Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:24])[NH:7][CH2:8][CH2:9][NH:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]=1[N+:21]([O-])=O)([CH3:4])([CH3:3])[CH3:2].CO>O1CCCC1.[Pt]=O>[C:1]([O:5][C:6](=[O:24])[NH:7][CH2:8][CH2:9][NH:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]=1[NH2:21])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NCCNc1ccc2ccccc2c1[N+](=O)[O-]
Agent: O=[Pt]
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)(C)OC(=O)NCCNc1ccc2ccccc2c1N
Temperature: 25 °C
Reaction time: 7 h
Yield: 95.3 %

Procedure:
tert-Butyl[2-[(1-nitro-2-naphthyl)amino]ethyl]carbamate (746 mg, 2.25 mmol) was dissolved in tetrahydrofuran (7.5 mL), and methanol (7.5 mL), the solution was added with platinum oxide (7.5 mg), and the mixture was stirred at room temperature for 7 hours under a hydrogen atmosphere. The catalyst was separated by filtration, then the solvent was evaporated under reduced pressure, and the residue was washed with hexane to give the title compound (646 mg, yield 95%) as brown crystals.
Reaction SMILES: [Cl:1][C:2]1[NH:3][N:4]=[C:5]2[C:10]=1[CH:9]=[CH:8][CH:7]=[CH:6]2.[CH2:11]=[O:12]>O>[Cl:1][C:2]1[N:3]([CH2:11][OH:12])[N:4]=[C:5]2[C:10]=1[CH:9]=[CH:8][CH:7]=[CH:6]2
Reactant: Clc1[nH]nc2ccccc12
Reactant: C=O
Solvent: O
Product: OCn1nc2ccccc2c1Cl
Temperature: 25 °C
Yield: 99.7 %

Procedure:
In a 250 mL round bottom flask, 3-chloro-2H-indazole (1.95 g, 10 mmol), 30% HCHO (2 mL, 20 mmol) were mixed in water (10 mL). The reaction mixture was refluxed for 2 hours. After cooling down to room temperature, the solid was filtered, washed with water, and dried under vacuum to provide (3-chloro-2H-indazol-2-yl)methanol (1.82 g, 99% yield).
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:5]([C:7]([N:9]2[CH2:14][C@H:13]3[C@H:11]([CH2:12]3)[C@H:10]2[CH2:15][NH2:16])=[O:8])[N:6]=1.[CH3:24][N:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([C:34](O)=[O:35])=[CH:26]1>>[NH2:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:5]([C:7]([N:9]2[CH2:14][C@H:13]3[C@H:11]([CH2:12]3)[C@H:10]2[CH2:15][NH:16][C:34]([C:27]2[C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)[N:25]([CH3:24])[CH:26]=2)=[O:35])=[O:8])[N:6]=1
Reactant: Cn1cc(C(=O)O)c2ccccc21
Reactant: NC[C@@H]1[C@H]2C[C@H]2CN1C(=O)c1nc(N)sc1-c1cccc(F)c1
Product: Cn1cc(C(=O)NC[C@@H]2[C@H]3C[C@H]3CN2C(=O)c2nc(N)sc2-c2cccc(F)c2)c2ccccc21

Procedure:
prepared by reaction of [2-Amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((1S,2S,5R)-2-aminomethyl-3-aza-bicyclo[3.1.0]hex-3-yl)-methanone with 1-Methyl-1H-indole-3-carboxylic acid. LC-MS (basic): tR=0.80 min; [M+H]+=490.1.
Reaction SMILES: C(OC)(=O)C(C)=C.[Na].S([CH:13]([CH2:25]C(OCCCCCCCC)=O)[C:14]([O:16][CH2:17][CH2:18][CH2:19][CH2:20]CCCC)=[O:15])(O)(=O)=O.[Al]>>[C:14]([O:16][CH2:17][CH2:18][CH2:19][CH3:20])(=[O:15])[CH:13]=[CH2:25]
Reactant: CCCCCCCCOC(=O)CC(C(=O)OCCCCCCCC)S(=O)(=O)O
Agent: C=C(C)C(=O)OC
Agent: [Al]
Agent: [Na]
Product: C=CC(=O)OCCCC

Procedure:
Using the emulsion polymerization process described above for the two stage copolymer, a two stage copolymer composed of methyl methacrylate: butyl acrylate ratio of 60:40 was synthesized to yield a polymer latex with 204 nm average particles (no clay). The emulsifier used in the polymerization process was 1.28% of a 75% solution of dioctyl sulfosuccinate sodium salt. The total solids content of the emulsion was 48.55 weight percent. A portion of the emulsion was coated onto a 0.002 cm thick aluminum sheet to yield a 0.069 cm thick film. The entire arrangement of film and substrate was dried overnight in a vacuum oven at 75° C. After drying a disk of surface area 2.7318 cm2 was cut from the laminate and evaluated, by dielectric relaxation spectroscopy., for assessment of the magnitude of the dielectric storage factor. The data listed in TABLE VI, reveal the value of the dielectric storage factor. A list of the mechanical properties are given in TABLE VII.
Reaction SMILES: [CH3:1][CH:2]1[C:6]2[C:7]3[C:12]([C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=4[C:5]=2[CH:4]=[C:3]1[Si:19]([CH3:22])([CH3:21])Cl)=[CH:11][CH:10]=[CH:9][CH:8]=3.CCCCCC.[C:29]([NH2:33])([CH3:32])([CH3:31])[CH3:30]>C1(C)C=CC=CC=1>[CH3:1][CH:2]1[C:6]2[C:7]3[C:12]([C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=4[C:5]=2[CH:4]=[C:3]1[Si:19]([CH3:22])([CH3:21])[NH:33][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:11][CH:10]=[CH:9][CH:8]=3
Reactant: CC1C([Si](C)(C)Cl)=Cc2c1c1ccccc1c1ccccc21
Reactant: CC(C)(C)N
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: CC1C([Si](C)(C)NC(C)(C)C)=Cc2c1c1ccccc1c1ccccc21

Procedure:
To a 500 ml round bottom flask containing 1.699 g (0.00526 mole) of (1-methyl-1H-cyclopenta[l]phenanthrene-2-yl)dimethylchlorosilane and 100 ml of hexane and 150 ml toluene was added 0.975 g (0.0132 mole) of t-butylamine. The reaction mixture was allowed to stir for several days, then filtered using diatomaceous earth filter aid (Celite™), washed twice with hexane. The product was isolated by removing residual solvent under reduced pressure. The isolated yield was 1.785 g (94.6 percent). 1H NMR analysis indicated the predominant isomer was substituted at the 2 position.
Reaction SMILES: C(N([CH2:6][CH2:7][O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=1)CC)C.[C:18]([O-])([O-])=O.[Cs+].[Cs+].BrCC[CH2:27][Cl:28]>CN(C=O)C>[Cl:28][CH2:27][CH2:6][CH2:7][O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([O:15][CH3:18])=[O:14])=[CH:11][CH:10]=1
Reactant: CCN(CC)CCOc1ccc(C(=O)O)cc1
Reactant: ClCCCBr
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(OCCCCl)cc1
Reaction time: 0.5 h

Procedure:
A solution of Methyl 4-hydroxy benzoic acid (23-2) (Aldrich) (4.56 g, 30 mmol) in DMF (100 mL) was treated with Cs2CO3 (14.67 g, 45 mmol) at room temperature. After 0.5 hours, 3-bromo-1-chloropropane (5.94 mL, 60 mmol) was added and the solution was stirred for 4 hours. The reaction mixture was filtered and concentrated to give 27-1 as a white solid. Rf (10% EtOAc/hexanes) 0.36.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([NH:11][NH2:12])=[N:3][CH:2]=1.[C:13]1([CH3:21])[C:14](C=O)=[CH:15][CH:16]=[CH:17][CH:18]=1.[CH3:22]O>>[CH3:21][C:13]1[CH:18]=[CH:17][C:16]([CH:22]=[N:12][NH:11][C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:1]=[CH:2][N:3]=2)=[CH:15][CH:14]=1
Reactant: CO
Reactant: Cc1ccccc1C=O
Reactant: NNc1ncnc2ccccc12
Product: Cc1ccc(C=NNc2ncnc3ccccc23)cc1
Yield: 87 %

Procedure:
A solution of quinazolin-4-yl-hydrazine (Gewald et al., J. Prakt. Chem./Chem.-Ztg. 1996, 338, 206-213) (265 mg, 1.65 mmol) was refluxed with tolualdehyde (400 μl, 3.39 mmol) in methanol for 1 hour. The solvent was evaporated and the resulting solid was triturated with water and filtered to give a yellow powder in 87% yield: mp 211-214° C.; 1H-NMR (DMSO-d6) 2.37 (s, 3H), 7.29 (d, 2H), 7.47 (dt, 2H), 7.67 (t, 1H), 7.88 (d, 3H), 8.20 (m, 1H), 8.51 (s, 1H), 11.65 (s, 1H); HR-MS (EI) m/z 262.1223 (M+).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][O:7][C:8]1[C:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:12][C:11]([C:20]([OH:22])=[O:21])=[CH:10][C:9]=1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.N12CCCN=C1CCCC[CH2:30]2.IC>C1COCC1>[CH3:30][O:21][C:20]([C:11]1[CH:10]=[C:9]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:8]([O:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])=[C:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:12]=1)=[O:22]
Reactant: C1CCC2=NCCCN2CC1
Reactant: COCCOCOc1c(-c2ccccc2)cc(C(=O)O)cc1-c1ccccc1
Solvent: C1CCOC1
Solvent: CI
Product: COCCOCOc1c(-c2ccccc2)cc(C(=O)OC)cc1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 92 %

Procedure:
At 0° C., to a stirred solution of 2′-(2-methoxyethoxymethoxy)-[1,1′;3′,1″]terphenyl-5′-carboxylic acid (1.72 g, 4.55 mmol) in THF (4.55 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene. After 0.5 h, to the reaction was added iodomethane and the reaction was stirred for 16 h, eventually warming to ambient temperature. The reaction was filtered and the filtrate concentrated. The crude product was dissolved in EtOAc, washed sequentially with sat. aq. NaHCO3 (3×), with 1 N HCl (3×), brine (3×), dried (K2CO3) and concentrated. Purification on Biotage KP-Sil eluting with 20% acetone/hexane gave 1.641 g (92%) of the title compound as a yellow oil. 1H NMR (DMSO-d6) δ 2.77-2.80 (m, 2H), 2.88-2.91 (m, 2H), 3.01 (s, 3H), 3.87 (s, 3H), 4.40 (s, 2H), 7.40-7.53 (m, 6H), 7.60-7.62 (m, 4H), 7.90 (s, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[C:11]([C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[CH:14]=1)=O.C(OP([CH2:31][C:32]#[N:33])(=O)OCC)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].O1C2C=CC(C(C3C=C(OC)C=C(OC)C=3)=CC#N)=CC=2OCC1>C1COCC1>[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[C:11]([C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[CH:14]=1)=[CH:31][C:32]#[N:33]
Reactant: COc1cc(OC)cc(C(=O)c2cccc(OC)c2OC)c1
Reactant: CCOP(=O)(CC#N)OCC
Agent: COc1cc(OC)cc(C(=CC#N)c2ccc3c(c2)OCCO3)c1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1cc(OC)cc(C(=CC#N)c2cccc(OC)c2OC)c1
Yield: 90.5 %

Procedure:
(2,3-Dimethoxyphenyl)-(3,5-dimethoxyphenyl)methanone (1.19 g, 3.94 mmol), cyanomethylphosphonic acid diethyl ester (1.24 ml, 7.87 mmol) in anhydrous THF (20 ml), and lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 7.9 ml, 7.87 mmol) were treated in the same manner as described above for the synthesis of 3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-3-(3,5-dimethoxyphenyl)acrylonitrile. The crude material was purified via flash column chromatography (5% EtOAc in hexane gradient to 20% EtOAc in hexane in about 40 min.) to give 3-(2,3-Dimethoxy-phenyl)-3-(3,5-dimethoxy-phenyl)-acrylonitrile as a clear light pink oil (1.16 g, 91%): 1HNMR (DMSO-d6) δ 7.21-7.08 (m, 2H, Ar), 6.83-6.79 (m, 1H, Ar), 6.62-6.56 (m, 1H, Ar), 6.47-6.46 (m, 2H, Ar), 6.00 (s, 1H, double bond proton), 3.86-3.72 (multiple singlets, 12H, 4OCH3): 13C NMR (CDCl3) δ 161.0, 160.9, 160.7, 160.4, 153.2, 153.1, 147.3, 146.7, 140.5, 140.1, 133.9, 131.7, 124.3, 124.0, 122.5, 122.2, 117.7, 117.5, 114.1, 107.0, 105.7, 102.0, 101.9, 97.8, 97.2, 60.9, 60.7, 56.1, 56.0, 55.7, 55.6; Anal. Calcd. For C19H19NO4: C, 73.20; H, 5.80; N, 4.74. Found: C, 73.10; H, 5.72; N, 4.68.
Reaction SMILES: [C:1]12([CH2:13][CH:12]([NH2:14])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[O:5]1)[CH2:4][CH2:3][CH2:2]2.[CH:15]1([O:20][C:21]2[C:26]([O:27][CH3:28])=[CH:25][CH:24]=[CH:23][C:22]=2[CH2:29][CH2:30][CH2:31][C:32]([OH:34])=O)[CH2:19][CH2:18][CH2:17][CH2:16]1.CCN=C=NCCCN(C)C.[ClH:46].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>ClCCl>[Cl:46][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[O:5][C:1]1([CH2:4][CH2:3][CH2:2]1)[CH2:13][C@H:12]2[NH:14][C:32](=[O:34])[CH2:31][CH2:30][CH2:29][C:22]1[CH:23]=[CH:24][CH:25]=[C:26]([O:27][CH3:28])[C:21]=1[O:20][CH:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: Cl
Reactant: NC1CC2(CCC2)Oc2ccccc21
Reactant: COc1cccc(CCCC(=O)O)c1OC1CCCC1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cccc(CCCC(=O)N[C@@H]2CC3(CCC3)Oc3c(Cl)cccc32)c1OC1CCCC1

Procedure:
The title compound was prepared from Intermediate 3 (150 mg, 0.619 mmol) and 4-(2-cyclopentyloxy-3-methoxyphenyl)butanoic acid (205 mg, 0.739 mmol) in presence of EDCI.HCl (193 mg, 1.012 mmol), HOBt (154 mg, 1.012 mmol) and triethylamine (279 μl, 2.043 mmol) in dichloromethane (10 ml) as described in Example 1 to give 149 mg of the product as a white solid; IR (KBr) 3315, 2945, 1642, 1438, 1244, 1040 cm−1; 1H NMR (300 MHz, CDCl3) δ 1.57-1.70 (m, 10H), 1.97-2.04 (m, 4H), 2.14-2.20 (m, 4H), 2.40-2.47 (m, 2H), 2.66-2.72 (m, 2H), 3.80 (s, 3H), 4.79 (br s, 1H), 5.28 (d, J=6.3 Hz, 1H), 5.56 (d, J=8.4 Hz, 1H), 6.66-6.77 (m, 3H), 6.90-7.04 (m, 2H), 7.14-7.20 (m, 1H); ESI-MS (m/z) 484.26 (M)+.
Reaction SMILES: [H-].[Na+].[CH2:3]([C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[CH2:7][C@@H:8]([CH3:20])[O:9][CH:10]2[C:15](OCC)=O)[CH3:4].C[N:22]([CH:24]=O)[CH3:23].IC.CCOC(C)=O.C(Cl)Cl.[CH2:37]([N:39](CC)CC)C>>[CH2:3]([C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[CH2:7][C@@H:8]([CH3:20])[O:9][C:10]2([C:23]1[NH:39][CH2:37][CH2:24][N:22]=1)[CH3:15])[CH3:4]
Reactant: CCOC(=O)C1O[C@H](C)Cc2c(CC)cccc21
Reactant: CN(C)C=O
Reactant: CCN(CC)CC
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCc1cccc2c1C[C@@H](C)OC2(C)C1=NCCN1
Reaction time: 2 h

Procedure:
The mixture of NaH (0.39 g), (3R)-ethyl 5-ethyl-3-methylisochroman-1-carboxylate (0.6 g) and DMF (7 ml) was stirred for 2 hrs in ice-bath temperature. Iodomethane (1.5 ml) was added and the mixture was stirred at ambient temperature for 16 hrs. The intermediate (3R)-ethyl 5-ethyl-1,3-dimethylisochroman-1-carboxylate (0.5 g) was purified with separation method A and the title compound was synthesized using the procedure of synthesis method A step 3 and separation method E (EtOAc/DCM/triethyl amine 10/20/1). (Yield 0.06 g).
Reaction SMILES: [OH-].[K+].[OH:3][C:4]([C:25]1[S:26][CH:27]=[CH:28][N:29]=1)([C:7]1[CH:8]=[N:9][CH:10]=[C:11]([O:13][CH2:14][C:15]2[CH:24]=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:16]=2)[CH:12]=1)[CH2:5][CH3:6].[CH3:30]I>CS(C)=O>[CH3:30][O:3][C:4]([C:25]1[S:26][CH:27]=[CH:28][N:29]=1)([C:7]1[CH:8]=[N:9][CH:10]=[C:11]([O:13][CH2:14][C:15]2[CH:24]=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:16]=2)[CH:12]=1)[CH2:5][CH3:6]
Reactant: CCC(O)(c1cncc(OCc2ccc3ccccc3c2)c1)c1nccs1
Reactant: CI
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Product: CCC(OC)(c1cncc(OCc2ccc3ccccc3c2)c1)c1nccs1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 62 %

Procedure:
Powdered potassium hydroxide (0.155 g) was added to a solution of 2-[1-hydroxy-1-[5-(naphth-2-ylmethoxy)pyrid-3-yl]propyl]thiazole (0.218 g) in dimethylsulphoxide (2 ml) and the mixture was stirred at ambient temperature for 5 minutes. Methyl iodide (0.073 ml) was added and the mixture was stirred at ambient temperature for 30 minutes. The mixture was partitioned between water and methylene chloride (3×20 ml). The organic extracts were combined, dried (Na2SO4) and evaporated. The residue was purified by column chromatography eluting with increasingly polar mixtures of petrol (b.p. 60°-80° C.) and ethyl acetate to give 2-[1-methoxy-1-[5-(naphth-2-ylmethoxy)pyrid-3-yl]propyl]thiazole (0.14 g, 62%), m.p. 93°-95° C.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH2:10](O)[CH2:11][OH:12].C1(C)C=CC(S(O)(=O)=O)=CC=1.O.C1(C)C=CC=CC=1>>[Br:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]1[O:12][CH2:11][CH2:10][O:5]1
Reactant: O=Cc1ccccc1Br
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: Brc1ccccc1C1OCCO1

Procedure:
A 12 L 3-necked flask fitted with an overhead stirrer was charged with 2-bromobenzaldehyde (800 g, 4.324 moles), ethylene glycol (402.6 g, 6.485 moles), p-toluenesulfonic acid·H2O (3.95 g, 0.021 moles) and toluene (3.785 kg, 41.074 moles).
Reaction SMILES: [N:1]([CH2:4][CH2:5][CH2:6][CH2:7][C:8]([OH:10])=[O:9])=[N+:2]=[N-:3].O[N:12]1[C:16](=[O:17])[CH2:15][CH2:14][C:13]1=[O:18].Cl.C(N=C=NCCCN(C)C)C.O>ClCCl>[N:1]([CH2:4][CH2:5][CH2:6][CH2:7][C:8]([O:10][N:12]1[C:16](=[O:17])[CH2:15][CH2:14][C:13]1=[O:18])=[O:9])=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=NCCCCC(=O)O
Reactant: O=C1CCC(=O)N1O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: O
Product: [N-]=[N+]=NCCCCC(=O)ON1C(=O)CCC1=O
Temperature: 25 °C
Reaction time: 12 h
Yield: 70 %

Procedure:
To a suspension of 5-azidovaleric acid (715 mg; 5 mmol; Example 2.2) and N-hydroxysuccinimide (632 mg; 5.5 mmol; Aldrich) in 30 ml dichloromethane, was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.05 g; 5.5 mmol; Aldrich), and the reaction was stirred 12 h at room temperature. To the reaction mixture, was added water (50 ml), and the separated organic phase was washed with water (100 ml) and brine (100 ml), dried over sodium sulfate, dried in vacuo. The product was purified via flash chromatography on silica gel (240-400 mesh) in 3:1 (v/v) hexane:ethyl acetate. Yield: 843 mg (3.5 mmol, 70% yield). M+H+: expected, 241.09.7; found, 241.03.
Reaction SMILES: [F:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([F:18])=[C:4](F)[C:3]=1[F:20].[Cl:21][C:22]1[C:28]([Cl:29])=[CH:27][C:26]([Cl:30])=[C:25]([Cl:31])[C:23]=1[NH2:24]>>[Cl:21][C:22]1[C:28]([Cl:29])=[CH:27][C:26]([Cl:30])=[C:25]([Cl:31])[C:23]=1[NH:24][C:4]1[C:3]([F:20])=[C:2]([F:1])[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]=1[F:18].[Cl:21][C:22]1[C:28]([Cl:29])=[CH:27][C:26]([Cl:30])=[C:25]([Cl:31])[C:23]=1[NH:24][C:4]1[C:3]([NH:24][C:23]2[C:25]([Cl:31])=[C:26]([Cl:30])[CH:27]=[C:28]([Cl:29])[C:22]=2[Cl:21])=[C:2]([F:1])[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]=1[F:18]
Reactant: O=C1c2ccccc2C(=O)c2c(F)c(F)c(F)c(F)c21
Reactant: Nc1c(Cl)c(Cl)cc(Cl)c1Cl
Product: O=C1c2ccccc2C(=O)c2c(F)c(Nc3c(Cl)c(Cl)cc(Cl)c3Cl)c(F)c(F)c21
Product: O=C1c2ccccc2C(=O)c2c(F)c(Nc3c(Cl)c(Cl)cc(Cl)c3Cl)c(Nc3c(Cl)c(Cl)cc(Cl)c3Cl)c(F)c21
Reaction time: 10 h

Procedure:
2 g of 1,2,3,4-Tetrafluoroanthraquinone and 30 g of 2,3,5,6-tetrachloroaniline were charged in a 50 cc, four necked flask and then the reaction was carried out at 210° C. for about 10 hours. After completion of reaction, 2,3,5,6-tetrachloroaniline was distilled out from the reaction solution and a column purification thereof using a column with a silica gel was effected to give rise to 0.62 g of 2-(2,3,5,6-tetrachloroanilino)-1,3,4-trifluoroanthraquinone (Dye 11') (yield 17.8 mol %) and 0.53 g of 2,3-bis(2,3,5,6-tetrachloroanilino)-1,4-difluoroanthraquinone (Dye 27') (yield 10.6 mol %). The physical properties of Dye 11' and analytical values defining the compound are tabulated in Table 22 and the physical properties of Dye 27' and analytical values defining the compound are tabulated in Table 23.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([S:25](=[O:28])(=[O:27])[NH2:26])[C:17]=1[S:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:12]([OH:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=[O:31])C>OO>[CH2:1]([NH:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([S:25](=[O:28])(=[O:27])[NH2:26])[C:17]=1[S:18]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:31])[C:12]([OH:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=O)O
Reactant: NS(=O)(=O)c1cc(C(=O)O)cc(NCc2ccccc2)c1Sc1ccccc1
Agent: OO
Product: NS(=O)(=O)c1cc(C(=O)O)cc(NCc2ccccc2)c1S(=O)c1ccccc1

Procedure:
To a suspension of 3-benzylamino-4-phenylthio-5-sulphamyl-benzoic acid (0.8 g) in acetic acid (20 ml), perhydrol (1.5 ml of 30% hydrogen peroxide in water) was added while stirring. The reaction mixture was stirred for an additional 75 hours at room temperature, after which the 3-benzylamino-4-phenylsulphinyl-5-sulphamyl-benzoic acid was collected by filtration and washed with acetic acid. After recrystallization from aqueous methanol and drying, the acid had a melting point of 234° C.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5]Br)[CH3:2].[OH:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=1>CN1CCCC1=O.C(OCC)C>[CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5][O:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=1)[CH3:2]
Reactant: O=Cc1ccc(O)cc1
Reactant: CCOC(CBr)OCC
Solvent: CCOCC
Solvent: CN1CCCC1=O
Product: CCOC(COc1ccc(C=O)cc1)OCC
Yield: 96.6 %

Procedure:
Bromoacetaldehyde-diethyl-acetal (98.5 g, 0.5 m) and p-hydroxybenzaldehyde (76.4 g, 0.63 m) were dissolved in N-methylpyrrolidone (250 cm3) and heated at 120° for 12 hours. The reaction mixture was cooled, diluted with diethyl ether and the ether layer was extracted four times with 5% sodium hydroxide solution to remove excess of p-hydroxybenzaldehyde. The ether was removed and the product distilled under reduced pressure to give 115 g (97%) of p-formylphenoxy-acetaldehyde-diethyl-acetal, b. 139°-140°/1.5 mbs. Acetylbenzene-sulphonic acid (sodium salt, 40 g, 0.18 m) was dispersed in a mixture of methanol (400 cm3) and 10% aqueous sodium hydroxide (150 cm3).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[N:7]([C:12]1[CH:17]=[C:16]([NH:18][CH:19]([CH2:22][CH3:23])[CH2:20][CH3:21])[N:15]=[C:14]([CH3:24])[N:13]=1)[CH2:6][CH2:5]2.[Br-:25].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>ClCCl>[Br:25][C:17]1[C:12]([N:7]2[C:8]3[C:4](=[CH:3][C:2]([Cl:1])=[CH:10][C:9]=3[Cl:11])[CH2:5][CH2:6]2)=[N:13][C:14]([CH3:24])=[N:15][C:16]=1[NH:18][CH:19]([CH2:22][CH3:23])[CH2:20][CH3:21]
Reactant: CCC(CC)Nc1cc(N2CCc3cc(Cl)cc(Cl)c32)nc(C)n1
Reactant: [Br-]
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CCC(CC)Nc1nc(C)nc(N2CCc3cc(Cl)cc(Cl)c32)c1Br
Yield: 93.2 %

Procedure:
4-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-6-(1-ethylpropylamino)-2-methylpyrimidine (1.15 g, 3.14 mmol) and pyridinium tribromide (1.16 g, 3.63 mmol) were stirred in dry dichloromethane (20 mL) at 20° C. for 16 h. The reaction mixture was quenched with saturated aqueous Na2S2O5 (6 mL) and diluted with EtOAc (200 mL). The EtOAc was washed with water, brine, dried and stripped in vacuo. The residue was chromatographed on silica gel using 20% EtOAc/hexanes to give the product, 5-bromo-4-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-6-(1-ethylpropylamino)-2-methylpyrimidine (1.30 g, 93% yield).
Reaction SMILES: [F:1][C:2]1[C:3]([NH:37][CH:38]([C:45]2([CH3:50])[CH2:49][CH2:48][CH2:47][CH2:46]2)[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[N:10](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:9]=2)=[N:6][CH:7]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[F:1][C:2]1[C:3]([NH:37][CH:38]([C:45]2([CH3:50])[CH2:46][CH2:47][CH2:48][CH2:49]2)[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][N:9]=2)=[N:6][CH:7]=1
Reactant: CCOC(=O)CC(Nc1nc(-c2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c3ncc(F)cc23)ncc1F)C1(C)CCCC1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCOC(=O)CC(Nc1nc(-c2n[nH]c3ncc(F)cc23)ncc1F)C1(C)CCCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of racemic ethyl 3-[[5-fluoro-2-(5-fluoro-1-trityl-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-4-yl]amino]-3-(1-methylcyclopentyl)propanoate, 148a, (0.240 g, 0.357 mmol) in dichloromethane (20 mL) was added triethylsilane (0.285 mL, 1.784 mmol) followed by trifluoroacetic acid (0.275 mL, 3.567 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the resulting crude residue was purified by silica gel chromatography (5% MeOH/CH2Cl2) to afford the desired product: 1H NMR (400 MHz, CDCl3) δ 11.80 (s, 2H), 8.59 (d, J=12.3 Hz, 2H), 8.48 (d, J=7.9 Hz, 1H), 6.60 (d, J=8.3 Hz, 1H), 5.07 (s, 1H), 4.09 (q, J=7.0 Hz, 2H), 2.97-2.59 (m, 2H), 1.70 (dd, J=27.7, 13.9 Hz, 6H), 1.57-1.33 (m, 2H), 1.16 (dd, J=18.1, 11.1 Hz, 6H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=2.97 minutes (M+H) 431.24.