochloric acid and ethyl acetate were added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with water and saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (2:1-1:1, volume ratio) to give the title compound (4.02 g, yield 90%) as colorless crystals. The crystals were recrystallized from ethyl acetate-hexane to give colorless prism crystals. melting point 126-127° C.