Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC(C)([O-])C.[K+].CS(C)=O.Br[CH:12]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][CH:16]=1)[CH2:13]Br>C(O)(C)(C)C>[CH:13]#[C:12][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][CH:16]=1
Reactant: BrCC(Br)c1ccc(-c2ccccc2)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CC(C)(C)O
Product: C#Cc1ccc(-c2ccccc2)cc1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 90.5 %

Procedure:
To a solution of 26 g of potassium t-butoxide in 400 ml of a 1:1 mixture (v/v) of dimethyl sulfoxide and t-butanol at 10°-15° was added with stirring a solution of 39 g of 4-(1,2-dibromoethyl)biphenyl in 400 ml of the same solvent mixture. After stirring for 20 minutes, the reaction mixture was poured into ice-water. The resulting mixture was extracted with diethyl ether. The diethyl ether then was washed successively with water, five percent aqueous sodium bicarbonate, and water, and dried over anhydrous sodium sulfate. The diethyl ether was distilled under reduced pressure and the solid residue crystallized from aqueous ethanol to give 18.5 g of crude 4-biphenylacetylene, mp 79°-81°. Two recrystallizations from hexane gave pure 4-biphenylacetylene, mp 82°-85°. The following elemental analysis was obtained:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]2[CH2:16][CH:15]=[CH:14][CH2:13][C:12]2=[O:17])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[H][H]>[Pd].C(O)C>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C:12]2=[O:17])[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1
Reactant: [H][H]
Reactant: COc1cc(OC)cc(C2CC=CCC2=O)c1
Agent: [Pd]
Solvent: CCO
Product: COc1cc(OC)cc(C2CCCCC2=O)c1

Procedure:
A mixture of 23.6 g. 2-(3,5-dimethoxyphenyl)-4-cyclohexen-1-one, 300 ml. ethanol and 3 g. 10% Pd/C catalyst was hydrogenated at 40 psi (2.8 kg./cm.2). After hydrogen uptake ceased, the mixture was filtered, the filtrate evaporated in vacuo and the residue recrystallized from isopropyl ether to obtain 17 g. of product, M.P. 61°-62° C., lit. [J. Org. Chem., 27, 376 (1962)], M.P. 62.5°-63° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH2:6][NH:7][C:8](=[O:17])[C:9]1[CH:14]=[CH:13][C:12]([CH:15]=O)=[CH:11][CH:10]=1)[CH3:2].[CH:19]1([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.C(O)(=O)C.C([BH3-])#N.[Na+]>C(O)C>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH2:6][NH:7][C:8](=[O:17])[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:29][C:28]2[CH:30]=[CH:31][C:25]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[CH:26][CH:27]=2)=[CH:11][CH:10]=1)[CH3:2]
Reactant: Nc1ccc(C2CCCCC2)cc1
Reactant: CCOC(=O)CCNC(=O)c1ccc(C=O)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCO
Product: CCOC(=O)CCNC(=O)c1ccc(CNc2ccc(C3CCCCC3)cc2)cc1
Reaction time: 0.17 h
Yield: 80.4 %

Procedure:
To a well stirred solution of 3-(4-formylbenzoylamino)propionic acid ethyl ester (13.8 g, 55.3 mmol) in ethanol (150 mL) was added a solution of 4-cyclohexylaniline (9.70 g, 55.3 mmol) in ethanol (75 mL). The mixture was heated to reflux for 30 minutes, and then acetic acid (50 mL) and sodium cyanoborohydride (3.50 g, 55.5 mmol) were added. After 10 minutes of additional heating, the mixture was cooled on an ice-bath. The solid precipitate was collected by filtration, washed several times with cold water and dried in a vacuum oven overnight to afford 18.16 g (80%) of 3-{4-[(4-cyclohexylphenylamino)methyl]benzoylamino}propionic acid ethyl ester.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[OH:11].O.[C:13](OC(=O)C)(=[O:15])[CH3:14]>>[C:13]([O:11][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:2]=1[Cl:1])[C:6]([OH:8])=[O:7])(=[O:15])[CH3:14]
Reactant: O=C(O)c1ccc(Cl)c(O)c1
Reactant: CC(=O)OC(C)=O
Solvent: O
Product: CC(=O)Oc1cc(C(=O)O)ccc1Cl

Procedure:
4-Chloro-3-hydroxybenzoic acid (1.00 g, 5.80 mmol) was suspended in acetic anhydride (11 ml) and heated to reflux for 3 h. After cooling, water (11 ml) was added and the mixture was refluxed again for 1 h. After cooling, crystals formed overnight which were collected by suction filtration and dried in vacuo to yield the title compound (630 mg).
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[CH:18]([N:22]1C(=O)C2C(=CC=CC=2)C1=O)[CH:19]([CH3:21])[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.NN.O>CCO>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[CH:18]([NH2:22])[CH:19]([CH3:20])[CH3:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)C(c1cc2cc(Cl)ccc2n1Cc1ccccc1)N1C(=O)c2ccccc2C1=O
Agent: NN
Solvent: CCO
Solvent: O
Product: CC(C)C(N)c1cc2cc(Cl)ccc2n1Cc1ccccc1
Temperature: 80 °C
Reaction time: 8 h
Yield: 41.6 %

Procedure:
To a solution of product of step 7 (0.4 mmol) in 10 mL of EtOH, was added hydrazine (4 mmol) at 0° C. The mixture was stirred at 80° C. overnight. The solution was poured into water, and extracted with EtOAc (×3). The organic layers were combined, washed with 10% NaOH, H2O (×3), brine (×3), dried (Na2SO4), filtered, and the filtrate was concentrated. The material was purified by flash chromatography (20% EtOAc:hexane) to yield 52 mg of 1-(1-benzyl-5-chloro-1H-indole-2-yl)-2-methylpropan-1-amine.
Reaction SMILES: [I-:1].[CH3:2][N:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[CH2:8][N+](C)(C)C.[C:13]1([P:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(#N)C>[I-:1].[CH3:2][N:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[CH2:8][P+:19]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: Cn1cccc1C[N+](C)(C)C
Agent: [I-]
Solvent: CC#N
Product: Cn1cccc1C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Yield: 80.8 %

Procedure:
Subsequently, to a suspension of (1-methylpyrrol-2-yl)methyl trimethylammonium iodide (55.34 g, 197.5 mmol) obtained above in acetonitrile (400 ml) was added triphenylphosphine (62.20 g, 237.1 mmol) with stirring, and the resulting mixture was stirred at 80° C. for 10 hours. After cooling, the reaction mixture was concentrated to about one-half of its initial volume, to which was added ethyl acetate (200 ml). The crystals precipitated were collected by filtration, washed with ethyl acetate and dried in vacuo to afford the title compound (77.14 g, yield: 81%).
Reaction SMILES: [Br:1][C:2]1[C:6]2=[CH:7][NH:8][C:9](=[O:11])[CH:10]=[C:5]2[S:4][CH:3]=1.[H-].[Na+].[CH3:14]I.O>CN(C=O)C>[Br:1][C:2]1[C:6]2=[CH:7][N:8]([CH3:14])[C:9](=[O:11])[CH:10]=[C:5]2[S:4][CH:3]=1
Reactant: CI
Reactant: O=c1cc2scc(Br)c2c[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cn1cc2c(Br)csc2cc1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 48.2 %

Procedure:
To a suspension of 3-bromothieno[3,2-c]pyridin-6(5H)-one (235 mg, 1.02 mmol) in DMF (3.9 mL) was added sodium hydride (25.7 mg, 1.07 mmol). The mixture stirred 1 h at room temperature, and then methyl iodide (69.9 μL, 1.12 mmol) was added. The reaction stirred a further 1 h at room temperature and then was poured into water (100 mL). The mixture was extracted with dichloromethane (3×50 mL). The combined organic fractions were washed with water (3×50 mL), dried over sodium sulfate, filtered, and concentrated. Trituration with diethyl ether (˜5 mL) and filtration to collect the resultant solid afforded 120 mg (48%) of the title compound as a tan solid. 1H NMR (400 MHz, CDCl3): δ 7.84 (s, 1 H), 6.91 (s, 1 H), 6.89 (d, J=0.8 Hz, 1 H), 3.75 (s, 3 H); MS (ESI): 244.03, 245.98 [M+H]+; HPLC tR=2.76 min (ZQ3, polar—4 min).
Reaction SMILES: [Si]([O:8][CH2:9][CH2:10][O:11][C:12]1[C:13]([F:42])=[C:14]([CH:20]([NH:33][C:34]2[CH:41]=[CH:40][C:37]([C:38]#[N:39])=[CH:36][CH:35]=2)[C:21]2[NH:25][C:24](=[O:26])[N:23]([C:27]3[N:32]=[CH:31][CH:30]=[CH:29][N:28]=3)[N:22]=2)[CH:15]=[C:16]([O:18][CH3:19])[CH:17]=1)(C(C)(C)C)(C)C>C(O)(=O)C.O>[F:42][C:13]1[C:12]([O:11][CH2:10][CH2:9][OH:8])=[CH:17][C:16]([O:18][CH3:19])=[CH:15][C:14]=1[CH:20]([NH:33][C:34]1[CH:35]=[CH:36][C:37]([C:38]#[N:39])=[CH:40][CH:41]=1)[C:21]1[NH:25][C:24](=[O:26])[N:23]([C:27]2[N:28]=[CH:29][CH:30]=[CH:31][N:32]=2)[N:22]=1
Reactant: COc1cc(OCCO[Si](C)(C)C(C)(C)C)c(F)c(C(Nc2ccc(C#N)cc2)c2nn(-c3ncccn3)c(=O)[nH]2)c1
Solvent: O
Solvent: CC(=O)O
Product: COc1cc(OCCO)c(F)c(C(Nc2ccc(C#N)cc2)c2nn(-c3ncccn3)c(=O)[nH]2)c1
Temperature: 50 °C
Reaction time: 8 h
Yield: 82 %

Procedure:
After dissolving 3.4 g of 4-[({3-[2-(t-butyldimethylsilanyloxy)ethoxy]-2-fluoro-5-methoxyphenyl}-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl)amino]benzonitrile in 100 ml of acetic acid, 5 ml of water was added and the mixture was stirred overnight at 50° C. The reaction mixture was concentrated, and the residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate) to give the title compound (2.25 g) as a light yellow solid.
Reaction SMILES: [Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4](Cl)[N:3]=1.[NH:25]1[CH2:29][CH2:28][C@H:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:26]1>C(#N)C>[Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4]([N:25]2[CH2:29][CH2:28][C@H:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:26]2)[N:3]=1
Reactant: COc1ccc(CN2Cc3c(F)c(Cl)nc(Cl)c3C2=O)c(OC)c1
Reactant: CC(C)(C)OC(=O)N[C@H]1CCNC1
Solvent: CC#N
Product: COc1ccc(CN2Cc3c(F)c(N4CC[C@H](NC(=O)OC(C)(C)C)C4)nc(Cl)c3C2=O)c(OC)c1
Temperature: 100 °C
Yield: 55.8 %

Procedure:
A tube containing 4,6-dichloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (300 mg, 0.808 mmol) and (S)-tert-butyl pyrrolidin-3-ylcarbamate (301 mg, 1.616 mmol) dissolved in ACN (4 mL) was sealed and heated at 100° C. for 2 d. The reaction mixture was concentrated and dissolved in EtOAc (20 mL) and washed with saturated aq NaHCO3 (10 mL) and brine (10 mL). The organic extracts were dried over Na2SO4 and evaporated to give a crude product, which was purified via preparative HPLC. Pure fractions were collected and evaporated to give the title compound (235 mg, 55.8%). [M+H] calc'd for C25H30ClFN4O5, 521. found, 521.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([N:9]([CH2:20][C:21]([OH:23])=O)[S:10]([C:13]2[C:14]([CH3:19])=[CH:15][CH:16]=[CH:17][CH:18]=2)(=[O:12])=[O:11])=[CH:5][CH:4]=1.[CH2:24]([NH:26][CH2:27][C:28]1[N:29]([CH3:33])[CH:30]=[CH:31][CH:32]=1)[CH3:25]>>[CH2:24]([N:26]([CH2:27][C:28]1[N:29]([CH3:33])[CH:30]=[CH:31][CH:32]=1)[C:21](=[O:23])[CH2:20][N:9]([C:6]1[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[S:10]([C:13]1[C:14]([CH3:19])=[CH:15][CH:16]=[CH:17][CH:18]=1)(=[O:12])=[O:11])[CH3:25]
Reactant: COc1ccc(N(CC(=O)O)S(=O)(=O)c2ccccc2C)cn1
Reactant: CCNCc1cccn1C
Product: CCN(Cc1cccn1C)C(=O)CN(c1ccc(OC)nc1)S(=O)(=O)c1ccccc1C

Procedure:
prepared by reaction of [(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-acetic acid with ethyl-(1-methyl-1H-pyrrol-2-ylmethyl)-amine
Reaction SMILES: Br[CH2:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[N:11]=[CH:10][CH:9]=[CH:8]2.[N-:13]=[N+:14]=[N-:15].[Na+]>CN(C=O)C.CCOC(C)=O>[N:13]([CH2:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[N:11]=[CH:10][CH:9]=[CH:8]2)=[N+:14]=[N-:15]
Reactant: [N-]=[N+]=[N-]
Reactant: BrCc1cccc2cccnc12
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: [N-]=[N+]=NCc1cccc2cccnc12
Reaction time: 4.5 h

Procedure:
To a solution of 1.0119 g (4.56 mmol) 20 in 25 mL of DMF was added 0.3557 g (5.47 mmol) sodium azide. After 4.5 h at room temperature, the reaction mixture was diluted with 80 mL EtOAc and washed with 40 mL brine. The aqueous layer was extracted with 20 mL EtOAc. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (60×220 mm silica gel, linear gradient 5-20% (EtOAc:hexane) provided 21. 1H NMR (CDCl3, 400 MHz) δ 8.965 (dd, 1H, J=1.74, 4.21 Hz, ArH); 8.185 (dd, 1H, J=1.74, 8.32 Hz, ArH); 7.823 (dd, 1H, J=1.12, 8.32 Hz, ArH); 7.743 (d, 1H, J=6.95 Hz, ArH); 7.555 (dd, 1H, J=7.18, 8.10 Hz, ArH); 7.455 (dd, 1H, J=4.21, 8.23 Hz, ArH); 5.065 (s, 2H, ArCH2).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:27])[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([OH:26])[CH:19]=2)=[CH:12][CH:11]=1.Br[CH2:29][CH2:30][CH2:31][N:32]1[C:40](=[O:41])[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:33]1=[O:42].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:27])[C:10]1[CH:11]=[CH:12][C:13]([CH2:16][NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:29][CH2:30][CH2:31][N:32]3[C:40](=[O:41])[C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[C:33]3=[O:42])[CH:19]=2)=[CH:14][CH:15]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCBr
Reactant: COc1ccc(NCc2ccc(C(=O)Nc3ccccc3N)cc2)cc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(NCc2ccc(C(=O)Nc3ccccc3N)cc2)cc1OCCCN1C(=O)c2ccccc2C1=O
Temperature: 100 °C
Yield: 46.2 %

Procedure:
To a solution of N-(2-amino-phenyl)-4-[(3-hydroxy-4-methoxy-phenylamino)-methyl]-benzamide (212e) (586 mg, 0.66 mmol) in DMF (10 ml) were added 2-(3-bromo-propyl)isoindole-1,3-dione (238) (176 mg, 0.66 mmol) and K2CO3 (365 mg, 2.64 mmol) at room temperature. The reaction mixture was heated at 100° C. for 1 h then overnight at 60° C., cooled, filtered and concentrated in vacuo. The residue was purified by flash chromatography (eluent from AcOEt-hexane (40:60) to pure AcOEt) to afford 239 (168 mg, 46% yield). 1H NMR: (DMSO) δ (ppm): 9.57 (bs, 1H), 7.88 (d, J=8.0 Hz, 2H), 7.84-7.75 (m, 4H), 7.44 (d, J=8.0 Hz, 2H), 7.12 (d, J=7.2 Hz, 1H), 6.92 (t, J=8.8 Hz, 1H), 6.75 (dd, J=1.2, 7.6 Hz, 1H), 6.57 (d, J=8.4 Hz, 2H), 6.27 (d, J=2.4 Hz, 1H), 6.00-5.93 (m, 2H), 4.87 (s, 2H), 4.27 (d, J=6.0 Hz, 2H), 3.89 (dd, J=5.6, 6.0 Hz, 2H), 3.74 (dd, J=6.4, 6.8 Hz, 2H), 3.42 (s, 3H), 2.06-2.01 (m, 2H). LRMS: (calcd.) 550.4; (found.) 551.5(MH)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:25])=[C:14]([C:20](OCC)=[O:21])[C:15](=[O:19])[NH:16]3)=[N:11][CH:10]=2)=[CH:4][CH:3]=1.[O:26]1[CH2:30][CH2:29][CH2:28][CH:27]1[CH2:31][NH2:32]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:25])=[C:14]([C:20]([NH:32][CH2:31][CH:27]4[CH2:28][CH2:29][CH2:30][O:26]4)=[O:21])[C:15](=[O:19])[NH:16]3)=[N:11][CH:10]=2)=[CH:4][CH:3]=1
Reactant: CCOC(=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2[nH]c1=O
Reactant: NCC1CCCO1
Product: O=C(NCC1CCCO1)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2[nH]c1=O

Procedure:
This compound was prepared from ethyl 7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate and (±)-(tetrahydro-2-furanylmethyl)amine employing methods similar to those described in Example 2 and was obtained as a white solid: 1H NMR (d6-DMSO) δ 11.9 (1H, br), 10.60 (1H, br), 8.37 (1H, br), 7.39 (1H, s), 7.30 (2H, m), 7.15 (2H, t, J=8.6 Hz), 4.06 (2H, br s), 3.96 (1H, m), 3.80 (1H, q, J˜7 Hz), 3.64 (1H, q, J˜7 Hz), 3.50-3.20 (2H, m), 2.00-1.52 (4H, m); ES+ MS: 398 (M+H+, 100).
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4]2[C:10]([CH2:11][CH3:12])=[C:9]([C:13]3[CH:18]=[CH:17][C:16]([C:19](=[O:21])[CH3:20])=[CH:15][CH:14]=3)[N:8]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:5]2=[N:6][CH:7]=1.Cl[CH2:31][CH:32]=O>CCO>[CH2:11]([C:10]1[C:4]2[N:3]3[CH:31]=[CH:32][N:1]=[C:2]3[CH:7]=[N:6][C:5]=2[N:8]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:27])[CH3:28])[C:9]=1[C:13]1[CH:14]=[CH:15][C:16]([C:19](=[O:21])[CH3:20])=[CH:17][CH:18]=1)[CH3:12]
Reactant: CCc1c(-c2ccc(C(C)=O)cc2)n(COCC[Si](C)(C)C)c2ncc(N)nc12
Reactant: O=CCCl
Solvent: CCO
Product: CCc1c(-c2ccc(C(C)=O)cc2)n(COCC[Si](C)(C)C)c2ncc3nccn3c12
Temperature: 80 °C
Yield: 52.2 %

Procedure:
1-(4-(2-Amino-7-ethyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-6-yl)phenyl)ethanone (0.217 g, 0.529 mmol) in EtOH (5 mL) was treated with 2-chloroacetaldehyde (˜50 wt % solution in water, 0.100 g, 0.634 mmol). The mixture was heated to about 80° C. for about 2 h then cooled to rt and concentrated under reduced pressure. The material was purified by on a 10 gram silica column with EtOAc then 9:1 DCM/MeOH as eluents to give 1-(4-(1-ethyl-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-2-yl)phenyl)ethanone (0.12 g, 52%): LC/MS (Table 2, Method a) Rt=3.06 min; MS m/z 435 (M+H)+.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][S:4][C:5]1[N:10]2[CH:11]=[CH:12][N:13]=[C:9]2[CH:8]=[CH:7][CH:6]=1.[C:14]1(=[O:24])[O:19][C:17](=[O:18])[C:16]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:15]12>C(Cl)(Cl)Cl>[C:17]([C:16]1[CH:20]=[CH:21][CH:22]=[CH:23][C:15]=1[C:14]([NH:1][CH2:2][CH2:3][S:4][C:5]1[N:10]2[CH:11]=[CH:12][N:13]=[C:9]2[CH:8]=[CH:7][CH:6]=1)=[O:24])([OH:19])=[O:18]
Reactant: O=C1OC(=O)c2ccccc21
Reactant: NCCSc1cccc2nccn12
Solvent: ClC(Cl)Cl
Product: O=C(O)c1ccccc1C(=O)NCCSc1cccc2nccn12
Temperature: 25 °C
Reaction time: 14 h
Yield: 84.8 %

Procedure:
To a solution of 5-[2-(amino)ethylthio]imidazo[1,2-a]pyridine (1.12 g, 5.8 mmoles) in chloroform (58 ml) was added phthalic anhydride (1.12 g, 7.56 mmoles) and the mixture was stirred at room temperature for 14 hours and then heated at reflux for 5 hours. The reaction mixture was cooled by standing. The crystals precipitated were filtered off, washed with chloroform and dried to obtain 1.68 g of the desired product (84.8%, colorless crystals).
Reaction SMILES: CO.[CH2:3]([O:7][C:8]1[CH:13]=[C:12](Cl)[C:11]([O:15][CH2:16][CH2:17][CH2:18][CH3:19])=[CH:10][C:9]=1[N+:20]([O-:22])=[O:21])[CH2:4][CH2:5][CH3:6].[CH3:23][C:24]1[CH:29]=[CH:28][C:27]([SH:30])=[CH:26][CH:25]=1.C[O-].[Na+]>O>[C:24]1([CH3:23])[CH:29]=[CH:28][C:27]([S:30][C:13]2[C:8]([O:7][CH2:3][CH2:4][CH2:5][CH3:6])=[C:9]([N+:20]([O-:22])=[O:21])[CH:10]=[C:11]([O:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH:12]=2)=[CH:26][CH:25]=1
Reactant: CCCCOc1cc([N+](=O)[O-])c(OCCCC)cc1Cl
Reactant: Cc1ccc(S)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CCCCOc1cc(Sc2ccc(C)cc2)c(OCCCC)c([N+](=O)[O-])c1
Temperature: 50 °C
Reaction time: 1 h

Procedure:
To 110 parts of methanol was added 51 parts of 2,5-dibutoxy-4-chloronitrobenzene, and the mixture was warmed to 50° C. A methanol (50 parts) solution of 21.5 parts of p-thiocresol and 9.8 parts of sodium methylate was added dropwise thereto over a period of about one hour to carry out a reaction therebetween. After completion of the dropwise addition, the reaction was further continued under reflux for 5 hours. After completion of the reaction, 85 parts of water was added to the reaction mixture to precipitate a crystal. The crystal was recovered by filtration and recrystallized from methanol to obtain 58.5 parts of 4-tolylthio-2,5-dibutoxynitrobenzene (m.p.: 44° to 45° C.).
Reaction SMILES: Br[C:2]1[C:6]([CH2:7][CH2:8][CH2:9][CH3:10])=[CH:5][S:4][C:3]=1[CH:11]=[O:12].C([O-])([O-])=O.[Na+].[Na+].CCO.[CH3:22][O:23][CH2:24][O:25][C:26]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[CH:28][C:27]=1B(O)O>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:7]([C:6]1[C:2]([C:27]2[CH:28]=[CH:29][C:30]([O:32][CH3:33])=[CH:31][C:26]=2[O:25][CH2:24][O:23][CH3:22])=[C:3]([CH:11]=[O:12])[S:4][CH:5]=1)[CH2:8][CH2:9][CH3:10]
Reactant: CCCCc1csc(C=O)c1Br
Reactant: COCOc1cc(OC)ccc1B(O)O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCCCc1csc(C=O)c1-c1ccc(OC)cc1OCOC
Yield: 71.1 %

Procedure:
To a solution of 3-Bromo-4-n-butylthiophene-2-carboxaldehyde of Example 1(b) 1.87 g, 7.57 imuol) in toluene (35 mL) was added (PPh3)4Pd (0.30 g, 0.20 mmol), Na2CO3 (2 M, 9 ML), EtOH (25 mL) and (2-methoxymethoxy-4-methoxyphenyl)boronic acid (1.76 g, 8.30 mmol), respectively. The resulting mixture was stirred at reflux for 3 h. After quenching with water and extraction with EtOAc, the organic extract was washed with H2O, brine and dried (MgSO4). The solvent was removed under reduced pressure and column chromatography (silica gel, EtOAc/Hexane, 25:75) of the residue afforded the title compound as an oil (1.80 g, 71%)
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][CH:6]=1)=[O:4].[N-:12]=[N+:13]=[N-:14].[Na+]>CO>[N:12]([CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][CH:6]=1)=[O:4])=[N+:13]=[N-:14]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C(CBr)c1ccc(Br)cc1
Agent: [Na+]
Solvent: CO
Product: [N-]=[N+]=NCC(=O)c1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 83.4 %

Procedure:
A solution of 2,4′-dibromoacetophenone (1.390 g, 5.0 mmol) in MeOH (10 mL) was poured over 10 mL of an aqueous solution of sodium azide (0.325 g, 5.00 mmol) in an ice bath. The mixture was stirred at room temperature for 18 hours. The solvent was removed and then extracted with ethyl ether (20 mL) and water (20 mL). The organic layer was dried over MgSO4 and concentrated in vacuo to obtain 2-azido 4′-bromoacetophenone (1.0 g, 4.17 mmol, 83% yield). 1H NMR (CDCl3) 5.45 (s, 2H), 7.67 (d, J=8.4 Hz, 2H), 7.79 (d, J=8.4 Hz, 2H) ppm.
Reaction SMILES: C[O:2][C:3](=[O:32])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:31]=[CH:30][C:13]3[S:14][C:15]([CH2:17][CH:18]4[CH2:22][CH2:21][N:20]([CH:23]5[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]5)[C:19]4=[O:29])=[CH:16][C:12]=3[CH:11]=2)=[CH:6][CH:5]=1.O[Li].O.O1CCOCC1.Cl>O>[CH:23]1([N:20]2[CH2:21][CH2:22][CH:18]([CH2:17][C:15]3[S:14][C:13]4[CH:30]=[CH:31][C:10]([C:7]5[CH:8]=[CH:9][C:4]([C:3]([OH:32])=[O:2])=[CH:5][CH:6]=5)=[CH:11][C:12]=4[CH:16]=3)[C:19]2=[O:29])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]1
Reactant: COC(=O)c1ccc(-c2ccc3sc(CC4CCN(C5CCCCC5)C4=O)cc3c2)cc1
Agent: Cl
Agent: [Li]O
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)c1ccc(-c2ccc3sc(CC4CCN(C5CCCCC5)C4=O)cc3c2)cc1
Yield: 39.6 %

Procedure:
Heat a mixture of 4-[2-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-benzo[b]thiophen-5-yl]-benzoic acid methyl ester (250 mg, 0.64 mmol), LiOH.H2O (10 eq) into a dioxane (5 mL) and water (2 mL) at 80° C. for 1 hour. Add 2 M HCl (1 mL) and extract the mixture with ethyl acetate. Dry over sodium sulfate, filter, and concentrate. Purify by silica gel (20-50% ethyl acetate in hexanes) to give the title compound as a white powder (110 mg, 65%): MS (APCI-pos mode) m/z (rel intensity): 434.1 (M+H, 100%).