Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[F:9].[Cl:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=1[OH:19])[CH:14]=[O:15].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[F:9][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[CH2:2][O:19][C:18]1[CH:17]=[CH:16][C:13]([CH:14]=[O:15])=[CH:12][C:11]=1[Cl:10]
Reactant: O=Cc1ccc(O)c(Cl)c1
Reactant: Fc1ccccc1CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=Cc1ccc(OCc2ccccc2F)c(Cl)c1
Temperature: 90 °C
Reaction time: 8 h
Yield: 98.9 %

Procedure:
0.5 M solution of 1-bromomethyl-2-fluoro-benzene (1.5 g, 8 mmol) in DMF was added dropwise to a suspension of 3-chloro-4-hydroxy-benzaldehyde (1.14 g, 7.3 mmol), K2CO3 (1.51 g, 11 mmol) and KI (120 mg, 0.73 mmol) in DMF (100 ml). The reaction mixture was stirred at 90° C. overnight. After cooling, the solid residue was filtered off and the solvent was evaporated under vacuum. The residue was dissolved in ethyl acetate and the organic layer washed twice with NaOH 1M, dried over Na2SO4 and evaporated to dryness. The residue was purified on silica gel, obtaining 1.91 g of the title compound, yield 100%.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[O:10][C@@H:9]2[CH2:11][OH:12])=[CH:4][C:3]=1[F:13].[Na]>COCCOC.CCOCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([OH:10])[CH2:9][CH2:11][OH:12])=[CH:4][C:3]=1[F:13]
Reactant: OC[C@H]1O[C@@H]1c1ccc(Cl)c(F)c1
Agent: [Na]
Solvent: CCOCC
Solvent: COCCOC
Product: OCC[C@H](O)c1ccc(Cl)c(F)c1
Temperature: 0 °C
Reaction time: 3 h
Yield: 98.5 %

Procedure:
((2R,3R)-3-(4-Chloro-3-fluorophenyl)oxiran-2-yl)methanol (10.55 g, 52.07 mmol) was dissolved in 1,2-dimethoxyethane (150 mL) and cooled to 0° C. Sodium bis(2-methohyethoxy) aluminum hydride (“Red-Al”) (17.46 mL, 57.28 mmol) was added dropwise. The mixture was agitated for 3 hours at room temperature, diluted with ether (250 mL) and quenched with HCl solution (20 mL, 6M HCl+60 mL water). After agitating for 30 minutes, the aqueous phase was separated and extracted twice with ethyl acetate. The combined organics were washed with brine, dried with MgSO4, and evaporated to give (S)-1-(4-chloro-3-fluorophenyl)propane-1,3-diol (10.5 g, 51.31 mmol, 98.55% yield) as thick oil.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:9][SiH:10]([O:14][CH2:15][CH3:16])[O:11][CH2:12][CH3:13]>[Pt].C1(C)C=CC=CC=1>[CH2:1]([CH2:9][SiH:10]([O:14][CH2:15][CH3:16])[O:11][CH2:12][CH3:13])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CCO[SiH](C)OCC
Reactant: C=Cc1ccccc1
Agent: [Pt]
Solvent: Cc1ccccc1
Product: CCO[SiH](CCCc1ccccc1)OCC
Temperature: 80 °C
Yield: 63 %

Procedure:
Comparative Example 5. The platinum-catalyzed reaction of styrene and methyldiethoxysilane in the absence of a hydro(acyloxy)silane compound. A 212 mg sample of styrene (2 mmoles) and 279 mg of methyldiethoxysilane (HSi(CH3)(OEt)2, 2.1 mmoles) were placed in a glass reaction tube. This was followed by the addition of 0.001 mL of a toluene solution (platinum content=0.4 wt %) of a zero-valent platinum complex with divinylsiloxane. The reaction tube was subsequently sealed with Teflon™ tape, placed in an oil bath heated to 80° C., and heated for 1 hour. After cooling, analysis of the contents by gas chromatography showed an approximately 65% conversion of the vinyl group in the styrene. The hydrosilylate yield was 63% phenethylmethyldiethoxysilane. The α-phenethyl adduct: β-phenethyl adduct ratio was 1:1.65.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][NH:8][CH3:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].S(O[CH2:23][CH2:24][S:25][C@H:26]1[CH2:43][CH2:42][C@@:41]2([CH3:44])[C@H:28]([CH2:29][CH2:30][C@@H:31]3[C@@H:40]2[CH2:39][CH2:38][C@@:36]2([CH3:37])[C@:32]3([OH:50])[CH2:33][CH2:34][C@@H:35]2[C:45]2[CH:49]=[CH:48][O:47][CH:46]=2)[CH2:27]1)(C1C=CC(C)=CC=1)(=O)=O.O>CN(C)C=O>[N:1]1([CH2:6][CH2:7][N:8]([CH3:9])[CH2:23][CH2:24][S:25][C@H:26]2[CH2:43][CH2:42][C@@:41]3([CH3:44])[C@H:28]([CH2:29][CH2:30][C@@H:31]4[C@@H:40]3[CH2:39][CH2:38][C@@:36]3([CH3:37])[C@:32]4([OH:50])[CH2:33][CH2:34][C@@H:35]3[C:45]3[CH:49]=[CH:48][O:47][CH:46]=3)[CH2:27]2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1ccc(S(=O)(=O)OCCS[C@H]2CC[C@@]3(C)[C@H](CC[C@@H]4[C@@H]3CC[C@]3(C)[C@@H](c5ccoc5)CC[C@]43O)C2)cc1
Reactant: CNCCN1CCCC1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CN(CCS[C@H]1CC[C@@]2(C)[C@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H](c4ccoc4)CC[C@]32O)C1)CCN1CCCC1
Temperature: 25 °C
Yield: 60.7 %

Procedure:
To a solution of 0.34 g of N-(2-(1-pyrrolidinyl)ethyl) methylamine in 5 ml of dimethylformamide, 0.045 g of NaH (60% dispersion in mineral oil) were added under nitrogen and the mixture was stirred at room temperature for half an hr; a solution of 0.50 g of 3β-(2-tosyloxyethylthio)-17β-(3-furyl)-5β-androstan-14β-ol, prepared as described in Ex. 51, in 2 ml of dimethylformamide was added, the mixture was stirred for another 4 hrs and then 7 ml of water were poured in. The residue was extracted with ethyl acetate, the organic solution was washed with water to neutral pH, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The crude product was purified by flash-chromatography (SiO2) using methylene chloride/methanol 95/5 as eluant to give 0.28 g of the title compound (I-ca)as an amorphous solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@H:13]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C@@H:12]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@H:11]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C@@H:10]([CH2:38][O:39][CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[O:9]2)=[CH:4][C:3]=1[CH2:47][C:48]#[N:49].Br[CH2:51][CH2:52]Br.[OH-].[Na+]>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@H:13]([O:14][CH2:15][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[C@@H:12]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@H:11]([O:30][CH2:31][C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[C@@H:10]([CH2:38][O:39][CH2:40][C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[O:9]2)=[CH:4][C:3]=1[C:47]1([C:48]#[N:49])[CH2:52][CH2:51]1
Reactant: BrCCBr
Reactant: N#CCc1cc([C@@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)ccc1Cl
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: N#CC1(c2cc([C@@H]3O[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)ccc2Cl)CC1
Temperature: 25 °C
Reaction time: 15 h
Yield: 72.2 %

Procedure:
To a solution of β-39 (4.0 g, 5.93 mmol) in toluene (40 mL) were added 1,2-dibromethane (0.8 mL, 8.90 mmol), tetrabutylammonium bromide (0.4 g, 1.19 mmol) and aq. 50% NaOH solution (40 mL). The mixture was stirred at room temperature for 15 h. After dilution with water, the mixture was extracted with EtOAc. The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified by silica column chromatography to provide the titled compound 42 (3.0 g, 71%).
Reaction SMILES: [Si]([O:18][CH2:19][CH2:20][C:21]1([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[N:25]([C:26]2[S:27][C:28]3[CH2:29][NH:30][CH2:31][CH2:32][C:33]=3[N:34]=2)[N:24]=[C:23]([C:35]2[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:36]=2[F:42])[S:22]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C=O.[C:51](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])([O-])=O.[Na+].[Na+]>ClCCCl>[F:42][C:36]1[CH:37]=[CH:38][C:39]([F:41])=[CH:40][C:35]=1[C:23]1[S:22][C:21]([CH2:20][CH2:19][OH:18])([C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[N:25]([C:26]2[S:27][C:28]3[CH2:29][N:30]([CH3:51])[CH2:31][CH2:32][C:33]=3[N:34]=2)[N:24]=1
Reactant: CC(C)(C)[Si](OCCC1(c2ccccc2)SC(c2cc(F)ccc2F)=NN1c1nc2c(s1)CNCC2)(c1ccccc1)c1ccccc1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: C=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCCl
Product: CN1CCc2nc(N3N=C(c4cc(F)ccc4F)SC3(CCO)c3ccccc3)sc2C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Preparation of 2-(2-(2-(tert-butyldiphenylsilyloxy)ethyl)-5-[2,5-c]pyridine: To a solution of 2-(2-(2-(tert-butyldiphenylsilyloxy)ethyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (0.157 g, 0.225 mmol) in 5 mL DCE was added formaldehyde (0.067 mL, 37 wt % in water, 0.901 mmol) followed by sodium triacetoxyborohydride (0.052 g, 0.248 mmol). The resulting suspension was stirred vigorously at room temperature overnight, then treated with saturated Na2CO3 solution (30 mL) and stirred for 10 minutes. The mixture was extracted with EtOAc (3×30 mL) and the combined organic phases were washed with brine (20 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (0-1% MeOH/DCM) to afford the desired product as a bright yellow foam, 0.119 g, 74%.
Reaction SMILES: [Na][C:2]([CH:4]([CH2:7][NH:8][CH:9]=[O:10])[C:5]#[N:6])=[O:3].S(OC)(O[CH3:15])(=O)=O>O1CCCC1>[CH3:15][O:3][CH:2]=[C:4]([CH2:7][NH:8][CH:9]=[O:10])[C:5]#[N:6]
Reactant: N#CC(CNC=O)C(=O)[Na]
Reactant: COS(=O)(=O)OC
Solvent: C1CCOC1
Product: COC=C(C#N)CNC=O
Temperature: 70 °C
Reaction time: 5 h

Procedure:
To the residue of α-sodioformyl-β-formylaminopropionitrile is added 300 parts by volume of tetrahydrofuran and 138 parts of dimethyl sulfate. The mixture is reacted under stirring at 70°C for 5 hours. After completion of the reaction, the mixture is cooled at 25°C. The precipitated sodium methyl sulfate is removed and the filtrate is concentrated and kept standing overnight, whereby 135 parts of α-methoxymethylene-β-formylaminopropionitrile is obtained as crystals.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11]1[CH2:10][CH2:9][CH:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:7][C:6]2=1.[H-].[Na+].[CH3:24][N:25]([CH2:27][CH2:28][CH2:29]Cl)[CH3:26].O>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:29][CH2:28][CH2:27][N:25]([CH3:26])[CH3:24])[C:11]1[CH2:10][CH2:9][CH:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:7][C:6]2=1
Reactant: CN(C)CCCCl
Reactant: COc1ccc2[nH]c3c(c2c1)CC(c1ccccc1)CC3
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc2c(c1)c1c(n2CCCN(C)C)CCC(c2ccccc2)C1
Temperature: 100 °C

Procedure:
A mixture containing 6-methoxy-3-phenyl-1,2,3,4-tetrahydrocarbazole (5.5 g), 50% sodium hydride (1.0 g) in dimethylformamide (30 ml) is heated at 100° C. for 11/2 hours, and then dimethylamino propyl chloride is added. The mixture is heated at 80° C. for 2 hours, then cooled and water (40 ml) is added. The solid which precipitates is recrystallized with methylene chloride:ether (1:1).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[O:10][C:9]([C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=1[O:21][CH:22]([CH3:24])[CH3:23])=[CH:8][C:7]2=[O:25])([OH:3])=[O:2].S(Cl)(Cl)=O.O1CCO[CH2:32][CH2:31]1>>[C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[O:10][C:9]([C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=1[O:21][CH:22]([CH3:23])[CH3:24])=[CH:8][C:7]2=[O:25])([O:3][CH2:31][CH3:32])=[O:2]
Reactant: Cc1ccc(OC(C)C)c(-c2cc(=O)c3cc(C(=O)O)ccc3o2)c1
Reactant: C1COCCO1
Solvent: O=S(Cl)Cl
Product: CCOC(=O)c1ccc2oc(-c3cc(C)ccc3OC(C)C)cc(=O)c2c1

Procedure:
6-carboxy-2'-isopropoxy-5'-methyl-flavone (4.8 g) in dioxane (30 ml) was treated with thionyl chloride (4 ml) at the reflux temperature for 2 hours. After cooling, the reaction mixture was evaporated to dryness and reacted with an excess of anhydrous ethanol at 50° C. for 1 hour. The mixture was concentrated to a small volume and diluted with water so obtaining, by filtration, 6-carbethoxy-2'-isopropoxy-5'-methyl-flavone (4.7 g).
Reaction SMILES: [OH-].[K+].[C:3]([O:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])(OC(C)(C)C)=O.C(OC1[CH:29]=[CH:28][C:25]([CH:26]=[CH2:27])=[CH:24][CH:23]=1)(=O)C>CO.C(OCC)(=O)C>[C:14]([O:13][C:11]([O:10][C:3]1[CH:27]=[CH:26][C:25]([CH:28]=[CH2:29])=[CH:24][CH:23]=1)=[O:12])([CH3:15])([CH3:16])[CH3:17]
Reactant: C=Cc1ccc(OC(C)=O)cc1
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Agent: [K+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CO
Product: C=Cc1ccc(OC(=O)OC(C)(C)C)cc1
Yield: 103.4 %

Procedure:
A solution of 85 grams (1.3 moles) of potassium hydroxide in 161 grams of methanol was added in periodic additions along with 229 grams (1.0 moles) of di-t-butyl dicarbonate to a stirred solution of 101 grams (0.65 moles) of 4-acetoxystyrene in 505 grams of ethyl acetate over a period of about 40 minutes. The reagents were added concurrently in approximately equal aliquots while the reaction mixture wa kept at 25° C. with an ice bath. After an additional 2 hours of reaction at 25° C., the reaction slurry was washed well with water to remove solids. The volatile components of the organic layer were stripped under vacuum to give 148 grams (83% crude yield) of 4-tertiary-butoxycarbonyloxystyrene. Vacuum distillation afforded 87 grams (65% yield) of pure product, b.p. 111° C./0.25 mm.
Reaction SMILES: CO[C:3](=[O:21])[C:4]([OH:20])=[CH:5][C:6](=[O:19])[N:7]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[C:13]([Cl:18])[CH:12]=1)[O:8][CH3:9].C=O.CN.ClC1C=C(C=CC=1Cl)[CH2:30][N:31](C)[C:32](C1CN(C)C(=O)C=1O)=O>>[Cl:18][C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][C:14]=1[F:17])[CH2:10][N:7]([O:8][CH3:9])[C:6]([C:5]1[CH2:30][N:31]([CH3:32])[C:3](=[O:21])[C:4]=1[OH:20])=[O:19]
Reactant: CN1CC(C(=O)N(C)Cc2ccc(Cl)c(Cl)c2)=C(O)C1=O
Reactant: COC(=O)C(O)=CC(=O)N(Cc1ccc(F)c(Cl)c1)OC
Agent: C=O
Agent: CN
Product: CON(Cc1ccc(F)c(Cl)c1)C(=O)C1=C(O)C(=O)N(C)C1
Yield: 60 %

Procedure:
3-[(3-Chloro-4-fluorobenzyl)-methoxy-carbamoyl]-2-hydroxy-acrylic acid methyl ester (48-C) was treated with paraformaldehyde and methylamine as described in the preparation of Compound 12 to give the title compound as a white solid (60% yield); mp 148° C. dec. 1HNMR 400 MHz (CDCl3) δ (ppm): 3.10 (3H, s, NCH3), 3.75 (3H, s, OCH3), 4.15 (2H, s, NCH2), 4.81 (2H, s, NCH2), 7.12 (1H, m, aromatic), 7.22 (1H, m, aromatic), 7.38 (1H, m, aromatic). Anal. calcd for C14H14Cl2N2O4: C, 51.15; H, 4.29; N, 8.52. Found: C, 51.19; H, 4.17; N, 8.50.
Reaction SMILES: [Br:1]Br.[C:3]1([N:9]2[CH:13]=[CH:12][CH:11]=[N:10]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.O.C([O-])(O)=O.[Na+]>C(O)(=O)C.C(OCC)(=O)C>[Br:1][C:12]1[CH:11]=[N:10][N:9]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:13]=1
Reactant: BrBr
Reactant: c1ccc(-n2cccn2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Solvent: O
Product: Brc1cnn(-c2ccccc2)c1
Temperature: 100 °C
Yield: 96.8 %

Procedure:
A solution of bromine (1.1 g, 6.94 mmol) in acetic acid (10 mL) was added to a mixture of 1-phenylpyrazole (Aldrich, 1 g, 6.94 mmol) in acetic acid (10 mL). This mixture was warmed to 100° C. in a pressure tube for 8 h. The material was cooled to ambient temperature, poured into ice and H2O neutralized with excess saturated, aqueous NaHCO3. Ethyl acetate (50 mL) was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×15 mL) and the combined organic extract was dried over Na2SO4 and concentrated under reduced pressure to give a crude solid. Purification by column chromatography (SiO2, 50% hexanes-EtOAc) provided the title compound (1.5 g, 6.72 mmol, 97% yield). MS (DCl/NH3) m/z 223, 225 (M+H)+.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[C:11]([C:19]([F:22])([F:21])[F:20])=[CH:10][C:9]=1[NH:23][C:24](=[O:41])[CH2:25][C:26]([C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]2[CH:39]=[CH:38][N:37]=[C:36]([CH3:40])[CH:35]=2)[CH:29]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:40][C:36]1[CH:35]=[C:34]([C:30]2[CH:29]=[C:28]([C:26]3[CH2:25][C:24](=[O:41])[NH:23][C:9]4[CH:10]=[C:11]([C:19]([F:21])([F:22])[F:20])[C:12]([N:14]5[CH2:15][CH2:16][CH2:17][CH2:18]5)=[CH:13][C:8]=4[N:7]=3)[CH:33]=[CH:32][CH:31]=2)[CH:39]=[CH:38][N:37]=1
Reactant: Cc1cc(-c2cccc(C(=O)CC(=O)Nc3cc(C(F)(F)F)c(N4CCCC4)cc3NC(=O)OC(C)(C)C)c2)ccn1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1cc(-c2cccc(C3=Nc4cc(N5CCCC5)c(C(F)(F)F)cc4NC(=O)C3)c2)ccn1

Procedure:
The title compound was prepared from (2-{3-[3-(2-methyl-pyridin-4-yl)-phenyl]-3-oxo-propionylamino}-5-pyrrolidin-1-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M278) (0.34 g, 0.58 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (217 mg, 80%).
Reaction SMILES: [N:1](/[C:4](=[CH:9]\[C:10]1[C:11]([S:16][CH3:17])=[N:12][CH:13]=[CH:14][CH:15]=1)/[C:5]([O:7][CH3:8])=[O:6])=[N+]=[N-]>C1(C)C=C(C)C=C(C)C=1>[CH3:17][S:16][C:11]1[C:10]2[CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[NH:1][C:15]=2[CH:14]=[CH:13][N:12]=1
Reactant: COC(=O)/C(=C/c1cccnc1SC)N=[N+]=[N-]
Solvent: Cc1cc(C)cc(C)c1
Product: COC(=O)c1cc2c(SC)nccc2[nH]1
Temperature: 25 °C

Procedure:
A solution of methyl (2Z)-2-azido-3-[2-(methylthio)pyridin-3-yl]prop-2-enoate (1.00 g, 4.00 mmol) in mesitylene (50 mL) was heated at 160° C. for a period of 1 h. The reaction mixture was cooled to room temperature then to 0° C., the precipitate was filtered and washed with cold mesitylene to provide the title compound.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:10]([C:11]#[CH:12])=[CH:9][N:8]([C@@H:13]3[O:19][C@H:18]([CH2:20][OH:21])[C@@H:16]([OH:17])[C@H:14]3[OH:15])[C:4]=2[N:5]=[CH:6][N:7]=1.[Si]([N:26]=[N+:27]=[N-:28])(C)(C)C.CN(C=O)C>CO.[Cu]I>[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[N:26]=[N:27][NH:28][CH:12]=3)=[CH:9][N:8]([C@@H:13]3[O:19][C@H:18]([CH2:20][OH:21])[C@@H:16]([OH:17])[C@H:14]3[OH:15])[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: C#Cc1cn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c2ncnc(N)c12
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: [Cu]I
Solvent: CN(C)C=O
Solvent: CO
Product: Nc1ncnc2c1c(-c1c[nH]nn1)cn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Temperature: 100 °C
Reaction time: 24 h
Yield: 24 %

Procedure:
An argon purged mixture of 7-ethynyltubericidine 2o {compound from example 15} (200 mg, 0.69 mmol), CuI (6.5 mg, 0.03 mmol) and TMSN3 (150 μl, 1.15 mmol) in MeOH (0.2 ml)/DMF (1.8 ml) was stirred 100° C. for 24 h. Volatiles were evaporated under reduced pressure, the residue was twice co-evaporated with MeOH and rest was suspended in MeOH and filtered through celite. Filtrate was co-evaporated with silica and column chromatography on silica afforded title compound 2p as yellowish solid (55 mg, 24%). Compound was recrystallized from water. Mp 286-288° C. [α]D −70 (c 0.217, DMSO). 1H NMR (499.8 MHz, DMSO-d6, t=60° C.): 3.58 (dd, 1H, Jgem=11.9, J5′b,4′=4.2, H-5′b); 3.68 (dd, 1H, Jgem 11.9, J5′a,4′=3.9, H-5′a); 3.93 (ddd, 1H, J4′,5′=4.2, 3.9, J4′,3′=3.6, H-4′); 4.15 (dd, 1H, J3′,2′=5.3, J3′,4′=3.6, H-3′); 4.45 (dd, 1H, J2′,1′=6.0, J2′,3′=5.3, H-2′); 4.93, 5.04 and 5.17 (3×bs, 3×1H, OH-2′,3′,5′); 6.08 (d, 1H, J1′,2′=6.0, H-1′); 7.85 (bs, 2H, NH2); 7.91 (s, 1H, H-6); 8.09 (s, 1H, H-2); 8.23 (s, 1H, H-5-triazole). 13C NMR (125.7 MHz, DMSO-d6, t=60° C.): 61.83 (CH2-5′); 70.54 (CH-3′); 73.72 (CH-2′); 85.15 (CH-4′); 87.41 (CH-1′); 100.16 (C-4a); 105.83 (C-5); 120.80 (CH-6); 126.16 (CH-5-triazole); 141.51 (C-4-triazole); 151.04 (C-7a); 152.35 (CH-2); 158.04 (C-4). MS (ESI) m/z 334 (M+H), 356 (M+Na). HRMS (ESI) for C13H16N7O4 [M+H] calcd: 334.1258. found: 334.1258. Anal. Calcd for C13H15N7O4: C, 46.85; H, 4.54; N, 29.42. Found: C, 47.12; H, 4.82; N, 27.96.
Reaction SMILES: [NH2:1][CH:2]([CH3:15])[CH2:3][N:4]1[C:12]2[N:11]=[CH:10][NH:9][C:8]=2[C:7](=[O:13])[NH:6][C:5]1=[S:14].[CH3:16][O:17][C:18]1[CH:33]=[CH:32][CH:31]=[CH:30][C:19]=1[O:20][CH2:21][CH2:22][N:23]1[CH:27]=[CH:26][CH:25]=[C:24]1[CH:28]=O>>[CH3:16][O:17][C:18]1[CH:33]=[CH:32][CH:31]=[CH:30][C:19]=1[O:20][CH2:21][CH2:22][N:23]1[CH:27]=[CH:26][CH:25]=[C:24]1[CH2:28][NH:1][CH:2]([CH3:15])[CH2:3][N:4]1[C:12]2[N:11]=[CH:10][NH:9][C:8]=2[C:7](=[O:13])[NH:6][C:5]1=[S:14]
Reactant: CC(N)Cn1c(=S)[nH]c(=O)c2[nH]cnc21
Reactant: COc1ccccc1OCCn1cccc1C=O
Product: COc1ccccc1OCCn1cccc1CNC(C)Cn1c(=S)[nH]c(=O)c2[nH]cnc21
Yield: 12.9 %

Procedure:
The title compound was prepared in accordance with the general method described above using 3-(2-aminopropyl)-2-thioxo-1,2,3,7-tetrahydro-6H-purin-6-one (0.18 g, 0.54 mmol, obtained from Example 29(c)) and 1-[2-(2-methoxyphenoxy)ethyl]-1H-pyrrole-2-carbaldehyde (125.8 mg; 0.513 mmol), which after preparative HPLC generated 0.17 g of the product. Further purification was accomplished with a portion of this material (0.76 g) by trituration with water, which after drying in vacuo, generated 30.0 mg (29% yield) of the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH:13][CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[C:20](=O)([O-])[O-].[Cs+].[Cs+].CI>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]([N:13]([CH3:20])[CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]
Reactant: COC(=O)c1cc(Br)cc(NC2CCOCC2)c1C
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CI
Solvent: CC#N
Product: COC(=O)c1cc(Br)cc(N(C)C2CCOCC2)c1C
Temperature: 80 °C
Yield: 76.1 %

Procedure:
To a stirred solution of methyl 5-bromo-2-methyl-3-((tetrahydro-2H-pyran-4-yl)amino)benzoate (1.0 g, 3.15 mmol) in acetonitrile (15 mL), cesium carbonate (1.97 g, 6.10 mmol) and methyl iodide (2.15 g, 15.27 mmol) were added; resulting solution was heated at 80° C. for 20 h. The solution was cooled to room temperature, filtered, and the residue was washed with ethyl acetate. The filtrate was concentrated and the product purified by column chromatography to afford methyl 5-bromo-2-methyl-3-(methyl(tetrahydro-2H-pyran-4-yl)amino)benzoate (0.82 g, 80%).
Reaction SMILES: [Br:1][C:2]1[C:11]2[C:6]3=[C:7]([C:12]([O:14][C:15](=[O:16])[C:5]3=[CH:4][CH:3]=1)=O)[CH:8]=[CH:9][CH:10]=2.[CH:17]([C:20]1[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]([CH3:29])[CH3:28])[C:21]=1[NH2:22])([CH3:19])[CH3:18]>CN1CCCC1=O.C([O-])(=O)C.[Zn+2].C([O-])(=O)C>[Br:1][C:2]1[C:11]2[C:6]3=[C:7]([C:12](=[O:14])[N:22]([C:21]4[C:23]([CH:27]([CH3:28])[CH3:29])=[CH:24][CH:25]=[CH:26][C:20]=4[CH:17]([CH3:19])[CH3:18])[C:15](=[O:16])[C:5]3=[CH:4][CH:3]=1)[CH:8]=[CH:9][CH:10]=2
Reactant: CC(C)c1cccc(C(C)C)c1N
Reactant: O=C1OC(=O)c2ccc(Br)c3cccc1c23
Agent: CC(=O)[O-]
Agent: [Zn+2]
Solvent: CN1CCCC1=O
Product: CC(C)c1cccc(C(C)C)c1N1C(=O)c2cccc3c(Br)ccc(c23)C1=O
Yield: 60.1 %

Procedure:
27.7 g of 4-bromonaphthalene-1,8-dicarboxylic anhydride, 19.0 g of 2,6-diisopropylaniline and 9.2 g of anhydrous zinc acetate in 65 ml of N-methylpyrrolidone were heated at 200° C. for 3 hours. After cooling, the precipitate formed was filtered off, washed and dried to give 26.2 g of 4-bromo-N-(2,6-diisopropylphenyl)naphthalene-1,8-dicarboximide having a melting point of 277° C.