Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH:13]=[O:14])=[C:5]1[C:15]([F:18])([F:17])[F:16])[C:2]#[CH:3].[C:19](Br)#[CH:20].[Mg].[Mg].P(O)(O)([O-])=O.[Na+].C(OC(C)C)(C)C>O1CCCC1>[CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH:13]([OH:14])[C:19]#[CH:20])=[C:5]1[C:15]([F:18])([F:16])[F:17])[C:2]#[CH:3]
Reactant: C#CBr
Reactant: C#CCn1c(C(F)(F)F)c(C=O)c2ccccc21
Agent: O=P([O-])(O)O
Agent: [Mg]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(C)OC(C)C
Product: C#CCn1c(C(F)(F)F)c(C(O)C#C)c2ccccc21
Temperature: -5 °C
Reaction time: 1 h

Procedure:
4.5 g of 1-(2-propynyl)-2-trifluoromethyl-3-formyl-(1H)-indole in 30 ml of tetrahydrofuran were cooled at -15° C. and over 15 minutes, 26 ml of a solution of magnesium ethynyl bromide in tetrahydrofuran (0.8M ) were added. After stirring for one hour at -5° C., another 5 ml of magnesium solution were added, and the mixture was allowed to return to ambient temperature. After stirring for 30 minutes and then pouring into a saturated aqueous solution of monosodium phosphate, extraction was carried out with isopropyl ether. The solvent was eliminated under reduced pressure to obtain 5.89 g of crude product which was purified by chromatography over silica (eluent: hexane-ethyl acetate 9-1) to obtain 1.91 g of 1(RS) [1-(2-propynyl)-2-trifluoromethyl-(1H)-indol-3-yl]-prop-2-ynyl alcohol melting at 98° C.
Reaction SMILES: [F:1][C:2]1([F:10])[CH2:7][CH2:6][CH:5]([CH2:8][OH:9])[CH2:4][CH2:3]1.C(N(CC)CC)C.[S:18](Cl)([C:21]1[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19]>ClCCl>[F:1][C:2]1([F:10])[CH2:7][CH2:6][CH:5]([CH2:8][O:9][S:18]([C:21]2[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=2)(=[O:20])=[O:19])[CH2:4][CH2:3]1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: OCC1CCC(F)(F)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OCC2CCC(F)(F)CC2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of Example 184A (8.5 g, 57 mmol) in dichloromethane (100 mL) were added triethylamine (Aldrich, 25 mL, 180 mmol) and tosyl chloride (Aldrich, 11.4 g, 60 mmol). The reaction mixture was stirred at room temperature for 16 hours and washed with water (50 mL) and brine (50 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-50% ethyl acetate in hexanes) to afford the title compound. 1H NMR (300 MHz, chloroform-d) δ ppm 1.17-1.42 (m, 2 H) 1.57-1.69 (m, 1 H), 1.70-1.91 (m, 4 H), 1.93-2.18 (m, 2 H), 2.46 (s, 3 H), 3.86 (d, J=6.4 Hz, 2 H), 7.35 (d, J=8.5 Hz, 2 H), 7.78 (d, J=8.1 Hz, 2 H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][C:10]2[C:15]3[CH:16]=[CH:17][CH2:18][O:19][C:14]=3[C:13]([O:20][CH3:21])=[C:12]([O:22][CH3:23])[CH:11]=2)=[CH:4][N:3]=1.ClC1C=CC=C(C(OO)=[O:32])C=1>CN(C=O)C>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][C:10]2[C:15]3[CH:16]=[CH:17][CH2:18][O:19][C:14]=3[C:13]([O:20][CH3:21])=[C:12]([O:22][CH3:23])[CH:11]=2)=[CH:4][N+:3]=1[O-:32]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COc1cc(Cc2cnc(N)nc2N)c2c(c1OC)OCC=C2
Solvent: CN(C)C=O
Product: COc1cc(Cc2c[n+]([O-])c(N)nc2N)c2c(c1OC)OCC=C2
Reaction time: 18 h

Procedure:
To a solution of 2,4-diamino-5-(7,8-dimethoxy-2H-1-benzopyran-5-ylmethyl)pyrimidine (0.993 g, 3.16 mmol) in DMF (80 mL) was added a solution of m-chloroperbenzoic acid (0.641 g, 3.16 mmol as 85%) in DMF (10 mL) dropwise over 30 min. After 18 hr, the solvent was evaporated and the residue chromatographed on silica gel eluted with 10-15% methanol-methylene chloride. Recovered starting material eluted first (0.40 g) followed by title compound as a white power (0.47 g). Recrystallization from absolute ethanol gave white crystals, mp 233°-234° dec.; assignment of N-1 oxide based on 13C-NMR: C-4 shifts from 154.40 to 161.28 ppm on acidification. Anal. Calcd for C16H18N4O4 : C, 58.17; H, 5.49; N, 16.96. Found: C, 57.81; H, 6.11; N, 16.84.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH3:19])[N:9]=[C:10]([C:11]3[O:12][C:13]([N+:16]([O-:18])=[O:17])=[CH:14][CH:15]=3)[C:3]=12.[CH3:20][NH:21][CH3:22]>C(OCC)(=O)C>[CH3:20][N:21]([CH3:22])[C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH3:19])[N:9]=[C:10]([C:11]3[O:12][C:13]([N+:16]([O-:18])=[O:17])=[CH:14][CH:15]=3)[C:3]=12
Reactant: Cn1nc(-c2ccc([N+](=O)[O-])o2)c2c(Cl)ncnc21
Reactant: CNC
Solvent: CCOC(C)=O
Product: CN(C)c1ncnc2c1c(-c1ccc([N+](=O)[O-])o1)nn2C

Procedure:
A mixture of 10.0 grams of 4-chloro-1-methyl-3-(5-nitro-2-furyl)-1H-pyrazolo[3,4-d]pyrimidine, 6.0 grams of dimethylamine and 600 milliliters of ethyl acetate was heated at reflux for 30 minutes, cooled and filtered. The filtrate was extracted with three 100 milliliters portions of water. The organic layer was dried over anhydrous magnesium sulphate and evaporated down to dryness. The crystalline product was collected, washed with ethanol and dried. Recrystallisation from ethyl acetate gave 4-dimethylamino-1-methyl-3-(5-nitro-2-furyl)-1H-pyrazolo[3,4-d]pyrimidine having melting point 161°C.
Reaction SMILES: C([O:8][C:9]1[N:14]=[C:13]2[NH:15][CH:16]=[N:17][C:12]2=[CH:11][CH:10]=1)C1C=CC=CC=1.[CH:18]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1B(O)O)([CH3:20])[CH3:19]>>[CH:18]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N:15]1[C:13]2=[N:14][C:9]([OH:8])=[CH:10][CH:11]=[C:12]2[N:17]=[CH:16]1)([CH3:20])[CH3:19]
Reactant: CC(C)c1ccccc1B(O)O
Reactant: c1ccc(COc2ccc3nc[nH]c3n2)cc1
Product: CC(C)c1ccccc1-n1cnc2ccc(O)nc21

Procedure:
From 5-(benzyloxy)-3H-imidazo[4,5-b]pyridine and 2-isopropylphenylboronic acid, prepared in a similar manner as the one described in Example 1.26, the title compound was obtained. LCMS m/z=254.1 [M+H]+.
Reaction SMILES: [CH2:1](O)COCCOCCO.C(Cl)(Cl)=O.C1(C)C=CC=CC=1.[CH2:22]([OH:40])[CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][OH:39]>CCOC(C)=O>[CH3:1][O:39][CH2:38][CH2:37][O:36][CH2:35][CH2:34][O:33][CH2:32][CH2:31][O:30][CH2:29][CH2:28][O:27][CH2:26][CH2:25][O:24][CH2:23][CH2:22][OH:40]
Reactant: OCCOCCOCCO
Reactant: OCCOCCOCCOCCOCCOCCO
Agent: O=C(Cl)Cl
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: COCCOCCOCCOCCOCCOCCO
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
The following description refers to the scheme illustrated in FIG. 10. Non-polydispersed activated hexaethylene glycol monomethyl ether was prepared analogously to that of non-polydispersed triethylene glycol in Example 39 above. A 20% phosgene in toluene solution (35 mL, 6.66 g, 67.4 mmol phosgene) was chilled under a N2 atmosphere in an ice/salt water bath. Non-polydispersed hexaethylene glycol 50 (1.85 mL, 2.0 g, 6.74 mmol) was dissolved in 5 mL anhydrous EtOAc and added to the phosgene solution via syringe. The reaction mixture was kept stirring in the ice bath for one hour, removed and stirred a further 2.5 hours at room temperature. The phosgene, EtOAc, and toluene were removed by vacuum distillation, leaving non-polydispersed compound 51 as a clear, oily residue.
Reaction SMILES: [Cl:1][CH2:2][CH:3]([OH:6])[CH2:4][Cl:5].[Br-].[Li+].C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:20][O:21][CH2:22]OC>>[CH3:20][O:21][CH2:22][O:6][CH:3]([CH2:4][Cl:5])[CH2:2][Cl:1]
Reactant: OC(CCl)CCl
Reactant: COCOC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Br-]
Agent: [Li+]
Product: COCOC(CCl)CCl
Temperature: 25 °C
Reaction time: 72 h
Yield: 57.5 %

Procedure:
1,3-Dichloro-2-propanol (10.0 g, 77.5 mmol) was dissolved in dimethoxymethane (150 ml), lithium bromide (20.2 g, 232.5 mmol) and p-toluenesulfonic acid (1.33 g, 7.8 mmol) were added, and the mixture was stirred at room temperature for 3 days. After completion of the reaction, the reaction mixture was neutralized and partitioned with 5% aqueous sodium hydrogencarbonate solution (50 ml) and dried over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was filtered off and the filtrate was concentrated to give a crude title compound (12.44 g). The crude title compound was distilled under reduced pressure (15 mmHg, 83° C.) to give a pure title compound (7.7 g, yield 57.5%).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:13]([OH:15])=[O:14])[CH:7]=[C:8]([CH:12]=1)[C:9]([OH:11])=[O:10])([O-])=O.C(O)(=O)C.[C:20]1(=O)[O:25][C:23](=[O:24])[CH:22]=[CH:21]1>[OH-].[Na+].[Pd].O1CCOCC1>[C:20]1(=[O:25])[N:1]([C:4]2[CH:5]=[C:6]([C:13]([OH:15])=[O:14])[CH:7]=[C:8]([CH:12]=2)[C:9]([OH:11])=[O:10])[C:23](=[O:24])[CH:22]=[CH:21]1
Reactant: O=C(O)c1cc(C(=O)O)cc([N+](=O)[O-])c1
Reactant: O=C1C=CC(=O)O1
Agent: [Pd]
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CC(=O)O
Product: O=C(O)c1cc(C(=O)O)cc(N2C(=O)C=CC2=O)c1

Procedure:
211.2 g (1.0 mol) of 5-nitroisophthalic acid are dissolved in 1,590 g of aqueous sodium hydroxide (90.0 g of sodium hydroxide in 1,500 ml of water) and the solution is rendered neutral with 15 ml of anhydrous acetic acid and hydrogenated in the presence of 10 g of a palladium-on-charcoal catalyst (5% by weight of Pd). The catalyst is filtered off and a solution of 118.0 g (1.2 mols) of maleic anhydride in 150 ml of dioxane is added to the filtrate in the course of 2 hours, whilst stirring vigorously. A white suspension is formed and is stirred overnight at 20°-25° C., 250 ml of acetic acid are then added and the mixture is stirred for a further 2 hours. The amide-acid which has precipitated is filtered off, washed with water and methanol and dried at 30° C. in vacuo for 24 hours. The reaction product (315 g) is then heated, in 2,500 ml of acetic anhydride, whilst stirring, to 80°-85° C. for 30 minutes. About 1.8 liters of liquid (acetic acid + acetic anhydride) are distilled off under a waterpump vacuum. The residual suspension is poured onto 2,000 g of ice and the mixture is stirred overnight. The reaction product which has precipitated is filtered off, washed with water and methanol and dried at 60° C. in vacuo for 12 hours. 210 g of white, crystalline 5-maleimidylisophthalic acid are obtained; melting point > 300° C. (= 80% of theory, based on the nitroisophthalic acid).
Reaction SMILES: S(Cl)([Cl:3])=O.[CH3:5][C:6]1[C:11]([CH3:12])=[C:10]([NH:13][CH2:14][CH2:15][CH2:16][CH2:17]O)[C:9]([N+:19]([O-:21])=[O:20])=[C:8]([O:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:7]=1>ClCCl>[Cl:3][CH2:17][CH2:16][CH2:15][CH2:14][NH:13][C:10]1[C:9]([N+:19]([O-:21])=[O:20])=[C:8]([O:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:7]=[C:6]([CH3:5])[C:11]=1[CH3:12]
Reactant: Cc1nc(Oc2ccccc2)c([N+](=O)[O-])c(NCCCCO)c1C
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: Cc1nc(Oc2ccccc2)c([N+](=O)[O-])c(NCCCCCl)c1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.9 %

Procedure:
Thionyl chloride (3.14 mL, 43 mmol) was added over a period of 5 minutes to a chilled (0° C.) solution of 4-[(2,3-dimethyl-5-nitro-6-phenoxypyridin-4-yl)amino]butan-1-ol (12.95 g, 39.08 mmol) in dichloromethane (130 mL). The reaction was allowed to warm to ambient temperature and was stirred overnight under a nitrogen atmosphere. The reaction mixture was diluted with dichloromethane (130 mL), washed sequentially with saturated aqueous sodium bicarbonate (2×65 mL), water (80 mL) and brine (100 mL), dried over magnesium sulfate, filtered and then concentrated under reduced pressure to provide 12.57 g of N-(4-chlorobutyl)-2,3-dimethyl-5-nitro-6-phenoxypyridin-4-amine as a yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]=O)=[CH:6][CH:5]=1.[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>O.ClCCCl>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:6][CH:5]=1
Reactant: C1COCCN1
Reactant: COC(=O)c1ccc(C=O)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCCl
Product: COC(=O)c1ccc(CN2CCOCC2)cc1
Temperature: 10 °C
Reaction time: 0.08 h

Procedure:
A 2 L, three-neck flask fitted with a mechanical stirrer, addition funnel, and thermocouple probe was charged with 4-formyl-benzoic acid methyl ester (50.0 g, 0.31 mol, 1.0 eq) and 1,2-dichloroethane (700 mL). The resulting mixture was cooled to 10° C. Morpholine (53 mL, 0.61 mol, 2.0 eq) was then added dropwise over 10 min. After 5 min, sodium triacetoxyborohydride (90 g, 0.43 mol, 1.4 eq) was added in portions over 5 min. After stirring 30 min, the reaction mixture was warmed to room temperature. At this point, a slow and steady temperature increase was observed, and a water bath was used to keep the temperature of the reaction mixture below 25° C. The reaction mixture was stirred for 22 hrs at room temperature. Water/ice (100 mL) was added to the reaction and the reaction mixture was stirred for 15 min. NaOH solution (1.0 M in water, 400 mL) was added in several portions, followed by the addition of water (250 mL). The resulting mixture was stirred for 45 min. The layers were separated, and the aqueous layer was extracted with dichloromethane (150 mL). The combined organic layer was washed with brine (150 mL) and then dried over Na2SO4. The solvent was removed in vacuo to yield the title compound as a pale yellow, viscous oil.
Reaction SMILES: [NH2:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[C:9](O)[C:5]([N+:6]([O-:8])=[O:7])=[C:4]([NH2:15])[C:3]=1[N+:16]([O-:18])=[O:17].P([O-])([O-])(O)=O.[NH4+:24].[NH4+].O>S1(CCCC1)(=O)=O>[C:9]1([NH2:24])[C:10]([N+:11]([O-:13])=[O:12])=[C:2]([NH2:1])[C:3]([N+:16]([O-:18])=[O:17])=[C:4]([NH2:15])[C:5]=1[N+:6]([O-:8])=[O:7]
Reactant: [NH4+]
Reactant: Nc1c([N+](=O)[O-])c(N)c([N+](=O)[O-])c(O)c1[N+](=O)[O-]
Agent: O=P([O-])([O-])O
Solvent: O=S1(=O)CCCC1
Solvent: O
Product: Nc1c([N+](=O)[O-])c(N)c([N+](=O)[O-])c(N)c1[N+](=O)[O-]
Temperature: 177 °C
Reaction time: 2 h

Procedure:
Diaminopicric acid (0.193 g, 0.748 mmol) and diammonium hydrogen phosphate (0.990 g, 7.50 mmol) are suspended in dry sulfolane (3 ml) and stirred in a Teflon® capped glass pressure tube (8 ml). The suspension is heated with stirring from ambient temperature to 177° C. over a 2 hr period. Stirring and heating (177° C.) is continued for an additional 6 hours. The reaction tube is cooled to 4° C. and the resulting suspension is mixed with water (40 ml). The precipitated product is collected, washed with water and dried to yield TATB in the form of a brown solid (0.154 g, 80%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:38])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19](=[O:37])[C:20]4[C:21]([O:29][C:30]=3[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[C:22]3[C:26](=[CH:27][CH:28]=4)[NH:25][N:24]=[CH:23]3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:41]I>CN(C=O)C>[C:1]([O:5][C:6](=[O:38])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:19](=[O:37])[C:20]4[CH:28]=[CH:27][C:26]5[C:22](=[CH:23][N:24]([CH3:41])[N:25]=5)[C:21]=4[O:29][C:30]=3[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CI
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3c(-c4ccccc4)oc4c(ccc5[nH]ncc54)c3=O)cc2)CCC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cn1cc2c(ccc3c(=O)c(-c4ccc(C5(NC(=O)OC(C)(C)C)CCC5)cc4)c(-c4ccccc4)oc32)n1
Reaction time: 0.08 h
Yield: 32.4 %

Procedure:
To a solution of {1-[4-(4-oxo-2-phenyl-4,7-dihydro-pyrano[2,3-e]indazol-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (65 mg, 0.13 mmol) in DMF (3 mL) at 0° C. under an atmosphere of N2 was added sodium hydride (60% in mineral oil, 6 mg, 0.15 mmol). After 5 min, methyl iodide (10 μL, 0.16 mmol) was added. After a further 2 hours, the reaction was quenched with H2O, partitioned between EtOAc and H2O and the phases were separated. The organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 50 to 70% ethyl acetate in cyclohexane) to afford the title compound as a white solid (22 mg, 32%). LCMS (Method B): RT=4.26 min, [M+H]+=522. Also obtained was {1-[4-(7-methyl-4-oxo-2-phenyl-4,7-dihydro-pyrano[2,3-e]indazol-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester as an oil (41 mg, 60%). LCMS (Method B): RT=4.42 min, [M+H]+=522.
Reaction SMILES: [CH2:1]([C:13]1[CH:17]=[C:16]([CH2:18]O)[O:15][N:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].P(Br)(Br)[Br:21]>ClCCl>[Br:21][CH2:18][C:16]1[O:15][N:14]=[C:13]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH:17]=1
Reactant: CCCCCCCCCCCCc1cc(CO)on1
Reactant: BrP(Br)Br
Solvent: ClCCl
Product: CCCCCCCCCCCCc1cc(CBr)on1
Reaction time: 1.5 h

Procedure:
To a stirred, chilled (+3° C.) solution of 3-dodecyl-5-isoxazole methanol (1.0 g, 0.0037 mol) in dichloromethane (20 mL) was added in one portion phosphorous tribromide (0.13 mL, 0.0014 mol), and the solution was stirred at +3° C. for 1.5 hours, then at room temperature for 3 days. The mixture was washed carefully with saturated sodium bisulfite, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried (MgSO4) and rotoevaporated to a yellow oil which solidified upon standing; yield 1.12 g (93%); mp 31.5°-35° C.
Reaction SMILES: Cl[C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[CH2:18]([O:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1)[CH3:19].[OH-].[K+]>C(Cl)Cl>[N+:15]([C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([N+:12]([O-:14])=[O:13])[C:2]=1[O:27][C:24]1[CH:25]=[CH:26][C:21]([O:20][CH2:18][CH3:19])=[CH:22][CH:23]=1)[C:6]([O:8][CH3:9])=[O:7])([O-:17])=[O:16]
Reactant: CCOc1ccc(O)cc1
Reactant: COC(=O)c1cc([N+](=O)[O-])c(Cl)c([N+](=O)[O-])c1
Agent: [K+]
Agent: [OH-]
Solvent: ClCCl
Product: CCOc1ccc(Oc2c([N+](=O)[O-])cc(C(=O)OC)cc2[N+](=O)[O-])cc1
Temperature: 150 °C
Yield: 74 %

Procedure:
A mixture of 13 g (50 mmole) of methyl 4-chloro-3,5-dinitrobenzoate, 7.45 g (54 mmole) of 4-ethoxyphenol, and 13 ml of potassium hydroxide solution (3.03 g, 54 mmole) was heated under argon at 150° C. for 4 h. The mixture was cooled and partitioned between 130 ml of 2 N sodium hydroxide solution and 400 ml of dichloromethane. The organic layer was washed with 2×100 ml of saturated sodium bicarbonate solution, dried over magnesium sulfate and evaporated under high vacuum to give 14.5 g, which was chromatographed on a silica gel column (5 cm×50 cm), eluting with 25% hexane/75% dichloromethane to give 13.2 g (74% yield). TLC (silica gel, CH2Cl2), Rf0.80. NMR: 1H (300 MHz) (CDCl3) 1.39 (3H, t, —CH3); 3.97 (2H, q, —CH2—); 4.02 (3H, s, —OCH3); 6.81 (4H, s, arom); and 8.70 ppm (2H, s, arom).
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH2:8][CH:9]([CH3:11])[CH3:10])=[CH:6][C:5]([SH:12])=[C:4]([CH:13]([CH3:15])[CH3:14])[CH:3]=1.Br[C:17]1C(C(C)C)=CC(S)=C(C(C)C)C=1>>[CH3:17][S:12][C:5]1[CH:6]=[C:7]([CH2:8][CH:9]([CH3:11])[CH3:10])[C:2]([Cl:1])=[CH:3][C:4]=1[CH:13]([CH3:15])[CH3:14]
Reactant: CC(C)c1cc(Br)c(C(C)C)cc1S
Reactant: CC(C)Cc1cc(S)c(C(C)C)cc1Cl
Product: CSc1cc(CC(C)C)c(Cl)cc1C(C)C

Procedure:
4-Chloro-2-isopropyl-5-isobutylphenyl methyl sulfide was prepared using the procedure of Example 1C except that 4-chloro-2-isopropyl-5-isobutylbenzenethiol was substituted for the 4-bromo-2,5-diisopropylbenzenethiol. The resulting product had a boiling point of 89°C at 0.08 mm Hg.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24](C)[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1I.CC1(C)C(C)(C)OB([C:37]2[CH:38]=[C:39]([OH:43])[CH:40]=[CH:41][CH:42]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:15](=[O:23])[C:14]3=[CH:24][CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1[C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([OH:43])[CH:38]=1
Reactant: Cc1ccn2nc([C@H](C)Nc3ncnc(N)c3I)n(-c3ccccc3)c(=O)c12
Reactant: CC1(C)OB(c2cccc(O)c2)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: C[C@H](Nc1ncnc(N)c1-c1cccc(O)c1)c1nn2cccc2c(=O)n1-c1ccccc1
Yield: 13.8 %

Procedure:
(S)-2-(1-((6-Amino-5-iodopyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (134 mg, 0.28 mol) was treated with 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (94 mg, 0.43 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (25 mg, 0.03 mol) and sodium carbonate (2M, 425 μl, 0.85 mol) according to the method described in Example 3 to give 26 mg (21% yield) of the title compound as a white solid. Purity 98%.