Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:21]([NH2:22])=[N:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[CH3:23][S:24]([C:27]1[CH:28]=[C:29]([S:33](Cl)(=[O:35])=[O:34])[CH:30]=[CH:31][CH:32]=1)(=[O:26])=[O:25]>N1C=CC=CC=1.ClC1C=CC=CC=1Cl>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([NH:11][C:12]2[C:21]([NH:22][S:33]([C:29]3[CH:30]=[CH:31][CH:32]=[C:27]([S:24]([CH3:23])(=[O:26])=[O:25])[CH:28]=3)(=[O:35])=[O:34])=[N:20][C:19]3[C:14]([N:13]=2)=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1
Reactant: CS(=O)(=O)c1cccc(S(=O)(=O)Cl)c1
Reactant: COc1cc(Nc2nc3ccccc3nc2N)cc(OC)c1
Solvent: c1ccncc1
Solvent: Clc1ccccc1Cl
Product: COc1cc(Nc2nc3ccccc3nc2NS(=O)(=O)c2cccc(S(C)(=O)=O)c2)cc(OC)c1
Temperature: 100 °C
Yield: 21 %

Procedure:
N-(3,5-dimethoxyphenyl)quinoxaline-2,3-diamine (50 mg, 0.17 mmol), 3-(methylsulfonyl)benzenesulfonyl chloride (64 mg, 0.26 mmol, commercially available from Matrix) are dissolved in a 1 to 1 mixture of pyridine and 1,2-dichlorobenzene (0.4 ml) and the reaction mixture is heated at 100° C. in the microwave for 20 min. When TLC confirms the total consumption of the starting material, the reaction mixture is cooled down to rt. The precipitate formed is filtered and purified by column chromatography, using CHCl3: MeOH as eluent, to afford 18 mg (21%) of the title compound as a light brown solid. HPLC (max plot) 84%, rt. 4.2 min. LC/MS: (ES+): 515.
Reaction SMILES: [Li][CH2:2]CCC.[O:6]([C:13]1[CH:14]=[C:15]([C:19]23[CH2:26][CH2:25][C:22]([CH2:27][CH2:28][CH2:29][CH:30]=O)([CH2:23][CH2:24]2)[CH2:21][O:20]3)[CH:16]=[CH:17][CH:18]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.CCCCCC>[CH2:27]([C:22]12[CH2:25][CH2:26][C:19]([C:15]3[CH:16]=[CH:17][CH:18]=[C:13]([O:6][C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)[CH:14]=3)([CH2:24][CH2:23]1)[O:20][CH2:21]2)[CH2:28][CH2:29][CH:30]=[CH2:2]
Reactant: [Li]CCCC
Reactant: O=CCCCC12CCC(c3cccc(Oc4ccccc4)c3)(CC1)OC2
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: C=CCCCC12CCC(c3cccc(Oc4ccccc4)c3)(CC1)OC2
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 81 %

Procedure:
To a 0° C. mixture of methyl triphenylphosphonium bromide (236 mg, 0.66 mmol) in THF (8 mL) was added dropwise n-BuLi (0.27 mL of a 2.5 M solution in hexane, 0.66 mmol). The reaction mixture was stirred at 0° C. for 30 min, and a solution of 4-(1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)butanal (116 mg, 0.33 mmol) in THF (2 mL) was added at 0° C. The reaction mixture was warmed to rt and stirred for 2 h, then was quenched with sat′d aq. NH4Cl, and extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4), and concentrated in vacuo. The crude material was purified by flash chromatography (SiO2; gradient from 0 to 30% EtOAc:hexanes) to afford the title compound as a colorless oil (94 mg; 81% yield). 1H NMR (400 MHz, CDCl3) δ 7.34-7.23 (m, 4H), 7.16-7.05 (m, 2H), 6.98 (dd, J=8.7, 1.0 Hz, 2H), 6.83 (ddd, J=8.0, 2.4, 1.0 Hz, 1H), 5.79 (ddt, J=17.0, 10.3, 6.6 Hz, 1H), 5.03-4.93 (m, 1H), 3.79 (s, 2H), 2.06-1.93 (m, 5H), 1.70-1.52 (m, 6H), 1.48-1.22 (m, 3H), 1.21-1.03 (m, 2H).
Reaction SMILES: [Si:1]([O:18][CH2:19][CH:20](OC(OC1C=CC=CC=1)=S)[C:21]([F:32])([F:31])[CH2:22][P:23](=[O:30])([O:27][CH2:28][CH3:29])[O:24][CH2:25][CH3:26])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([SnH](CCCC)CCCC)CCC.CC(N=NC(C#N)(C)C)(C#N)C>C1(C)C=CC=CC=1>[Si:1]([O:18][CH2:19][CH2:20][C:21]([F:32])([F:31])[CH2:22][P:23](=[O:30])([O:24][CH2:25][CH3:26])[O:27][CH2:28][CH3:29])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOP(=O)(CC(F)(F)C(CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)OC(=S)Oc1ccccc1)OCC
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: CCCC[SnH](CCCC)CCCC
Solvent: Cc1ccccc1
Product: CCOP(=O)(CC(F)(F)CCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)OCC

Procedure:
A solution of diethyl 4-(tert-butyldiphenylsilyloxy)-3-phenoxythiocarbonyloxy-2,2-difluorobutylphosphonate (1 mmole) in toluene (1 mL) was treated with tri-n-butyltin hydride (1.5 mmole) and AIBN (0.1 mmole), and the resulting reaction mixture was heated to reflux for 2 h. Evaporation and chromatography gave diethyl 4-(tert-butyldiphenylsilyloxy)-2,2-difluorobutylphosphonate as a clear oil.
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH:5]=[CH:6]1)[CH2:3][CH:2]2[NH:8][C:9]([NH:11][NH2:12])=[S:10].[F:13][C:14]([F:24])([F:23])[C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH:18]=O>>[CH:1]12[CH2:7][CH:4]([CH:5]=[CH:6]1)[CH2:3][CH:2]2[NH:8][C:9](=[S:10])[NH:11][N:12]=[CH:18][C:17]1[CH:20]=[CH:21][CH:22]=[C:15]([C:14]([F:13])([F:23])[F:24])[CH:16]=1
Reactant: O=Cc1cccc(C(F)(F)F)c1
Reactant: NNC(=S)NC1CC2C=CC1C2
Product: FC(F)(F)c1cccc(C=NNC(=S)NC2CC3C=CC2C3)c1

Procedure:
The title compound was prepared from a mixture of N1-bicyclo[2.2.1]hept-5-en-2-ylhydrazine-1-carbothioamide (100 mg, 0.56 mmol) and 3-(trifluoromethyl)benzaldehyde (75 μL, 0.56 mmol) similar to Example 3 and isolated as a white solid (15 mg, 8%). 1H NMR (CDCl3): 9.43 (s, 1H), 7.86-7.80(m, 3H), 7.67 (d, J=8.1 Hz, 1H), 7.56 (t, J=7.7 Hz, 1H), 7.45 (d, J=6.6 Hz, 1H), 6.25-6.15 (m, 2H), 4.32-4.28 (m, 1H), 3.08 (s, 1H), 2.99 (s, 1H), 1.96-1.89 (m, 1H), 1.69 (d, J=9.0 Hz, 1H), 1.50 (d, J=9.6 Hz, 1H), 1.48-1.41 (m, 1H).
Reaction SMILES: [CH2:1]([C:8]1[CH:26]=[CH:25][C:11]([N:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.Cl[Si:33]([CH3:36])([CH3:35])[CH3:34].CCCCCC>O1CCCC1>[C:13]1([N:12]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:11]2[CH:10]=[CH:9][C:8]([CH:1]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[Si:33]([CH3:36])([CH3:35])[CH3:34])=[CH:26][CH:25]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: C[Si](C)(C)Cl
Reactant: c1ccc(Cc2ccc(N(c3ccccc3)c3ccccc3)cc2)cc1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: C[Si](C)(C)C(c1ccccc1)c1ccc(N(c2ccccc2)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 84 %

Procedure:
4-benzyl-N,N-diphenylaniline (5.0 g, 14.9 mmol) was dissolved in tetrahydrofuran (80 mL) under a nitrogen atmosphere. n-Butyllithium (10.3 mL, 16.4 mmol) was slowly added to the reaction solution at −78° C., and then the reaction mixture solution was stirred at room temperature for 1 hour. Also, the reaction mixture solution with chlorotrimethylsilane (1.8 g, 16.4 mmol) added thereto was stirred at room temperature for 1 hour. The reaction mixture solution was passed through a silica gel column by using hexane as an eluant. After the solvent is removed, the residue material was dried in vacuum to thereby a white solid (5.1 g, yield: 84%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]=[C:10]=[S:11].Cl.C([O:15][C:16](=O)[CH2:17][NH:18][CH3:19])C.C(N(CC)CC)C>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]1[C:16](=[O:15])[CH2:17][N:18]([CH3:19])[C:10]1=[S:11]
Reactant: Cc1cccc(Cl)c1N=C=S
Reactant: CCOC(=O)CNC
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: Cc1cccc(Cl)c1N1C(=O)CN(C)C1=S
Yield: 55.7 %

Procedure:
The title compound was prepared by the procedure described in Example 1 using 9.2 g of 2-chloro-6-methylphenyl-isothiocyanate, 7.68 g of sarcosine ethyl ester hydrochloride, 12 g of triethyl amine, and 200 mL of chloroform. Crystallization from ethanol afforded the title compound (7.1 g) as an orange solid (7.1 g), m.p. 142°-145° C. Anal. Calcd. for. C11H11N2O S: C, 51.87; H, 4.35; N,11.00. Found: C, 51.96; H, 4.26; N, 10.97. Mass spectrum (El, M.+) m/z 254.
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:24])[CH2:10][C:11]1[C:12]([CH3:23])=[N:13][O:14][C:15]=1[C:16]1[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:25]([O:27][C:28]([C:30]1([C:33]2[CH:38]=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][CH:34]=2)[CH2:32][CH2:31]1)=[O:29])[CH3:26]>>[CH2:25]([O:27][C:28]([C:30]1([C:33]2[CH:38]=[CH:37][C:36]([C:19]3[CH:20]=[CH:21][C:16]([C:15]4[O:14][N:13]=[C:12]([CH3:23])[C:11]=4[CH2:10][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[O:24])=[CH:17][CH:18]=3)=[CH:35][CH:34]=2)[CH2:31][CH2:32]1)=[O:29])[CH3:26]
Reactant: Cc1noc(-c2ccc(Br)cc2)c1CC(=O)OCc1ccccc1
Reactant: CCOC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4CC(=O)OCc4ccccc4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 2, using [5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-acetic acid benzyl ester and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:17]O)[CH:5]=[N:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[F:16].[Br:19]P(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl>[Br:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])=[N:6][CH:5]=[C:4]([CH2:17][Br:19])[CH:3]=1
Reactant: BrP(Br)Br
Reactant: OCc1cnc(Oc2ccc(F)cc2F)c(Br)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: Fc1ccc(Oc2ncc(CBr)cc2Br)c(F)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 85.7 %

Procedure:
A solution of the product from Example 311b (0.73 g, 2.309 mmol) in dichloromethane (11.55 mL) under nitrogen was treated dropwise with tribromophosphine (0.218 mL, 2.309 mmol), stirred for one hour at ambient temperature and poured into ice water and the pH was adjusted to pH 9 by addition of solid sodium bicarbonate added portionwise. An emulsion formed that was partially removed by filtration. The aqueous layer was extracted with dichloromethane and the organics were combined, washed with saturated aqueous sodium chloride, dried (Na2SO4) filtered, and concentrated to afford the title compound (0.75 g, 86%).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH2:6]([OH:17])[CH2:7][C:8]1[CH:16]=[CH:15][C:13]([OH:14])=[C:10]([O:11][CH3:12])[CH:9]=1.C(N(CC)CC)C>ClCCl>[CH3:1][S:2]([O:17][CH2:6][CH2:7][C:8]1[CH:16]=[CH:15][C:13]([O:14][S:2]([CH3:1])(=[O:4])=[O:3])=[C:10]([O:11][CH3:12])[CH:9]=1)(=[O:4])=[O:3]
Reactant: COc1cc(CCO)ccc1O
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc(CCOS(C)(=O)=O)ccc1OS(C)(=O)=O
Temperature: 25 °C
Yield: 86.6 %

Procedure:
44 g (0.39 mole) methanesulfonyl chloride was slowly added to a solution of 30 g (0.178 mole) homovanillyl alcohol and 45.3 g (0.45 mmole) triethylamine in 500 ml dichloromethane at −10° C. After stirring at room temperature over night the salts were filtered off, the organic phase was washed with sodium bicarbonate and brine, dried (magnesium sulfate) and evaporated in vacuo to give 50 g (yield 86%) of 3-methoxy-4-(methylsulfonyloxy)phenethyl methanesulfonate.
Reaction SMILES: [CH3:1][O:2][C:3](/[CH:5]=[CH:6]/[C:7]([O:9][CH2:10][C:11]([OH:13])=O)=[O:8])=[O:4].C(Cl)(=O)C(Cl)=O.[CH2:20]([O:22][C:23](=[O:33])[CH2:24][NH:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:21].C(N(C(C)C)CC)(C)C>ClCCl.CN(C1C=CN=CC=1)C.CN(C)C=O>[C:7]([O:9][CH2:10][C:11](=[O:13])[N:25]([CH2:24][C:23]([O:22][CH2:20][CH3:21])=[O:33])[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)(=[O:8])/[CH:6]=[CH:5]/[C:3]([O:2][CH3:1])=[O:4]
Reactant: CCOC(=O)CNCc1ccccc1
Reactant: COC(=O)/C=C/C(=O)OCC(=O)O
Agent: CN(C)c1ccncc1
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)CN(Cc1ccccc1)C(=O)COC(=O)/C=C/C(=O)OC
Yield: 12.5 %

Procedure:
Following general procedure B2, 2-[(2E)-3-(methoxycarbonyl) prop-2-enoyloxy]acetic acid (23) (0.50 g, 2.65 mmol) was activated with oxalyl chloride (0.27 mL, 0.40 g, 3.15 mmol) in dichloromethane (DCM) at ca. 0° C. and in the presence of a catalytic amount of N,N-dimethylformamide (DMF). A DCM solution of the freshly prepared crude acid chloride was reacted ca. 0° C. (ice bath) with N-benzyl glycine ethyl ester (Bn-Gly-OEt) (0.61 g, 3.18 mmol) in DCM and an excess of diisopropylethylamine (DIEA) in the presence of a catalytic amount of 4-(N,N-dimethyl)aminopyridine (DMAP). After aqueous work-up and isolation, and purification by silica gel flash chromatography afforded 0.12 g (13% yield) of the title compound (36) as a white solid. 1H NMR (CDCl3, 400 MHz, all rotamers): δ 7.37-7.20 (m, 5H), 6.97-6.86 (m, 2H), 4.94-4.83 (2s, 2H), 4.63-4.55 (2s, 2H), 4.18-4.14 (m, 2H), 4.04-3.88 (2s, 2H), 3.79 (s, 3H), 1.24-1.20 (m, 3H). MS (ESI): m/z 364.15 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].C(O)C.[OH-].[Na+].Br[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]>O>[CH2:26]([S:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH2:1])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH3:15]
Reactant: CCCCCCCCCCCCBr
Reactant: Nc1ccccc1S
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCCCCCCCCCCCSc1ccccc1N
Reaction time: 0.25 h
Yield: 75 %

Procedure:
Into a 2-liter 3-necked round bottomed flask equipped with condenser, stirrer and heating mantle, were placed 125.0 g (1.0 mol) of 2-aminothiophenol, 350 ml of ethanol and 40 g (1.0 mol) of sodium hydroxide dissolved in 40 ml of water. Stirring was begun and after 15 min, 249.24 g (1.0 mol) of 1-bromododecane was added. Heating was begun and the solution heated at reflux overnight. Upon cooling, solvent was removed at reduced pressure and water (500 ml) and dichloromethane (500 ml) were added. The mixture was transferred to a 2-liter separatory funnel and the layers separated. The aqueous layer was discarded, the organic layer washed with 500 ml of aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The crude material was passed through a bed of silica, solvent was removed at reduced pressure, and the material distilled under vacuum to afford 220 g (75%) of 2-(dodecylthio)aniline (b.p. 180° C. at 0.25 mm).
Reaction SMILES: C(#N)C.BrC(F)COCC(F)Br.[CH3:13][C:14]1[CH:15]=[C:16]([O:21][C:22](F)([F:27])[C:23]([F:26])([F:25])Br)[CH:17]=[CH:18][C:19]=1[CH3:20]>[Zn].O.CCCCCC>[F:27][C:22]([O:21][C:16]1[CH:17]=[CH:18][C:19]([CH3:20])=[C:14]([CH3:13])[CH:15]=1)=[C:23]([F:25])[F:26]
Reactant: Cc1ccc(OC(F)(F)C(F)(F)Br)cc1C
Agent: FC(Br)COCC(F)Br
Agent: [Zn]
Solvent: O
Solvent: CCCCCC
Solvent: CC#N
Product: Cc1ccc(OC(F)=C(F)F)cc1C
Temperature: 50 °C
Yield: 87 %

Procedure:
Acetonitrile (200 mL) and zinc (50 g, 0.765 mol) are transferred to an oven-dried two liter three-necked Morton flask fitted with a mechanical stirrer, reflux condenser, and thermocouple. The mixture is stirred and heated to 50° C. by means of a heating mantle and temperature controller. The mixture is assayed for water (700 ppm) and the temperature is increased to 65° C. The bromofluoroethyl ether, 3,4-dimethyl-l-(2-bromotetrafluoroethoxy)benzene (187.04 g, 0.621 mole) is added over a period of thirty minutes to the stirring mixture. The temperature of the mixture is then increased to 77° C. and the mixture is stirred overnight. Gas chromatographic analysis of the mixture shows no remaining starting material. The mixture is transferred to a 2 L round-bottomed flask using hexane and water to rinse out the reaction vessel. The solvents (water, hexane and acetonitrile) are then removed by rotary evaporation at 65° C. and 100 mm Hg (13.33 kPa). Under these conditions a small amount of the product is carried over with the solvent. The pressure is then reduced to about 2 mm Hg (0.26 kPa) which causes the product, monomer, 3,4-dimethylphenyl perfluorovinyl ether, to distill over as a clear liquid. Yield 108 g (87 percent yield, purity 94 percent).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]2[CH:7]3[C:14]4([CH2:15][CH2:16][C:5]=2[CH:4]=1)[CH:10]([CH2:11][NH:12][CH2:13]4)[CH2:9][CH2:8]3.C(N(CC)CC)C.[C:26](OC(=O)C)(=[O:28])[CH3:27]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]2[CH:7]3[C:14]4([CH2:15][CH2:16][C:5]=2[CH:4]=1)[CH:10]([CH2:11][N:12]([C:26](=[O:28])[CH3:27])[CH2:13]4)[CH2:9][CH2:8]3
Reactant: COc1ccc2c(c1)CCC13CNCC1CCC23
Reactant: CC(=O)OC(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc2c(c1)CCC13CN(C(C)=O)CC1CCC23
Temperature: 25 °C
Reaction time: 2 h
Yield: 98.6 %

Procedure:
2-Methoxy-5,6,6a,7,8,9,10,11-octahydro-4bH-benzo[4,5]indeno[1,7a-c]pyrrole (Example 1A, compound 1A-b) (50.0 mg, 0.21 mmol) and triethylamine (86 μL, 0.61 mmol) were dissolved in CH2Cl2 (2 mL). Acetic anhydride (24 μl, 0.25 mmol) was added dropwise. The mixture was stirred at rt for 2 hr. It was then quenched with water (2 mL), and extracted with CH2Cl2 (5 mL×3). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 5% methanol in dichloromethane, providing 59.1 mg (100%) of the title compound.
Reaction SMILES: [N+](C1C=CC(C[O:11][C:12]([C:14]2[N:15]3[CH:18]([CH:19]([CH3:32])[C:20]=2[S:21][CH:22]2[CH2:26][CH:25]([CH2:27][O:28][C:29]([NH2:31])=[O:30])[O:24][CH2:23]2)[CH:17]([CH:33]([OH:35])[CH3:34])[C:16]3=[O:36])=[O:13])=CC=1)([O-])=O.C(=O)(O)[O-].[Na+:41].O>[Pd].O1CCOCC1>[Na+:41].[NH2:31][C:29]([O:28][CH2:27][CH:25]1[O:24][CH2:23][CH:22]([S:21][C:20]2[CH:19]([CH3:32])[CH:18]3[N:15]([C:16](=[O:36])[CH:17]3[CH:33]([OH:35])[CH3:34])[C:14]=2[C:12]([O-:13])=[O:11])[CH2:26]1)=[O:30]
Reactant: CC(O)C1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(SC3COC(COC(N)=O)C3)C(C)C12
Agent: [Pd]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CC(O)C1C(=O)N2C(C(=O)[O-])=C(SC3COC(COC(N)=O)C3)C(C)C12
Yield: 55.7 %

Procedure:
The title compound is prepared by the procedure of Example 18 using 0.126 g of product from Example 20, 0.0223 g of sodium bicarbonate, 1.4 ml of water, 7.8 ml of dioxane, and 0.070 g of 10% palladium/carbon to give 0.055 g of the desired product as a yellow solid.
Reaction SMILES: S(=O)(O)[O-].[Na+].[Cl:6][C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[CH:9]=O.[S:15]1[C:23]2[CH2:22][CH2:21][NH:20][CH2:19][C:18]=2[CH:17]=[CH:16]1.[C-:24]#[N:25].[Na+]>O>[Cl:6][C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[CH:9]([N:20]1[CH2:21][CH2:22][C:23]2[S:15][CH:16]=[CH:17][C:18]=2[CH2:19]1)[C:24]#[N:25]
Reactant: O=Cc1ccccc1Cl
Reactant: c1cc2c(s1)CCNC2
Reactant: [C-]#N
Agent: O=S([O-])O
Agent: [Na+]
Solvent: O
Product: N#CC(c1ccccc1Cl)N1CCc2sccc2C1
Temperature: 45 °C

Procedure:
To a solution of 8.98 g (86.33 mmole) sodium bisulfite in water (27 mL), o-chlorobenzaldehyde 12.4 g (86.33 mmole) was added resulting in a white precipitate. To the precipitate, 15 g (0.107 moles) of 6,7-dihydro-4H-thieno[3,2-c]pyridine was added, followed by addition of 4.4 g (89.7 mmoles) NaCN (dissolved in 15 mL water). The reaction mixture was heated at 40-50° C. for 6 hrs and was quenched by pouring in water (50 mL). The mixture was extracted with 2×100 mL of ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The yield of the title product is 24 g (97%).
Reaction SMILES: [CH3:1][C:2]1[C:3]([CH:13]=[O:14])=[CH:4][NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[H-].[Na+].C1OCCOCCOCCOCCOC1.[CH3:32][N:33]1[CH:37]=[C:36]([S:38](Cl)(=[O:40])=[O:39])[N:35]=[C:34]1[CH3:42]>>[CH3:32][N:33]1[CH:37]=[C:36]([S:38]([N:5]2[C:6]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[C:2]([CH3:1])[C:3]([CH:13]=[O:14])=[CH:4]2)(=[O:40])=[O:39])[N:35]=[C:34]1[CH3:42]
Reactant: Cc1nc(S(=O)(=O)Cl)cn1C
Reactant: Cc1c(C=O)c[nH]c1-c1ccccc1
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Product: Cc1c(C=O)cn(S(=O)(=O)c2cn(C)c(C)n2)c1-c1ccccc1

Procedure:
By a reaction under similar conditions as in Reference Example 65 and using 4-methyl-5-phenyl-1H-pyrrole-3-carbaldehyde (185 mg), sodium hydride (60% in oil, 60 mg), 15-crown-5 (0.30 mL) and (1,2-dimethyl-1H-imidazol-4-yl)sulfonyl chloride (253 mg), the title compound was obtained as a colorless solid (yield 294 mg, 86%).
Reaction SMILES: [OH:1][CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](Br)[CH:10]=2)[C:4](=[O:5])[O:3]1.[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[CH2:20])=[CH:17][CH:16]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.CS(C)=O>[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18](/[CH:19]=[CH:20]/[C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[C:4](=[O:5])[O:3][CH:2]3[OH:1])=[CH:17][CH:16]=1
Reactant: O=C1OC(O)c2cc(Br)ccc21
Reactant: C=Cc1ccc(OC)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CS(C)=O
Solvent: O
Solvent: CCN(CC)CC
Product: COc1ccc(/C=C/c2ccc3c(c2)C(O)OC3=O)cc1
Reaction time: 5 h

Procedure:
A mixture of 9.9 gm 3-hydroxy-5-bromophthalide, 5.8 gm p-methoxystyrene, 0.09 gm palladium acetate, 0.47 gm tri-(o-tolyl)-phosphine, 7 ml triethylamine and 35 ml dimethylsulfoxide were heated with stirring at 95° for 5 hours. The reaction mixture was cooled and added to 400 ml water. The product was extracted into ethyl acetate, which solution was washed with water and dried over magnesium sulfate. Removal of solvent left 8.0 gm yellow solid melting at 140°-148°.
Reaction SMILES: [F:1][C:2](I)([F:25])[C:3]([F:24])([F:23])[C:4]([F:22])([F:21])[C:5]([F:20])([F:19])[C:6]([F:18])([F:17])[C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10].[Br-:27]>[Cu](Br)Br>[F:1][C:2]([Br:27])([F:25])[C:3]([F:24])([F:23])[C:4]([F:22])([F:21])[C:5]([F:20])([F:19])[C:6]([F:18])([F:17])[C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10]
Reactant: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)I
Reactant: [Br-]
Agent: Br[Cu]Br
Product: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)Br
Temperature: 25 °C
Reaction time: 4 h
Yield: 83.5 %

Procedure:
13.0 g (0.09 mol) of finely ground copper bromide of the formula CuBr are put into a bomb tube of capacity 25 cm3 and made of glass, and are subjected to a temperature of 200° C. under a pressure of 10 Pa for 4 hours, in order to remove residual water. After the bomb tube has cooled to room temperature, anhydrous nitrogen is passed into it and 16.4 g (0.03 mol) of perfluorooctyl iodide are added, and the bomb tube is sealed by fusion and shaken for 50 hours at 240° to 250° C. 3 mol of bromide ions are employed per mol of bound iodine atom. When the reaction is complete, the bomb tube is opened and the organofluorine products are distilled out of the bomb tube by heating at 200° C. This gives 12.8 g of distillate which, according to analysis by gas chromatography is composed of 97.7% by weight of perfluorooctyl bromide; 1.9% by weight of unreacted perfluorooctyl iodide and 0.3% by weight of CF3 (CF2)7H. This corresponds to a yield of 83.5% of perfluorooctyl bromide, relative to perfluorooctyl iodide employed.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12](=[O:19])OCC(Cl)(Cl)Cl)[N:10]=2)[N:7]=1.[C:20]1([C:26]2[N:30]=[C:29]([N:31]3[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]3)[S:28][N:27]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C.O>CS(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([N:34]3[CH2:35][CH2:36][N:31]([C:29]4[S:28][N:27]=[C:26]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)[N:30]=4)[CH2:32][CH2:33]3)=[O:19])[N:10]=2)[N:7]=1
Reactant: O=C(Nc1cn2nc(Cl)ccc2n1)OCC(Cl)(Cl)Cl
Reactant: c1ccc(-c2nsc(N3CCNCC3)n2)cc1
Solvent: CS(C)=O
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Nc1cn2nc(Cl)ccc2n1)N1CCN(c2nc(-c3ccccc3)ns2)CC1
Temperature: 70 °C
Reaction time: 24 h
Yield: 46.6 %

Procedure:
A mixture of 2,2,2-trichloroethyl (6-chloroimidazo[1,2-b]pyridazin-2-yl)carbamate (700 mg, 2.04 mmol), 1-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine (456 mg, 1.85 mmol) and diisopropylethylamine (0.355 ml, 2.04 mmol) in dimethylsulfoxide (6.2 ml) was stirred at 70° C. for 1 day. Water was poured into the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Hexane was added to the residue, and a solid was separated by filtration, which was recrystallized from a mixed solvent of hexane and tetrahydrofuran to give 380 mg (42.3%) of the desired product as a solid.