Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C@H:2]1[C@H:9]2[C@H:5]([N:6]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[N+:20]([O-:22])=[O:21])(=[O:13])=[O:12])[C:7](=[O:10])[O:8]2)[CH2:4][CH2:3]1.N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])(=O)=O>C(Cl)Cl>[Si:37]([O:1][C@H:2]1[C@H:9]2[C@H:5]([N:6]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[N+:20]([O-:22])=[O:21])(=[O:13])=[O:12])[C:7](=[O:10])[O:8]2)[CH2:4][CH2:3]1)([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38]
Reactant: O=C1O[C@H]2[C@H](O)CC[C@H]2N1S(=O)(=O)c1ccccc1[N+](=O)[O-]
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: Cc1cccc(C)n1
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)O[C@@H]1CC[C@@H]2[C@H]1OC(=O)N2S(=O)(=O)c1ccccc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of (3aR*,6R*,6aR*)-6-hydroxy-3-((2-nitrophenyl)sulfonyl)hexahydro-2H-cyclo-penta[d]oxazol-2-one (1.2 g, 3.66 mmol) and 2,6-lutidine (0.851 mL, 7.31 mmol) in CH2Cl2 (25 mL) was added dropwise at 0° C. the tert-butyldimethylsilyl trifluoromethanesulfonate (1.091 mL, 4.75 mmol). The reaction mixture was stirred for 1 h at 0° C. followed by 2 h at RT. The reaction mixture was diluted with CH2Cl2 and washed with 20% aqueous NaH2PO4 solution and H2O, dried over MgSO4, filtered and concentrated. The title compound was obtained after crystallization from EtOAc/heptane as white solid (1.5 g, 88%): TLC (heptane/EtOAc 1:1) Rf=0.54; tR=1.58 min (UPLC 1), tR=1.43 min (LC-MS 3); ESI-MS: 460 [M+NH4]+ (LC-MS 3).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([Br:16])[CH:9]=2)=[O:4].C([O-])([O-])=O.[K+].[K+].[CH:23]1[CH:28]=[CH:27][C:26]([CH2:29]Br)=[CH:25][CH:24]=1>CN(C=O)C.CCOC(C)=O.O>[CH2:29]([O:15][C:14]1[C:13]2[C:8](=[CH:9][C:10]([Br:16])=[CH:11][CH:12]=2)[CH:7]=[N:6][C:5]=1[C:3]([O:2][CH3:1])=[O:4])[C:26]1[CH:27]=[CH:28][CH:23]=[CH:24][CH:25]=1
Reactant: BrCc1ccccc1
Reactant: COC(=O)c1ncc2cc(Br)ccc2c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1ncc2cc(Br)ccc2c1OCc1ccccc1
Temperature: 60 °C
Reaction time: 16 h

Procedure:
A mixture of 7-bromo-4-hydroxy-isoquinoline-3-carboxylic acid methyl ester (955.0 mg, 3.4 mmol), K2CO3 (1.2 g, 8.5 mmol), KI (56.2 mg, 0.3 mmol) and BnBr (0.6 mL, 4.7 mmol) in DMF (17 mL) was stirred at 60° C. for 16 hours. After cooling to room temperature, the mixture was diluted with EtOAc (100 mL) and H2O (100 mL). The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over MgSO4, concentrated, and purified by flash chromatography (0-20% EtOAc/CH2Cl2) to give the title compound in 1.1 g. MS: (+) m/z 372.20 (M+1).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5][CH2:6][OH:7].[S:11]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12]1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.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>[S:11]1[CH:15]=[CH:14][C:13]([C:2]2[CH:3]=[C:4]([CH2:5][CH2:6][OH:7])[CH:8]=[CH:9][CH:10]=2)=[CH:12]1
Reactant: OCCc1cccc(Br)c1
Reactant: OB(O)c1ccsc1
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: Cc1ccccc1
Product: OCCc1cccc(-c2ccsc2)c1
Temperature: 25 °C

Procedure:
A mixture of 3-bromo-phenethyl-alcohol (1 g, 4.97 mmol), 3-thiophene-boronic-acid (1.9 g, 14.9 mmol, 3.0 equiv), Pd(PPh3)4 (172 mg, 0.149 mmol, 0.03 equiv), and 2M Na2CO3 (10.8 mL, 22.4 mmol, 4.5 equiv) in toluene (40 mL) is heated to reflux 1 h, under an argon atmosphere. The resulting suspension is allowed to cool to RT and filtered through a pad of celite, washing the filter cake with CH2Cl2 and water. The layers are separated. The organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the crude material by silica gel column chromatography (CH2Cl2/Et2O, 95/5) affords the title compound: ES-MS: 205.0 [M+H]+; single peak at tR=4.27 min (System 2); Rf=0.32 (CH2Cl2/Et2O, 95/5).
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([N+:9]([O-:11])=[O:10])[C:3]=1[O:12][CH2:13][CH:14]([OH:16])[CH3:15].[C:17]1([CH3:27])[CH:22]=[CH:21][C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:19][CH:18]=1.C(OCC)(=O)C.Cl>N1C=CC=CC=1>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([N+:9]([O-:11])=[O:10])[C:3]=1[O:12][CH2:13][CH:14]([O:16][S:23]([C:20]1[CH:21]=[CH:22][C:17]([CH3:27])=[CH:18][CH:19]=1)(=[O:25])=[O:24])[CH3:15]
Reactant: CC(O)COc1c([N+](=O)[O-])ccc(F)c1F
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OC(C)COc2c([N+](=O)[O-])ccc(F)c2F)cc1
Reaction time: 4 h
Yield: 87.2 %

Procedure:
To a solution of 4.5 g of the compound obtained in Example 5 in 8.6 ml of pyridine was added 4.36 g of p-toluenesulfonyl chloride and the mixture was stirred under cooling with ice for 4 hours, and then at room temperature for 4 hours. To the mixture were added ethyl acetate and 1 N hydrochloric acid. The mixture was shaken, and the organic layer was separated. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified through silica gel column chromatography to yield 6.52 g of the titled compound.
Reaction SMILES: [S-:1][C:2]#[N:3].[K+].[F:5][CH:6]([F:15])[O:7][C:8]1[N:13]=[CH:12][C:11]([NH2:14])=[CH:10][CH:9]=1.BrBr.O>C(O)(=O)C>[F:15][CH:6]([F:5])[O:7][C:8]1[N:13]=[C:12]2[S:1][C:2]([NH2:3])=[N:14][C:11]2=[CH:10][CH:9]=1
Reactant: N#C[S-]
Reactant: Nc1ccc(OC(F)F)nc1
Agent: BrBr
Agent: [K+]
Solvent: O
Solvent: CC(=O)O
Product: Nc1nc2ccc(OC(F)F)nc2s1
Temperature: 25 °C
Yield: 36.1 %

Procedure:
To acetic acid (10 mL) cooled in an ice bath was added potassium thiocyanate (3.18 g, 32.8 mmol) and 6-(difluoromethoxy)pyridin-3-amine (1 g, 4.1 mmol). The reaction was cooled in an ice-salt bath until the reaction temperature reached <0° C. A solution of bromine (0.65 mL, 12.7 mmol) in acetic acid (3 mL) was added dropwise over 2 hours at a rate that maintained the reaction temperature <0° C. This gave a very thick mixture. After the addition was complete, the mixture was left to stir and allowed to slowly warm to room temperature overnight. After stirring overnight, water (5 mL) was added and the mixture was heated to 85° C. in an oil bath. This mixture was then filtered while still hot. The yellow filter cake was returned to the reaction flask, and an additional 5 mL acetic acid was added. The mixture was heated again to 85° C., and then filtered while still hot. The combined filtrates were cooled in an ice bath and neutralized to pH 8 with concentrated ammonium hydroxide. A yellow precipitate formed which was then collected by filtration. This crude material was purified by column chromatography (12-100% ethyl acetate/hexanes) to afford 5-(difluoromethoxy)thiazolo[5,4-b]pyridin-2-amine (321 mg, 1.48 mmol, 36.1% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.64-7.81 (m, 2H), 6.92 (d, J=8.53 Hz, 1H). MS (LC/MS) R.T.=1.66; [M+H]+=218.10.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([O:12][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[O:19][CH:18]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:17][CH2:16]3)=[CH:10][CH:11]=1)=[O:4].C(=O)([O-])[O-].[K+].[K+].[OH:35][CH:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1.O>C(#N)C>[OH:35][CH:36]1[CH2:41][CH2:40][N:39]([CH2:2][C:3]([NH:5][C:6]2[CH:7]=[N:8][C:9]([O:12][C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[O:19][CH:18]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:17][CH2:16]4)=[CH:10][CH:11]=2)=[O:4])[CH2:38][CH2:37]1
Reactant: O=C(CCl)Nc1ccc(Oc2ccc3c(c2)CCC(c2ccccc2)O3)nc1
Reactant: OC1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: O=C(CN1CCC(O)CC1)Nc1ccc(Oc2ccc3c(c2)CCC(c2ccccc2)O3)nc1
Temperature: 25 °C

Procedure:
To a solution of 2-Chloro-N-[6-(2-phenylchroman-6-yloxy)-pyridin-3-yl]-acetamide (200 mg) in acetonitrile was added potassium carbonate (133 mg) and 4-hydroxypiperidine (62 mg). The mixture was stirred at room temperature. Water was added to the reaction mixture. Solution was extracted with ethyl acetate. Organic extract was dried and evaporated. Product was purified by column chromatography using 10% methanol in methylene chloride as eluant. 2-(4-Hydroxypiperidin-1-yl)-N-[6-(2-phenyl-chroman-6-yloxy)-pyridin-3-yl]-acetamide was isolated as its hydrochloride salt. 1H-NMR (400 MHz; d4-MeOH) δ: 8.41 (s, 1H), 8.06 (dd, 1H, J 2.7, 9.0 Hz), 7.45-7.28 (m, 5H), 6.95-6.85 (m, 4H), 5.10 (dd, 1H, J 2.1, 10.0 Hz), 4.13 (s, 2H), 3.72-3.68 (m, 1H), 3.48-3.43 (m, 3H), 3.25-3.10 (m, 1H), 3.02-2.97 (m, 1H), 2.81-2.75 (m, 1H), 2.26-1.76 (m, 6H). (M)+=459 (5.8%), 360 (7.4%), 114 (100%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[C:14]([CH:23]=[CH:24][C:25]([OH:27])=[O:26])=[CH:13]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1>C1COCC1.[Pd]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[C:14]([CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[CH:13]2)(=[O:10])=[O:11])=[CH:5][CH:4]=1
Reactant: COc1ccc(S(=O)(=O)n2cc(C=CC(=O)O)c3cc(OC)ccc32)cc1
Agent: [Pd]
Solvent: C1CCOC1
Product: COc1ccc(S(=O)(=O)n2cc(CCC(=O)O)c3cc(OC)ccc32)cc1
Reaction time: 8 h

Procedure:
To a solution of 3-[1-(4-Methoxy benzenesulfonyl)-5-methoxy-1H-indol-3-yl]-acrylic acid 118 (1.0 g, 2.6 mmol) dissolved in THF (14 mL), Pd/C (67 mg) was added in one portion. The solution was attached to the Parr hydrogenator. The reaction was allowed to proceed overnight at 20-22 psi. The solution was filtered over celite, and the palladium-celite pad was washed with ethyl acetate (40 mL), and methanol (20 mL). The combined washes/solution was evaporated under reduced pressure to afford straw colored oil that solidified after cooling under high vacuum. The crude was triturated with diethyl ether to leave behind off white solid as product 1. (0.620 g, 62%) 1H NMR(DMSO) δ 7.86 (d, J=9.2 Hz, 1H), 7.75 (d, J=8.4 Hz, 1H), 6.92 (dd, J=2.4 Hz, 9.2 Hz, 1H), 6.88 (s, 1H), 6.83 (d, J=9.2 Hz, 2H), 3.76 (s, 3H), 2.96 (t, J=7.6 Hz, 14.8 Hz, 2H), 2.74 (t, J=7.6 Hz, 14.8 Hz, 2H) (M−1=388.6).
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][N:12]2[CH:15]=[N:16][N:17]=[C:11]2[CH:10]=1)C1C=CC=CC=1>C(O)C.[Pd]>[N:17]1[N:16]=[CH:15][N:12]2[CH:13]=[CH:14][C:9]([OH:8])=[CH:10][C:11]=12
Reactant: c1ccc(COc2ccn3cnnc3c2)cc1
Agent: [Pd]
Solvent: CCO
Product: Oc1ccn2cnnc2c1
Reaction time: 3 h

Procedure:
To a solution of 7-(benzyloxy)-[1,2,4]triazolo[4,3-a]pyridine (0.512 g, 2.27 mmol) in ethanol (30 mL) was added Pd/C (0.5 g). After stirring under a hydrogen balloon for 3 hours, the mixture was filtered through celite and washed with ethanol (30 mL). The filtrate was concentrated under reduced pressure and chromatographed (20:1 dichloromethane/methanol) to provide the product.
Reaction SMILES: [O:1]=[C:2]1[CH2:6][S:5][C:4](=[S:7])[N:3]1[CH:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]([OH:16])=[O:15])[CH2:9]1.[F:17][C:18]([F:33])([F:32])[C:19]1[CH:20]=[C:21]([C:25]2[O:29][C:28]([CH:30]=O)=[CH:27][CH:26]=2)[CH:22]=[CH:23][CH:24]=1.C(O)C>CO.ClCCl.[Cl-].[NH4+]>[F:33][C:18]([F:17])([F:32])[C:19]1[CH:20]=[C:21]([C:25]2[O:29][C:28]([CH:30]=[C:6]3[S:5][C:4](=[S:7])[N:3]([CH:8]4[CH2:13][CH2:12][CH2:11][CH:10]([C:14]([OH:16])=[O:15])[CH2:9]4)[C:2]3=[O:1])=[CH:27][CH:26]=2)[CH:22]=[CH:23][CH:24]=1
Reactant: O=Cc1ccc(-c2cccc(C(F)(F)F)c2)o1
Reactant: O=C(O)C1CCCC(N2C(=O)CSC2=S)C1
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Solvent: CCO
Solvent: CO
Product: O=C(O)C1CCCC(N2C(=O)C(=Cc3ccc(-c4cccc(C(F)(F)F)c4)o3)SC2=S)C1
Temperature: 25 °C
Reaction time: 65 h
Yield: 73.7 %

Procedure:
3-(4-Oxo-2-thioxo-thiazolidin-3-yl)-cyclohexanecarboxylic acid (80 mg, 0.31 mmol), 5-(3-trifluoromethyl-phenyl)-furan-2-carbaldehyde (79 mg, 0.33 mmol) (purchased from Aldrich Chemical Company), and diethylenediamine diacetate (59 mg, 0.33 mmol) were combined in a 20 mL vial with ethanol (5 mL) and stirred at room temperature for 65 h. The reaction mixture was diluted with 10% methanol in dichloromethane (200 mL) and aqueous ammonium chloride (20 mL) and stirred at room temperature for 15 minutes. The layers were separated and the aqueous layer was extracted with 10% methanol in dichloromethane (2×100 mL). The combined organic extracts were washed with 0.6 N sodium hydrogensulfite (1×20 mL) and then brine (1×20 mL), dried (sodium sulfate) and concentrated under vacuum. The residue was triturated with dichloromethane/hexanes (1:5, 30 mL), filtered and dried overnight in a vacuum oven at 55° C. to afford 3-{5-[1-[5-(3-trifluoromethyl-phenyl)-furan-2-yl]-methylidene]-4-oxo-2-thioxo-thiazolidin-3-yl}-cyclohexanecarboxylic acid (110 mg, 74%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ 1.25-1.41 (2H, m), 1.67 (1H, m), 1.87-1.92 (3H, m), 2.29-2.45 (3H, m), 4.97 (1H, m), 7.37 (1H, d, J=3.6 Hz), 7.55 (1H, d, J=3.6 Hz), 7.62 (1H, s), 7.77-7.85 (2H, m), 8.11-8.18 (2H, m), 12.18 (1H, s); APCI-MS: 481.47; HPLC: 95%.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:14][CH2:15][CH2:16][C:17](O)=[O:18].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:15](=[O:14])[CH2:16][CH2:17][OH:18])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: O=C(O)CCO
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCN(C(=O)CCO)CC1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of 1-tert-butoxycarbonylpiperazine, 3-hydroxypropionic acid, 1-hydroxybenzotriazole (HOBt), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI), and DMF was stirred at ambient temperature for 24 hours to yield 3-(4-tert-butoxycarbonylpiperazin-1-yl)-3-oxopropan-1-ol, which was stirred together with 4M HCl-dioxane solution and MeOH at ambient temperature for 16 hours to yield 3-oxo-3-piperazin-1-ylpropan-1-ol hydrochloride.
Reaction SMILES: CC1(C)[O:7][C:6]2C=CC([N+]([O-])=O)=C[C:5]=2NC1=O.[NH2:17][C:18]1[CH:23]=[C:22]([Cl:24])[C:21]([N+:25]([O-:27])=[O:26])=[CH:20][C:19]=1[OH:28]>>[Cl:24][C:22]1[C:21]([N+:25]([O-:27])=[O:26])=[CH:20][C:19]2[O:28][CH2:5][C:6](=[O:7])[NH:17][C:18]=2[CH:23]=1
Reactant: Nc1cc(Cl)c([N+](=O)[O-])cc1O
Reactant: CC1(C)Oc2ccc([N+](=O)[O-])cc2NC1=O
Product: O=C1COc2cc([N+](=O)[O-])c(Cl)cc2N1

Procedure:
This compound was prepared using the general procedure described for 2,2-Dimethyl-6-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one above except 2-amino-4-chloro-5-nitrophenol was used as starting material.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1.[CH3:13][O:14][C:15]1[CH:16]=[C:17]([S:23](Cl)(=[O:25])=[O:24])[CH:18]=[CH:19][C:20]=1[O:21][CH3:22]>>[CH3:13][O:14][C:15]1[CH:16]=[C:17]([S:23]([NH:1][C:2]2[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=2)(=[O:24])=[O:25])[CH:18]=[CH:19][C:20]=1[O:21][CH3:22]
Reactant: CCOC(=O)Cc1csc(N)n1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1OC
Product: CCOC(=O)Cc1csc(NS(=O)(=O)c2ccc(OC)c(OC)c2)n1

Procedure:
The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 3,4-dimethoxybenzenesulfonyl chloride as described in the synthetic METHOD B to give a white solid (19.3 mg) with purity >90%. LCMS (pos) m/z 387.2.
Reaction SMILES: Br[C:2]1[N:6]2[C:7]3[CH:19]=[CH:18][CH:17]=[N:16][C:8]=3[NH:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:5]2=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:28]2[CH:33]=[CH:32][C:31]([C:34]3([NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[CH2:37][CH2:36][CH2:35]3)=[CH:30][CH:29]=2)O1.C([O-])(O)=O.[Na+].O>C1(C)C(CCO)=CC=CC=1.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>[N:4]1[CH:3]=[C:2]([C:28]2[CH:29]=[CH:30][C:31]([C:34]3([NH:38][C:39](=[O:45])[O:40][C:41]([CH3:43])([CH3:42])[CH3:44])[CH2:35][CH2:36][CH2:37]3)=[CH:32][CH:33]=2)[N:6]2[C:5]=1[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[NH:9][C:8]1[N:16]=[CH:17][CH:18]=[CH:19][C:7]2=1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CCC1
Reactant: Brc1cnc2n1-c1cccnc1Nc1ccccc1-2
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cc1ccccc1CCO
Agent: O=C([O-])O
Solvent: O
Product: CC(C)(C)OC(=O)NC1(c2ccc(-c3cnc4n3-c3cccnc3Nc3ccccc3-4)cc2)CCC1
Temperature: 25 °C

Procedure:
A mixture of 3-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepine (1.48 g, 4.7 mmol), tert-butyl {1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclobutyl}carbamate (2.12 g, 5.7 mmol), sat.NaHCO3 (4 mL), and tetrakis(triphenylphosphine)palladium(0) (0.55 g, 0.47 mmol) in toluene-ethanol (1/1, 40 mL) was heated to refluxed temperature for 15 hours. After cooling to room temperature the reaction mixture was poured into water and extracted with ethyl acetate. The organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration the solvent was evaporated in vacuo. The crude product was purified by silica gel chromatography (hexane/ethyl acetate) to give a yellow solid (quant.). 1HNMR (CDCl3) 400 MHz δ: 8.09-8.06 (m, 2H), 7.39 (s, 1H), 7.37(d, J=8.0 Hz, 2H), 7.30 (td, J=7.6, 1.5 Hz, 1H), 7.15 (d, J=8.0 Hz, 2H), 7.16-7.10 (m, 1H), 6.98 (dd, J=8.0, 1.2 Hz, 1H), 6.95 (d, J=8.0 Hz, 1H), 6.70 (dd, J=7.7, 4.9 Hz, 1H), 6.27 (s, 1H), 5.08 (s, 1H), 2.57-2.39 (m, 4H), 2.18-2.07 (m, 1H), 1.93-1.84 (m, 1H), 1.48-1.19 (brs, 9H); LC/MS [M+H]: 480.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH2:6][N:7]2[CH:16]=[CH:15][C:9]3[CH:10]=[CH:11][CH:12]=[C:13]([CH:14]=1)[C:8]2=3)=[O:4].[H][H]>[Pd].O1CCCC1>[CH3:1][O:2][C:3]([CH:5]1[CH2:14][C:13]2[C:8]3=[C:9]([CH:15]=[CH:16][N:7]3[CH2:6]1)[CH:10]=[CH:11][CH:12]=2)=[O:4]
Reactant: COC(=O)C1=Cc2cccc3ccn(c23)C1
Reactant: [H][H]
Agent: [Pd]
Solvent: C1CCOC1
Product: COC(=O)C1Cc2cccc3ccn(c23)C1

Procedure:
4H-Pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid methyl ester (10.9 g, 51.1 mmol) and palladium on carbon (5%, 1.1 g) were taken into tetrahydrofuran (300 mL), and the mixture was stirred under 60 psi of hydrogen at room temperature for 8 hours. Additional palladium on carbon (5%, 0.6 g) was added, and the mixture stirred under 60 psi of hydrogen for another 15 hours. Filtration and concentration of filtrate gave the desired compound.
Reaction SMILES: F[B-](F)(F)F.[CH2:6]([SH+:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[F:21][Sb-:22]([F:27])([F:26])([F:25])([F:24])[F:23].[Na+]>C(Cl)Cl>[F:21][Sb-:22]([F:27])([F:26])([F:25])([F:24])[F:23].[CH2:14]([S+:13]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: c1ccc(C[SH+]Cc2ccccc2)cc1
Agent: F[B-](F)(F)F
Agent: F[Sb-](F)(F)(F)(F)F
Agent: [Na+]
Solvent: ClCCl
Product: c1ccc(C[S+](Cc2ccccc2)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 191.3 %

Procedure:
A mixture of 123.0 g (0.325 mol) of dibenzylsulfonium tetrafluoroborate in 400 ml of methylene chloride is dissolved in a 2 liter round-bottomed flask at RT under N2 to give a clear solution. 117.8 g of sodium hexafluoroantimonate are then added and the mixture is stirred at RT for 31/2 h. The suspension is now filtered over silica gel and the solvent is removed from the filtrate using a rotary evaporator. The slightly reddish viscous residue is dissolved again in 250 ml of methanol, and after addition of 250 ml of water the product is allowed to crystallize at RT for 1-2 h. The suspension is filtered and the residue is washed with water. The product is then dried under a high vacuum at RT overnight. 163.9 g (95% of theory) of dibenzylphenylsulfonium hexafluoroantimonate are obtained as white crystals of melting point 105°-109° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([CH3:13])[CH:4]=1.[Br:14]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.O>C(Cl)(Cl)(Cl)Cl>[Br:14][CH2:13][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[CH:12]=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8]
Reactant: COC(=O)c1ccc(OC)cc1C
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: O
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1ccc(OC)cc1CBr
Temperature: 25 °C
Yield: 144.7 %

Procedure:
To a solution of methyl 4-methoxy-2-methylbenzoate (1 g, 5.6 mmol) in CCl4 (25 mL) was added dropwise N-bromosuccinimide (1.1 g, 6.2 mmol) previously dissolved in CCl4 (5 mL) and a catalytic amount of benzoyl peroxide. The mixture was refluxed for 2 hours, cooled to room temperature and poured onto iced water. The aqueous mixture was extracted with DCM (3×), and the combined organics were dried over MgSO4, filtered, and concentrated in vacuo to provide 2.1 g of the titled product as light yellow solid (˜100% yield): [M+H+] m/z 260.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][N:8]=[CH:9]2)([O-])=O>CO.[Pd]>[NH2:1][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][N:8]=[CH:9]2
Reactant: O=[N+]([O-])c1cccc2cnccc12
Agent: [Pd]
Solvent: CO
Product: Nc1cccc2cnccc12
Yield: 112 %

Procedure:
5-Nitroisoquinoline (16.4 g) was dissolved in methanol (200 ml) and hydrogenated over palladium on charcoal (1.64 g) at 45 psi. When the hydrogenation was complete, the catalyst was removed by filtration and the solvent removed in vacuo to yield 15.2 g of 5-aminoisoquinoline as a brown powder. This was recrystallized from chloroform-ligroin (b.p. 60°-90° C.) to yield 5-aminoisoquinoline (12.1 g) as a light tan powder, m.p. 127°-129° C. (lit. value, 128° C.).
Reaction SMILES: [N+:1]([C:4]1[C:5]([S:13][CH3:14])=[N:6][C:7]([CH3:12])=[CH:8][C:9]=1[S:10][CH3:11])([O-])=O.O1CCOCC1.[H][H]>[Ni].CO>[NH2:1][C:4]1[C:5]([S:13][CH3:14])=[N:6][C:7]([CH3:12])=[CH:8][C:9]=1[S:10][CH3:11]
Reactant: CSc1cc(C)nc(SC)c1[N+](=O)[O-]
Reactant: [H][H]
Agent: [Ni]
Solvent: C1COCCO1
Solvent: CO
Product: CSc1cc(C)nc(SC)c1N
Yield: 85 %

Procedure:
A mixture of 18.9 g (0.082 mol) 3-nitro-2,4-bis(methylthio)-6-methylpyridine and 18.9 g Raney nickel in 600 ml. 1,4-dioxane and 300 ml methanol was shaken with hydrogen (15 psi) in a Parr hydrogenation apparatus for 3.5 hours. The catalyst was filtered and the filtrate was concentrated to dryness in vacuo. The solid residue was chromatographed on silica gel (650 g), eluting with 9:1 hexane/ethyl acetate to yield 14.0 g. (85% yield) of the title compound as an off white solid.
Reaction SMILES: [CH2:1]([O:4]C(=O)NC1CC(=O)OC1OCC)[CH:2]=C.[O:17]=[C:18]1[O:22][CH:21]([O:23][CH2:24][CH2:25]C2C=CC=CC=2)[CH:20]([NH:32][C:33]([CH:35]2[CH2:39][CH2:38][CH2:37][N:36]2[C:40](=[O:54])[CH:41]([NH:43][C:44](=[O:53])[C:45]2[CH:50]=[CH:49][C:48]([NH2:51])=[C:47]([Cl:52])[CH:46]=2)[CH3:42])=[O:34])[CH2:19]1>>[CH2:24]([O:23][CH:21]1[CH:20]([NH:32][C:33]([CH:35]2[CH2:39][CH2:38][CH2:37][N:36]2[C:40](=[O:54])[CH:41]([NH:43][C:44](=[O:53])[C:45]2[CH:50]=[CH:49][C:48]([NH:51][C:1](=[O:4])[CH3:2])=[C:47]([Cl:52])[CH:46]=2)[CH3:42])=[O:34])[CH2:19][C:18](=[O:17])[O:22]1)[CH3:25]
Reactant: C=CCOC(=O)NC1CC(=O)OC1OCC
Reactant: CC(NC(=O)c1ccc(N)c(Cl)c1)C(=O)N1CCCC1C(=O)NC1CC(=O)OC1OCCc1ccccc1
Product: CCOC1OC(=O)CC1NC(=O)C1CCCN1C(=O)C(C)NC(=O)c1ccc(NC(C)=O)c(Cl)c1

Procedure:
Prepared from (2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester and 97b following the method used for 98a. The title compound was isolated as a white solid (51 mg, 18% yield). 1H-NMR (500 MHz, 1:1 CDCl3:CD3OD) δ 1.08-1.35 (m, 3H), 1.35-1.55 (m, 3H), 1.75-2.44 (m, 4H), 2.26 (s, 3H), 2.44-3.07 (m, 2H), 3.48-3.97 (m, 2H), 4.18-4.92 (m, 5H), 5.32 (d, 0.4H), 5.47 (d, 0.1H), 5.58 (d, 0.4H), 5.64 (d, 0.1H), 7.70-8.35 (m, 3H). Analytical HPLC 10.37, 10.54 min. LC-MS (ES+) m/e=509.2 (M+H+).