Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]4[N:21]=[N:22][N:23]([CH3:37])[C:24]=4[NH:25][C:26]([O:28][C@@H:29]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH3:30])=[O:27])=[CH:16][CH:15]=3)=[CH:10][CH:9]=2)[CH2:7][CH2:6]1)=[O:4].[OH-].[Na+]>C1COCC1.C(O)C>[CH3:37][N:23]1[C:24]([NH:25][C:26]([O:28][C@@H:29]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH3:30])=[O:27])=[C:20]([C:17]2[CH:18]=[CH:19][C:14]([C:11]3[CH:10]=[CH:9][C:8]([C:5]4([C:3]([OH:4])=[O:2])[CH2:7][CH2:6]4)=[CH:13][CH:12]=3)=[CH:15][CH:16]=2)[N:21]=[N:22]1
Reactant: COC(=O)C1(c2ccc(-c3ccc(-c4nnn(C)c4NC(=O)O[C@H](C)c4ccccc4)cc3)cc2)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: C[C@@H](OC(=O)Nc1c(-c2ccc(-c3ccc(C4(C(=O)O)CC4)cc3)cc2)nnn1C)c1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 97.8 %

Procedure:
[5-(4-Bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid (R)-1-phenyl-ethyl ester (from Example 1, 566 mg, 1.41 mmol), methyl 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylate (511 mg, 1.69 mmol), X-Phos (134 mg, 0.28 mmol), palladium acetate (31.7 mg, 0.14 mmol) and potassium phosphate (898 mg, 4.23 mmol) were combined in toluene (12 mL) and degassed water (3 mL) was added. The mixture was degassed and sealed. The mixture was stirred at 95° C. for 3 hrs and cooled to room temperature. The mixture was extracted with ethyl acetate and water. The organic layer was washed with brine and dried. Solvents were evaporated and the residue was purified by flash column chromatography (40 g silica gel, ethyl acetate in hexanes 10% to 70% in 15 minutes) to give 1-{4′-[1-methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazol-4-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid methyl ester as a pale yellow solid (370 mg, 52.8% yield). LC/MS calcd for C29H28N4O4 (m/e) 496.0, obsd 497.0 (M+H); 1H-NMR (400 MHz, CDCl3) δ ppm 1.25 (m, 3H), 1.66 (m, 4H), 3.67 (s, 3H), 3.93 (s, 3H), 5.91 (m, 1H), 6.44 (br, 1H), 7.29-7.40 (m, 5H), 7.44 (d, J=8.1 Hz, 2H), 7.57 (d, J=8.3 Hz, 2H), 7.61 (d, J=8.3 Hz, 2H), 7.78 (br d, J=6.6 Hz, 2H). 1-{4′-[1-Methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazol-4-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid methyl ester (50 mg) was dissolved in 1 mL of THF and 1 mL of ethanol. To this mixture was added 1N sodium hydroxide solution (1 mL). The clear solution was stirred at room temperature for 12 hrs. Solvents were evaporated and the residue was treated with 2N hydrochloric acid (1.4 mL). The solid was filtered and rinsed with water, dried in the air, to give 1-{4′-[1-methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazol-4-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid (47.5 mg, 97.8% yield). LC/MS calcd for C28H26N4O4 (m/e) 482.0, obsd 483.0 (M+H); 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.14-1.24 (m, 3H), 1.49 (m, 2H), 1.59 (m, 2H), 3.86 (s, 3H), 5.80 (m, 1H), 7.28-7.50 (m, 7H), 7.63 (d, J=8.1 Hz, 2H), 7.71 (m, 2H), 7.80 (d, J=7.6 Hz, 2H), 9.95 and 9.62 (br s, 1H), 12.35 (s, 1H).
Reaction SMILES: [H-].[Na+].Cl[CH2:4][CH2:5][S:6](Cl)(=[O:8])=[O:7].[CH3:10][C:11]1[CH:12]=[C:13]([C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:20][CH:19]=2)[C:14]([NH2:17])=[N:15][CH:16]=1>C1COCC1>[CH3:10][C:11]1[CH:12]=[C:13]([C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:20][CH:19]=2)[C:14]2[N:15]([CH:16]=1)[CH2:4][CH2:5][S:6](=[O:8])(=[O:7])[N:17]=2
Reactant: Cc1cnc(N)c(-c2ccc(Oc3ccccc3)cc2)c1
Reactant: O=S(=O)(Cl)CCCl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC1=CN2CCS(=O)(=O)N=C2C(c2ccc(Oc3ccccc3)cc2)=C1
Reaction time: 0.08 h

Procedure:
To a suspension of NaH (60%, 229 mg) in THF (dry) (10 mL) was added 2-chloroethanesulfonyl chloride (0.361 mL) at 0° C. and the mixture was stirred for 5 min at the same temperature. A solution of 5-methyl-3-(4-phenoxyphenyl)pyridin-2-amine (316 mg) in THF (dry) (20 mL) was added at 0° C. and the mixture was stirred at room temperature for 30 min. The mixture was quenched with water. Water and EtOAc were added and the extracted organic layer was washed with brine. Silica-gel was added and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (silica gel, eluted with MeOH in EtOAc) to give 7-methyl-9-(4-phenoxyphenyl)-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide (158.2 mg) as a white solid. Platinum(IV) oxide (30.0 mg) was added to a solution of 7-methyl-9-(4-phenoxyphenyl)-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide (141 mg) in THF (dry) (15 mL) and MeOH (15 mL) and the mixture was stirred at 50° C. under hydrogen overnight. Platinum(IV) oxide (30.0 mg) was added and the mixture was stirred at 50° C. under hydrogen for 1 day. The insoluble material was removed by filtration, silica-gel was added and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (silica gel, eluted with MeOH in EtOAc) and crystallized from THF/IPE to give the title compound (35.4 mg) as colorless crystals.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C@H:13]([NH:19][C:20]([C@@H:22](/[CH:35]=[CH:36]/[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43](=[O:51])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[C@@:23]([OH:34])([CH2:31][CH2:32][OH:33])[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:21])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:8][CH:7]=1)[C:2]#[C:3][CH3:4].[C:52](OC(=O)C)(=[O:54])[CH3:53].C(N(CC)CC)C.CN(C1C=CC=CN=1)C>ClCCl>[C:52]([O:33][CH2:32][CH2:31][C@:23]([OH:34])([C@@H:22]([C:20](=[O:21])[NH:19][C@H:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:12][C:9]1[CH:8]=[CH:7][C:6]([O:5][CH2:1][C:2]#[C:3][CH3:4])=[CH:11][CH:10]=1)/[CH:35]=[CH:36]/[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43](=[O:51])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[C:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])=[O:25])(=[O:54])[CH3:53]
Reactant: CC(=O)OC(C)=O
Reactant: CC#CCOc1ccc(C[C@H](NC(=O)[C@@H](/C=C/CCCCCCC(=O)CCCCCCC)[C@@](O)(CCO)C(=O)OC(C)(C)C)C(=O)OCC)cc1
Agent: CN(C)c1ccccn1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC#CCOc1ccc(C[C@H](NC(=O)[C@@H](/C=C/CCCCCCC(=O)CCCCCCC)[C@@](O)(CCOC(C)=O)C(=O)OC(C)(C)C)C(=O)OCC)cc1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 78 %

Procedure:
tert-Butyl (E)-(2S,3S)-3-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-ethoxycarbonyl-ethylcarbamoyl]-2-hydroxy-2-(2-hydroxy-ethyl)-12-oxo-nonadec-4-enoate (3.22 g, 4.51 mmol) was dissolved in dichloromethane (64 mL), and the mixture was then cooled to 0° C. in an ice bath. Acetic anhydride (1.07 mL, 11.3 mmol), triethylamine (0.63 mL, 4.52 mmol), and dimethylaminopyridine (55.1 mg, 0.451 mmol) were added in this order, and the mixture was then stirred at 0° C. for 1.5 hours. The mixture was quenched with water (46 mL), and then extracted with dichloromethane (46 mL). The organic layer was washed with a saturated aqueous solution (33 mL) of sodium chloride, then dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off under reduced pressure. The residue was purified on Biotage (silica gel, n-hexane/ethyl acetate) to obtain 2.65 g (3.51 mmol, 78% yield) of No. 5328456.
Reaction SMILES: C[N:2](CC1CCCCC1=O)C.C1(=O)CCCC1.[O:18]=[C:19]1[CH2:23][CH2:22][CH2:21][CH:20]1[CH2:24][CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C:26]1=[O:31]>>[O:18]=[C:19]1[CH2:23][CH2:22][CH2:21][CH:20]1[CH2:24][CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C:26]1=[O:31].[CH2:21]1[C:20]2[C:19](=[N:2][C:26]3[CH2:27][CH2:28][CH2:29][CH2:30][C:25]=3[CH:24]=2)[CH2:23][CH2:22]1
Reactant: CN(C)CC1CCCCC1=O
Agent: O=C1CCCCC1CC1CCCC1=O
Solvent: O=C1CCCC1
Product: c1c2c(nc3c1CCC3)CCCC2

Procedure:
2-(oxo-cyclopentyl)methyl cyclohexanone is prepared from 2-(dimethylaminomethyl)-cyclohexanone and cyclopentanone according to the method described in Ann.Chim.,1963, 53 (6), 819 and is isolated as a colourless oil in 80% yield b.p. 92°/0.05 mm. 5,6,7,8-Tetrahydro-2,3-dihydro-1H-cyclopenta [b]quinoline is prepared from 2-(2-oxocylopentyl)methylcyclohexanone according to the method described in Ann.Chim., 1963, 53,(6), 819 and is isolated in 65% yield as a colourless oil b.p. 80°/0.05 mm. The hydrochloride is prepared for characterisation by treating an ethereal solution of the base with ethereal HC1 and is isolated as the hemi-hydrate as colourless needles from ethanol-ester m.p. 104° C(Found: C65.7; H,7.8; N,6.6 C12H16N.HC1.1/2H2O requires: C,65.8; H,7.8; N,6.4%. 5,6,7,8-tetrahydro-2,3-dihydro-1H-cyclopenta[b]-quinoline is converted to methyl 5,6,7,8-tetrahydro-2,3-dihydro-1H-cyclopenta[b]quinoline-5-carboxylate following the method described in Example 19 and this is converted to 5,6,7,8-tetrahydro-2,3-dihydro-1H-cyclopenta[b]-quinoline-5-carboxamide following the method described in Example 22. The amide is converted to the title compound, following the procedure of Example 23, and is recrystallised from isopropanol, dissolved in ether and treated with an excess of ethereal HC1. The resultant solid is recrystallised from ethanol-ether to give the hydrochloride of the title compound as the monohydrate m.p. 118° C. )Found: C,54.6; H,6.3; N,10.0 C13H16N2S.HCl H2O requires: C,54.4; H,6.6; N,9.8%).
Reaction SMILES: [NH2:1][C@@H:2]([C:5]([CH3:8])([CH3:7])[CH3:6])[CH2:3][OH:4].[CH:9](=O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[BH4-].[Na+]>C1C=CC=CC=1>[CH2:9]([NH:1][C@@H:2]([C:5]([CH3:8])([CH3:7])[CH3:6])[CH2:3][OH:4])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=Cc1ccccc1
Reactant: CC(C)(C)[C@H](N)CO
Agent: [BH4-]
Agent: [Na+]
Solvent: c1ccccc1
Product: CC(C)(C)[C@@H](CO)NCc1ccccc1
Reaction time: 0.5 h
Yield: 81.4 %

Procedure:
(S)-2-Amino-3,3-dimethylbutan-1-ol (4.01 g, 34.2 mmol) was dissolved in benzene (120 mL). Benzaldehyde (3.65 mL, 35.9 mmol) and p-TsOH monohydrate (1.302 mg, 6.84 μmmol) were added. The reaction mixture was heated at reflux for 5 h using Dean-Stark to remove water, the mixture was then concentrated. The residue was dissolved in anhydrous MeOH (100 mL), cooled down in an ice-water bath, and added sodium borohydride (1.942 g, 51.3 mmol) slowly. The reaction mixture was stirred for 30 min, quenched with 1 N NaOH solution, diluted with water, and extracted with ethyl acetate. The combined organics were washed with water, dried over anhydrous Na2SO4, filtered, then concentrated to give the title compound (5.77 g) as a colorless oil without further purification. LCMS m/z=208.2 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 0.88 (s, 9H), 2.33 (dd, J=6.4 and 4.7 Hz, 1H), 3.34 (dd, J=10.6 and 6.4 Hz, 1H), 3.59 (dd, J=10.6 and 4.7 Hz, 1H), 3.76 and 3.85 (dd, J=12.8 Hz, 2H), 7.20-7.27 (m, 5H).
Reaction SMILES: [C:1]([O-:4])([O-])=O.[K+].[K+].[Br:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1O>CC(C)=O>[Br:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[O:4][CH3:1]
Reactant: Oc1ccc(Cl)cc1Br
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COc1ccc(Cl)cc1Br
Temperature: 25 °C

Procedure:
A mixture of K2CO3 (68 g, 0.5 mol), 2-bromo-4-chlorophenol (50 g, 0.24 mol) and Mel (42.6 g, 0.3 mol) in acetone (1000 mL) was heated to reflux for 5 hr and then cooled to room temperature. The solid was filtered off and washed with dichloromethane (100 mL×3). The combined filtrate was concentrated to dryness. The residue was diluted with diethyl ether (500 mL) and washed with HCl (1 M, 100 mL×2), H2O (100 mL×2) and brine (200 mL). The separated organic layer was dried over Na2SO4 and concentrated to give 2-bromo-4-chloroanisole 1a as a light yellow liquid. 1H NMR (CDCl3): δ 7.52 (d, J=2.8 Hz, 1H), 7.24 (q, J1=8.8 Hz, J2=2.8 Hz, 1H), 6.81 (d, J=8.8 Hz, 1H), 3.86 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([NH2:24])[S:12][C:13]=2[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)=[CH:5][CH:4]=1.[F:25][C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[CH:28][CH:27]=1>>[F:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([NH:24][C:11]2[S:12][C:13]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=3)=[C:9]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[N:10]=2)=[O:31])=[CH:28][CH:27]=1
Reactant: O=C(Cl)c1ccc(F)cc1
Reactant: COc1ccc(-c2nc(N)sc2Cc2ccc([N+](=O)[O-])cc2)cc1
Product: COc1ccc(-c2nc(NC(=O)c3ccc(F)cc3)sc2Cc2ccc([N+](=O)[O-])cc2)cc1
Yield: 81.3 %

Procedure:
A procedure similar to that in Example 4 was used. 4-(4-methoxy-phenyl)-5-(4-nitro-benzyl)-thiazol-2-ylamine prepared in Example 6 and p-fluorobenzoyl chloride were used as starting materials, allowed to react at 35-40° C. for 48 hours, followed by post-treatment to obtain a crude product, which was purified by a silica gel column chromatography eluted with petroleum ether and ethyl acetate (4:1) to obtain a product as a yellow solid in a yield of 81.3%, mp: 188-189 └. 1H-NMR (CDCl3, 400 MHz) δ: 3.82 (3H, s, OCH3), 4.33 (2H, s, CH2), 6.87 (2H, d, J=8.68 Hz, ArH), 7.10 (2H, t, 3JFH=3JHH=8.68 Hz, ArH), 7.37 (2H, d, J=8.40 Hz, ArH), 7.39 (2H, d, J=8.68 Hz, ArH), 7.89 (2H, dd, 3JHH=8.68, 4JFH=5.02 Hz, ArH), 8.19 (2H, d, J=8.68 Hz, ArH); EI-MS m/e (%): 463.1 (M+, 60), 123.0 (100); HREI-MS Calcd. for C24H18FN3O4S: 463.1002. found: 463.1000. Anal. Calcd. for C24H18FN3O4S: C, 62.19; H, 3.91; N, 9.07. found: C, 62.21; H, 3.82; N, 9.02.
Reaction SMILES: [CH3:1][CH2:2][CH:3]([C:6]1[CH:7]=[C:8]([CH:15]=[CH:16][CH:17]=1)[CH2:9][C@@H:10]([C:12]([OH:14])=[O:13])[NH2:11])[CH2:4][CH3:5].Cl.[CH3:19][C:20](=[CH2:22])[CH3:21]>O1CCOCC1>[CH3:5][CH2:4][CH:3]([C:6]1[CH:7]=[C:8]([CH:15]=[CH:16][CH:17]=1)[CH2:9][C@@H:10]([C:12]([O:14][C:20]([CH3:22])([CH3:21])[CH3:19])=[O:13])[NH2:11])[CH2:2][CH3:1]
Reactant: C=C(C)C
Reactant: CCC(CC)c1cccc(C[C@H](N)C(=O)O)c1
Agent: Cl
Solvent: C1COCCO1
Product: CCC(CC)c1cccc(C[C@H](N)C(=O)OC(C)(C)C)c1
Yield: 74 %

Procedure:
According to example 54, 0.60 g of 3-(3-pentyl)-L-phenylalanine.HCl was treated with 30 mL of isobutylene in 35 mL of 1,4-dioxane in the presence of 0.5 mL of conc. H2S4. Work-up in the usual manner followed by acidification with 2 mL of 1N ethereal HCl afforded 0.53 g (74%) of tert-butyl 3(3-pentyl)-L-phenylalaninate.HCl as a light yellow glass.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH:7]1[CH2:14][CH2:13][CH:12]2[CH:8]1[CH2:9][C:10](=[O:15])[CH2:11]2.O.[C:17](O)(=[O:19])[CH3:18]>>[C:17]([O:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH:7]1[CH2:14][CH2:13][CH:12]2[CH:8]1[CH2:9][C:10](=[O:15])[CH2:11]2)(=[O:19])[CH3:18]
Reactant: O=C1CC2CCC(CCCCCO)C2C1
Reactant: CC(=O)O
Solvent: O
Product: CC(=O)OCCCCCC1CCC2CC(=O)CC12
Temperature: 75 °C

Procedure:
The starting material 2-(5-hydroxypent-1-yl)bicyclo[3.3.0]octan-7-one {hexahydro-4-(5-hydroxypentyl)-2(1H)-pentalenone} (0.8 g, 3.8 mmoles) is diluted with glacial acetic acid (7 ml). The reaction is stirred and heated in a 75° C. oil bath for 24 hours, after which time water (20 ml) is added and the reaction partitioned between ether. The ether layer is separated and the aqueous phase extracted again with ether (2×50 ml). The extracts and the organic phase are combined and neutralized with saturated sodium bicarbonate. The organic phase is dried over anhydrous magnesium sulfate and the remained solvent removed under vacuum leaving a pale yellow oil. The product is kugelrohred under reduced pressure leaving a clear, colorless oil (0.5 g, 2.0 mmoles).
Reaction SMILES: [CH3:1][NH2:2].[CH3:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][C:5]=1[CH:13]=O.[BH4-].[Na+].O>CO>[CH3:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][C:5]=1[CH2:13][NH:2][CH3:1]
Reactant: CN
Reactant: Cc1c(C=O)[nH]c2ccccc12
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CNCc1[nH]c2ccccc2c1C
Reaction time: 5 h
Yield: 71.3 %

Procedure:
Methylamine (0.34 mL, 8.4 mmol, 33% in ethanol) was added to a solution of 3-methylindole-2-carboxaldehyde (447 mg, 2.8 mmol) in methanol (10 mL) and stirred for 5 hours. Sodium borohydride (104 mg, 2.8 mmol) was slowly added at 0° C. The resultant mixture was warmed to room temperature and stirred overnight. Water (2 mL) was added slowly at 0° C. and the mixture was evaporated to a paste. The paste was partitioned between water (2 mL) and dichloromethane (15 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (2×15 mL). The combined organic phases were dried and evaporated to afford title compound (348 mg, 71%). 1H NMR (400 MHz, DMSO-d6): 10.63 (s, 1H), 7.38 (d, J=7.7 Hz, 1H), 7.25 (d, J=8.0 Hz, 1H), 6.99 (t, J=8.0 Hz, 1H), 6.92 (t, J=6.6 Hz, 1H), 3.73 (s, 2H), 2.25 (s, 3H), 2.19 (s, 3H).
Reaction SMILES: N#N.[Li]CCCC.[O:8]1[CH:12]=[CH:11][CH:10]=[C:9]1[C:13]1([CH3:18])[O:17][CH2:16][CH2:15][O:14]1.CN([CH:22]=[O:23])C.[NH4+].[Cl-]>CCCCCC.C1COCC1>[CH3:18][C:13]1([C:9]2[O:8][C:12]([CH:22]=[O:23])=[CH:11][CH:10]=2)[O:14][CH2:15][CH2:16][O:17]1
Reactant: CC1(c2ccco2)OCCO1
Reactant: CN(C)C=O
Agent: N#N
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC1(c2ccc(C=O)o2)OCCO1
Temperature: -78 °C
Reaction time: 1 h
Yield: 166.7 %

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of n-BuLi (14.6 mL of a 1.6M solution in hexane, 23.35 mmol) in THF (21 mL) at −78° C. was added dropwise a solution of 2-furan-2-yl-2-methyl-[1,3]dioxolane (3.00 g, 19.46 mmol) in THF (6.0 mL). The reaction mixture was then stirred for 1 h at −78° C. before DMF (4.52 mL, 58.38 mmol) was added dropwise. The reaction mixture was stirred for 1 h at −78° C. Sat. aq. NH4Cl (50 mL) was added and the mixture was extracted with EA (2×50 mL). The combined org. extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure to give 5.91 g of crude 5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-carbaldehyde as an orange oil. LC-MS-conditions 02: tR=0.75 min; [M+H]+=183.23. The crude material was dissolved, under inert atmosphere (N2) in MeOH (59.0 mL) and treated at 0° C., portionwise, over 20 min, with NaBH4 (1.53 g, 38.92 mmol in five equal portions). The reaction mixture was stirred for 45 min at rt. The reaction mixture was poured on water (80 mL) and the aq. layer was extracted with EA (2×60 mL). The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (50:50 hept-EA) gave the title compound: TLC:rf (50:50 hept-EA)=0.27. LC-MS-conditions 02: tR=0.65 min; [M+H]+=185.28.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:7])[C:4](Cl)=[O:5].[C:8]([C:11]1[CH:30]=[CH:29][C:14]([O:15][CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:21]=[C:22]([C:24]([CH3:28])=[CH:25][C:26]=2[Br:27])[NH2:23])=[C:13]([CH2:31][CH2:32][CH3:33])[C:12]=1[OH:34])(=[O:10])[CH3:9].C(N(CC)CC)C>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:7])[C:4]([NH:23][C:22]1[C:24]([CH3:28])=[CH:25][C:26]([Br:27])=[C:20]([O:19][CH2:18][CH2:17][CH2:16][O:15][C:14]2[CH:29]=[CH:30][C:11]([C:8](=[O:10])[CH3:9])=[C:12]([OH:34])[C:13]=2[CH2:31][CH2:32][CH3:33])[CH:21]=1)=[O:5]
Reactant: COC(=O)C(=O)Cl
Reactant: CCCc1c(OCCCOc2cc(N)c(C)cc2Br)ccc(C(C)=O)c1O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCc1c(OCCCOc2cc(NC(=O)C(=O)OC)c(C)cc2Br)ccc(C(C)=O)c1O
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
In the course of approximately 5 minutes a solution of 3.2 ml of chloro-oxalic acid methyl ester in 10 ml of methylene chloride is added dropwise to a solution, cooled to 0°, of 14.0 g (32 mmol) of 3-[3-(4-acetyl-3-hydroxy-2-n-propylphenoxy)-propoxy]-4-bromo-6-methylaniline and 4.9 ml of triethylamine in 140 ml of methylene chloride and the whole is then stirred at room temperature for a further 90 minutes. The reaction mixture is poured onto ice-water and the organic phase is separated off, washed with water, dried over sodium sulphate and concentrated under reduced pressure. Crystallisation from ethyl acetate/ether/petroleum ether yields N-{3-[3-(4-acetyl-3-hydroxy-2-n-propylphenoxy)-propoxy]-4-bromo-6-methylphenyl}-oxamic acid methyl ester having a melting point of 92°-93°.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:42](=[CH:43][CH:44]=1)[C:7]1=[CH:8][C:9]3[C:10]([C:32]4[CH:41]=[CH:40][C:39]5[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=5)[CH:33]=4)(O)[C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=4[C:17]([C:21]4[CH:30]=[CH:29][C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH:22]=4)(O)[C:18]=3[CH:19]=[C:6]1[C:5]2([CH3:46])[CH3:45].[PH2]([O-])=O.[Na+]>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:42](=[CH:43][CH:44]=1)[C:7]1=[CH:8][C:9]3[C:10]([C:32]4[CH:41]=[CH:40][C:39]5[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=5)[CH:33]=4)=[C:11]4[C:16](=[C:17]([C:21]5[CH:30]=[CH:29][C:28]6[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=6)[CH:22]=5)[C:18]=3[CH:19]=[C:6]1[C:5]2([CH3:46])[CH3:45])[CH:15]=[CH:14][CH:13]=[CH:12]4
Reactant: CC1(C)c2cc(Br)ccc2-c2cc3c(cc21)C(O)(c1ccc2ccccc2c1)c1ccccc1C3(O)c1ccc2ccccc2c1
Agent: O=[PH2][O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: CC1(C)c2cc(Br)ccc2-c2cc3c(-c4ccc5ccccc5c4)c4ccccc4c(-c4ccc5ccccc5c4)c3cc21
Reaction time: 5 h
Yield: 75.9 %

Procedure:
2-bromo-13,13-dimethyl-6,11-di(naphthalen-2-yl)-11,13-dihydro-6H-indeno[1,2-b]anthracene-6,11-diol (5 g, 0.0075 mol), KI (12.45 g, 0.075 mol), and Sodium hypophosphite (6 g, 0.037 mol) were placed in a flask, and acetic acid (200 ml) was added thereto. The reaction mixture was stirred for five hours while heating. After the reaction was terminated, the reaction solution was added to an excess of distilled water. The resultant solid was washed with distilled water, filtered, and purified by column chromatography to give 2-bromo-13,13-dimethyl-6,11-di(naphthalen-2-yl)-13H-indeno[1,2-b]anthracene (3.56 g, yield=76%).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[C:7]([O:11][C:12](=[O:33])[N:13]([CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([Br:32])[CH:27]=1)[CH2:14][CH2:15][NH:16]C(=O)C(F)(F)F)([CH3:10])([CH3:9])[CH3:8]>CO>[C:7]([O:11][C:12](=[O:33])[N:13]([CH2:14][CH2:15][NH2:16])[CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([Br:32])[CH:27]=1)([CH3:8])([CH3:10])[CH3:9]
Reactant: CC(C)(C)OC(=O)N(CCNC(=O)C(F)(F)F)CCOc1cccc(Br)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: CC(C)(C)OC(=O)N(CCN)CCOc1cccc(Br)c1
Temperature: 50 °C
Reaction time: 5 h
Yield: 102.7 %

Procedure:
Potassium carbonate [584-08-7] (35.8 g, 259.2 mmol) was added to a solution of [2-(3-bromo-phenoxy)-ethyl]-[2-(2,2,2-trifluoro-acetylamino)-ethyl]-carbamic acid tert-butyl ester (4.7 g, 10.3 mmol) in 10% (v/v) aqueous methanol (200 mL) and stirred at 50° C. for 5 h. The reaction mixture was filtered, the filtrate evaporated to dryness, dissolved in ethyl acetate, washed with brine, dried (CaSO4) and evaporated to yield 3.8 g of (2-amino-ethyl)-[2-(3-bromo-phenoxy)-ethyl]-carbamic acid tert-butyl ester as a clear yellow oil. LRMS (ESI) m/z 359.1/361.1 [(M+H)]+, calc'd for C15H23BrN2O3: 359.27.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[C:11]1[N:19]2[C:14]([CH:15]=[N:16][C:17]([S:20][CH3:21])=[N:18]2)=[CH:13][CH:12]=1.ClC1C=C(C=CC=1)C(OO)=[O:27]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[C:11]1[N:19]2[C:14]([CH:15]=[N:16][C:17]([S:20]([CH3:21])=[O:27])=[N:18]2)=[CH:13][CH:12]=1
Reactant: COc1ccc(-c2ccc3cnc(SC)nn23)c(OC)c1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: COc1ccc(-c2ccc3cnc(S(C)=O)nn23)c(OC)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
7-(2,4-Dimethoxy-phenyl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (592 mg, 1.00 equiv) and m-chloroperoxybenzoic acid (77%, 462 mg, 1.05 equiv) were dissolved in methylene chloride and stirred for 2 hours at room temperature. Partitioned between methylene chloride and saturated aqueous sodium bicarbonate. Dried over magnesium sulfate. Triturated with ether to afford 7-(2,4-dimethoxy-phenyl)-2-methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazine as a yellow solid, 605 mg. LCMS (E/I+) 318 (M+H). NMR 1H (CDCl3) 9.02 (s, 1H), 7.22-7.34 (m, 2H), 7.03 (s, 1H), 6.67-6.77 (m, 2H), 3.93 (s, 3H), 3.86 (s, 3H), 3.02 (s, 3H).