Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[CH:15]=[CH:14][C:8](/[CH:9]=[CH:10]/[C:11]([OH:13])=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.Cl.CN(C)CCCN=C=NCC.[NH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CCOC(C)=O>[C:1]([C:5]1[CH:6]=[CH:7][C:8](/[CH:9]=[CH:10]/[C:11]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:13])=[CH:14][CH:15]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)c1ccc(/C=C/C(=O)O)cc1
Reactant: Nc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(C)(C)c1ccc(/C=C/C(=O)Nc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a 10 mL glass vial was added 4-tert-butyl-trans-cinnamic acid (200 mg, 0.98 mmol, EMKA-Chemie) followed by CH2Cl2 (5 mL), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (225 mg, 1.17 mmol, Bachem) and aniline (98 uL, 100 mg, 1.08 mmol, Aldrich). The reaction mixture was magnetically stirred at 25° C. for 24 h. EtOAc was added (60 mL) and the mixture washed successively with 1 N NaOH (2×20 mL), 1 N HCl (20 mL), water (20 mL) and satd NaCl (20 mL), dried over MgSO4, filtered and concentrated. Recrystallization from hexane and CH2Cl2 provided the title product as white crystals. MP 141° C. MS (ESI, pos. ion) m/z: 280 (M+1).
Reaction SMILES: [F:1][C:2]([F:53])([F:52])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[C:43]([CH3:44])=[CH:42][C:37]([C:38]([NH:40][NH2:41])=[O:39])=[CH:36][C:35]=5[CH3:45])[CH:29]=[N:30][C:31]=4[O:32][CH3:33])=[CH:24][N:23]=[C:22]([N:46]4[CH2:49][CH:48]([F:50])[CH2:47]4)[N:21]=3)[C@H:14]2[CH3:51])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C1N=CN([C:59](N2C=NC=C2)=[O:60])C=1>C1COCC1>[F:10][C:9]([F:12])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[C:43]([CH3:44])=[CH:42][C:37]([C:38]6[O:39][C:59](=[O:60])[NH:41][N:40]=6)=[CH:36][C:35]=5[CH3:45])[CH:29]=[N:30][C:31]=4[O:32][CH3:33])=[CH:24][N:23]=[C:22]([N:46]4[CH2:49][CH:48]([F:50])[CH2:47]4)[N:21]=3)[C@H:14]2[CH3:51])[CH:4]=[C:3]([C:2]([F:1])([F:52])[F:53])[CH:8]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: COc1ncc(-c2c(C)cc(C(=O)NN)cc2C)cc1-c1cnc(N2CC(F)C2)nc1CN1C(=O)O[C@H](c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@@H]1C
Solvent: C1CCOC1
Product: COc1ncc(-c2c(C)cc(-c3n[nH]c(=O)o3)cc2C)cc1-c1cnc(N2CC(F)C2)nc1CN1C(=O)O[C@H](c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@@H]1C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(3-fluoroazetidin-1-yl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3,5-dimethylbenzohydrazide (Step A, 90 mg, 0.120 mmol) in THF (1.2 mL) was treated with N,N-carbonyldiimidazole (58.6 mg, 0.361 mmol). The reaction was stirred at room temperature overnight. The reaction was purified directly by silica gel chromatography, eluting with a gradient of 25-100% ethyl acetate/hexanes to give the titled compound. LCMS (M+H)+: 774.6. 1H NMR (CDCl3, 500 MHz): δ 9.12 (br, 1H), 8.17 (s, 1H), 8.03 (d, 1H), 7.89 (s, 1H), 7.74 (s, 2H), 7.61 (d, 2H), 7.31 (d, 1H), 5.71 (d, 1H), 5.51 (m, 0.5H), 5.40 (m, 0.5H), 4.71 (d, 1H), 4.47 (m, 3H), 4.31 (m, 2H), 4.01 (m, s, 4H), 2.16 (s, 3H), 2.15 (s, 3H), 0.76 (d, 3H). RTA IC50: 8 nM
Reaction SMILES: [N:1]1[C:8](Cl)=[N:7][C:5]([Cl:6])=[N:4][C:2]=1[Cl:3].CC(C)=O.[OH-].[Na+].[C:16]1([CH:23]=[CH:22][CH:21]=[C:19]([OH:20])[CH:18]=1)[OH:17]>O>[Cl:6][C:5]1([O:17][C:16]2[CH:23]=[CH:22][CH:21]=[C:19]([O:20][C:5]3([Cl:6])[N:4]=[C:2]([Cl:3])[N:1]=[CH:8][NH:7]3)[CH:18]=2)[N:4]=[C:2]([Cl:3])[N:1]=[CH:8][NH:7]1
Reactant: Clc1nc(Cl)nc(Cl)n1
Reactant: Oc1cccc(O)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)=O
Product: ClC1=NC(Cl)(Oc2cccc(OC3(Cl)N=C(Cl)N=CN3)c2)NC=N1
Reaction time: 4 h
Yield: 890.2 %

Procedure:
A 1 L jacketed reaction flask equipped with a gas inlet, a mechanical stirrer, two liquid inlets and a condenser is purged with argon and charged with 37.3 g (0.0200 mol) of cyanuric chloride and 300 mL of acetone. The stirred mixture is cooled below −15° C. and 30 mL of deionized water are added. A 10% aqueous sodium hydroxide solution (88 g) are added over a 66-minute period via a peristaltic pump. Six minutes after the sodium hydroxide addition is started, a resorcinol solution (11.0 g, 0.100 mol in 50 mL of water) addition is begun also via a peristaltic pump. The resorcinol solution is then added over a 60-minute period concurrent with the sodium hydroxide solution. A slight exotherm occurs causing the temperature to rise to −12° C. The mixture is then stirred for an additional four hours at between −15° C. and −20° C. A 200 mL poriton of water is added and the white solids formed are collected by vacuum filtration followed by washing with three 50 mL portions of water. The solids are dried at 60° C. under reduced pressure to afford 36.5 g of the title compound as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[Mg]Br.C([O:14][CH:15]1[CH2:23][C:22]([CH3:25])([CH3:24])[CH:21]2[CH:17]([CH2:18][N:19]([CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:20]2)[C:16]1=[O:33])(=O)C.[Cl-].[NH4+]>O1CCCC1.C(OCC)C>[CH2:26]([N:19]1[CH2:18][CH:17]2[CH:21]([C:22]([CH3:25])([CH3:24])[CH2:23][CH:15]([OH:14])[C:16]2([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[OH:33])[CH2:20]1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: CC(=O)OC1CC(C)(C)C2CN(Cc3ccccc3)CC2C1=O
Reactant: COc1ccccc1[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: COc1ccccc1C1(O)C(O)CC(C)(C)C2CN(Cc3ccccc3)CC21
Temperature: 0 °C
Yield: 35.1 %

Procedure:
To a suspension of 33.8 g of 2-methoxyphenylmagnesium bromide in 75 cm3 of tetrahydrofuran is added dropwise, at room temperature and with stirring, a solution of 6.6 g of (3aRS,5RS,7aRS)-5-acetoxy-2-benzyl-7,7-dimethyl-4-perhydroisoindolone in 75 cm3 of tetrahydrofuran. The reaction mixture is stirred at room temperature for 15 hours, treated with 200 cm3 of saturated aqueous ammonium chloride solution and taken up in 200 cm3 of ethyl ether and 100 g of ice. The organic phase is extracted with 3 times 100 cm3 of ethyl ether, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized in 500 cm3 of petroleum ether. 2.8 g of (3aRS,4RS,5RS,7aRS)-2-benzyl-7,7-dimethyl-4-(2-methoxyphenyl)-4,5-perhydroisoindolediol are obtained, melting at 190° C.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:28][Si:29]([CH3:37])([CH3:36])[C:30]#[C:31]/[CH:32]=[CH:33]/[CH2:34]O>ClCCl>[Br:1][CH2:34][CH:33]=[CH:32][C:31]#[C:30][Si:29]([CH3:37])([CH3:36])[CH3:28]
Reactant: C[Si](C)(C)C#C/C=C/CO
Reactant: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: C[Si](C)(C)C#CC=CCBr
Temperature: 25 °C
Reaction time: 2 h
Yield: 43.1 %

Procedure:
N-Bromosuccinimide (85.3 g, 0.48 mol) was added in portions to a nearly homogeneous solution of triphenylphosphine (128.2 g, 0.49 mol) and 2E-5-trimethylsilylpent-2-en-4-yn-1-ol (72.5 g, 0.47 mol) in dichloromethane (600 mL) under nitrogen and cooled in a dry ice/2-propanol bath to an initial temperature of below −20° C. The internal temperature of the reaction mixture was maintained at −10° C. to 0° C. throughout the addition by adjusting the rate of addition. The bath was allowed to warm to ambient temperature. After 2 hours, the reaction was complete. The reaction mixture was concentrated under vacuum to a thick paste and the residue was triturated with hexane (250 mL). The suspension was filtered and the solids and silica gel were rinsed with hexane (10×150 mL). The filtrate was concentrated under vacuum (30° C./60 mtorr) to obtain 44 g (89% yield) of 1-bromo-5-trimethylsilylpent-2-en-4-yne, a compound of formula (P), as a pale yellow oil: 1H-NMR (300 mHz, CDCl3) δ0.19 (s, 9H), 3.95 (d, 2H), 5.75 (d, 1H), 6.31 (dt, 1H) ppm.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][NH:7][CH:8]=1)([O-:3])=[O:2].S(OC)(O[CH3:13])(=O)=O>[OH-].[Na+]>[CH3:13][N:6]1[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:8]=[N:7]1
Reactant: COS(=O)(=O)OC
Reactant: O=[N+]([O-])c1cn[nH]c1
Agent: [Na+]
Agent: [OH-]
Product: Cn1cc([N+](=O)[O-])cn1
Temperature: 25 °C
Reaction time: 72 h
Yield: 76.5 %

Procedure:
To a 500 mL round bottom flask containing 4-nitro-1-H-pyrazole (5 g, 44.2 mmol) was added sodium hydroxide (1M, 200 mL) and dimethyl sulfate (31 mL, 330 mmol). The mixture was stirred at room temperature for 72 h and the mixture was extracted with CH2Cl2 (2×150 mL). The organic layer was separated and the solvent was distilled off to yield 1-methyl-4-nitro-1H-pyrazole as a white solid (4.30 g, 76%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12])[C:5](O)=[O:6].C(Cl)(=O)C([Cl:17])=O.CN(C=O)C>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12])[C:5]([Cl:17])=[O:6]
Reactant: O=C(O)c1ccc([N+](=O)[O-])c(F)c1
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)c1ccc([N+](=O)[O-])c(F)c1
Temperature: 25 °C
Yield: 99.8 %

Procedure:
Into a solution of 3-fluoro-4-nitro-benzoic acid (4.0 g, 21.6 mmol) in anhydrous CH2Cl2 (200 mL) at 0° C. was slowly added oxalyl chloride (2.45 mL, 28.0 mmol) and a drop of DMF. The solution was stirred and allowed to warm to RT overnight before concentrating under reduced pressure to give 3 (4.39 g, 100%).
Reaction SMILES: Cl[C:2]1[C:11]([N:12]([CH:14]([CH3:16])[CH3:15])[CH3:13])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:17]([O:19][CH3:20])=[O:18])[CH:8]=2)[N:3]=1.[O:21]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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:21]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[C:23]([C:2]2[C:11]([N:12]([CH:14]([CH3:16])[CH3:15])[CH3:13])=[N:10][C:9]3[C:4](=[CH:5][CH:6]=[C:7]([C:17]([O:19][CH3:20])=[O:18])[CH:8]=3)[N:3]=2)=[CH:22]1
Reactant: COC(=O)c1ccc2nc(Cl)c(N(C)C(C)C)nc2c1
Reactant: CC1(C)OB(c2coc3ccccc23)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: COC(=O)c1ccc2nc(-c3coc4ccccc34)c(N(C)C(C)C)nc2c1
Temperature: 95 °C
Reaction time: 0.67 h
Yield: 57.5 %

Procedure:
To a solution of methyl 2-chloro-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate (Scheme I, 150 mg, 0.51 mmol) in 1,4-dioxane (3 mL) was added 2-(benzofuran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (312 mg, 1.28 mmol), K3PO4 (326 mg, 1.53 mmol), Pd(PPh3)4 (30 mg, 0.03 mmol) and water (3 drops). After stirring 40 min at 95° C. under nitrogen atmosphere, the reaction mixture was dissolved in water (10 mL), extracted with dichloromethane (3×30 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to afford a residue, which was purified by a silica gel column with 1% ethyl acetate in petroleum ether to afford methyl 2-(benzofuran-3-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate as a light yellow solid (110 mg, 57%).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[CH:7][C:8]2[O:13][CH2:12][CH:11]([C:14]([O:16]CC)=O)[O:10][C:9]=2[CH:19]=1)(=[O:3])[CH3:2].[CH2:20]([NH2:23])[CH:21]=[CH2:22]>C(O)C>[C:1]([NH:4][C:5]1[CH:6]=[CH:7][C:8]2[O:13][CH2:12][CH:11]([C:14]([NH:23][CH2:20][CH:21]=[CH2:22])=[O:16])[O:10][C:9]=2[CH:19]=1)(=[O:3])[CH3:2]
Reactant: CCOC(=O)C1COc2ccc(NC(C)=O)cc2O1
Reactant: C=CCN
Solvent: CCO
Product: C=CCNC(=O)C1COc2ccc(NC(C)=O)cc2O1
Reaction time: 18 h

Procedure:
A mixture of 3.5 g of 4A, 30 ml of 2-propenylamine and 25 ml of ethanol was stirred for 18 hours. The volatile materials were evaporated under reduced pressure and the residue was co-evaporated with ethanol until a solid formed. The solid was dissolved in a minimum amount of hot ethanol. The solution was filtered through charcoal, chilled and the solid product was separated. The solvent was evaporated under reduced pressure. The residue was held in a freezer over a weekend. 20 ml of water was added with stirring and the solid was collected. The solid was stirred with a further 20 ml of water; the solid was collected, washed with ether, and triturated with hexane until a gum precipitated. The solvent phase was separated. The gum was again triturated with hexane and the solvent phase was separated. The two extracts were combined; the solvent was evaporated under reduced pressure, and the residue was washed with ether, then dried to 4, as a solid, mp: 138°-140° C.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][OH:7].C(N(CC)CC)C.[CH2:15]([O:22][C:23](OC1CC(=O)NC1=O)=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>ClCCl>[C:23]([NH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][OH:7])([O:22][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:24]
Reactant: NCCOCCO
Reactant: O=C1CC(OC(=O)OCc2ccccc2)C(=O)N1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(NCCOCCO)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 87.9 %

Procedure:
To 2-(2-aminoethoxy)ethanol (20 g) dissolved in dichloromethane (200 ml) was added stepwise triethylamine (26.5 ml) and benzyloxy(carbonyloxy)succinimide (47.47 g). The reaction mixture was stirred overnight at room temperature. The solvent was distilled off under reduced pressure and the residue was dissolved in deionized water (500 ml). The insoluble layer was separated, and the aqueous layer was mixed with 50 g of NaCl and the pH adjusted to 5.0 with 5% H3PO4. The product was extracted with dichloromethane (100 ml, 50 ml, and 50 ml) and the extract was dried with MgSO4, filtered, and evaporated to dryness under reduced pressure. The residue was dried under vacuum overnight, then combined with the previously separated insoluble layer and dissolved in dichloromethane (300 ml). The solution was washed with 5-% aqueous NaCl solution (3×50 ml) and dried with MgSO4. The solvent was distilled under reduced pressure, and the residue was dried overnight under vacuum, giving 40 g of the desired product.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([O:9][CH3:10])[CH:5]=[CH:4][C:3]=1[C:11](=[O:21])[C:12]([C:14]1[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][CH:15]=1)=[CH2:13].S(=O)(=O)(O)O>ClCCl>[Br:20][C:17]1[CH:16]=[CH:15][C:14]([CH:12]2[CH2:13][C:4]3[C:3](=[C:2]([Cl:1])[C:7]([Cl:8])=[C:6]([O:9][CH3:10])[CH:5]=3)[C:11]2=[O:21])=[CH:19][CH:18]=1
Reactant: C=C(C(=O)c1ccc(OC)c(Cl)c1Cl)c1ccc(Br)cc1
Agent: O=S(=O)(O)O
Solvent: ClCCl
Product: COc1cc2c(c(Cl)c1Cl)C(=O)C(c1ccc(Br)cc1)C2
Reaction time: 0.5 h

Procedure:
2',3'-Dichloro-4'-methoxy-2-(4-bromophenyl)acrylophenone (143 g., 0.37 mole) dissolved in dichloromethane (2 l.) is drizzled into cold 36 N sulfuric acid (1 l.)-dichloromethane (1 l.) in an ice bath over 4 hours. After stirring for an additional half hour, the reaction mixture is slowly added to crushed ice, the dichloromethane layer separated, washed with saturated salt solution, concentrated in vacuo to give 134.8 g. of 2-(4-bromophenyl)-5-methoxy-6,7-dichloro-1-indanone which melts at 202°-203° C. after trituration with water followed by crystallization from benzene:hexane, 1:1.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[CH:6][C:7]([O:28][CH2:29][C:30]2[CH:35]=[C:34]([CH2:36][CH3:37])[CH:33]=[CH:32][N:31]=2)=[C:8]([C:10]2[CH:27]=[CH:26][C:13]3[CH2:14][CH2:15][N:16](C(OC(C)(C)C)=O)[CH2:17][CH2:18][C:12]=3[CH:11]=2)[CH:9]=1)(=[O:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:36]([C:34]1[CH:33]=[CH:32][N:31]=[C:30]([CH2:29][O:28][C:7]2[CH:6]=[CH:5][C:4]([C:1](=[O:3])[CH3:2])=[CH:9][C:8]=2[C:10]2[CH:27]=[CH:26][C:13]3[CH2:14][CH2:15][NH:16][CH2:17][CH2:18][C:12]=3[CH:11]=2)[CH:35]=1)[CH3:37]
Reactant: CCc1ccnc(COc2ccc(C(C)=O)cc2-c2ccc3c(c2)CCN(C(=O)OC(C)(C)C)CC3)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCc1ccnc(COc2ccc(C(C)=O)cc2-c2ccc3c(c2)CCNCC3)c1
Temperature: 25 °C

Procedure:
To a solution of 1,1-dimethylethyl 7-(5-acetyl-2-{[(4-ethyl-2-pyridinyl)methyl]oxy}phenyl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate, (0.217 g) in DCM (3 ml) was added TFA (0.4 ml). This was stirred at room temperature. After completion of reaction by tlc, the reaction mixture was concentrated in vacuo and purified by preparative hplc. Product fractions were concentrated in vacuo and the product obtained was partitioned between DCM and aqueous sodium bicarbonate. The organics were dried over sodium sulphate and concentrated in vacuo to yield the title compound, 0.035 g
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([C:15](=[O:17])[CH3:16])[CH:8]=[C:9]([OH:14])[C:10]=1[O:11][CH2:12][CH3:13])([CH3:4])([CH3:3])[CH3:2].[CH2:18](I)[CH3:19].[H-].[Na+]>CN(C=O)C.CC(=O)OCC>[C:1]([C:5]1[CH:6]=[C:7]([C:15](=[O:17])[CH3:16])[CH:8]=[C:9]([O:14][CH2:18][CH3:19])[C:10]=1[O:11][CH2:12][CH3:13])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCI
Reactant: CCOc1c(O)cc(C(C)=O)cc1C(C)(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOc1cc(C(C)=O)cc(C(C)(C)C)c1OCC
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
1-(3-tert-Butyl-4-ethoxy-5-hydroxyphenyl)ethanone (O3.010; 470 mg) and ethyl iodide (193 μl) were dissolved in DMF (6.2 ml), and sodium hydride (57 mg) was added. After stirring at RT for 0.5 h, the DMF was drawn off and the residue was taken up in EA, washed with water, dried and concentrated. The residue was purified using silica gel (40 g cartridge, n-heptane/EA gradient 0-30% within 60 min). 420 mg of the title compound were obtained.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([NH2:23])(=[O:22])=[O:21])=[CH:16][CH:15]=1)[C:6]([C:24](=[O:27])[CH2:25][CH3:26])=[C:5]2[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(N(CC)CC)C.[C:41](Cl)(=[O:44])[O:42][CH3:43]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]1[CH:15]=[CH:16][C:17]([S:20]([NH:23][C:41](=[O:44])[O:42][CH3:43])(=[O:21])=[O:22])=[CH:18][CH:19]=1)[C:6]([C:24](=[O:27])[CH2:25][CH3:26])=[C:5]2[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: COC(=O)Cl
Reactant: CCC(=O)c1c(-c2ccccc2)c2cc(Br)ccc2c(=O)n1Cc1ccc(S(N)(=O)=O)cc1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCC(=O)c1c(-c2ccccc2)c2cc(Br)ccc2c(=O)n1Cc1ccc(S(=O)(=O)NC(=O)OC)cc1

Procedure:
To a mixture of 4-(6-bromo-1-oxo-4-phenyl-3-propionyl-1H-isoquinolin-2-ylmethyl)benzenesulfonamide (0.2 g), triethylamine (0.11 ml), 4-dimethylaminopyridine (23 mg) and methylene chloride (2.0 ml) was added methyl chlorocarbonate (35 μl) at room temperature with stirring, and the mixture was stirred at the same temperature for 1 hr. After the completion of the reaction, the reaction mixture was washed with 1N hydrochloric acid, and the organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by medium pressure preparative LC (hexane/ethyl acetate=3/1-1/1), crystallized from hexane/ethyl acetate=3/2 to give the title compound (0.15 g) as colorless crystals. 1H NMR (CDCl3) δ: 0.48 (3H, t, J=6.9 Hz), 1.69 (2H, q, J=6.9 Hz), 3.68 (3H, s), 5.38 (2H, s), 7.23-7.32 (2H, m), 7.41 (2H, d, J=8.7 Hz), 7.44-7.53 (5H, m), 7.69 (1H, dd, J=2.1, 8.4 Hz) 7.98 (2H, d, J=8.7 Hz), 8.40 (1H, d, J=8.4 Hz).
Reaction SMILES: [H-].[Na+].[C:3]([O:7][C:8]([NH:10][O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].S(C1C=CC(C)=CC=1)(O[CH2:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][O:31][CH3:32])(=O)=O>CN(C=O)C>[C:3]([O:7][C:8]([N:10]([CH2:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][O:31][CH3:32])[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: COCCOCCOCCOS(=O)(=O)c1ccc(C)cc1
Reactant: CC(C)(C)OC(=O)NOCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCCOCCOCCN(OCc1ccccc1)C(=O)OC(C)(C)C
Temperature: 72 °C
Yield: 77.3 %

Procedure:
N-(tert-Butoxycarbonyl)-N-(3,6,9-trioxadecyl)-O-benzylhydroxylamine (14 ) was synthesized by adding sodium hydride (80% oil dispersion, 0.488 g, 16.3 mmol) to N-(tert-butoxycarbonyl)-O-benzylhydroxylamine [Ramasamy, supra] (2.66 g, 11.9 mmol) in dry DMF (20 mL), and stirring was continued for several minutes. 3,6,9-Trioxadecyl tosylate [Schultz et al, supra] (4.93 g, 15.5 mmol) in DMF (3 mL) was added by syringe, and the suspension was heated at 72° C. for 18 hours under nitrogen. After cooling, the reaction was quenched with water (100 mL) and then extracted with ether (4×50 mL). The combined organic layers were washed with brine (100 mL) and the solvent was removed in vacuo. Column chromatography with 4% EtOH/CHCl3 produced 3.40 g (77%) of (14) as a liquid: NMR δ 1.50 (s, 9 H), 3.31 (s, 3 H), 3.5-3.7 (m, 12 H), 4.82 (s, 2 H), 7.25-7.41 (m, 5 H), Analysis: (C19H31NO6) C, H, N.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C:13]([CH2:20][O:21][S:22]([CH3:25])(=[O:24])=[O:23])([CH2:14][O:15][S:16]([CH3:19])(=[O:18])=[O:17])[O:12][C@@H:11]([N:26]2[CH:34]=[N:33][C:32]3[C:27]2=[N:28][CH:29]=[N:30][C:31]=3[NH:35][C:36](=[O:43])[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@H:10]1I)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:45]=[N+:46]=[N-:47].[Na+].[N-]=[N+]=[N-]>CN(C=O)C.O>[N:45]([C@@H:10]1[C@H:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:13]([CH2:20][O:21][S:22]([CH3:25])(=[O:24])=[O:23])([CH2:14][O:15][S:16]([CH3:19])(=[O:18])=[O:17])[O:12][C@H:11]1[N:26]1[CH:34]=[N:33][C:32]2[C:27]1=[N:28][CH:29]=[N:30][C:31]=2[NH:35][C:36](=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[N+:46]=[N-:47]
Reactant: [N-]=[N+]=[N-]
Reactant: CS(=O)(=O)OCC1(COS(C)(=O)=O)O[C@@H](n2cnc3c(NC(=O)c4ccccc4)ncnc32)[C@@H](I)[C@@H]1OCc1ccccc1
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CS(=O)(=O)OCC1(COS(C)(=O)=O)O[C@@H](n2cnc3c(NC(=O)c4ccccc4)ncnc32)[C@H](N=[N+]=[N-])[C@@H]1OCc1ccccc1
Temperature: 80 °C
Reaction time: 8 h

Procedure:
Compound 87 (30 mg) was dissolved in DMF/water 1:1 (2 ml) and followed by sodium azide (26 mg, 10 equiv.). The reaction mixture stirred at 80° C. overnight. LCMS confirms conversion of starting material to product substituted with azide.
Reaction SMILES: [CH2:1]([NH:3][CH2:4][CH3:5])[CH3:2].Br[CH2:7]/[CH:8]=[CH:9]\[Sn:10]([CH2:19][CH2:20][CH2:21][CH3:22])([CH2:15][CH2:16][CH2:17][CH3:18])[CH2:11][CH2:12][CH2:13][CH3:14]>C1COCC1>[CH2:1]([N:3]([CH2:4][CH3:5])[CH2:7]/[CH:8]=[CH:9]\[Sn:10]([CH2:19][CH2:20][CH2:21][CH3:22])([CH2:15][CH2:16][CH2:17][CH3:18])[CH2:11][CH2:12][CH2:13][CH3:14])[CH3:2]
Reactant: CCCC[Sn](/C=C\CBr)(CCCC)CCCC
Reactant: CCNCC
Solvent: C1CCOC1
Product: CCCC[Sn](/C=C\CN(CC)CC)(CCCC)CCCC
Reaction time: 3 h

Procedure:
Diethylamine (19 mL) was added to a solution of ((Z)-3-bromoprop-1-enyl)-tributyl-stannane (Intermediate 4, 7.52 g) in THF (60 mL) and the mixture was stirred for 3 hours. The reaction mixture was evaporated to dryness and the residue was purified by chromatography on a silica column which had been pre-washed with 20% triethylamine in acetonitrile. The column was eluted with a mixture of ethyl acetate and pentane with a gradient of 0-10% to give N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (4.75 g) as an orange oil.
Reaction SMILES: Cl[C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[CH:10]=[CH:9][NH:8][C:7]=12>CCO.[Pd]>[NH:8]1[C:7]2=[CH:2][N:3]=[CH:4][CH:5]=[C:6]2[CH:10]=[CH:9]1
Reactant: Clc1nccc2cc[nH]c12
Agent: [Pd]
Solvent: CCO
Product: c1cc2cc[nH]c2cn1
Temperature: 25 °C
Yield: 76.6 %

Procedure:
A suspension of 7-chloro-1H-pyrrolo[2,3-c]pyridine (650 mg, 4.2 mmol) and Pd/C (10%, 50 mg) in EtOH (25 mL) was stirred at RT under H2 atmosphere (balloon pressure). The reaction mixture was filtered through a celite pad, and the filter cake was washed with EtOAc (10 mL). The filtrate was concentrated and purified via flash chromatography (DCM/MeOH/NH4OH, 9/1/0.1), affording 1H-Pyrrolo[2,3-c]pyridine as a white solid (380 mg, 75% yield).