Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:33])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21](Br)[N:22]=3)[N:17]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2].[F:34][C:35]([F:46])([F:45])[C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1.C(=O)([O-])[O-].[K+].[K+].C(=O)(O)[O-].[Na+]>O1CCOCC1.O.[Cl-].[Cl-].C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd+2].C(OCC)(=O)C>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:33])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:39]4[CH:40]=[CH:41][C:36]([C:35]([F:46])([F:45])[F:34])=[CH:37][CH:38]=4)[N:22]=3)[N:17]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2]
Reactant: C[Si](C)(C)CCOCn1cc(C(=O)N[C@@H](C(=O)N2CC(C#N)C2)C2CC2)c2nc(Br)cnc21
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Agent: [Fe+2]
Agent: [Pd+2]
Agent: O=C([O-])O
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: C[Si](C)(C)CCOCn1cc(C(=O)N[C@@H](C(=O)N2CC(C#N)C2)C2CC2)c2nc(-c3ccc(C(F)(F)F)cc3)cnc21
Temperature: 150 °C
Yield: 66.8 %

Procedure:
In a microwave vial, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (80 mg, 0.15 mmol) was dissolved in 1.5 mL of 1,4-dioxane and 0.35 mL of water. The solution was purged with Ar gas then 4-(trifluoromethyl)phenylboronic acid (31 mg, 0.165 mmol), palladium bis-(diphenylphosphino)ferrocene dichloride, dichloromethane complex (6.1 mg, 0.008 mmol) and potassium carbonate (62 mg, 0.45 mmol) were added. The reaction vessel was sealed and heated in a microwave reactor at 150° C. for 30 min. The reaction was cooled and water and ethyl acetate were added. The mixture was poured into ethyl acetate and sodium bicarbonate solution. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) to give 60 mg (66%) of 2-(4-trifluoromethylphenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide.
Reaction SMILES: [CH3:1][C:2]1([CH3:27])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([CH:14]([OH:17])[C:15]#[CH:16])[CH:5]=[C:4]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=3)[C:3]1=2.I[C:29]1[CH:37]=[CH:36][C:32]([C:33]([OH:35])=[O:34])=[CH:31][CH:30]=1>[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:17][CH:14]([C:6]1[CH:5]=[C:4]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)[C:3]2[C:2]([CH3:27])([CH3:1])[CH2:11][CH2:10][C:9]([CH3:12])([CH3:13])[C:8]=2[CH:7]=1)[C:15]#[C:16][C:29]1[CH:37]=[CH:36][C:32]([C:33]([OH:35])=[O:34])=[CH:31][CH:30]=1
Reactant: C#CC(O)c1cc(OCc2ccc(C)cc2)c2c(c1)C(C)(C)CCC2(C)C
Reactant: O=C(O)c1ccc(I)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: I[Cu]I
Product: Cc1ccc(COc2cc(C(O)C#Cc3ccc(C(=O)O)cc3)cc3c2C(C)(C)CCC3(C)C)cc1
Yield: 67 %

Procedure:
In a manner similar to that of Example 1g, by reacting 1.22 g (3.3 mmol) of 1-[5,5,8,8-tetramethyl-4-(4-methylbenzyloxy)-5,6,7,8-tetrahydro-2-naphthyl]prop-2-yn-1-ol with 680 mg (2.8 mmol) of 4-iodobenzoic acid in the presence of 27 mg of copper iodide and 49 mg of bis(triphenylphosphine)dichloropalladium. The desired product is obtained in the form of beige-colored crystals (m=900 mg; yield=67%; m.p.=219° C.).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH2:6][C:7]3[CH:11]=[CH:10][S:9][C:8]=3[C:2]1=2.[OH-].[K+].[I-].[Na+].[CH2:16](Br)[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>CS(C)=O.O>[CH2:16]([C:6]1([CH2:7][CH2:8][CH2:2][CH2:3][CH2:4][CH3:5])[C:7]2[CH:11]=[CH:10][S:9][C:8]=2[C:2]2[S:1][CH:5]=[CH:4][C:3]1=2)[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCCBr
Reactant: c1cc2c(s1)-c1sccc1C2
Agent: [I-]
Agent: [K+]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCCCCCC1(CCCCCC)c2ccsc2-c2sccc21
Temperature: 25 °C
Reaction time: 17 h

Procedure:
4H-Cyclopenta[2,1-b;3,4-b′]dithiophene (1.5 g, 0.00843 mol) was dissolved in DMSO (50 mL). The solution was purged with nitrogen, and grounded KOH (1.89 g, 0.0337 mol) and sodium iodide (50 mg) were added, followed by hexyl bromide (3.02 g, 0.0169 mol). The reaction was stirred for 17 h under nitrogen at room temperature. Water was added and the reaction was extracted with t-butyl-methyl ether. The organic layer was separated and dried over magnesium sulfate. Solvent was removed under vacuum and the residue was purified by chromatography using hexanes as eluent. Fractions containing pure 4,4-dixeyl-4H-cyclopenta[2,1-b;3,4-b′]dithiophene product were combined and the solvents evaporated. The product was obtained as a colorless oil. Yield: 2.36 g (81%).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][C:9]([CH3:16])=[CH:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H]>C(OCC)(=O)C.[C].[Pd]>[C:1]1([CH2:7][CH2:8][CH:9]([CH3:16])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [H][H]
Reactant: CCOC(=O)C=C(C)CCc1ccccc1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCOC(=O)CC(C)CCc1ccccc1

Procedure:
(1.00 g, 4.58 mmol) obtained in the above item (a) was dissolved in ethyl acetate (10 ml), and the resulting solution was subjected to hydrogen catalytic reduction by using 10% palladium-carbon (0.2 g) as a catalyst. The catalyst was filtered off and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/30) to obtain 0.82 g of ethyl 5-phenyl-3-methylpentanoate.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2OC(=O)[S:11][N:10]=2)=[CH:5][CH:4]=1)[CH3:2].[F:15][C:16]([F:28])([C:24]([F:27])([F:26])[F:25])[C:17]#[C:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].ClC1C=CC=C(Cl)C=1>>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:17]([C:16]([F:28])([F:15])[C:24]([F:25])([F:26])[F:27])[S:11][N:10]=2)=[CH:5][CH:4]=1)[CH3:2]
Reactant: CCc1ccc(-c2nsc(=O)o2)cc1
Reactant: CCOC(=O)C#CC(F)(F)C(F)(F)F
Solvent: Clc1cccc(Cl)c1
Product: CCOC(=O)c1c(-c2ccc(CC)cc2)nsc1C(F)(F)C(F)(F)F
Temperature: 150 °C
Reaction time: 16 h
Yield: 67.5 %

Procedure:
Into a 10-mL sealed tube, was placed 5-(4-ethylphenyl)-2H-1,3,4-oxathiazol-2-one (155 mg, 0.75 mmol, 1.00 equiv), ethyl 4,4,5,5,5-pentafluoropent-2-ynoate (250 mg, 1.16 mmol, 1.55 equiv), 1,3-dichlorobenzene (3 mL). The resulting solution was stirred for 16 h at 150° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:19). The resulted in a mixture of the product 0.192 g as the yellow oil. Mass spectrum (ESI, m/z): Calcd. for C16H14F5NO2S, 380.3 (M+H). found 380.3.
Reaction SMILES: Cl.[Cl:2][C:3]1[C:4]([CH2:9][NH2:10])=[N:5][CH:6]=[CH:7][N:8]=1.[CH3:11][N:12]1[C:16](=[O:17])[CH2:15][CH:14]([C:18](O)=[O:19])[CH2:13]1.C(N(CC)C(C)C)(C)C.C(N=C=NCCCN(C)C)C.Cl.ON1C2N=CC=CC=2N=N1>ClCCl.ClCCl.CO>[Cl:2][C:3]1[C:4]([CH2:9][NH:10][C:18]([CH:14]2[CH2:15][C:16](=[O:17])[N:12]([CH3:11])[CH2:13]2)=[O:19])=[N:5][CH:6]=[CH:7][N:8]=1
Reactant: NCc1nccnc1Cl
Reactant: CN1CC(C(=O)O)CC1=O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CO
Product: CN1CC(C(=O)NCc2nccnc2Cl)CC1=O
Temperature: 0 °C
Reaction time: 8 h
Yield: 66 %

Procedure:
(3-Chloropyrazin-2-yl)methanamine hydrochloride (content 77%, 1.634 g, 6.99 mmol) and 1-methyl-5-oxopyrrolidine-3-carboxylic acid (1.000 g, 6.99 mmol) were suspended in dichloromethane (20 ml) and the reaction mixture was cooled to 0° C. under an argon atmosphere. N,N-diisopropylethylamine (3.05 ml, 17.48 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) hydrochloride (1.474 g, 7.69 mmol) and 1-hydroxy-7-azabenzotriazole (0.476 g, 3.50 mmol) were added and the reaction mixture was stirred at room temperature overnight. Reaction was worked up by evaporting the solvents and a dark brown oil was obtained. This crude product was submitted to column chromatography (silica gel; dichloromethane/methanol 96/4) to yield impure material that was further purified by column chromatography (silica gel; dichloromethane/methanol 99/1) to give N-((3-chloropyrazin-2-yl)methyl)-1-methyl-5-oxopyrrolidine-3-carboxamide (1.24 g).
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH:9]1[CH2:14][C:15]([OH:17])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH2:18]([N:25]1[CH2:31][CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:18]([N:25]1[CH2:31][CH2:30][CH2:29][N:28]([C:15](=[O:17])[CH2:14][CH:9]2[CH2:10][O:11][CH2:12][CH2:13][N:8]2[C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:27][CH2:26]1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: c1ccc(CN2CCCNCC2)cc1
Reactant: CC(C)(C)OC(=O)N1CCOCC1CC(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CCOCC1CC(=O)N1CCCN(Cc2ccccc2)CC1
Temperature: 0 °C
Reaction time: 2 h
Yield: 85.7 %

Procedure:
4-N-Boc-morpholine-3-acetic acid (500 mg, 2.04 mmol) and benzyl homopiperazine (388 mg, 2.04 mmol) were dissolved in DMF (20 mL) and cooled to 0° C. DIPEA (553 mg, 4.28 mmol) and HBTU (773 mg, 2.04 mmol) were added and the reaction mixture was stirred for 2 h. The solvents were removed in vacuo and the residue was partitioned between DCM (100 mL) and water (50 mL). The organic fraction was washed with 1 M aq Na2CO3 (25 mL), brine (25 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by reverse phase column chromatography to give the title compound (730 mg, 86%) as a light yellow gum. LCMS (ES+): 418.4 [MH]+.
Reaction SMILES: O1CCCCC1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]3[N:20]=[CH:19][N:18](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:17]=3)=[CH:13][CH:14]=2)[C:9]([C:40]2[CH:41]=[C:42]([CH:47]=[CH:48][CH:49]=2)[C:43](OC)=[O:44])=[N:8]1.[OH-].[Li+].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH3:74][O:75][CH2:76][CH2:77][NH2:78]>O1CCCC1.O.C(OCC)(=O)C.Cl.O1CCOCC1>[NH:18]1[CH:19]=[N:20][C:16]([C:12]2[CH:11]=[C:10]3[C:15](=[CH:14][CH:13]=2)[NH:7][N:8]=[C:9]3[C:40]2[CH:41]=[C:42]([C:43]([NH:78][CH2:77][CH2:76][O:75][CH3:74])=[O:44])[CH:47]=[CH:48][CH:49]=2)=[N:17]1
Reactant: COCCN
Reactant: COC(=O)c1cccc(-c2nn(C3CCCCO3)c3ccc(-c4ncn(C(c5ccccc5)(c5ccccc5)c5ccccc5)n4)cc23)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Solvent: C1CCOC1
Product: COCCNC(=O)c1cccc(-c2n[nH]c3ccc(-c4nc[nH]n4)cc23)c1
Temperature: 50 °C
Reaction time: 8 h
Yield: 9 %

Procedure:
The title compound was prepared by dissolving methyl 3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazol-3-yl}benzoate (0.403 g, 0.62 mmol) and lithium hydroxide (0.052 g, 2.17 mmol) in tetrahydrofuran (3 mL) and water (2 mL). This reaction mixture was heated to 50° C. reacted overnight. The reaction was monitored by thin layer cluomatography (100% ethyl acetate). To this reaction, 1-hydroxybenzotriazole (0.256 g, 1.89 mmol), 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.369 g, 1.92 mmol), and 2-methoxyethylamine (0.16 mL, 1.87 mmol) were added and allowed to stir overnight at room temperature. The reaction was then diluted with ethyl acetate and washed with a 1:1 solution of sodium chloride (saturated aqueous): sodium bicarbonate (saturated aqueous) and partitioned. The aqueous layer was extracted with ethyl acetate (2×), and the organic layers were combined, dried with sodium sulfate, filtered, and condensed. The crude solid was subsequently taken up in 4 N hydrochloride solution in dioxane (8 mL), and stirred at 50° C. overnight. The reaction was quenched by adding the mixture dropwise to sodium bicarbonate (saturated aqueous) (100 mL). The mixture was then extracted with ethyl acetate (3×), and the organics combined, dried with sodium sulfate, filtered, and condensed. The compound was purified by preparative HPLC (10–80% acetonitrile in H2O, 20 min.) (0.019 g, 9% yield): 1H NMR (CD3OD) δ 8.74 (s, 1H), 8.41 (t, 1H), 8.25 (br s, 1H), 8.15 (dt, 1H), 8.07 (d, 1H), 7.86 (dt, 1H), 7.63 (dd, 2H), 3.58 (s, 4H), 3.35 (s, 3H); ES-MS (m/z) 363 [M+1]+.
Reaction SMILES: [C:1]1([C@H:7]2[C@@H:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:10](C(OC(C)(C)C)=O)[C:9](SC)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH3:27]>C(O)CO>[C:12]1([C@H:11]2[C@@H:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[NH:8][C:9]([NH2:10])=[N:27]2)[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CSC1=N[C@@H](c2ccccc2)[C@@H](c2ccccc2)N1C(=O)OC(C)(C)C
Reactant: N
Solvent: OCCO
Product: NC1=N[C@@H](c2ccccc2)[C@@H](c2ccccc2)N1
Temperature: 115 °C

Procedure:
A solution of intermediate 59 (1.0 g, 2.71 mmol) in ethylene glycol (10 mL) is saturated with ammonia and is heated in a pressure tube at 115° C. for 3 h. The reaction mixture is cooled to rt, and saturated with ammonia, and heated is heated at 115° C. overnight. The reaction mixture is cooled to rt, and the product is precipitated by the addition of addition of water to give 226 mg of the product 122. 1H NMR (DMSO-d6) δ 7.10-6.80 (m, 10 H), 6.40 (bs, 3 H), 5.10 (s, 2 H); LC/MS: 2.89 min, m/z 238 (M++1).
Reaction SMILES: [C:1]([O:9][CH2:10][C@@H:11]1[C:15]([O:17][C:18](=[O:20])[CH3:19])([CH3:16])[C@:14]([F:22])([CH3:21])[CH:13]([N:23]2[CH:31]=[N:30][C:29]3[C:24]2=[N:25][CH:26]=[N:27][C:28]=3Cl)[O:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:33][O:34][C:35]1[CH:36]=[C:37]([CH:40]=[CH:41][CH:42]=1)[CH2:38][NH2:39].O>C(O)C>[C:1]([O:9][CH2:10][C@@H:11]1[C:15]([O:17][C:18](=[O:20])[CH3:19])([CH3:16])[C@:14]([F:22])([CH3:21])[CH:13]([N:23]2[CH:31]=[N:30][C:29]3[C:24]2=[N:25][CH:26]=[N:27][C:28]=3[NH:39][CH2:38][C:37]2[CH:40]=[CH:41][CH:42]=[C:35]([O:34][CH3:33])[CH:36]=2)[O:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1cccc(CN)c1
Reactant: CC(=O)OC1(C)[C@@H](COC(=O)c2ccccc2)OC(n2cnc3c(Cl)ncnc32)[C@]1(C)F
Solvent: O
Solvent: CCO
Product: COc1cccc(CNc2ncnc3c2ncn3C2O[C@H](COC(=O)c3ccccc3)C(C)(OC(C)=O)[C@@]2(C)F)c1
Yield: 20.6 %

Procedure:
To a stirred solution of ((2R,4R)-3-acetoxy-5-(6-chloro-9H-purin-9-yl)-4-fluoro-3,4-dimethyl-tetrahydrofuran-2-yl)methyl benzoate (about 0.4 g, 0.86 mmol) in ethanol (about 5 ml) was added 3-methoxybenzylamine (about 1.34 ml, 10.38 mmol) and refluxed for about 20 minutes. Completion of the reaction monitored by thin-layer chromatography, water added to the reaction mixture and the aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine and dried over sodium sulphate. Concentration under reduced pressure and purification by silica gel column chromatography using 40% ethyl acetate in hexane as eluent furnished title compound (0.10 g) as a colorless gummy mass. Yield: 21%; 1H NMR (300 MHz, CDCl3): δ 8.42 (s, 1H), 8.03-7.98 (m, 3H), 7.60-7.42 (m, 3H), 6.99-6.94 (m, 2H), 6.84-6.81 (m, 2H), 6.55 (d, 1H, J=23.1 Hz), 6.31 (bs, 1H), 4.84-4.78 (m, 3H), 4.49-4.45 (m, 1H), 3.79 (s, 3H), 2.18 (s, 3H), 1.89 (d, 3H, J=2.4 Hz), 1.47 (d, 3H, J=23.1 Hz); Mass: [M+1]+ 564 (100%), [M+Na]+ 586 (40%); IR cm−: 3430, 2928, 2381, 2170, 1734, 1624, 1461, 1053, 950, 713; HPLC: 90.1%.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=O.[N+:12]([CH:15]=[C:16](SC)[S:17]([CH3:19])=O)([O-:14])=[O:13].C[O-].[Na+]>C(O)C.CO>[CH3:19][S:17][C:16]1[NH:2][CH:3]=[C:4]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:15]=1[N+:12]([O-:14])=[O:13]
Reactant: NCC(=O)c1ccccc1
Reactant: CSC(=C[N+](=O)[O-])S(C)=O
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: CCO
Product: CSc1[nH]cc(-c2ccccc2)c1[N+](=O)[O-]
Reaction time: 0.17 h
Yield: 60.4 %

Procedure:
α-Aminoacetophenone hydrochloride (6.87 g, 0.040 mol) was mixed with 1-nitro-2-methylthio-2-methylsulphinylethylene (7.25 g, 0.040 mol) in 300 ml dry ethanol and warmed at 60°. Sodium methoxide (from 0.92 g sodium, 0.080 g atom) in methanol (25 ml) was added dropwise, with stirring, over about 10 minutes. After addition, the mixture was stirred at 60° for one hour, and then filtered to give 2-methylthio-3-nitro-4-phenylpyrrole 5.66 g, m.p. 259°-261° dec.
Reaction SMILES: Br[C:2]1[C:10]2[C:9]([NH:11][C@H:12]([C:14]3[N:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:18](=[O:26])[C:17]4=[C:27]([CH3:30])[CH:28]=[CH:29][N:16]4[N:15]=3)[CH3:13])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:3]=1.[CH3:39][O:40][C:41]1[CH:46]=[CH:45][C:44]([S:47]([NH:50][C:51]2[CH:56]=[CH:55][CH:54]=[C:53](B3OC(C)(C)C(C)(C)O3)[CH:52]=2)(=[O:49])=[O:48])=[CH:43][CH:42]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[CH3:39][O:40][C:41]1[CH:42]=[CH:43][C:44]([S:47]([NH:50][C:51]2[CH:52]=[CH:53][CH:54]=[C:55]([C:2]3[C:10]4[C:9]([NH:11][C@H:12]([C:14]5[N:19]([C:20]6[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=6)[C:18](=[O:26])[C:17]6=[C:27]([CH3:30])[CH:28]=[CH:29][N:16]6[N:15]=5)[CH3:13])=[N:8][CH:7]=[N:6][C:5]=4[N:4]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:3]=3)[CH:56]=2)(=[O:49])=[O:48])=[CH:45][CH:46]=1
Reactant: COc1ccc(S(=O)(=O)Nc2cccc(B3OC(C)(C)C(C)(C)O3)c2)cc1
Reactant: Cc1ccn2nc([C@H](C)Nc3ncnc4c3c(Br)cn4COCC[Si](C)(C)C)n(-c3ccccc3)c(=O)c12
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: COc1ccc(S(=O)(=O)Nc2cccc(-c3cn(COCC[Si](C)(C)C)c4ncnc(N[C@@H](C)c5nn6ccc(C)c6c(=O)n5-c5ccccc5)c34)c2)cc1
Yield: 81 %

Procedure:
(S)-2-(1-((5-Bromo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (75 mg, 0.13 mmol) was treated with 4-methoxy-N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzenesulfonamide (236 mg, 0.61 mmol), sodium carbonate (64 mg, 0.61 mmols) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (18 mg, 0.03 mmol) in 1,2-dimethoxyethane (1.2 ml) and water (0.30 ml) according to the method described in Preparation 62. The residue was purified using SP1® Purification System (0% to 35%, hexane-ethyl acetate) to give 82 mg (81% yield, 73% purity) of the title compound.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Cl.[NH2:8][OH:9].[C:10]([C@@H:12]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:13][CH:14]1[CH2:16][CH2:15]1)#[N:11]>O.C(O)C>[NH2:11]/[C:10](=[N:8]\[OH:9])/[C@@H:12]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:23])[CH3:22])[CH2:13][CH:14]1[CH2:16][CH2:15]1
Reactant: CC(C)(C)OC(=O)N[C@H](C#N)CC1CC1
Reactant: NO
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCO
Product: CC(C)(C)OC(=O)N[C@@H](CC1CC1)/C(N)=N/O
Reaction time: 72 h
Yield: 92.7 %

Procedure:
Potassium carbonate (2.18 g, 16 mmol) was dissolved in water (8 mL) and hydroxylamine hydrochloride (1.1 g, 16 mmol) was added. A solution of (S)-tert-butyl 1-cyano-2-cyclopropylethylcarbamate (3.31 g, 16 mmol) in ethanol (24 mL) was added thereto and the resulting reaction mixture was stirred for 72 h. After evaporation of solvents, the residue was dissolved with ethyl acetate (20 mL) and then filtered. The filtrate was concentrated to yield crude product as yellow solid (3.61 g, 94%); MS (EI): m/e 244.2 [M+H]+.
Reaction SMILES: C(O)C.[CH3:4][C:5]([C:7]1[CH:8]=[CH:9][C:10]([OH:14])=[CH:11][C:12]=1[OH:13])=O>O>[CH2:5]([C:7]1[CH:8]=[CH:9][C:10]([OH:14])=[CH:11][C:12]=1[OH:13])[CH3:4]
Reactant: CC(=O)c1ccc(O)cc1O
Solvent: CCO
Solvent: O
Product: CCc1ccc(O)cc1O

Procedure:
In a three necked round bottom flask (equipped with a condenser, additional funnel and mechanical stirrer) was added the catalyst or combination of the catalysts. 100 ml of a mixture of 50:50 ethanol:water was added and the reaction was heated to reflux conditions. 2,4-dihydroxy acetophenone in 100 ml of water:ethanol mixture with or without acids was placed in the additional funnel and was added to the mixture (dropwise-2-4 hrs). The reaction was filtered through a milipore filter and concentrated in vacuo to give a solid. This solid was crystalized from 1,2-dichloroethane to give 4-ethyl resorcinol. The unreacted 2,4-dihydroxy acetophenone is recovered from the media and recycled. The structure of 4-ethyl resorcinol and 2,4-dihydroxy acetophenone were characterized by NMR, Gas Chromatography, IR and Mass spectroscopy
Reaction SMILES: [F:1][C:2]([CH2:9][CH:10]=[CH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH:16]=[CH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:3][CH2:4][CH2:5][CH2:6][CH2:7][OH:8].CC(C)=[O:25].OS(O)(=O)=O.O=[Cr](=O)=O.C(O)(C)C>CC(C)=O>[F:1][C:2]([CH2:9][CH:10]=[CH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH:16]=[CH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:3][CH2:4][CH2:5][CH2:6][C:7]([OH:25])=[O:8]
Reactant: CC(C)=O
Reactant: CCCCCC=CCCCCC=CCC(F)=CCCCCO
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)O
Product: CCCCCC=CCCCCC=CCC(F)=CCCCC(=O)O
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a solution of the alcohol prepared in 2K (21 mg, 0.067 mmoles) in acetone (2 ml) cooled to 0° C. was added dropwise 2.67M Jones reagent until the organe color was stable. The mixture was stirred 15 min at 0° C. The excess of Jones reagent was reacted with isopropanol. The acetone was evaporated under reduced pressure without heating. The residue was taken with water and extracted three times with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to leave an oil (20 mg). Flash chromatography on silicagel and elution with a 25:75 mixture of ethyl acetate and hexane gave pure title acid (14 mg, 64%). NMR (H1, CDCl3, 360 MHz): 0.89 (t, JHH ~7 Hz, 3), 1.21 to 1.45 (m, 10), 1.51 (quint, JHH ~7 Hz, 2), 1.98 to 2.12 (m, 8), 2.37 (t, JHH ~7 Hz, 2), 2.96 (dd, JHF =23 Hz, JHH =6.8 Hz, 2), 4.98 (dt, JHH =21.2Hz, JHH =7.9 Hz, ]), 5.3 to 5.5 (m, 4).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][Cl:5].[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1.[OH-].[K+]>CN(C=O)C>[Cl:5][CH2:4][CH2:3][CH2:2][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1
Reactant: ClCCCBr
Reactant: c1ccc2[nH]ccc2c1
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: ClCCCn1ccc2ccccc21
Temperature: 20 °C
Reaction time: 15 h
Yield: 70.6 %

Procedure:
To a solution of 1-bromo-3-chloropropane (2.00 g, 12.7 mmol) in DMF (7.0 mL) was added indole (500 mg, 4.24 mmol) followed by powdered KOH (262 mg, 4.66 mmol) at 20° C. The reaction mixture was then stirred for 15 h at 20° C. The reaction was quenched by addition of H2O and the product was extracted with Et2O. The organic solution was washed with H2O and brine, dried over MgSO4, filtered and concentrated in vacuo. 1-(3-Chloro-1-propyl)indole (580 mg, 71%) was isolated by flash chromatography on a silica gel column by elution with EtOAc/Hexanes a pale yellow oil. 1H NMR (CDCl3, 300 MHz) δ2.28 (qu, 2H, J=6.3 Hz), 3.46 (t, 2H, J=6.2 Hz), 4.36 (t, 2H, J=6.6 Hz), 6.51 (d, 1H, J=3.3 Hz), 7.09-7.18 (m, 2H), 7.20-7.25 (m, 1H), 7.38 (d, 1H, J=8.5 Hz), 7.64 (d, 1H, J=7.7 Hz) ppm.