Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N(CC)CC)C.[CH3:8][C:9]([Si:12]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[O:13][CH:14]1[CH:17]([CH2:18][O:19][Si:20]([C:33]([CH3:36])([CH3:35])[CH3:34])([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:16][CH:15]1[OH:37])([CH3:11])[CH3:10].[CH3:50][S:51](Cl)(=[O:53])=[O:52]>C(Cl)Cl>[CH3:50][S:51]([O:37][CH:15]1[CH2:16][CH:17]([CH2:18][O:19][Si:20]([C:33]([CH3:34])([CH3:35])[CH3:36])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:14]1[O:13][Si:12]([C:9]([CH3:8])([CH3:10])[CH3:11])([C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)(=[O:53])=[O:52]
Reactant: CC(C)(C)[Si](OCC1CC(O)C1O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)(c1ccccc1)c1ccccc1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)[Si](OCC1CC(OS(C)(=O)=O)C1O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 59.8 %

Procedure:
Freshly distilled triethylamine (1.28 g, 8.2 mmol) was dissolved in 75 mL of freshly distilled methylene chloride. To this solution was added 2.3 g (3.9 mmol) of 2-O-((1,1-dimethylethyl)diphenylsilyl)-3-(((1,1-dimethylethyl)diphenyl-silyl)oxymethyl)-1,2-cyclobutanediol from Step K and the resultant solution was cooled to -78° C. with stirring, under a nitrogen atmosphere. Methanesulfonyl chloride (0.99 g, 8.2 mmol) was added and the reaction mixture was allowed to warm to ambient temperature. After 3.5 h, the reaction mixture was diluted with 125 mL of methylene chloride and this solution was washed with 100 mL of water, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue (2.9 g) was dissolved in 25 mL of 10% acetone in hexane and purified on a 2.5×45 cm silica gel column eluted at 2 psi with 500 mL of 5% acetone in hexane, followed by 250 mL of 10% acetone in hexane, to give 1.57 g (60% yield) of the title compound; MS DCI-NH3M/Z: 690 (M+NH4)+ ; 1H NMR (CDCl3) δ 1.95 (m, 1H), 2.20 (m, 1H), 2.77 (m, 1H), 2.90 (s, 3H), 3.39 (d, 2H), 4.39 (m, 1H), 4.88 (m, 1H), 7.30-7.54 (m, l5H), 7.60-7.70 (m, 5H).
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:6])[CH2:4][OH:5].Cl[C:8]1[N:13]=[C:12]([C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)[N:11]=[C:10]([NH:20][S:21]([CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)(=[O:23])=[O:22])[C:9]=1[O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[O:39][CH3:40].Cl>CN(C=O)C>[OH:5][CH2:4][CH2:3][O:6][C:8]1[N:13]=[C:12]([C:14]2[CH:15]=[CH:16][N:17]=[CH:18][CH:19]=2)[N:11]=[C:10]([NH:20][S:21]([CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)(=[O:23])=[O:22])[C:9]=1[O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[O:39][CH3:40]
Reactant: COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)CCc1ccccn1
Reactant: OCCO
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccccc1Oc1c(NS(=O)(=O)CCc2ccccn2)nc(-c2ccncc2)nc1OCCO
Temperature: 90 °C
Reaction time: 40 h

Procedure:
To a suspension of NaH (701 mg, 60% in mineral oil) in DMF (15 ml) was added ethylene glycol (15 ml). After the evolution of gas had ceased, 2-pyridin-2-yl-ethanesulfonic acid [6-chloro-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-amide (800 mg) was added and the resulting solution was stirred at 90° C. for 40 h. The solution was neutralised with 2 N aq. HCl (7 ml) before it was evaporated. The brown residue was purified by chromatography on prep. tlc-plates with EA:methanol:sat. aq. ammonia 10:2:1. The product was further purified by crystallisation from methanol:diethyl ether:pentane to give 2-pyridin-2-yl-ethanesulfonic acid [6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-amide (280 mg) as beige crystals. 1H-NMR(300 MHz, CDC3): 3.36–3.43(m, 2H), 3.86–3.90(m, 2H), 3.94(s, 3H), 4.23–4.30(m, 2H), 4.564.62(m, 2H), 6.91(dt, Jd=1.5, Jt=7.7, 1H, 7.00(dd, J=1.7, 8.2, 1H, 7.08–7.20(m, 4H), 7.57(dt, Jd=1.8, Jt=7.9, 1H), 8.15(dd, J=1.7, 4.6, 2H), 8.43(d, J=4.4, 1H), 8.72(dd, J=1.7, 4.6, 2H); LC-MS: tR=3.23 min, [M+1]+=524.48, [M−1]−=522.25.
Reaction SMILES: [CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13](Br)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18].[Cl:19][C:20]1[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>ClCCl>[CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([C:23]4[CH:22]=[CH:21][C:20]([Cl:19])=[CH:25][C:24]=4[Cl:26])=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18]
Reactant: OB(O)c1ccc(Cl)cc1Cl
Reactant: CN1C(=O)CC[C@]2(C)c3ccc(Br)cc3CC[C@@H]12
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: CN1C(=O)CC[C@]2(C)c3ccc(-c4ccc(Cl)cc4Cl)cc3CC[C@@H]12
Yield: 64.5 %

Procedure:
A 15 mL round bottom flask was charged with (+)-(4aR)-(10bR)-4-methyl-8-bromo-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one (200 mg, 0.65 mmol), tetrakis (triphenylphosphine)palladium(0) (23 mg, 0.02 mmol), 2,4-dichlorophenylboronic acid (149 mg, 0.78 mmol), 0.65 mL of 2M sodium carbonate solution and 1.5 mL of toluene fitted with a reflux condenser, and the stirred mixture was heated at 80°, under nitrogen, for 24 h. The mixture was cooled, diluted with dichloromethane (75 mL) and washed with brine (2×25 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (ethyl acetate eluent), followed by recrystallization from ethyl acetate to give 157 mg (65%) of the title compound as an amorphous foam. mp 45°-48°. FDMS: m/e=374.
Reaction SMILES: C(OC(Cl)=O)C.[C:7]([C:10]12[CH2:17][CH2:16][C:13]([C:18]#[N:19])([CH2:14][CH2:15]1)[CH2:12][CH2:11]2)(O)=[O:8].C([N:22](CC)CC)C.N>C(Cl)(Cl)Cl>[NH2:22][C:7]([C:10]12[CH2:17][CH2:16][C:13]([C:18]#[N:19])([CH2:14][CH2:15]1)[CH2:12][CH2:11]2)=[O:8]
Reactant: N#CC12CCC(C(=O)O)(CC1)CC2
Reactant: CCN(CC)CC
Agent: CCOC(=O)Cl
Agent: N
Solvent: ClC(Cl)Cl
Product: N#CC12CCC(C(N)=O)(CC1)CC2
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 86 %

Procedure:
2.6 ml of ethylchloroformate are rapidly added, dropwise, to a solution of 4.9 g of 1-carboxy-4-cyano-bicyclo[2.2.2]-octane and 3.8 ml of triethylamine in 130 ml of chloroform at -10° C. After 15 minutes of stirring, ammonia gas is introduced to the mixture for 10 minutes. The mixture is stirred for 10 minutes at 0° C., warmed to ambient temperature and after an hour, evaporated to dryness. The residue is stirred with water under heating, cooled, suction filtered, washed with water and dried. The 1-aminocarbonyl-4-cyano-bicyclo[2.2.2]octane [4.2 g (86% of theory); Rf value: 0.78 (Silica gel; methylene chloride/methanol/conc. aqueous ammonia=4:1:0.2)] obtained is suspended in 100 ml of acetonitrile/water (1:1), combined with 15.0 g of bis(trifluoroacetoxy) iodobenzene and stirred for 18 hours at ambient temperature. The reaction mixture is evaporated down to half its volume, shaken twice with ethyl acetate and the aqueous phase is adjusted to a pH of 12 to 13. The aqueous phase is extracted 3 times with ethyl acetate and the combined organic phases are washed with saturated saline solution and dried. The residue is dissolved in ethyl acetate acid and a little acetone and ethereal hydrochloric acid are added. The mixture is cooled in an ice-bath, suction filtered and the product is washed with ethyl acetate.
Reaction SMILES: C1N=CN([C:6](N2C=NC=C2)=[S:7])C=1.[OH:13][CH2:14][C:15]([NH:18][C:19]1[S:20][CH:21]=[C:22]([C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=2)[N:23]=1)([CH3:17])[CH3:16]>O1CCCC1>[CH3:16][C:15]1([CH3:17])[CH2:14][O:13][C:6](=[S:7])[N:18]1[C:19]1[S:20][CH:21]=[C:22]([C:24]2[CH:25]=[CH:26][C:27]([C:28]#[N:29])=[CH:30][CH:31]=2)[N:23]=1
Reactant: S=C(n1ccnc1)n1ccnc1
Reactant: CC(C)(CO)Nc1nc(-c2ccc(C#N)cc2)cs1
Solvent: C1CCOC1
Product: CC1(C)COC(=S)N1c1nc(-c2ccc(C#N)cc2)cs1
Temperature: 25 °C
Reaction time: 2 h
Yield: 11.4 %

Procedure:
1,1-Thiocarbonyldiimidazole (652 mg, 3.6 mmol) was added to a solution of 4-{2-[(2-hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}benzonitrile (1.0 g, 3.6 mmol), prepared in the previous step, in 60 mL of dry tetrahydrofuran at 0° C. The solution was allowed to warm to room temperature. After 2 h, starting material remained. The reaction was heated to reflux. After 12 h, the reaction was cooled to room temperature and concentrated under reduced pressure. Purification of the residue by reverse phase HPLC using a continuous gradient of 70-83% acetonitrile-water over 10 min gave the title compound (130 mg, 11%) as a tan solid. mp>240° C. (dec.)
Reaction SMILES: [C:1]1([C:7]([CH3:9])=[CH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[S:10](Cl)([Cl:13])(=[O:12])=[O:11]>CN(C)C=O>[C:1]1([C:7]([CH3:9])=[CH:8][S:10]([Cl:13])(=[O:12])=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=S(=O)(Cl)Cl
Reactant: C=C(C)c1ccccc1
Solvent: CN(C)C=O
Product: CC(=CS(=O)(=O)Cl)c1ccccc1

Procedure:
Following the procedure of Preparation A, 2-phenylpropene is reacted with sulfuryl chloride in N,N-dimethylformamide to give 2-phenylpropene-1-sulfonyl chloride, which is then treated with ammonia to give 2-phenylpropene-1-sulfonamide, m.p. 101°-102.5° C.
Reaction SMILES: C([O:4][C:5]1[C:13]2[O:12][C:11]([CH3:14])=[CH:10][C:9]=2[CH:8]=[C:7]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:6]=1)(=O)C.C(=O)([O-])[O-].[K+].[K+]>C(O)C.ClCCl>[OH:4][C:5]1[C:13]2[O:12][C:11]([CH3:14])=[CH:10][C:9]=2[CH:8]=[C:7]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:6]=1
Reactant: CCOC(=O)c1cc(OC(C)=O)c2oc(C)cc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: ClCCl
Product: CCOC(=O)c1cc(O)c2oc(C)cc2c1
Temperature: 60 °C
Reaction time: 3 h
Yield: 81 %

Procedure:
Ethyl 7-(Acetyloxy)-2-methyl-1-benzofuran-5-carboxylate was dissolved in absolute ethanol (200 mL). Potassium carbonate (18 g, 0.13 mol) was added. The reaction mixture was stirred for 3 h at 60° C. and diluted with 200 mL of dichloromethane. The suspension was filtered. The precipitate was washed by 100 mL of dichloromethane. The combined solutions were washed by 200 mL of a 10% aqueous solution of citric acid and evaporated in vacuum to dryness. The residue was and crystallized from ether/hexane mixture, 1:5 to give the desired product 8.5 g (38 mmol, 81%) as a cream solid. 1H NMR (DMSO-D6): δ ppm 1.35 (t, 3H), 2.40 (s, 3H), 4.20 (qt, 2H), 6.65 (s, 1H), 7.32 (s, 1H), 7.65 (s, 1H); MS (APCI, pos): 221.1.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]2[N:11]([CH3:12])[CH2:10][CH2:9][N:5]2[C:6](=[O:8])[N:7]=1.[H-].[Na+].[F:15][C:16]1[CH:17]=[C:18]([CH:30]=[C:31]([F:33])[CH:32]=1)[O:19][C:20]1[CH:27]=[CH:26][C:25]([CH2:28][OH:29])=[CH:24][C:21]=1[C:22]#[N:23]>CN(C=O)C>[F:15][C:16]1[CH:17]=[C:18]([CH:30]=[C:31]([F:33])[CH:32]=1)[O:19][C:20]1[CH:27]=[CH:26][C:25]([CH2:28][O:29][C:2]2[CH:3]=[C:4]3[N:11]([CH3:12])[CH2:10][CH2:9][N:5]3[C:6](=[O:8])[N:7]=2)=[CH:24][C:21]=1[C:22]#[N:23]
Reactant: CN1CCn2c1cc(Cl)nc2=O
Reactant: N#Cc1cc(CO)ccc1Oc1cc(F)cc(F)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN1CCn2c1cc(OCc1ccc(Oc3cc(F)cc(F)c3)c(C#N)c1)nc2=O

Procedure:
Prepared in a manner similar to that described for E1 using 7-chloro-1-methyl-2,3-dihydroimidazo[1,2-c]pyrimidin-5(1H)-one (50 mg, 0.269 mmol), sodium hydride (21.55 mg, 0.539 mmol) and 2-(3,5-difluorophenoxy)-5-(hydroxymethyl)benzonitrile (70.4 mg, 0.269 mmol) in DMF (2 mL).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]2[C:11](=[N:12][C:13]=1[CH3:14])[N:10]=[CH:9][C:8]([C:15]([O:17]CC)=[O:16])=[C:7]2[OH:20])[CH3:2].[OH-].[Na+]>O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]2[C:11](=[N:12][C:13]=1[CH3:14])[N:10]=[CH:9][C:8]([C:15]([OH:17])=[O:16])=[C:7]2[OH:20])[CH3:2]
Reactant: CCOC(=O)c1cnc2nc(C)c(OCC)cc2c1O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCOc1cc2c(O)c(C(=O)O)cnc2nc1C
Temperature: 25 °C

Procedure:
A mixture of ethyl 6-ethoxy-4-hydroxy-7-methyl-1,8-naphthyridine-3-carboxylate (10.0 g), 5M sodium hydroxide solution (200 ml), IMS (64 ml) and water (64 ml) was boiled under reflux for 2 hours. The mixture was cooled to ambient temperature and then filtered. The residue was dissolved in water, acidified to pH5 with glacial acetic acid and filtered. The residue was triturated with hot IMS, cooled and filtered to give 6-ethoxy-4-hydroxy-7-methyl-1,8-naphthyridine-3-carboxylic acid, m.p. 259°-261° C.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH:5]=[C:6]2[C@@H:11]([NH:12][CH2:13][C@H:14]([C@@H:16]([NH:20][C:21](=[O:25])[CH2:22][O:23][CH3:24])[CH2:17][CH:18]=[CH2:19])[OH:15])[CH2:10][C:9]3([CH2:28][CH2:27][CH2:26]3)[O:8][C:7]=12.[CH3:34][N:35]1[CH:39]=[CH:38][N:37]=[C:36]1[Sn](CCCC)(CCCC)CCCC>C1COCC1.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>[CH3:32][C:30]([CH3:31])([CH3:33])[CH2:29][C:4]1[CH:5]=[C:6]2[C@@H:11]([NH:12][CH2:13][C@H:14]([C@@H:16]([NH:20][C:21](=[O:25])[CH2:22][O:23][CH3:24])[CH2:17][CH:18]=[CH2:19])[OH:15])[CH2:10][C:9]3([CH2:28][CH2:27][CH2:26]3)[O:8][C:7]2=[C:2]([C:36]2[N:35]([CH3:34])[CH:39]=[CH:38][N:37]=2)[N:3]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1nccn1C
Reactant: C=CC[C@H](NC(=O)COC)[C@H](O)CN[C@H]1CC2(CCC2)Oc2c1cc(CC(C)(C)C)nc2Cl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: C=CC[C@H](NC(=O)COC)[C@H](O)CN[C@H]1CC2(CCC2)Oc2c1cc(CC(C)(C)C)nc2-c1nccn1C
Temperature: 160 °C

Procedure:
A solution of N-((1S)-1-((1R)-2-(((4′S)-8′-chloro-6′-(2,2-dimethylpropyl)-3′,4′-dihydrospiro[cyclobutane-1,2′-pyrano[2,3-c]pyridin]-4′-yl)amino)-1-hydroxyethyl)-3-buten-1-yl)-2-methoxyacetamide (225 mg, 469 μmol) and tetrakis(triphenylphosphine)palladium (108 mg, 93.7 μmol) in THF (3.0 mL) is added to a vial with 1-methyl-2-(tributylstannyl)-1H-imidazole (217 mg, 586 μmol). The reaction was heated in the microwave at 160° C. for 20 min. The residue was diluted with H2O (10 mL) and extracted with CH2Cl2 (3×10 ml). The organic layers were dried (MgSO4), concentrated and purified by reverse phase HPLC to give the title compound as a white amorphous solid. MS m/z=526.3 [M+H]+.
Reaction SMILES: CS(O[CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)(=O)=O.C1CCN2C(=NCCC2)CC1>C1COCC1>[N:9]1([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH:7]=[CH:6][CH2:11][CH2:10]1
Reactant: CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: CC(C)(C)OC(=O)N1CC=CCC1
Temperature: 0 °C

Procedure:
A solution of tert-butyl 4-[(methylsulfonyl)oxy]piperidine-1-carboxylate (312 g, 1.12 mol) and DBU (400 g, 2.24 mol) in THF (4.5 L) was heated to reflux overnight. The mixture was poured into ice-water (2 L) and then extracted with EtOAc (2 L). The combined organic phase was washed with 1 M HCl solution (4 L×2), aq. NaHCO3 (4 L), and dried over anhydrous sodium sulfate. The residue was concentrated to afford tert-butyl 3,6-dihydropyridine-1(2H)-carboxylate, which was used in the next step without further purification.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:33][N:32]=[C:31]2[C:7]=1[CH2:8][CH:9]1[CH:22]3[CH:13]([C:14]4[CH:15]=[CH:16][C:17]([O:23]CC5C=CC=CC=5)=[CH:18][C:19]=4[CH2:20][CH2:21]3)[CH2:12][CH2:11][C:10]12[CH3:34])=[O:5])[CH3:2]>[Pd].C1COCC1.C(O)C>[CH2:1]([O:3][C:4]([C:6]1[NH:33][N:32]=[C:31]2[C:7]=1[CH2:8][CH:9]1[CH:22]3[CH:13]([C:14]4[CH:15]=[CH:16][C:17]([OH:23])=[CH:18][C:19]=4[CH2:20][CH2:21]3)[CH2:12][CH2:11][C:10]12[CH3:34])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1[nH]nc2c1CC1C3CCc4cc(OCc5ccccc5)ccc4C3CCC21C
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: CCOC(=O)c1[nH]nc2c1CC1C3CCc4cc(O)ccc4C3CCC21C
Reaction time: 72 h

Procedure:
Palladium on charcoal (100 mg, 5%Pd) was added to a solution of 2-Benzyloxy-6a-methyl-4b,5,6,6a,8,10,10a,10b,11,12-decahydro-7,8-diaza-pentaleno[2,1-a]phenanthrene-9-carboxylic acid ethyl ester (913 mg, 2.0 mmol, CAB03049) in THF (30 mL) and ethanol (30 mL). The resulting mixture was stirred under a hydrogen-atmosphere (balloon) for 72 hours, filtered through a 3 cm layer of celite and concentrated under reduced pressure. The residue was crystallised from acetone/cyclohexane. Yield: 602 mg (82%) pale yellow crystals. 1H-NMR (DMSO-d6, 400 MHz), δ: 0.92 (s, 3H, —CH3), 1.12-2.84 (m, 16H), 4.14-4.40 (m, 2H, OCH2CH3), 6.45 (d, J=2.3 Hz, 1H), 6.50 (dd, J=8.6, 2.3 Hz, 1H), 7.05,(d, J=8.6 Hz, 1H), 9.01 (s, 1H, —OH), 13.07 (s, 1H, NH). LRMS (FAB+): 367.2 (100, [M+H]+). HRMS (FAB+): 367.203796 C22H27N2O3 requires 367.202168
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].[CH3:9][N:10]([CH3:22])[C:11]1[CH:18]=[CH:17][C:14]([CH:15]=O)=[C:13]([N+:19]([O-:21])=[O:20])[CH:12]=1>>[S:8]1[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[N:1]=[C:15]1[C:14]1[CH:17]=[CH:18][C:11]([N:10]([CH3:9])[CH3:22])=[CH:12][C:13]=1[N+:19]([O-:21])=[O:20]
Reactant: CN(C)c1ccc(C=O)c([N+](=O)[O-])c1
Reactant: Nc1ccccc1S
Product: CN(C)c1ccc(-c2nc3ccccc3s2)c([N+](=O)[O-])c1

Procedure:
The amine may be obtained, for example in analogy to methods described in DE-A-2333378. For example, the educts 2-aminothiophenol and 4-dimethylamino-2-nitrobenzaldehyde may be reacted to obtain (4-benzothiazol-2-yl-3-nitrophenyl)-dimethylamine, whose nitro group may be reduced to the amine in a conventional manner (e.g. using SnCl2/HCl), and the product is reacted with methane sulfochloride.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][NH:8]2.C1(C)C=C(C)C=C(C)C=1S(O[NH2:25])(=O)=O.O>O1CCCC1>[Cl:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[NH2:25]
Reactant: Cc1cc(C)c(S(=O)(=O)ON)c(C)c1
Reactant: Clc1cccc2[nH]ccc12
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: Nn1ccc2c(Cl)cccc21
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 94.3 %

Procedure:
Sodium hydride (60 %wt suspension in mineral oil; 0.86 g, 21.5 mmol) is suspended in dry tetrahydrofuran (THF, 20 mL) and is cooled to 0° C. A mixture of 4-chloroindole (2.5 g, 16.5 mmol) and THF (10 mL) is added to the slurry at 4° C. After the addition is completed, the mixture is stirred for 30 min. Then a mixture of O-mesitylenesulfonylhydroxylamine (3.02 g, 14 mmol) and THF (25 mL) is added slowly at a temperature below 5° C. After the addition is completed, the reaction mixture is allowed to reach room temperature and is subsequently stirred for 3 h. Then the mixture is cooled again to 0° C., and a second aliquot of O-mesitylenesulfonylhydroxylamine (3.02 g, 14 mmol) in THF (25 mL) is added slowly. The mixture is allowed to reach ambient temperature and was subsequently stirred overnight. The reaction mixture is worked up by adding it to water, extracting into ethyl acetate, and drying over sodium sulfate. The crude product (4 g) is obtained after filtration of the drying agent and evaporation of the solvent. The aminated indole (2,2 g) is obtained as a black oil (mixture of starting material and product) after flash chromatography, using toluene as eluent.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:9]=[CH:10][CH:11]=1)[NH2:8])(=[O:3])[CH3:2].[CH2:12](Cl)[CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].C(=O)([O-])[O-].[Na+].[Na+]>>[C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:9]=[CH:10][CH:11]=1)[NH:8][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])(=[O:3])[CH3:2]
Reactant: CCCCCCCl
Reactant: CC(=O)Nc1cccc(N)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: CCCCCCNc1cccc(NC(C)=O)c1

Procedure:
3-Acetylaminoaniline (15 parts) was reacted with n-hexyl chloride (12.1 parts) at 100° to 110° C. for 4 hours in the presence of anhydrous sodium carbonate (5.3 parts) to obtain 3-acetylamino-N-hexylaniline. Thereafter, reaction was further continued at 120° to 130° C. for 4 hours with addition of n-amyl chloride (10.7 parts) and anhydrous sodium carbonate (5.3 parts) to obtain 3-acetylamino-N-n-hexyl-N-n-pentylaniline (coupling component). In the same manner as in Example 1, 2-cyano-4-nitro-6-chloroaniline was diazotized and coupled with the above coupling component to obtain 42.5 parts of a dye (6).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:23])[CH:5]([NH:12][C:13](=O)[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[F:21])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1)[CH3:2].P(Cl)(Cl)(Cl)=O>ClCCCl>[F:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[CH2:14][C:13]1[N:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]2=[C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:23])[N:12]=1
Reactant: CCOC(=O)C(NC(=O)Cc1ccccc1F)c1ccccn1
Solvent: O=P(Cl)(Cl)Cl
Solvent: ClCCCl
Product: CCOC(=O)c1nc(Cc2ccccc2F)n2ccccc12

Procedure:
2.72 g (8.60 mmol) of ethyl {[(2-fluorophenyl)acetyl]amino}(pyridin-2-yl)acetate from example 6A are introduced into 30 ml of 1,2-dichloroethane, and 4.81 ml (51.6 mmol) of phosphoryl chloride are added. The mixture is heated to reflux for 9 h and then concentrated in vacuo, and the residue is taken up in ethyl acetate. The solution is washed with saturated sodium carbonate solution, dried over sodium sulfate and purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 2:1). 2.16 g (84% of theory) of the desired compound are obtained as a dark oil.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][CH2:7][CH:6]=[CH:5]2.C(=O)(O)[O-:13].[Na+].C1C=C(Cl)C=C(C(OO)=O)C=1>ClCCl.C1C=C(Cl)C=C(C(OO)=O)C=1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([CH2:8][CH2:7][C@H:6]3[O:13][C@H:5]32)=[CH:10][CH:11]=1
Reactant: Brc1ccc2c(c1)C=CCC2
Reactant: O=C([O-])O
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: ClCCl
Product: Brc1ccc2c(c1)[C@@H]1O[C@@H]1CC2
Temperature: 2.5 °C
Reaction time: 1.5 h
Yield: 98 %

Procedure:
To a solution of 6-bromo-1,2-dihydronaphthalene (250 g, 1.20 mol) in dichloromethane (3.75 L) add saturated aqueous sodium bicarbonate (1250 mL) and cool to 0-5° C. Add MCPBA (77%, 275 g, 1.23 mol, 1.03 eq) in portions. Stir the mixture mechanically at 0-5° C. for 1.5 hr. and allow to warm to room temperature. Stir at room temperature for approximately 1.5 hr. and add additional MCPBA (77%, 15.0 g, 67 mmol, 0.05 eq) at room temperature and stir for approximately one hour. Dilute the mixture with dichloromethane (3750 mL) and separate the layers. Wash the organic layer with saturated aqueous sodium bicarbonate (3 L). Mix a 10% aqueous sodium bisulfate solution (3750 mL) with aqueous saturated sodium bicarbonate (1250 mL) to prepare a solution with a final pH of approximately 7. Add this solution to the dichloromethane layer and stir at room temperature for about 10 min. Separate the layers, wash the organic layer with saturated aqueous sodium bicarbonate (3 L) and brine (3 L). Concentrate in vacuo to obtain the title compound as an oil (263 g, 98%). GC/MS m/z (79Br/81Br) 224/226 [M+].
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]#[C:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[CH:3][CH:2]=1.Cl.Cl[CH2:18][C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[N:1]1[CH:6]=[CH:5][C:4]([C:7]#[C:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:13][CH:14]=2)=[CH:3][CH:2]=1
Reactant: ClCc1ccc2ccccc2n1
Reactant: Oc1ccc(C#Cc2ccncc2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: C(#Cc1ccc(OCc2ccc3ccccc3n2)cc1)c1ccncc1

Procedure:
A mixture of 4-(2-(pyridin-4-yl)ethynyl)phenol (335 mg, 1.72 mmol), 2-(chloromethyl)quinoline hydrochloride (385 mg, 1.8 mmol), and cesium carbonate (2.2 g, 6.87 mmol) was stirred in dimethylformamide (8 mL) at 65° C. for 3 h. Water (20 mL) was added and the mixture was extracted with dichloromethane (3×15 mL). The organic layers were dried, concentrated, and the residue chromatographed on silica eluted with a gradient of 10% to 80% ethyl acetate-hexanes giving 450 mg (78%) of a yellow solid. 1H NMR (CDCl3, 400 mHz) δ 8.56 (m, 2H), 8.20 (d, 1H, J=8.7 Hz), 8.08 (d, 1H, J=8.3 Hz), 7.82 (d, 1H, J=7.9 Hz), 7.74 (ddd, 1H, J=8.4, 7, 1Hz), 7.63 (d, 1H, J=8.7 Hz), 7.55 (ddd, 1H, J=8, 7, 1 Hz), 7.47 (m, 2H), 7.35 (m, 2H), 7.01 (m, 2H), 5.41 (s, 2H). MS (AP+) m/e 337 (MH+).