Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=1)=O.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:21].C(=O)(O)[O-].[Na+]>O1CCOCC1>[NH2:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[C:4](=[S:21])[NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=1
Reactant: Nc1ccccc1C(=O)NCc1ccc(Cl)c(Cl)c1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Product: Nc1ccccc1C(=S)NCc1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 47 %

Procedure:
A mixture of 2-amino-N-(3,4-dichlorobenzyl)benzamide (3.5 g) and phosphorus pentasulfide (4.74 g) in dioxane (56 ml) was stirred at room temperature for 5 hours. The reaction mixture was poured into an aqueous sodium bicarbonate and extracted with ethyl acetate. The extract was washed with water and dried. Evaporation of the solvent gave a residue, which was chromatographed on silica gel. Elution with chloroform followed by recrystallization from isopropyl ether gave 2-amino-N-(3,4-dichlorobenzyl)benzenecarbothioamide (1.56 g).
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]2=[O:20].C(O)C.C(=O)([O-])[O-].[Na+].[Na+].[O:30]=[C:31]1[CH:40]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:39][C:38]2[C:33](=[CH:34][C:35](B3OC(C)(C)C(C)(C)O3)=[CH:36][CH:37]=2)[NH:32]1>C1(C)C=CC=CC=1.C(Cl)Cl.O.[Pd](Cl)Cl.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]>[C:44]([O:43][C:42]([NH:41][CH:40]1[CH2:39][C:38]2[C:33](=[CH:34][C:35]([C:2]3[CH:3]=[CH:4][N:5]4[C:10]([C:11]=3[CH3:12])=[C:9]([CH:13]3[CH2:15][CH2:14]3)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]4=[O:20])=[CH:36][CH:37]=2)[NH:32][C:31]1=[O:30])=[O:48])([CH3:47])([CH3:45])[CH3:46]
Reactant: CC(C)(C)OC(=O)NC1Cc2ccc(B3OC(C)(C)C(C)(C)O3)cc2NC1=O
Reactant: COC(=O)c1cc(C2CC2)c2c(C)c(Cl)ccn2c1=O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Solvent: ClCCl
Solvent: O
Product: COC(=O)c1cc(C2CC2)c2c(C)c(-c3ccc4c(c3)NC(=O)C(NC(=O)OC(C)(C)C)C4)ccn2c1=O
Temperature: 80 °C
Yield: 55.4 %

Procedure:
Methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (45 mg, 0.15 mmol) was dissolved in toluene (330 μL), ethanol (96%) (243 μL) and 2M aqueous sodium carbonate solution (231 μL, 0.463 mmol). tert-Butyl 2-oxo-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinolin-3-ylcarbamate (78 mg, 0.20 mmol) was added and the mixture was degassed with argon. 1,1′-Bis(diphenylphosphino)-ferrocene palladium(II) dichloride (11.3 mg, 0.015 mmol) was added and the mixture was heated at 80° C. under an argon atmosphere for 16 h. After cooling, the mixture was diluted with DCM (3 mL) and water (3 mL) and the layers were separated. The aqueous layer was extracted with DCM (3×2 mL). The combined organic layers were concentrated and the yellow crude product was purified with flash silica column chromatography (heptane/ethyl acetate) (1:0 to 0:1) to afford the title compound as a yellow solid (43 mg, 53%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:21]=[CH:22][CH:23]=1)[CH2:6][CH2:7][NH:8][C:9](=[O:20])[CH2:10][CH2:11][NH:12]C(=O)OC(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH2:12][CH2:11][CH2:10][C:9]([NH:8][CH2:7][CH2:6][C:5]1[CH:21]=[CH:22][CH:23]=[C:3]([O:2][CH3:1])[CH:4]=1)=[O:20]
Reactant: COc1cccc(CCNC(=O)CCNC(=O)OC(C)(C)C)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1cccc(CCNC(=O)CCN)c1
Temperature: 0 °C

Procedure:
tert-butyl (3-((3-methoxyphenethyl)amino)-3-oxopropyl)carbamate was dissolved in dichloromethane (0.5 mL) then the solution was cooled to 0° C. in an ice bath. Trifluoroacetic acid (300 μL) was added then the solution was allowed to warm slowly to room temperature with stirring. Upon completion of the reaction the solvent is removed under reduced pressure to give crude product which is used without further purification.
Reaction SMILES: C(OC([N:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:13]=[C:14]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:15]=[CH:16][CH:17]=2)[C@@H:8]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=2[O:33][CH2:34][CH2:35][CH2:36][O:37][CH3:38])[CH2:7]1)=O)C.[OH-].[Na+]>C(O)C>[C:14]1([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:15]=[CH:16][CH:17]=[C:12]([C@H:9]2[CH2:10][CH2:11][NH:6][CH2:7][C@@H:8]2[O:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=2[O:33][CH2:34][CH2:35][CH2:36][O:37][CH3:38])[CH:13]=1
Reactant: CCOC(=O)N1CC[C@H](c2cccc(-c3ccccc3)c2)[C@@H](OCc2ccc(C)cc2OCCCOC)C1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COCCCOc1cc(C)ccc1CO[C@H]1CNCC[C@@H]1c1cccc(-c2ccccc2)c1
Temperature: 170 °C
Reaction time: 0.09 h

Procedure:
To a solution of the title D compound, (3R,4R)-4-biphenyl-3-yl-3-[2-(3-methoxy-propoxy)-4-methyl-benzyloxy]-piperidine-1-carboxylic acid ethyl ester (50 mg, 0.95 mmol) in 2 mL of absolute ethanol is added 2 mL of a 10% aqueous solution of sodium hydroxide. The resulting mixture is heated at 170° C. for 45 min in a microwave. The solvent is removed under reduced pressure and the resulting aqueous suspension is extracted twice with methylene chloride. The combined organic layers are dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified by preparative HPLC (Macherey-Nagel 250/4 nucleosil 100-10 C18 column, 20:80 CH3CN+0.1% TFA over 11 min, then 100% CH3CN+0.1% TFA for 5.5 min, 40 mL/min). To the combined fractions containing the desired product is added 1M aqueous sodium carbonate solution and the acetonitrile is removed under reduced pressure. The resulting aqueous suspension is extracted twice with ethyl acetate. The combined organic layers are dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure affording the title compound as a colorless oil. A solution of the compound in acetonitrile is lyophilized. MS 446.1 [M+H]. Rt (HPLC, Nucleosil C18, 10:90-100:0 CH3CN/H2O+0.1% TFA within 5 min, then 100% CH3CN+0.1% TFA): 5.48 min.
Reaction SMILES: [N:1]1([C:7]2[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:15]=[C:16]([CH2:20][S:21]([NH2:24])(=[O:23])=[O:22])[CH:17]=[CH:18][CH:19]=3)[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N:25]1[N:29]2CCCNC2=C[CH:26]=1>>[N:25]1[N:29]2[CH2:4][CH2:3][CH2:2][N:1]([C:7]3[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]4[CH:15]=[C:16]([CH2:20][S:21]([NH2:24])(=[O:23])=[O:22])[CH:17]=[CH:18][CH:19]=4)[N:8]=3)[C:6]2=[CH:5][CH:26]=1
Reactant: c1cc2n(n1)CCCN2
Reactant: NS(=O)(=O)Cc1cccc(Nc2ncnc(N3CCCCC3)n2)c1
Product: NS(=O)(=O)Cc1cccc(Nc2ncnc(N3CCCn4nccc43)n2)c1

Procedure:
B47 was prepared following the procedure reported for B1 using Al and 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine. 1H NMR (400 MHz, d6-DMSO, 300K) δ 2.11-2.22 (m, 2H), 4.10-4.20 (m, 4H), 4.22 (s, 2H), 6.85 (bs, 3H), 7.06 (d, J=8.2 Hz, 1H), 7.30 (d, J=8.3 Hz, 1H), 7.34 (s, 1H), 7.54-7.82 (bm, 2H), 8.47 (s, 1H), 10.00 (bs, 1H). MS (ES) C16H18N8O2S requires: 386. found: 387 (M+H)+.
Reaction SMILES: [CH:1]1([C:4]2[C:5]([O:14][CH2:15][C@H:16]3[CH2:21][CH2:20][C@H:19]([CH3:22])[CH2:18][CH2:17]3)=[CH:6][C:7]([F:13])=[C:8]([CH:12]=2)[C:9]([OH:11])=O)[CH2:3][CH2:2]1.Cl.C(N=C=NCCCN(C)C)C.[N:35]1([S:39]([NH2:42])(=[O:41])=[O:40])[CH2:38][CH2:37][CH2:36]1.Cl>CN(C)C1C=CN=CC=1.ClCCl>[N:35]1([S:39]([NH:42][C:9](=[O:11])[C:8]2[CH:12]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[C:5]([O:14][CH2:15][C@H:16]3[CH2:21][CH2:20][C@H:19]([CH3:22])[CH2:18][CH2:17]3)=[CH:6][C:7]=2[F:13])(=[O:41])=[O:40])[CH2:38][CH2:37][CH2:36]1
Reactant: C[C@H]1CC[C@H](COc2cc(F)c(C(=O)O)cc2C2CC2)CC1
Reactant: NS(=O)(=O)N1CCC1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: C[C@H]1CC[C@H](COc2cc(F)c(C(=O)NS(=O)(=O)N3CCC3)cc2C2CC2)CC1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a mixture of 5-cyclopropyl-2-fluoro-4-((trans-4-methylcyclohexyl)-methoxy)benzoic acid (0.255 g, 0.83 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.242 g, 1.26 mmol) and 4-dimethylaminopyridine (0.242 g, 1.98 mmol) in anhydrous dichloromethane (22 mL) was added azetidine-1-sulfonamide (0.173 g, 1.27 mmol). The reaction mixture was stirred at ambient temperature for 16 hours. The mixture was poured into 5% aqueous hydrochloric acid (50 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (4×50 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL); dried over anhydrous sodium sulfate; filtered and concentrated in vacuo. The residue was purified by column chromatography (0% to 40% ethyl acetate in hexanes) to afford the title compound (0.114 g, 33%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.66 (d, J=16.7 Hz, 1H), 7.59 (d, J=9.1 Hz, 1H), 6.57 (d, J=14.5 Hz, 1H), 4.25 (t, J=7.7 Hz, 4H), 3.83 (d, J=6.1 Hz, 2H), 2.27 (q, J=7.7 Hz, 1H), 2.11-2.02 (m, 1H), 1.92-1.75 (m, 5H), 1.41-1.29 (m, 1H), 1.25-0.90 (m, 10H), 0.70-0.64 (m, 2H); MS (ES−) m/z 423.26 (M−1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([C:14](=[O:16])[CH3:15])=[N:10]2)=[C:5]2[NH:17][CH:18]=[CH:19][C:4]=12.[BH4-].[Na+]>CO.C([O-])(O)=O.[Na+]>[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([CH:14]([OH:16])[CH3:15])=[N:10]2)=[C:5]2[NH:17][CH:18]=[CH:19][C:4]=12
Reactant: COc1cnc(-n2cnc(C(C)=O)n2)c2[nH]ccc12
Agent: O=C([O-])O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1cnc(-n2cnc(C(C)O)n2)c2[nH]ccc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 57.7 %

Procedure:
To a solution of 1-(1-(4-methoxy-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-1,2,4-triazol-3-yl)ethanone (50 mg, 0.194 mmol) in MeOH (3 mL) was added sodium borohydride (14.71 mg, 0.389 mmol) at 0° C. After stirring at room temperature for 3 h, the reaction was diluted with 5% NaHCO3 (5 mL) and extracted with EtOAc (2×30 mL). The organic layers were combined and concentrated. The residue was purified by prep. HPLC to give 1-(1-(4-methoxy-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-1,2,4-triazol-3-yl)ethanol (29 mg, 0.112 mmol, 57.5% yield). LCMS: m/z 260.2 (M+H)+, 1.47 min (method 8). 1H NMR (500 MHz, MeOD) δ ppm 9.17 (s, 1H) 7.51 (s, 1H) 7.45 (d, J=3.05 Hz, 1H) 6.67 (d, J=3.05 Hz, 1H) 5.09 (q, J=6.51 Hz, 1H) 4.02 (s, 3H) 1.63 (d, J=6.41 Hz, 3H).
Reaction SMILES: O1CCOCC1.[OH:7][CH:8]1[CH:12]([CH2:13][CH:14]=[CH2:15])[C:11](=[O:16])[CH:10]=[CH:9]1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>C(OCC)(=O)C.CCCCCC>[O:7]=[C:8]1[CH:12]([CH2:13][CH:14]=[CH2:15])[C:11](=[O:16])[CH:10]=[CH:9]1
Reactant: C=CCC1C(=O)C=CC1O
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: C1COCCO1
Product: C=CCC1C(=O)C=CC1=O
Reaction time: 16 h
Yield: 91.3 %

Procedure:
Into 6 ml of dioxane, were dissolved 500 mg of 4-hydroxy-5-allyl-2-cyclopentenone and 450 mg of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. The solution was left standing at room temperature for 16 hours and the precipitated 2,3-dichloro-5,6-dicyanohydroquinone was collected by filtration and washed with methylene chloride. The filtrate together with the washings was concentrated. The concentration residue was dissolved in 50 ml of methylene chloride, washed with a 10% aqueous sodium hydroxide solution, then with water until the washings had become neutral. The residue thus treated was dried over anhydrous sodium sulfate, stripped of the solvent by distillation, and purified by column chromatography using 20 g of a silica gel (Wako Gel C-200) and an ethyl acetate-n-hexane (2:3 by volume) mixture as eluent, to obtain 450 mg (91% yield) of 4-keto-5-allyl-2-cyclopentenone.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:15])[CH:11]=[C:12]([CH3:14])[CH3:13])[CH:5]=[CH:6][C:7]=1[CH3:8].[Cl-].[Al+3].[Cl-].[Cl-]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:5]([C:12]([CH3:13])([CH3:14])[CH2:11][C:10](=[O:15])[NH:9]2)=[CH:6][C:7]=1[CH3:8]
Reactant: CC(C)=CC(=O)Nc1ccc(C)c(Br)c1
Agent: [Al+3]
Agent: [Cl-]
Product: Cc1cc2c(cc1Br)NC(=O)CC2(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 65.7 %

Procedure:
To a solution of 3-methyl-but-2-enoic acid (3-bromo-4-methyl-phenyl)-amide (70.0 g, 261 mmol) at 90° C. was added portion wise, under argon, with vigorous stirring aluminum chloride (52.3 g, 391 mmol) over 1.5 hr. The reaction mixture was stirred for 2 hours at 110–120° C. The reaction mixture was cooled to room temperature and ice-water was carefully added. The solution was extracted with dichloromethane and the organic washed with 2N HCl, water, saturated aqueous NaHCO3, water and brine, dried (MgSO4), filtered and evaporated. The residue was crystallized from dichloromethane/hexane to give 46 g of 7-bromo-4,4,6-trimethyl-3,4- dihydro- 1H-quinoline-2-one. The mother liquor was further chromatographed on silica gel (20% ethyl acetate in hexane) to give 6.2 g more of product. (75%). 1H NMR (300 MHz; CDCl3): 1.30 (s, 6 H), 2.33 (s, 3 H), 2.46 (s, 2 H), 7.07 (s, 1 H), 7.10 (s, 1 H), 9.87 (br s, 1 H).
Reaction SMILES: [NH2:1][C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]([O:9][CH2:10][C:11]2[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=2)[C:14]#[N:15])[N:3]=1.[F:19][C:20]1[CH:29]=[CH:28][CH:27]=[CH:26][C:21]=1[CH2:22][N:23]=[C:24]=[O:25].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH4+].[Cl-]>CN(C=O)C>[C:14]([C:13]1[CH:12]=[C:11]([CH:18]=[CH:17][CH:16]=1)[CH2:10][O:9][C:4]1[N:3]=[C:2]([NH:1][C:24]([NH:23][CH2:22][C:21]2[CH:26]=[CH:27][CH:28]=[CH:29][C:20]=2[F:19])=[O:25])[C:7]([F:8])=[CH:6][N:5]=1)#[N:15]
Reactant: O=C=NCc1ccccc1F
Reactant: N#Cc1cccc(COc2ncc(F)c(N)n2)c1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: N#Cc1cccc(COc2ncc(F)c(NC(=O)NCc3ccccc3F)n2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 61.2 %

Procedure:
To a magnetically stirred mixture of 3-(4-amino-5-fluoropyrimidin-2-yloxymethyl)-benzonitrile (0.075 g, 0.31 mmol) and 2-fluorobenzylisocyanate (0.59 mL, 0.46 mmol) in dry DMF (1.5 mL) was added LiHMDS (1.0 M in THF, 0.31 ml, 0.30 mmol). The vial was capped and the mixture stirred at room temperature for 8 h. Saturated aq. NH4Cl (3 ml) was added and the mixture was stirred for 4 h. The heterogeneous mixture was filtered, and the solid was washed with hot water, washed with E2O, and then dried under vacuum to give the title compound (0.075 g, 62%) as a white solid: mp 177-178° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.04 (s, 1H), 8.90 (t, J=5.7 Hz, 1H), 8.37 (d, J=2.8 Hz, 1H), 7.85 (br s, 1H), 7.80 (d, J=7.5 Hz, 1H), 7.74 (d, J=8.0 Hz, 1H), 7.60 (t, J=7.8 Hz, 1H), 7.42-7.38 (m, 1H), 7.35-7.29 (m, 1H), 7.20-7.14 (m, 2H), 5.33 (s, 2H), 4.49 (d, J=5.8 Hz, 2H); HPLC-MS (ESI) m/z 396.3 (M+H)+, 394.3 (M−H)−.
Reaction SMILES: [C:1]1([C:7]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)=[N:11][N:10]=[N:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:38]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[C:32]1([C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]3[CH:24]=[CH:23][C:22]([CH2:25][Br:38])=[CH:21][CH:20]=3)=[N:11][N:10]=[N:9]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: BrCc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1

Procedure:
A mixture of N-triphenylmethyl-5 (4'-methylbiphenyl-2-yl)tetrazole (Example 11, 12.7 g), N-bromosuccinimide (4.6 g), carbon tetrachloride (300 mL), and benzoyl peroxide (75 mg) was heated at reflux for 2.5 hours. The cooled suspension was filtered and the filtrate was evaporated to give the title compound as a crystalline solid. 1H-NMR (CDCl3) δ8.2-6.7 (complex, 23H), 4.3 (s, 2H).
Reaction SMILES: [CH3:1][N:2]1[C:7]([SH:8])=[N:6][C:5](=[O:9])[C:4]([OH:10])=[N:3]1.C(N(CC)CC)C.[Si:18](Cl)([C:31]([CH3:34])([CH3:33])[CH3:32])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O1CCCC1>[CH3:1][N:2]1[C:7]([SH:8])=[N:6][C:5](=[O:9])[C:4]([O:10][Si:18]([C:31]([CH3:34])([CH3:33])[CH3:32])([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:3]1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: Cn1nc(O)c(=O)nc1S
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cn1nc(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c(=O)nc1S

Procedure:
A solution of 2-methyl-3-mercapto-6-hydroxy-2,5-dihydro-1,2,4-triazin-5-one (0.8 g) in dry tetrahydrofuran (25 ml) was stirred for 30 min with triethylamine (0.835 ml) and tert-butyldiphenylsilylchloride (1.53 ml). The reaction mixture was partitioned between 1% aqueous NaHCO3 and ethyl acetate. Removal of the solvent from the dried organic layer left a residue which crystallized by trituration with light petrol affording 2-methyl-3-mercapto-6-tert-butyldiphenylsilyloxy-2,5-dihydro-1,2,4-triazin-5-one (1.34 g), m.p. 135° C. (decomp.).
Reaction SMILES: O[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1N.OC1C=C([N+]([O-])=O)C=CC=1N.[OH:23][C:24]1C2C(=CC=C(N)C=2)[CH:27]=[C:26]([S:35]([OH:38])(=[O:37])=[O:36])[CH:25]=1.OC1C2C(=CC(N)=CC=2)C=C(S(O)(=O)=O)C=1>>[OH:23][C:24]1[C:3]2[C:4](=[C:5]([NH2:8])[CH:6]=[CH:7][CH:2]=2)[CH:27]=[C:26]([S:35]([OH:38])(=[O:37])=[O:36])[CH:25]=1
Reactant: Nc1ccc2cc(S(=O)(=O)O)cc(O)c2c1
Reactant: Nc1cc([N+](=O)[O-])ccc1O
Agent: Nc1ccc([N+](=O)[O-])cc1O
Agent: Nc1ccc2c(O)cc(S(=O)(=O)O)cc2c1
Product: Nc1cccc2c(O)cc(S(=O)(=O)O)cc12

Procedure:
On account of their easy accessibility and the neutral black shade obtainable therewith, particular interest attaches to the dyes that are derived from 1-hydroxy-2 amino-4-nitrobenzene or 1-hydroxy-2-amino-5-nitrobenzene as diazo components, and from 1-hydroxy-7-aminonaphthalene-3-sulphonic acid or 1-hydroxy-6-aminonaphthalene-3-sulphonic acid as coupling component.
Reaction SMILES: [BH4-].[Na+].[CH3:3][CH:4]1[CH2:12][C:11]2[C:6](=[C:7]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=3)[CH:8]=[CH:9][C:10]=2[CH3:13])[C:5]1=O.C1(C)C=CC=CC=1.S(=O)(=O)(O)O>CO>[CH3:3][C:4]1[CH2:12][C:11]2[C:6]([CH:5]=1)=[C:7]([C:14]1[CH:15]=[CH:16][C:17]([C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:18][CH:19]=1)[CH:8]=[CH:9][C:10]=2[CH3:13]
Reactant: Cc1ccc(-c2ccc(C(C)(C)C)cc2)c2c1CC(C)C2=O
Agent: O=S(=O)(O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: Cc1ccccc1
Product: CC1=Cc2c(-c3ccc(C(C)(C)C)cc3)ccc(C)c2C1
Temperature: 50 °C
Reaction time: 3 h

Procedure:
2.09 g (55.3 mmol) of sodium borohydride and 18.59 g (55.3 mmol) of 2,4-dimethyl-7-4′-tert-butylphenyl)-1-indanone (1d) together with 51 ml of toluene were placed in a reaction vessel. At 50° C., 9.8 ml of methanol were slowly added and the reaction mixture was stirred at 50° C. for 3 hours. After cooling to room temperature, 35 ml of 2N sulfuric acid were added and the mixture was stirred for 30 minutes. After phase separation, the organic phase was washed twice with a total of 60 ml of 2N sulfuric acid, most of the solvent was removed and the residue was taken up in 200 ml of toluene and admixed with 0.2 g of p-toluenesulfonic acid. Water was distilled off from this reaction mixture with the aid of a water separator by refluxing for 1.5 hours until the reaction was complete. The reaction mixture was washed once with 100 ml of saturated sodium hydrogen carbonate solution and dried over magnesium sulfate. After removal of the solvent, the residue was dried in an oil pump vacuum. This gave 16.8 g of the desired product (1e).
Reaction SMILES: S(=O)(=O)(O)O.S([O:16][C:17]1[C:22]([NH:23]S(C2C=CC(C)=CC=2)(=O)=O)=[CH:21][C:20]([CH3:34])=[C:19]([N+:35]([O-:37])=[O:36])[CH:18]=1)(C1C=CC(C)=CC=1)(=O)=O>O>[NH2:23][C:22]1[C:17]([OH:16])=[CH:18][C:19]([N+:35]([O-:37])=[O:36])=[C:20]([CH3:34])[CH:21]=1
Reactant: Cc1ccc(S(=O)(=O)Nc2cc(C)c([N+](=O)[O-])cc2OS(=O)(=O)c2ccc(C)cc2)cc1
Agent: O=S(=O)(O)O
Solvent: O
Product: Cc1cc(N)c(O)cc1[N+](=O)[O-]
Reaction time: 0.25 h
Yield: 85 %

Procedure:
To 120 ml of stirring concentrated sulfuric acid at room temperature was added 12.0 g (0.0252 mol) of 5-nitro-2-p-toluenesulfonamido-p-cresol tosylate. Complete solution occurred without exotherm in 15 minutes. After stirring 11/2 hours the reaction was poured into 1500 ml of water and extracted with ethyl acetate. The organic layer was washed with aqueous sodium carbonate, dried over magnesium sulfate and concentrated under reduced pressure to yield 3.6 g (85 percent) of pure product as an orange solid.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6](/[C:10](/[CH3:17])=[CH:11]/[C:12](OCC)=[O:13])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[H-].C([Al+]CC(C)C)C(C)C.O.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[N+:1]([C:4]1[CH:5]=[C:6](/[C:10](/[CH3:17])=[CH:11]/[CH2:12][OH:13])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: CCOC(=O)/C=C(\C)c1cccc([N+](=O)[O-])c1
Agent: CC(C)C[Al+]CC(C)C
Agent: O=C([O-])O
Agent: [H-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: Cc1ccccc1
Product: C/C(=C\CO)c1cccc([N+](=O)[O-])c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 97.5 %

Procedure:
To a solution of ethyl (E)-3-(3-nitrophenyl)-2-butenoate (Preparation 1, 102 g, 0.43 mol) in toluene (1400 ml) at −10° C. under nitrogen was added dropwise over 3 h diisobutylaluminium hydride (1.0 M in toluene, 1 l), then the mixture was stirred at 0° C. for 1 h. Water (400 ml) was carefully added, followed by sodium hydrogen carbonate (300 g). The resulting slurry was vigorously stirred for 10 min, then ethyl acetate (2 l) was added, and the mixture stirred for 1 h. The mixture was dried (MgSO4), filtered and concentrated in vacuo to give the title compound as a pale brown oil (81 g, 97%).
Reaction SMILES: [F:1][C:2]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:3]=1[C:4]([NH:6][C:7]1[S:8][C:9]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)=[C:10]([CH:12](O)[CH3:13])[N:11]=1)=[O:5].FC1C=CC=C(F)C=1C(NC1SC(C2C=CC=C(C(F)(F)F)C=2)=C(C(C)=C)N=1)=O>>[F:1][C:2]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:3]=1[C:4]([NH:6][C:7]1[S:8][C:9]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:22])([F:23])[F:24])[CH:16]=2)=[C:10]([CH:12]=[CH2:13])[N:11]=1)=[O:5]
Reactant: CC(O)c1nc(NC(=O)c2c(F)cccc2F)sc1-c1cccc(C(F)(F)F)c1
Agent: C=C(C)c1nc(NC(=O)c2c(F)cccc2F)sc1-c1cccc(C(F)(F)F)c1
Product: C=Cc1nc(NC(=O)c2c(F)cccc2F)sc1-c1cccc(C(F)(F)F)c1

Procedure:
Compound 75 was prepared from Compound 74 similarly as described for the preparation of Compound 68a.
Reaction SMILES: [C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F-].[K+].Br[C:13]1[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][C:14]=1[CH3:20]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.C1COCC1>[CH3:20][C:14]1[CH:15]=[CH:16][C:17]([CH3:19])=[CH:18][C:13]=1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OB(O)c1ccccc1
Reactant: Cc1ccc(C)c(Br)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C
Solvent: C1CCOC1
Product: Cc1ccc(C)c(-c2ccccc2)c1
Yield: 81.8 %

Procedure:
An oven dried resealable Schlenk tube was evacuated and backfilled with argon and charged with palladium acetate (2.2 mg, 0.01 mmol, 1.0 mol %), 2-(di-tert-butylphosphino)biphenyl (6.0 mg, 0.020 mmol, 2.0 mol %), phenylboronic acid (183 mg, 1.5 mmol), and potassium fluoride (174 mg, 3.0 mmol). The tube was evacuated and backfilled with argon, and THF (1 mL) and 2-bromo-p-xylene (0.138 ML, 1.0 mmol) were added through a rubber septum. The tube was sealed with a teflon screwcap, and the reaction mixture was stirred at room temperature until the starting aryl bromide had been completely consumed as judged by GC analysis. The reaction mixture was then diluted with ether (30 mL), filtered through celite, and concentrated. The crude material was purified by flash chromatography on silica gel to afford 149 mg (82%) of the title compound.