Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Mg].II.ClC(C)C.[CH3:8][O:9][Si](OC)(OC)OC.CO.C([Si:22]([CH:28]([CH3:30])[CH3:29])([CH:25]([CH3:27])[CH3:26])[O:23][CH3:24])(C)C>COC(C)(C)C>[CH:25]([Si:22]([CH:28]([CH3:30])[CH3:29])([O:9][CH3:8])[O:23][CH3:24])([CH3:27])[CH3:26]
Reactant: CO[Si](OC)(OC)OC
Reactant: CO[Si](C(C)C)(C(C)C)C(C)C
Agent: CC(C)Cl
Agent: II
Agent: [Mg]
Solvent: COC(C)(C)C
Solvent: CO
Product: CO[Si](OC)(C(C)C)C(C)C

Procedure:
Under an inert gas, 24.2 g magnesium chips (1.0 mol) were combined with about 20 ml methyl-tert-butylether, an iodine crystal and 3.1 g 2-chloropropane (0.04 mol). To start the reaction a solution of 61.9 g tetramethoxysilane (0.41 mol) and 75.4 g 2-chloropropane (0.96 mol) in 140 ml methyl-tert-butylether was added dropwise, with stirring, to the first mixture at a rate to maintain a moderate reflux. After addition of the solution, the reaction was allowed to reflux for six more hours. After cooling the reaction mixture, 6.0 g methanol (0.19 mol) was added, the mixture was stirred for a few minutes and then the resulting precipitate was removed by filtration. After washing the filter cake with several portions of methyl-tert-butylether, the solvent was distilled from the combined filtrates. The remaining residue consisted of 70.5 g diisopropyldimethoxysilane (98% of the theoretical yield) which had a purity of 98% according to GC. Triisopropylmethoxysilane was not detected by GC.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[Si:7]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]#[N:22])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].O>CCOCC>[NH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][O:14][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]
Reactant: CC(C)(C)[Si](C)(C)OCCCCCCC#N
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCCCCCCCN
Reaction time: 2 h

Procedure:
To a solution of lithium aluminium hydride (600 mg, Aldrich) in ether (50 mL) was added dropwise the product (3.8 g) from Example 4 in ether (50 mL). After 1-3 h, the mixture was poured into water and stirred for 30 min. The insoluble aluminium hydroxide was filtered through a celite pad, and the aqueous layer was extracted with ether three times. The ether extracts were washed with brine solution, dried and concentrated. The crude product was distilled at 0.25 Torr and 82° C. High resolution mass spectrum for C13 H31 O N Si: calculated 245.2175, found 245.2159.
Reaction SMILES: [C:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1)([OH:3])=[O:2].[NH:12]1[CH:16]=[CH:15][CH:14]=[CH:13]1>C(O)(=O)CC>[C:1]([C:4]1[CH:11]=[CH:10][C:7]([C:8]2[C:16]3[NH:12][C:13]([C:8]([C:7]4[CH:10]=[CH:11][C:4]([C:1]([OH:3])=[O:2])=[CH:5][CH:6]=4)=[C:13]4[N:12]=[C:16]([C:8]([C:7]5[CH:10]=[CH:11][C:4]([C:1]([OH:3])=[O:2])=[CH:5][CH:6]=5)=[C:13]5[NH:12][C:16](=[C:8]([C:7]6[CH:6]=[CH:5][C:4]([C:1]([OH:3])=[O:2])=[CH:11][CH:10]=6)[C:13]6[CH:14]=[CH:15][C:16]=2[N:12]=6)[CH:15]=[CH:14]5)[CH:15]=[CH:14]4)=[CH:14][CH:15]=3)=[CH:6][CH:5]=1)([OH:3])=[O:2]
Reactant: c1cc[nH]c1
Reactant: O=Cc1ccc(C(=O)O)cc1
Solvent: CCC(=O)O
Product: O=C(O)c1ccc(-c2c3nc(c(-c4ccc(C(=O)O)cc4)c4ccc([nH]4)c(-c4ccc(C(=O)O)cc4)c4nc(c(-c5ccc(C(=O)O)cc5)c5ccc2[nH]5)C=C4)C=C3)cc1
Yield: 17.5 %

Procedure:
In refluxed propionic acid, 30 g of 4-carboxybenzaldehyde was reacted with 13.4 g of pyrrole to obtain 6.9 g of 5,10,15,20-tetra(4-carboxyphenyl)porphine. In a mixed solvent of 200 ml ofdistilled water and 300 ml of methanol was dissolved 10 g of polyvinyl alcohol having a polymerization degree of 2,000 and a saponification degree of 100%, and 0.066 g of the so-synthesized 5,10,15,20-tetra(4-carboxyphenyl)porphine was added to the solution. The solution was dried in a Petri dish to obtain a film having a guest concentration of 10-2M and a thickness of 0.5 mm. The sample was cooled to the liquid helium temperature and irradiated with a laser beam having a wavelength of 645 nm and an intensity of 1 mW/cm2 for 30 seconds to form a PHB hole. Then, the temperature of the film was elevatedto a predetermined level, the film was again cooled to the liquid helium temperature, and the half width of the PHB hole was measured.
Reaction SMILES: OC[C@@H](N[C:11](=[O:26])[C@:12]([CH3:25])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:13][CH2:14][C:15]([CH3:18])([CH3:17])[CH3:16])C1C=CC=CC=1.S(=O)(=O)(O)[OH:28]>O1CCOCC1>[CH3:25][C@@:12]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)([CH2:13][CH2:14][C:15]([CH3:16])([CH3:17])[CH3:18])[C:11]([OH:26])=[O:28]
Reactant: O=S(=O)(O)O
Reactant: CC(C)(C)CC[C@](C)(C(=O)N[C@H](CO)c1ccccc1)c1ccccc1
Solvent: C1COCCO1
Product: CC(C)(C)CC[C@](C)(C(=O)O)c1ccccc1
Yield: 90 %

Procedure:
To a solution of Example 48A (4.48 g, 12.7 mmol) in 1,4-dioxane (60 mL) was added 4 M sulfuric acid (60 mL) and the reaction was stirred at reflux for 48 hours. The solution was concentrated in vacuo, dissolved in 1 N NaOH (250 mL), and washed with hexane (200 mL). The aqueous layer was acidified to pH 1 with 6 N HCl and extracted with ethyl acetate (3×200 mL). The combined ethyl acetate layers were dried over sodium sulfate, filtered, and concentrated in vacuo to give a clear oil (2.66 g, 90%). 1H NMR (300 MHz, CDCl3): δ ppm 0.86 (s, 9 H) 1.09 m, 2 H) 1.56 (s, 3 H) 1.99 m, 2 H) 7.33 m, 5 H).
Reaction SMILES: [CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][NH:17][CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[F:27][C:28]1[CH:36]=[CH:35][C:31]([C:32](Cl)=[O:33])=[CH:30][C:29]=1[C:37]([F:40])([F:39])[F:38]>ClCCl>[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][N:17]([C:32]([C:31]5[CH:35]=[CH:36][C:28]([F:27])=[C:29]([C:37]([F:40])([F:38])[F:39])[CH:30]=5)=[O:33])[CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1
Reactant: c1nc(C2CC2)cnc1O[C@@H]1C[C@H]2CNCCN2C1
Reactant: O=C(Cl)c1ccc(F)c(C(F)(F)F)c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(c1ccc(F)c(C(F)(F)F)c1)N1CCN2C[C@H](Oc3cnc(C4CC4)cn3)C[C@H]2C1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of Example 54F (47 mg, 0.18 mmol) and triethylamine (27 mg, 0.27 mmol) in dichloromethane (1 mL) was added 4-fluoro-3-(trifluoromethyl)benzoyl chloride (49 mg, 0.216 mmol). The mixture was stirred at room temperature for 3 hours.
Reaction SMILES: [NH2:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([C:6]([NH:8][CH2:9][CH2:10][N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])=[O:7])=[C:4]([OH:19])[CH:3]=1.Br[CH2:21][C:22](=[O:25])[CH2:23][CH3:24]>C(#N)C>[NH2:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([C:6]([NH:8][CH2:9][CH2:10][N:11]([CH2:12][CH3:13])[CH2:14][CH3:15])=[O:7])=[C:4]([O:19][CH2:21][C:22](=[O:25])[CH2:23][CH3:24])[CH:3]=1
Reactant: CCC(=O)CBr
Reactant: CCN(CC)CCNC(=O)c1cc(Cl)c(N)cc1O
Solvent: CC#N
Product: CCC(=O)COc1cc(N)c(Cl)cc1C(=O)NCCN(CC)CC
Reaction time: 2 h
Yield: 87.1 %

Procedure:
A solution of the tetrabutylammonium salt of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxybenzamide (5.3 g, 10 mmoles) in acetonitrile (100 ml) was treated with 1-bromo-2-butanone (1.5 g, 10 mmoles) and stirred at 20° for 2 hours. The residue after concentration was treated with water and extracted with ethyl acetate and methylene chloride-2-propanol (5:1). The insoluble solid material was collected and combined with the organic extracts. Concentration of this mixture gave sticky crystalline material which was recrystallized from acetonitrile-water (4:1) to give the title product (3.1 g, 86%), mp, 103.0-104.5°.
Reaction SMILES: [CH:1]1([NH:4][CH2:5][CH2:6][OH:7])[CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:15][O:16][C:17]1[CH:22]=[C:21]([CH3:23])[C:20]([S:24](Cl)(=[O:26])=[O:25])=[C:19]([CH3:28])[CH:18]=1>ClCCl>[CH:1]1([N:4]([CH2:5][CH2:6][OH:7])[S:24]([C:20]2[C:21]([CH3:23])=[CH:22][C:17]([O:16][CH3:15])=[CH:18][C:19]=2[CH3:28])(=[O:26])=[O:25])[CH2:3][CH2:2]1
Reactant: COc1cc(C)c(S(=O)(=O)Cl)c(C)c1
Reactant: OCCNC1CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1cc(C)c(S(=O)(=O)N(CCO)C2CC2)c(C)c1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 20 %

Procedure:
To a cold (0° C.) solution of 2-cyclopropylamino-ethanol (8 mmol) in dichloromethane (24 ml) and triethylamine (2.5 equiv.) a solution of 4-methoxy-2,6-dimethylbenzenesulfonyl chloride (7 mmol) in dichloromethane (12 ml) was added dropwise maintaining the temperature at 0° C. After complete addition the reaction mixture was stirred at 25° C. for 90 min by which time the reaction was complete (TLC). The reaction mixture was diluted with dichloromethane (200 ml) and washed with water and finally with brine. The organic layer was dried over sodium sulfate and evaporated to dryness to obtain the pure product. Yield: 20%
Reaction SMILES: FC(F)(F)S(O[Si](C)(C)C)(=O)=O.[CH2:13]([C@@H:20]1[CH2:24][O:23][C:22](=[O:25])[N:21]1[C:26]([C@@H:28]1[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][C@H:29]1[CH2:35][O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:27])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C[Si](C)(C)[O:46][CH2:47][CH2:48]O[Si](C)(C)C.C(N(CC)CC)C>C(Cl)Cl>[CH2:13]([C@@H:20]1[CH2:24][O:23][C:22](=[O:25])[N:21]1[C:26]([C@@H:28]1[CH2:33][CH2:32][C:31]2([O:46][CH2:47][CH2:48][O:34]2)[CH2:30][C@H:29]1[CH2:35][O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:27])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: O=C1CC[C@@H](C(=O)N2C(=O)OC[C@H]2Cc2ccccc2)[C@H](COCc2ccccc2)C1
Reactant: C[Si](C)(C)OCCO[Si](C)(C)C
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C1OC[C@@H](Cc2ccccc2)N1C(=O)[C@@H]1CCC2(C[C@H]1COCc1ccccc1)OCCO2
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Trimethylsilyl trifluoromethanesulfonate (2.5 mL) was added dropwise to a 0° C. solution of (4R)-4-benzyl-3-({(1R,2R)-2-[(benzyloxy)methyl]-4-oxocyclohexyl}carbonyl)-1,3-oxazolidin-2-one (57.89 g, 138 mmol) and 1,2-bis-(trimethylsilyloxy)ethane (35.4 g, 172 mmol) in CH2Cl2 (400 mL) followed by stirring at rt for 4 h. Triethylamine (3 mL) was then added at 0° C. and the mixture was washed with saturated aqueous NaHCO3 solution and dried over Na2SO4. Concentration in vacuo gave (4R)-4-benzyl-3-({(7R,8R)-7-[(benzyloxy)methyl]-1,4-dioxaspiro[4.5]dec-8-yl}carbonyl)-1,3-oxazolidin-2-one as a thick, tan colored syrup. 1H NMR (500 MHz, d6-acetone) δ 7.36-7.22 (10H, m), 4.48 (1H, m), 4.42 (2H, s), 4.11 (1H, dd, J= 3.1, 8.9 Hz), 3.97 (4H, m), 3.94-3.90 (1H, t, J= 9.0 Hz), 3.67 (1H, m), 3.44-3.38 (2H, m), 3.09 (1H, dd, J= 3.3, 13.5 Hz), 2.92 (1H, dd, J= 8.3, 13.5 Hz), 2.52 (1H, m), 1.97 (1H, m), 1.86-1.76 (3H, m), 1.57-1.50 (1H, m), 1.44 (1H, t, J= 12.8 Hz).
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=1)C=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:17]([NH2:21])[CH:18](C)C.[C-]#N.[Na+]>>[O:1]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:7]=1[CH2:18][C:17]#[N:21])[C:8]1[CH:15]=[CH:14][CH:13]=[CH:10][CH:9]=1
Reactant: CC(C)CN
Reactant: O=Cc1cccc(Oc2ccccc2)c1
Agent: Cl
Agent: [C-]#N
Agent: [Na+]
Product: N#CCc1ccccc1Oc1ccccc1

Procedure:
3-Phenoxybenzaldehyde, isobutylamine hydrochloride and sodium cyanide were reacted on a 0.3 molar scale using essentially the same procedure as that described in Example 1. The product, α-(N-isobutylamino)-3-(phenoxybenzeneacetonitrile, was obtained as a golden oil (43.5 g). Proton nuclear magnetic resonance spectrum (d6 -acetone; δ in ppm): 0.9 (6H, d of d); 1.74 (1H, m); 2.52 (2H, d); 5.02 (1H, s); 6.9-7.6 (9H, m).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([O:8]S(C(F)(F)F)(=O)=O)[C:5]([N+:16]([O-:18])=[O:17])=[C:4]([C:19]2[O:20][CH:21]=[CH:22][CH:23]=2)[N:3]=1.[CH3:24][N:25]([CH3:29])[CH2:26][CH2:27]O.C1CCN2C(=NCCC2)CC1>COCCOC>[CH3:24][N:25]([CH3:29])[CH2:26][CH2:27][O:8][C:6]1[C:5]([N+:16]([O-:18])=[O:17])=[C:4]([C:19]2[O:20][CH:21]=[CH:22][CH:23]=2)[N:3]=[C:2]([NH2:1])[N:7]=1
Reactant: Nc1nc(OS(=O)(=O)C(F)(F)F)c([N+](=O)[O-])c(-c2ccco2)n1
Reactant: CN(C)CCO
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: CN(C)CCOc1nc(N)nc(-c2ccco2)c1[N+](=O)[O-]

Procedure:
From trifluoro-methanesulfonic acid 2-amino-6-furan-2-yl-5-nitro-pyrimidin-4-yl ester, 2-dimethylaminoethanol and DBU in DME. ES-MS m/e (%): 294 (M+H+, 100).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([S:9](=[O:12])(=[O:11])[NH2:10])=[CH:4][C:3]=1[S:13]([NH2:16])(=[O:15])=[O:14].[CH:17]1([CH:23]=O)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>>[CH:17]1([CH:23]2[NH:1][C:2]3[CH:7]=[C:6]([Cl:8])[C:5]([S:9](=[O:11])(=[O:12])[NH2:10])=[CH:4][C:3]=3[S:13](=[O:15])(=[O:14])[NH:16]2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: O=CC1CCCCC1
Reactant: Nc1cc(Cl)c(S(N)(=O)=O)cc1S(N)(=O)=O
Product: NS(=O)(=O)c1cc2c(cc1Cl)NC(C1CCCCC1)NS2(=O)=O

Procedure:
2-Amino-4-chloro-5-sulfamoylbenzenesulfonamide was transformed by Method G (using cyclohexanecarboxaldehyde). M.p. 274-276° C.
Reaction SMILES: C([NH:4][C:5]1[C:12]([CH3:13])=[CH:11][C:8]([CH2:9][NH2:10])=[CH:7][C:6]=1[Cl:14])(=O)C.Cl[C:16]([O:18][CH2:19][CH2:20][CH3:21])=[O:17]>>[NH2:10][CH2:9][C:8]1[CH:11]=[C:12]([CH3:13])[C:5]([NH:4][C:16](=[O:17])[O:18][CH2:19][CH2:20][CH3:21])=[C:6]([Cl:14])[CH:7]=1
Reactant: CC(=O)Nc1c(C)cc(CN)cc1Cl
Reactant: CCCOC(=O)Cl
Product: CCCOC(=O)Nc1c(C)cc(CN)cc1Cl

Procedure:
The procedure is exactly the same as preparing 4-acetamido-3-chloro-5-methylbenzylamine (Preparation D), except that propyl chloroformate was used instead of acetyl chloride.
Reaction SMILES: [C:1]([C:3]1[C:4](=[O:18])[NH:5][C:6](=[O:17])[N:7]([CH:16]=1)[C@@H:8]1[O:15][C@H:12]([CH2:13][OH:14])[C@@H:10]([OH:11])[CH2:9]1)#[CH:2].C(N(CC)CC)C.[C:26](Cl)(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(#N)C.Cl[Si](C)(C)C>[C:26]([N:5]1[C:4](=[O:18])[C:3]([C:1]#[CH:2])=[CH:16][N:7]([C@@H:8]2[O:15][C@H:12]([CH2:13][OH:14])[C@@H:10]([OH:11])[CH2:9]2)[C:6]1=[O:17])(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: C#Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Reactant: O=C(Cl)c1ccccc1
Agent: C[Si](C)(C)Cl
Solvent: CCN(CC)CC
Solvent: CC#N
Product: C#Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)n(C(=O)c2ccccc2)c1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 47.2 %

Procedure:
To a stirred suspension of 2'deoxy-5-ethynyluridine (J. Med. Chem., 26(5), 661-6, (1983)) (0.3 g, 1.19 mmoles) in dry acetonitrile (8 ml) and chlorotrimethylsilane (0.5 ml) was added, with ice cooling, triethylamine (0.85 ml, 6.1 mmoles) and the whole was stirred at room temperature for 2 hrs. Benzoylchloride (0.18 ml, 1.54 mmoles) was then added and the mixture stirred for a further 1.5 hrs and filtered. The filtrate was concentrated, the residue dissolved in ethanol (10 ml) and glacial acetic acid (0.4 g) was added. After stirring for 0.5 hr, the solvents were evaporated and the residue purified by column chromatography on silica gel eluting with methylene chloride/methanol (19:1) to give the title compound 0.2 g (47% yield) melting at 156°-7° C.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[Cl:7][C:8]1[C:16]([Cl:17])=[C:15]2[C:11]([CH2:12][C:13]([CH2:20][CH:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)([CH3:19])[C:14]2=[O:18])=[CH:10][C:9]=1[OH:26].[F:27][C:28]([F:34])([F:33])[S:29](Cl)(=[O:31])=[O:30]>CN(C)C=O>[F:27][C:28]([F:34])([F:33])[S:29]([O:26][C:9]1[CH:10]=[C:11]2[C:15](=[C:16]([Cl:17])[C:8]=1[Cl:7])[C:14](=[O:18])[C:13]([CH2:20][CH:21]1[CH2:22][CH2:23][CH2:24][CH2:25]1)([CH3:19])[CH2:12]2)(=[O:31])=[O:30]
Reactant: CC1(CC2CCCC2)Cc2cc(O)c(Cl)c(Cl)c2C1=O
Reactant: O=S(=O)(Cl)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC1(CC2CCCC2)Cc2cc(OS(=O)(=O)C(F)(F)F)c(Cl)c(Cl)c2C1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Anhydrous potassium carbonate (17.7 g., 0.128 mole) is added to a solution of 6,7-dichloro-2-cyclopentylmethyl-2,3-dihydro-5-hydroxy-2-methyl-1H-inden-1-one (13.35 g., 0.0426 mole) in dry dimethylformamide (60 ml.). The suspension is stirred for 1 hour at room temperature, cooled to 15° C. and then trifluoromethanesulfonyl chloride is added at 15°-18° C. After stirring for 1 hour at room temperature, the reaction mixture is poured into ice water (700 ml.). The oil that separates is extracted with ether (125 ml.). The combined organic extracts are washed with water, dried over magnesium sulfate and concentrated in vacuo to obtain the amber, oily product (18.8 g.), which is used in the next step without further purification.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6](B(O)O)[CH:7]=[CH:8][CH:9]=1)(=[O:3])[NH2:2].[F-].[K+].[CH2:15]([N:22]1[CH:27]2[CH2:28][CH2:29][CH:23]1[CH:24]=[C:25](OS(C(F)(F)F)(=O)=O)[CH2:26]2)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1COCC1>[CH2:15]([N:22]1[CH:27]2[CH2:28][CH2:29][CH:23]1[CH:24]=[C:25]([C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=1)[C:1]([NH2:2])=[O:3])[CH2:26]2)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: O=S(=O)(OC1=CC2CCC(C1)N2Cc1ccccc1)C(F)(F)F
Reactant: NC(=O)c1cccc(B(O)O)c1
Agent: [Fe+2]
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: C1CCOC1
Product: NC(=O)c1cccc(C2=CC3CCC(C2)N3Cc2ccccc2)c1
Temperature: 67 °C
Reaction time: 2 h

Procedure:
To the crude product of the previous step was added THF (420 mL) and the solution was purged with nitrogen for 5 min. To a 2 L flask was added 3-carbamoylphenyl boronic acid (98%, 33.0 g, 200 mmol), palladium (II) acetate (98%. 0.46 g, 2 mmol), 1,1′-bis(diphenylphosphino)ferrocene (97%, 1.1 g, 2 mmol). and potassium fluoride (34.9 g, 600 mmol) followed by the THF solution of trifluoro-methanesulfonic acid 8-benzyl-8-aza-bicyclo[3.2.1]oct-2-en-3-yl ester. The resulting mixture was purged with nitrogen for 5 min, heated to reflux (67° C.) under nitrogen and stirred for 2 h. The reaction mixture was cooled to 30° C., then EtOAc (500 mL) and 1 N NaOH (500 mL) were added and the mixture was stirred at 22° C. for 10 min. The layers were separated and the aqueous layer was discarded. The organic layer was washed with a mixture of brine (250 mL) and water (250 mL) and stirred for 5 min. The layers were separated and the aqueous layer was discarded. The organic layer was briefly dried over Na2SO4, filtered, and solvent was partially removed. Product precipitated as light yellow solids during solvent removal. The resulting slurry (about 200 mL) was filtered and the solids were washed with cold EtOAc (0° C., 100 mL) and dried under high vacuum at 25° C. to provide the title intermediate (42.5 g) as a light yellow solid.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@H:14]2[N:15]=[C:16]([N:18]([CH3:20])[CH3:19])[S:17][C@H:13]2[CH2:12][C@H:11]([CH2:21][O:22]CC2C=CC=CC=2)[C@H:10]1[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].CC(O)=O>CC(OC(C)=O)=O.CC(O)=O.[Cl-].[Cl-].[Zn+2]>[CH2:1]([O:8][C@@H:9]1[C@H:14]2[N:15]=[C:16]([N:18]([CH3:20])[CH3:19])[S:17][C@H:13]2[CH2:12][C@H:11]([CH2:21][OH:22])[C@H:10]1[O:30][CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CN(C)C1=N[C@@H]2[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@@H](COCc3ccccc3)C[C@@H]2S1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: CC(=O)OC(C)=O
Product: CN(C)C1=N[C@@H]2[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@@H](CO)C[C@@H]2S1
Temperature: 25 °C
Reaction time: 2 h
Yield: 45.9 %

Procedure:
At 15° C., to a solution of (3aR,4R,5R,6R,7aS)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-N,N-dimethyl-3a,4,5,6,7,7a-hexahydrobenzo[d]thiazol-2-amine (13) (0.950 g, 1.84 mmol) in mixed Ac2O/AcOH (10 mL/2 mL) was added anhydrous ZnCl2 (2.5 g, 18 mmol). The mixture was stirred at room temperature for 2 h and concentrated under vacuum at room temperature. The residue was diluted with DCM (50 mL) and saturated aqueous NaHCO3 (50 mL). The mixture was stirred for 30 min, and the solid was filtered off over a Celite 521 cake. The organic layer was collected from the filtrate, and the aqueous was extracted with DCM (3×30 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was dissolved in MeOH (15 mL). Anhydrous K2CO3 (0.47 g, 3.4 mmol) was added, and the mixture was stirred at room temperature for 2 h. AcOH (0.5 mL) was added and the reaction mixture was concentrated under reduced pressure at room temperature. The residue was diluted with saturated aqueous NaHCO3 (30 mL), and then extracted with DCM (3×30 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by flash column chromatography (EtOAc, then MeOH/DCM, 1:10), affording 14 as a sticky pale yellow foam (0.36 g, 46%). 1H NMR (400 MHz, CDCl3) δ 7.44-7.41 (m, 2H), 7.36-7.24 (m, 8H), 5.02 (d, J=11.0 Hz, 1H), 4.95 (d, J=11.2 Hz, 1H), 4.70 (d, J=11.0 Hz, 1H), 4.62 (d, J=11.2 Hz, 1H), 4.31-4.28 (m, 1H), 4.11 (t, J=7.3 Hz, 1H), 3.70 (t, J=8.4 Hz, 1H), 3.64-3.62 (m, 2H), 3.35 (dd, J=8.9, 10.2 Hz, 1H), 3.00 (s, 6H), 2.23 (s, br. 1H), 2.24-2.16 (m, 1H), 2.07-2.02 (m, 1H), 1.72-1.64 (m, 1H).
Reaction SMILES: Cl[C:2]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.Cl.[I-:19].[Na+].C(#N)C>C1COCC1.CCOCC.CCCCCC>[I:19][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: [I-]
Reactant: Clc1nc2ccccc2nc1-c1ccccc1
Agent: Cl
Agent: [Na+]
Solvent: CCCCCC
Solvent: CCOCC
Solvent: CC#N
Product: Ic1nc2ccccc2nc1-c1ccccc1
Yield: 95 %

Procedure:
To the 2-chloro-3-phenylquinoxaline (4.15 mmol) in dry THF (10 ml) was added a solution of 2 M HCl in ether (4 ml). After 5 minutes the solvents were removed by vacuum. Dry sodium iodide (41.5 mmol) and acetonitrile (30 ml) were added to the hydrochloride salt and refluxed for 5 hrs. The reaction was quenched by the addition of an aqueous solution of 10% K2CO3 and 5% NaHSO3 (15 ml). After extraction with dichloromethane, and drying the combined organic layers over MgSO4 the solvents were evaporated under reduced pressure. The resulting crude product was purified by silica gel chromatography with (1:10) EtOAc:hexane, to give 95% yield of the desired product.
Reaction SMILES: C(O[C:4](=[C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=2)[NH:13][C:12]1=[O:23])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)C.[C:24]([NH:27][CH2:28][C:29]1[CH:30]=[C:31]([CH:33]=[CH:34][CH:35]=1)[NH2:32])(=[O:26])[CH3:25]>CN(C=O)C>[C:24]([NH:27][CH2:28][C:29]1[CH:30]=[C:31]([NH:32]/[C:4](=[C:11]2\[C:12](=[O:23])[NH:13][C:14]3[C:19]\2=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=3)/[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:33]=[CH:34][CH:35]=1)(=[O:26])[CH3:25]
Reactant: CCOC(=C1C(=O)Nc2ccc([N+](=O)[O-])cc21)c1ccccc1
Reactant: CC(=O)NCc1cccc(N)c1
Solvent: CN(C)C=O
Product: CC(=O)NCc1cccc(N/C(=C2\C(=O)Nc3ccc([N+](=O)[O-])cc32)c2ccccc2)c1

Procedure:
Prepared analogously to Example 89 from 3-(1-ethoxy-1-phenyl-methylidene)-5-nitro-2-indolinone and 3-acetylaminomethyl-aniline in DMF.