Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:17][CH2:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=1>CN(C=O)C>[CH3:9][C:4]1[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([O:1][CH2:17][CH2:18][O:19][C:20]2[CH:21]=[CH:22][C:23]([N+:26]([O-:28])=[O:27])=[CH:24][CH:25]=2)[N:3]=1
Reactant: Cc1cc(C)nc(O)c1
Reactant: O=[N+]([O-])c1ccc(OCCBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(C)nc(OCCOc2ccc([N+](=O)[O-])cc2)c1
Temperature: 120 °C
Yield: 13.3 %

Procedure:
A mixture of 2-hydroxy-4,6-dimethylpyridine (1.7 g, 13.8 mmol), potassium carbonate (3.82 g, 27.6 mmol) and 1-(2-bromo-ethoxy)-4-nitro-benzene (4.0 g, 16.6 mmol) in DMF (30 mL) was heated to 120° C. and maintained for 15 h. The mixture was cooled to ambient temperature, filtered and concentrated to give a residue which was purified by column chromatography using 4% ethyl acetate/petroleum ether as eluent to afford 2,4-dimethyl-6-[2-(4-nitro-phenoxy)-ethoxy]-pyridine as yellow solid (530 mg, 11%).
Reaction SMILES: N1C=CC=CC=1.[F:7]N1N=C(F)C=C(F)N1.[NH2:16][C:17]1([C:22]2[N:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:23]=2[C:24](O)=[O:25])[CH2:21][CH2:20][CH2:19][CH2:18]1>ClCCl>[NH2:16][C:17]1([C:22]2[N:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:23]=2[C:24]([F:7])=[O:25])[CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: NC1(c2nc(Cl)ccc2C(=O)O)CCCC1
Reactant: FC1=CC(F)=NN(F)N1
Solvent: ClCCl
Solvent: c1ccncc1
Product: NC1(c2nc(Cl)ccc2C(=O)F)CCCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.3 %

Procedure:
0.34 ml (4.15 mmol) of pyridine and 0.53 ml (6.23 mmol) of 2,4,6-trifluorotriazine are added to a suspension of 1.0 g (4.15 mmol) of 2-(aminocyclopentyl)-6-chloronicotinic acid in 12 ml of dichloromethane. The mixture is stirred for 2 hours at ambient temperature and then diluted with dichloromethane. The organic phase is washed twice with an ice-cold solution of NaHCO3aq and then dried over Na2SO4, filtered, and concentrated under reduced pressure. 1 g of product is obtained in the form of a brown oil, which is used immediately in the next step. Quantitative crude yield.
Reaction SMILES: Br[C:2]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[Cu](C#N)[C:14]#[N:15]>CN1CCCC1=O.C(OCC)(=O)C>[NH2:4][C:3]1[CH:5]=[CH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[CH:8][C:2]=1[C:14]#[N:15]
Reactant: Nc1ccc(C(F)(F)F)cc1Br
Reactant: N#C[Cu]C#N
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: N#Cc1cc(C(F)(F)F)ccc1N
Reaction time: 0.08 h

Procedure:
In a 20 mL microwave vial, 2-bromo-4-(trifluoromethyl)aniline (238 mg, 1 mmol) and copper cyanide (90 mg, 1 mmol) were dissolved in N-methylpyrrolidone (NMP) (10 mL). The reaction was placed in a microwave reactor for 5 minutes at 200° C. The crude was dissolved in ethyl acetate and the precipitate was removed by filtration. The clear solution was washed with water. The organic layer was collected, dried over sodium sulfate, and evaporated under vacuum. The residue was purified by Varia HPLC (10% acetonitrile/water) to give the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[C:18]([O:20][CH2:21][CH:22]=[C:23]([Cl:25])[Cl:24])[CH:17]=[C:16]([Cl:26])[C:3]=1[O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][CH2:11][C:12](=[N:14][OH:15])[CH3:13].C(N(CC)CC)C.[C:34]1([CH3:44])[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1.Cl>O1CCCC1>[C:34]1([CH3:44])[CH:39]=[CH:38][C:37]([S:40]([O:15][N:14]=[C:12]([CH2:11][O:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][O:4][C:3]2[C:2]([Cl:1])=[CH:19][C:18]([O:20][CH2:21][CH:22]=[C:23]([Cl:25])[Cl:24])=[CH:17][C:16]=2[Cl:26])[CH3:13])(=[O:42])=[O:41])=[CH:36][CH:35]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC(COCCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl)=NO
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(COCCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl)=NOS(=O)(=O)c1ccc(C)cc1

Procedure:
First, 0.45 g of 5-(2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)pentyloxyacetone oxime, 0.12 g of triethylamine, and 10 ml of tetrahydrofuran are placed in a reaction vessel, to which a solution of 0.23 g of p-toluenesulfonyl chloride dissolved in 5 ml of tetrahydrofuran is slowly added dropwise with stirring under ice cooling. After completion of the addition, the reaction mixture is further stirred at room temperature for 30 minutes, poured into diluted hydrochloric acid, and extracted twice with diethyl ether. The diethyl ether layers are combined, washed with water, dried over anhydrous magnesium sulfate, and concentrated to give a crude product. This crude product is subjected to silica gel chromatography, which affords 5-(2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)pentyloxyacetone O-(p-toluenesulfonyl)oxime.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([O:13][CH2:14][C:15]([CH3:32])([C:17]2[O:21][N:20]=[C:19]([NH:22]C(OC3C=CC=CC=3)=O)[CH:18]=2)[CH3:16])(=[O:12])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].[O-2].[Mg+2].O1CCOCC1>O>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([O:13][CH2:14][C:15]([C:17]2[O:21][N:20]=[C:19]([NH2:22])[CH:18]=2)([CH3:16])[CH3:32])(=[O:11])=[O:12])=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: CC(C)(COS(=O)(=O)c1ccc([N+](=O)[O-])cc1)c1cc(NC(=O)Oc2ccccc2)no1
Agent: [Mg+2]
Agent: [O-2]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)(COS(=O)(=O)c1ccc([N+](=O)[O-])cc1)c1cc(N)no1
Temperature: 60 °C
Reaction time: 5 h
Yield: 87.9 %

Procedure:
A stirred mixture of 2-methyl-2-(3-(phenoxycarbonylamino)isoxazol-5-yl)propyl 4-nitrobenzenesulfonate (130 mg, 0.22 mmol), magnesium oxide (45 mg, 0.87 mmol), 1,4-dioxane (8 mL) and water (2 mL) was stirred at 60° C. for 5 h. The reaction mixture was cooled to rt and filtrated. The filtrate was concentrated under reduced pressure to give the crude product. Purification via recrystallization from a 1:1 mixture of diethyl ether and hexane, afforded 2-(3-aminoisoxazol-5-yl)-2-methylpropyl 4-nitrobenzenesulfonate (66 mg, 69%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.38-8.40 (m, 2H), 7.99-8.00 (m, 2H), 5.55 (s, 1H), 4.13 (s, 2H), 1.32 (s, 6H).
Reaction SMILES: [CH3:1][Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:11]([O:18][C:19](=[O:36])[CH2:20][CH2:21][C:22](=O)[CH2:23][CH2:24][C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.O>[CH2:11]([O:18][C:19](=[O:36])[CH2:20][CH2:21][C:22](=[CH2:1])[CH2:23][CH2:24][C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: O=C(CCC(=O)OCc1ccccc1)CCC(=O)OCc1ccccc1
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: C=C(CCC(=O)OCc1ccccc1)CCC(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 55.9 %

Procedure:
Methyltriphenylphosphonium bromide (536 mg, 1.5 mmol) was suspended in anhydrous THF (1.0 mL) at −5C. A THF solution of NaHMDS (1.0 M, 1.5 mL, 1.5 mmol) was added dropwise to keep the temperature below 0° C. The mixture was stirred at 0° C. for 0.5 h before cooled to −78° C. To this ylid solution was added a solution of dibenzyl-4-oxopimelate (354 mg, 1.0 mmol) in THF (1.0 mL) dropwise to keep the temperature below −50° C. The temperature was allowed to rise to room temperature in 1.5 h with stirring after addition. The reaction mixture was then poured in icy water (25 mL) and extracted with Et2O (2×25 mL). The organic layer was washed with brine (20 mL) and dried over Na2SO4. The solvent was removed under vacuum and the residue was subjected to silica chromatography (EtOAc/hexanes, up to 1/10) to give compound B4 (197 mg). The yield was 56%. 1H NMR (200 MHz, CDCl3) δ 7.37 (m, 10H), 5.11 (s, 4H), 4.78 (d, 2H, J=1.1 Hz), 2.53 (m, 4H), 2.39 (m, 4H); 13C NMR (50 MHz, CDCl3) δ 173.3, 146.6, 136.4, 129.0, 128.7, 110.5, 66.9, 33.2, 31.6; MS (MALDI-TOF) calcd (M+Na+) 375.4, found 375.6.
Reaction SMILES: [CH3:1][CH2:2][C:3]1([OH:29])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:16](=[CH:17][C:4]1=2)[C:15]1[N:18]=[C:19]2[C:24](=[CH:25][C:14]=1[CH2:13]3)[CH:23]=[C:22]([N+:26]([O-])=O)[CH:21]=[CH:20]2)=[O:11]>C(O)C.O1CCOCC1.[Pt]=O>[CH3:1][CH2:2][C@@:3]1([OH:29])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:16](=[CH:17][C:4]1=2)[C:15]1[N:18]=[C:19]2[C:24](=[CH:25][C:14]=1[CH2:13]3)[CH:23]=[C:22]([NH2:26])[CH:21]=[CH:20]2)=[O:11]
Reactant: CCC1(O)C(=O)OCc2c1cc1n(c2=O)Cc2cc3cc([N+](=O)[O-])ccc3nc2-1
Agent: O=[Pt]
Solvent: CCO
Solvent: C1COCCO1
Product: CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2cc3cc(N)ccc3nc2-1
Reaction time: 0.5 h
Yield: 96.2 %

Procedure:
10-Nitrocamptothecin (108 mg, 0.275 m-mol) is dissolved in ethanol (30 ml) and dioxane (20 ml). To this solution is added platinum oxide (20 mg), and the mixture is subjected to catalytic reduction for 30 minutes at room temperature under normal pressure. The catalyst is removed by filtration and the reaction mixture is evaporated under reduced pressure until dryness whereby 96 mg (yield: 96.2%) of 10-aminocamptothecin is obtained as a yellowish brown solid.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:8][O:9][CH2:10]Cl.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH3:8][O:9][CH2:10][O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Oc1ccccc1
Reactant: COCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COCOc1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 81.7 %

Procedure:
Under an ice bath, about 200 g of phenol and about 256 g of chloromethyl methyl ether were mixed and stirred in about 2 L of methylene chloride (MC), and about 740 ml of diisopropylethylamine (DIPEA) was gradually dropped. Next, the ice bath was removed and a temperature was increased, and then a synthesis reaction (see Equation 1 below) was performed while stirring for about 12 hours at room temperature. Next, distilled water was added in a reaction mixed liquid to complete the synthesis reaction and to extract an organic phase. Next, the organic phase was washed using about 0.5 N of HCl aqueous solution, distilled water, about 1 N of NaOH aqueous solution, and distilled water in the stated order, and then dried using magnesium sulphate. Next, the organic phase was filtered and concentrated to obtain about 240 g (a yield: about 81.7%) of methoxymethoxybenzene, and a structure of the methoxymethoxybenzene was observed by 1H-NMR (see FIG. 1):
Reaction SMILES: [NH2:1][C:2]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:10][C:3]=1[C:4]([NH:6][CH:7]([CH3:9])[CH3:8])=[O:5].[CH3:21][O:22][C:23]([C:25]1[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=1)=[O:24].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.CCN=C=NCCCN(C)C>CN(C=O)C>[CH:7]([NH:6][C:4]([C:3]1[CH:10]=[C:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:12]=[CH:13][C:2]=1[NH:1][C:29]([C:28]1[CH:32]=[CH:33][C:25]([C:23]([O:22][CH3:21])=[O:24])=[CH:26][CH:27]=1)=[O:30])=[O:5])([CH3:8])[CH3:9]
Reactant: COC(=O)c1ccc(C(=O)O)cc1
Reactant: CC(C)NC(=O)c1cc(Oc2ccccc2)ccc1N
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(C(=O)Nc2ccc(Oc3ccccc3)cc2C(=O)NC(C)C)cc1
Temperature: 65 °C
Yield: 84.8 %

Procedure:
A solution of 34C (72 mg, 0.27 mmol) in DMF (4 mL) was treated with 4-(methoxycarbonyl)benzoic acid (78 mg, 0.43 mmol), HOBt (66 mg, 0.43 mmol) and triethylamine (100 mg, 1.0 mmol). The solution was treated with EDCI (96 mg, 0.5 mmol) at room temperature for 15 minutes, and then warmed to 65° C. for 16 hours. The reaction mixture was partitioned between EtOAc (20 mL) and 1 M HCl (20 mL). The organic layer was washed with 1 N HCl (20 mL), 1 N NaOH (20 mL) and brine (20 mL). The reaction was dried (Na2SO4), filtered, and concentrated to a solid. The crude material was purified by chromatography (SiO2, 1:2 EtOAc in heptane) to afford 34D (99 mg, 85%).
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[S:32]([N:35]([CH3:37])[CH3:36])(=[O:34])=[O:33])=[N:4][C:5]([NH:8][C:9]2[C:22]([O:23][CH3:24])=[CH:21][C:12]3[CH2:13][CH2:14][N:15]([CH2:18][CH2:19][OH:20])[CH2:16][CH2:17][C:11]=3[CH:10]=2)=[N:6][CH:7]=1.C(OC([NH:45][C@H:46]([C:50](O)=[O:51])[CH:47]([CH3:49])[CH3:48])=O)(C)(C)C>>[Cl:1][C:2]1[C:3]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[S:32](=[O:34])(=[O:33])[N:35]([CH3:36])[CH3:37])=[N:4][C:5]([NH:8][C:9]2[C:22]([O:23][CH3:24])=[CH:21][C:12]3[CH2:13][CH2:14][N:15]([CH2:18][CH2:19][O:20][C:50](=[O:51])[C@@H:46]([NH2:45])[CH:47]([CH3:49])[CH3:48])[CH2:16][CH2:17][C:11]=3[CH:10]=2)=[N:6][CH:7]=1
Reactant: COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)N(C)C)n1)CCN(CCO)CC2
Reactant: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Product: COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)N(C)C)n1)CCN(CCOC(=O)[C@@H](N)C(C)C)CC2
Yield: 45 %

Procedure:
In an analogous manner to Example 1542, the product was prepared from [A] 2-{5-Chloro-2-[3-(2-hydroxy-ethyl)-8-methoxy-2,3,4,5-tetrahydro-1H-3-benzazepin-7-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide and N-(tert-Butoxycarbonyl)-L-valine. The product was isolated as a pale yellow foam (65 mg, 45%). 1H-NMR (CDCl3, 400 MHz) δ 9.36 (s, 1H), 8.55 (d, J=8 Hz, 1H), 8.16 (s, 1H), 8.02 (s, 1H), 7.90 (d, J=8 Hz, 1H), 7.58 (t, 1H), 7.51 (s, 1H), 7.26 (m, 1H), 6.67 (s, 1 h), 4.32-4.28 (m, 2H), 3.89 (s, 3H), 3.33 (d, J=5 Hz, 1H), 2.87 (m, 2H), 2.84 (m, 2H), 2.82-2.70 (m, 13H), 2.10 (m, 1H), 1.01 (d, J=7 Hz, 3H), 0.95 (d, J=7 Hz, 3H).
Reaction SMILES: [C:1]([NH:9][C:10]1[C:11]2[N:12]=[CH:13][N:14]([C:24]=2[N:25]=[CH:26][N:27]=1)[C@@H:15]1[O:23][C@H:20]([CH2:21][OH:22])[C@@H:18]([OH:19])[C@H:16]1[OH:17])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:28](Cl)([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(Cl)(Cl)Cl>N1C=CC=CC=1>[C:1]([NH:9][C:10]1[C:11]2[N:12]=[CH:13][N:14]([C:24]=2[N:25]=[CH:26][N:27]=1)[C@@H:15]1[O:23][C@H:20]([CH:21]([C:28]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[OH:22])[C@@H:18]([OH:19])[C@H:16]1[OH:17])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O)c1ccccc1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: c1ccncc1
Solvent: ClC(Cl)Cl
Product: O=C(Nc1ncnc2c1ncn2[C@@H]1O[C@H](C(O)C(c2ccccc2)(c2ccccc2)c2ccccc2)[C@@H](O)[C@H]1O)c1ccccc1

Procedure:
Compounds 6 and 7 are prepared by treating N6 -benzoyl adenosine with tritylchloride in pyridine and refluxing for 2 hours. N6 -benzoyl-5'-trityladenosine is isolated by extraction with chloroform. The water from the chloroform phase is removed by drying with sodium sulfate N6 -benzoyl-2',5'-di-O-trityladenosine and N6 -benzoyl-3',5'-di-O-trityladenosine are isolated by preparative silica gel thin layer chromatography in chloroform/ethanol. Compounds 6 and 7 are prepared by treating the isolated compounds with n-pentylchloride and n-heptylchloride, respectively, under reflux in a suspension of sodium hydroxide in benzene. The solution is neutralized by refluxing in acetic acid followed by the addition of diethyl ether and water. The reaction products are extracted with chloroform followed by thin layer chromatography with chloroform:methanol (4:1) on silica gel plates. The trityl and benzoyl groups are removed by refluxing in acetic acid for one hour, cooling, extraction with diethyl ether, followed by concentration and cooling to yield crystalline compounds 6 and 7. This method of preparation is carried out according to Blank, H. U., Franne, D., Myles, A. and Pfleiderer, W., Justus Liebigs Ann. Chem. 742, 34 (1970), which is incorporated herein by reference.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH2:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]3[CH:48]=[CH:47][C:46]([N:49]4[CH2:54][CH2:53][NH:52][C:51](=[O:55])[CH2:50]4)=[CH:45][CH:44]=3)=[CH:39][CH:38]=2)[N:12]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C:23](=[O:25])[N:22](COCC[Si](C)(C)C)[S:21]3(=[O:35])=[O:34])=[CH:16][CH:15]=2)[CH:13]=1.I[CH2:57][CH3:58]>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH2:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]3[CH:48]=[CH:47][C:46]([N:49]4[CH2:54][CH2:53][N:52]([CH2:57][CH3:58])[C:51](=[O:55])[CH2:50]4)=[CH:45][CH:44]=3)=[CH:39][CH:38]=2)[N:12]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C:23](=[O:25])[NH:22][S:21]3(=[O:34])=[O:35])=[CH:16][CH:15]=2)[CH:13]=1
Reactant: CCI
Reactant: C[Si](C)(C)CCOCN1C(=O)CN(c2ccc(-n3cc(-c4ccc(Cl)cc4Cl)nc3Cc3ccc(-c4ccc(N5CCNC(=O)C5)cc4)cc3)cc2)S1(=O)=O
Product: CCN1CCN(c2ccc(-c3ccc(Cc4nc(-c5ccc(Cl)cc5Cl)cn4-c4ccc(N5CC(=O)NS5(=O)=O)cc4)cc3)cc2)CC1=O

Procedure:
4-[4′-(4-(2,4-Dichloro-phenyl)-1-{4-[1,1,4-trioxo-5-(2-trimethylsilanyl-ethoxy methyl)-[1,2,5]thiadiazolidin-2-yl]-phenyl}-1H-imidazol-2-ylmethyl)-biphenyl-4-yl]-piperazin-2-one (17 mg, 0.02 mmol) was treated as described in general procedure L (using iodoethane) and general procedure W stepwise to give 4-(4′-{4-(2,4-dichloro-phenyl)-1-[4-(1,1,4-trioxo-[1,2,5]thiadiazolidin-2-yl)-phenyl]-1H-imidazol-2-ylmethyl}-biphenyl-4-yl)-1-ethyl-piperazin-2-one.
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].C(N(CC)CC)C.Cl>CS(C)=O>[O:1]=[CH:2][CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:9])([CH3:8])[CH3:10]
Reactant: CC(C)(C)OC(=O)NCCO
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)NCC=O
Reaction time: 1 h
Yield: 65.8 %

Procedure:
To a mixed solution of tert-butyl (2-hydroxyethyl)carbamate (10.0 g) in dimethyl sulfoxide (50 mL) and triethylamine (12.3 g) was added sulfur trioxide pyridine complex (15.0 g) under ice-cooling, and the mixture was stirred for 1 hr. The reaction mixture was further stirred at room temperature for 3 hr, 1 mol/L hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=17:3→13:7) to give the title compound as a pale-yellow oil (yield 6.50 g, 66%). 1H-NMR (CDCl3) δ: 1.46 (9H, s), 4.08 (2H, d, J=4.5 Hz), 5.19 (1H, brs), 9.66 (1H, s).
Reaction SMILES: [Cl:1][C:2]1[CH:28]=[CH:27][C:5]([NH:6][C:7]2[CH:15]=[C:14]([C:16]([OH:18])=O)[C:13]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)=[CH:12][C:8]=2[C:9]([OH:11])=O)=[CH:4][CH:3]=1.P(=O)(O)(O)O.CO>O.C(NN(NCC)S(C1C2=C3C(C4C5C(=CC=CC2=5)C=CC=4)=CC=CC3=CC=1CCC)(=O)=O)C>[CH:3]1[C:2]([Cl:1])=[CH:28][C:27]2[C:9]([C:8]3[C:7]([NH:6][C:5]=2[CH:4]=1)=[CH:15][C:14]1[C:16]([C:21]2[CH:22]=[C:23]([Cl:26])[CH:24]=[CH:25][C:20]=2[NH:19][C:13]=1[CH:12]=3)=[O:18])=[O:11]
Reactant: O=C(O)c1cc(Nc2ccc(Cl)cc2)c(C(=O)O)cc1Nc1ccc(Cl)cc1
Agent: CCCc1cc2cccc3c4cccc5cccc(c(c1S(=O)(=O)N(NCC)NCC)c23)c54
Agent: O=P(O)(O)O
Solvent: CO
Solvent: O
Product: O=c1c2cc(Cl)ccc2[nH]c2cc3c(=O)c4cc(Cl)ccc4[nH]c3cc12
Temperature: 113 °C
Reaction time: 3 h
Yield: 94.1 %

Procedure:
To 300 g of polyphosphoric acid (117% phosphoric acid) heated at 80° C. was added 2.5 g N,N-diethylaminopropyl perylenesulfonamide followed by 50 g of 2,5-di(4-chloroanilino)terephthalic acid added over a period of 40 minutes, the temperature being maintained below 110° C. by adjustment of the addition rate. The mixture was heated at 113° C. for 4.5 hours. After the melt was cooled to 98° C., the acid strength was adjusted to 111% by the dropwise addition of phosphoric acid. The resultant melt was slowly poured into 525 g of methanol, the temperature being maintained below 64° C. by external cooling and adjustment of melt addition rate. The slurry was heated at reflux for one hour, cooled to below 60° C., diluted with water, filtered, and washed until acid free. The presscake was dried to obtain 44.1 g of crude dichloroquinacridone, which was then salt ground for three hours using 306 g of a microsized salt and 57.9 g of a glycol. The salt was extracted using a slightly alkaline water slurry at 65° C. for one hour. After the slurry was filtered, the presscake was reslurried in slightly acidic water and held at 65° C. for one hour. The solid component was collected by filtration and washed with water. The wet cake can be dried or used as is for specific applications. Here, the wet cake was dried in an oven at 60° C. to give approximately 43 g of 2,9-dichloroquinacridone as a magenta pigment.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][N:9]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[N:11]=[CH:10]1.[Li]C(C)(C)C.CN([CH:26]=[O:27])C.C([O-])(O)=O.[Na+]>C1COCC1.O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][N:9]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[N:11]=[C:10]1[CH:26]=[O:27]
Reactant: CN(C)C=O
Reactant: c1ccc(CCn2cnc3ccccc32)nc1
Agent: O=C([O-])O
Agent: [Li]C(C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: O=Cc1nc2ccccc2n1CCc1ccccn1
Temperature: -40 °C
Reaction time: 1 h

Procedure:
Under an atmosphere of Ar, 1-(2-pyridin-2-yl-ethyl)-1H-benzimidazole (0.46 g, 2.1 mmol) (Ichikawa, M. et al. Chem. Pharm. Bull. 1981, 29, 3042-7) was dissolved in anhydrous THF (10 mL), cooled to −40° C., and treated with tert-BuLi (1.5 mL, 1.7M, 2.5 mmol) for 30 minutes. DMF (0.80 mL, 10.3 mmol) was then added and the solution slowly warmed to room temperature. After 1 hour, water (10 mL) and saturated aqueous NaHCO3 solution (10 mL) were added and the medium was extracted with EtOAc (3×25 mL). The combined organic phases were then dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was then purified by column chromatography with silica gel (50:1:0.1 MeOH:NH4OH:CH2Cl2) to afford 1-(2-pyridin-2-yl-ethyl)-1H-benzimidazole-2-carbaldehyde as a brown liquid that was used immediately in the next reaction (147 mg, 28%).
Reaction SMILES: [Si:1]([O:8][CH2:9][CH:10]1[O:15][CH2:14][CH2:13][NH:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)CC)C.[Cl:23][CH2:24][CH2:25][CH2:26]I>C(Cl)Cl>[Si:1]([O:8][CH2:9][CH:10]1[O:15][CH2:14][CH2:13][N:12]([CH2:26][CH2:25][CH2:24][Cl:23])[CH2:11]1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]
Reactant: ClCCCI
Reactant: CC(C)(C)[Si](C)(C)OCC1CNCCO1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCC1CN(CCCCl)CCO1
Temperature: 25 °C
Reaction time: 8 h
Yield: 20.1 %

Procedure:
A solution of 2-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine (2.1 g, 9.07 mmol) in DCM (20 mL) was treated with triethylamine (3.8 mL, 27.2 mmol) and 1-chloro-3-iodopropane (1.95 mL, 18.1 mmol). The reaction mixture was stirred at rt overnight. The reaction mixture was concentrated under reduced pressure then purified by MPLC (ISCO, 0% MeOH/100% DCM to 25% MeOH/75% DCM). The product was isolated as an oil (560 mg, 20%): HPLC MS RT=2.66 min, MH+=308.4, 310.4; 1H NMR (DMSO-d6) δ: 3.79-3.69 (1H, m), 3.63 (2H, t) 3.59-3.52 (1H, m), 3.50-3.36 (3H, m), 2.73 (1H, d), 2.61 (1H, d), 2.35 (2H, t), 1.94 (1H, td), 1.83 (2H, qt), 1.73 (1H, t), 0.83 (9H, s), 0.00 (6H, s).