Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N[C@H](C(O)=O)CC(=O)N.[NH2:10][C@H:11]([C:15]([OH:17])=[O:16])[CH:12]([CH3:14])[CH3:13].[NH2:18][CH:19]([NH2:21])[CH3:20].[C:22]([C:26]1[C:27]([NH:29][C:30](=[O:32])[CH:31]=1)=[O:28])(=[O:25])[CH2:23][CH3:24].[NH:33](C(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)[C@H:34]([C:43]([OH:45])=[O:44])[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([OH:42])=[CH:38][CH:37]=1>>[NH2:33][C@H:34]([C:43]([OH:45])=[O:44])[CH2:35][C:36]1[CH:37]=[CH:38][C:39]([OH:42])=[CH:40][CH:41]=1.[NH2:10][C@H:11]([C:15]([OH:17])=[O:16])[CH:12]([CH3:14])[CH3:13].[NH2:18][CH:19]([NH2:21])[CH3:20].[C:22]([C:26]1[C:27]([NH:29][C:30](=[O:32])[CH:31]=1)=[O:28])(=[O:25])[CH2:23][CH3:24]
Reactant: O=C(N[C@@H](Cc1ccc(O)cc1)C(=O)O)OCC1c2ccccc2-c2ccccc21
Agent: CC(C)[C@H](N)C(=O)O
Agent: CC(N)N
Agent: CCC(=O)C1=CC(=O)NC1=O
Product: N[C@@H](Cc1ccc(O)cc1)C(=O)O
Reaction time: 0.13 h

Procedure:
AF-Tyrosine-Valine-diaminoethane-propionyl-maleimide (5d) was prepared in the same manner as 5c, using Fmoc-Tyr for AA1. Yield: 36 mg (68%) of white solid. RP-HPLC analysis: >95% at 7.8 min; ESMS m/z=1201.67 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]([CH3:12])[C:9](=[O:11])[CH3:10])[CH:5]=[CH:6][CH:7]=1.[Cl:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18]Cl)=[CH:16][CH:15]=1.O.[OH-].[Cs+].C(OCC)(=O)C>C(Cl)Cl.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[Br:1][C:2]1[CH:3]=[C:4]([C:8]([CH3:12])([CH2:18][C:17]2[CH:20]=[CH:21][C:14]([Cl:13])=[CH:15][CH:16]=2)[C:9](=[O:11])[CH3:10])[CH:5]=[CH:6][CH:7]=1
Reactant: CC(=O)C(C)c1cccc(Br)c1
Reactant: ClCc1ccc(Cl)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cs+]
Agent: [I-]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: O
Product: CC(=O)C(C)(Cc1ccc(Cl)cc1)c1cccc(Br)c1
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
To a solution of 3-(3-bromophenyl)-2-butanone (2.0 g, 8.8 mmol) in methylene chloride (100 mL) was added 4-chlorobenzyl chloride (1.4 g, 8.8 mmol), tetrabutylammonium iodide (0.16 g, 0.44 mmol) and cesium hydroxide monohydrate (5.9 g, 35 mmol). After stirring at room temperature for 3.5 h, the reaction mixture was poured into ethyl acetate (100 mL) and water (100 mL). The organic layer was separated and the aqueous layer extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered, and concentrated to dryness to give the title compound. 1H NMR (400 MHz, CD3OD): δ 7.5-7.1 (m, 4H), 7.08 (d, 2H), 6.68 (d, 2H), 3.16 (ABq, 2H), 1.98 (s, 3H), 1.42 (s, 3H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:13])[NH:7][N:8]1[CH:12]=[CH:11][CH:10]=[CH:9]1)([CH3:4])([CH3:3])[CH3:2].[Cl:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Cl)=[CH:17][CH:16]=1.[H-].[Na+]>>[C:1]([O:5][C:6](=[O:13])[N:7]([CH2:19][C:18]1[CH:21]=[CH:22][C:15]([Cl:14])=[CH:16][CH:17]=1)[N:8]1[CH:12]=[CH:11][CH:10]=[CH:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nn1cccc1
Reactant: ClCc1ccc(Cl)cc1
Agent: [H-]
Agent: [Na+]
Product: CC(C)(C)OC(=O)N(Cc1ccc(Cl)cc1)n1cccc1

Procedure:
Prepared according to the benzylation condition used in Example 1 step b) from pyrrol-1-yl-carbamic acid tert-butyl ester (1.0 eq.), 4-chlorobenzyl chloride (1.03 eq.) and sodium hydride (1.3 eq.). ESI (m/z): 307 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:17])=[C:6]([CH:16]=1)[CH2:7][NH:8][C:9](=[O:15])[CH:10](OC)OC.OS(O)(=O)=O.OS(O)(=O)=O.O=S(=O)=O.C([O-])(O)=O.[Na+]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:17])=[C:6]2[C:16]=1[CH:10]=[C:9]([OH:15])[N:8]=[CH:7]2
Reactant: COC(OC)C(=O)NCc1cc(Br)ccc1F
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: O=S(=O)=O
Product: Oc1cc2c(Br)ccc(F)c2cn1
Temperature: 85 °C

Procedure:
To N-(5-bromo-2-fluorobenzyl)-2,2-dimethoxyacetamide (12.0 g, 39 mmol) were added concentrated H2SO4 (21 mL) and oleum (30%, 25.0 mL, 394 mmol). The mixture was heated at 85° C. for 2 h. The reaction mixture was cooled to ambient temperature and poured slowly into a cold aqueous satd. solution of NaHCO3 in a beaker with efficient stirring (Note: frothing occurs). The solid that formed was filtered off, washed with water (50 mL), and dried in vacuo to give the title compound as yellow solid. 1H NMR (DMSO-d6, 300 MHz) δ=7.03 (s, 1H), 7.11 (dd, J=7.2, 2.1 Hz, 1H), 7.98 (dd, J=7.2, 2.4 Hz, 1H), 9.15 (s, 1H). MS (ES+): m/z 242.11/244.13 [MH+]. HPLC: tR=2.63 min (ZQ2, polar—5 min).
Reaction SMILES: [CH2:1]([N:5]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)[S:6]([C:9]1[C:14]([F:15])=[C:13]([F:16])[C:12]([F:17])=[C:11]([F:18])[C:10]=1[F:19])(=[O:8])=[O:7])[CH2:2][CH:3]=[CH2:4].B.C1C[O:32]CC1.O.B(O[O-])=O.[Na+]>C1COCC1>[OH:32][CH2:4][CH2:3][CH2:2][CH2:1][N:5]([C:20]1[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=1)[S:6]([C:9]1[C:10]([F:19])=[C:11]([F:18])[C:12]([F:17])=[C:13]([F:16])[C:14]=1[F:15])(=[O:7])=[O:8]
Reactant: C1CCOC1
Reactant: C=CCCN(c1ccc(OC)cc1)S(=O)(=O)c1c(F)c(F)c(F)c(F)c1F
Agent: B
Agent: O=BO[O-]
Agent: [Na+]
Solvent: O
Product: COc1ccc(N(CCCCO)S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 64 %

Procedure:
To a solution of 1-(N-(3-butenyl)pentafluorophenylsulfonamido)-4-methoxybenzene (410 mg, 1.01 mmol) in THF (6.5 mL) at −78° C. was added BH3.THF (1.00 mL of a 1 M solution in THF, 1.00 mmol). After stirring at −78° C. for 1 h and at 0° C. for 1 h, the reaction mixture was treated with H2O (20 mL) and sodium perborate (513 mg, 5.14 mmol). After stirring at rt for 2 h, the mixture was poured onto H2O (20 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic extracts were washed with sat. NaCl (20 mL) and dried (MgSO4). Concentration followed by chromatography (2:1/hexanes:EtOAc) afforded 270 mg (64%) of product as a white solid, mp 88-90° C. 1H NMR (CDCl3): d 7.08 (m, 2H), 6.85 (m, 2H), 3.80 (s, 3H), 3.77 (m, 2H), 3.64 (t, J=6.0; 2H), 1.63-1.55 (m, 5H), 1.50 (bs, 1H). Anal. Calcd. for C17H16F5NO4S: C, 48.00; H, 3.79; N, 3.29; S, 7.54. Found: C, 48.08; H, 3.76; N, 3.34; S, 7.46.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[C:4]([Cl:10])[CH:3]=1.N1C=CN=C1.[C:16]([Si:20](Cl)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([CH3:19])([CH3:18])[CH3:17].O>CN(C)C=O>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][O:7][Si:20]([C:16]([CH3:19])([CH3:18])[CH3:17])([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:4]([Cl:10])[CH:3]=1
Reactant: OCc1ccc(Br)cc1Cl
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: c1c[nH]cn1
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](OCc1ccc(Br)cc1Cl)(c1ccccc1)c1ccccc1
Reaction time: 1 h
Yield: 97.2 %

Procedure:
To a solution of 4-bromo-2-chlorobenzyl alcohol (14.48 g) in N,N-dimethylformamide (72 ml) were added imidazole (5.34 g) and tert-butylchlorodiphenylsilane (19.8 g) under ice-cooling, and the mixture was stirred for 1 hr. Water was added to the reaction mixture and the resulting product was extracted twice with hexane. The organic layers were combined, washed successively with water, saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was applied to silica gel column chromatography (hexane) to give 4-bromo-1-((tert-butyldiphenylsiloxy)methyl)-2-chlorobenzene (29.22 g) as a colorless oil.
Reaction SMILES: CC(C)=[O:3].OS(O)(=O)=O.O=[Cr](=O)=O.[Br:14][C:15]1[C:16]([Cl:27])=[CH:17][C:18]([O:25][CH3:26])=[C:19]([CH2:21][CH2:22][CH:23]=[O:24])[CH:20]=1>CC(C)=O>[Br:14][C:15]1[C:16]([Cl:27])=[CH:17][C:18]([O:25][CH3:26])=[C:19]([CH2:21][CH2:22][C:23]([OH:3])=[O:24])[CH:20]=1
Reactant: CC(C)=O
Reactant: COc1cc(Cl)c(Br)cc1CCC=O
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Product: COc1cc(Cl)c(Br)cc1CCC(=O)O
Temperature: 25 °C
Reaction time: 12 h
Yield: 39.3 %

Procedure:
To a stirred solution of Jones reagent (3 mL, 5.4 mmol, 2.8 M) in acetone (20 mL), 3-(5-bromo-4-chloro-2-methoxyphenyl)propanal (860 mg, 3.1 mmol) was added. The reaction was stirred at RT for 12 h, quenched with iso-propylalcohol and then stirred for 10 min. The resulting mixture was diluted with water, extracted with ethyl acetate. The combined organic layer was washed with water and brine, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography on silica gel (ethyl acetate/petroleum ether=1:1) to afford the desired product (358 mg, 38% yield). ESI-MS m/z: 291.1[M+H]−.
Reaction SMILES: [C:1]([C:4]1[CH:31]=[CH:30][CH:29]=[C:28]([N+:32]([O-:34])=[O:33])[C:5]=1[C:6]([NH:8][C@H:9]([C:11]([N:13]1[CH2:27][CH2:26][CH2:25][C@H:14]1[C:15]([O:17]CC1C=CC=CC=1)=[O:16])=[O:12])[CH3:10])=[O:7])([OH:3])=[O:2].[OH-].[Na+].CO>O>[C:1]([C:4]1[CH:31]=[CH:30][CH:29]=[C:28]([N+:32]([O-:34])=[O:33])[C:5]=1[C:6]([NH:8][C@H:9]([C:11]([N:13]1[CH2:27][CH2:26][CH2:25][C@H:14]1[C:15]([OH:17])=[O:16])=[O:12])[CH3:10])=[O:7])([OH:3])=[O:2]
Reactant: C[C@H](NC(=O)c1c(C(=O)O)cccc1[N+](=O)[O-])C(=O)N1CCC[C@H]1C(=O)OCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: C[C@H](NC(=O)c1c(C(=O)O)cccc1[N+](=O)[O-])C(=O)N1CCC[C@H]1C(=O)O

Procedure:
The ester product from part (b) (1 g., 2.1 mmole) is stirred in a 10% sodium hydroxide and methanol solution at room temperature for 2.5 hours. The reaction solution is diluted with water and washed with ethyl ether. Upon acidification of the aqueous phase with 10% hydrochloric acid and saturation with sodium chloride, the diacid is extracted via multiple extractions into ethyl acetate. After drying (MgSO4) and evaporating, 0.5 g. of product is obtained as a white solid. In order to remove entrapped solvent, 300 mg. of material is dissolved in water and lyophilized to give pure 1-[N-(2-carboxy-6-nitrobenzoyl)-L-alanyl]-L-proline as a white solid; m.p. 134°-137°. TLC (silica gel Rf =0.28, ethyl acetate:pyridine:acetic acid:water; 45:20:6:11). [α]D =-57.2 (c=1.0, methanol).
Reaction SMILES: [N+:1]([O-:4])([OH:3])=[O:2].P(=O)(O)(O)O.[CH:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>[O-]P(=O)=O.[O-]P(=O)=O.[Ca+2]>[N+:1]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([O-:4])=[O:2].[N+:1]([O-:4])([OH:3])=[O:2]
Reactant: c1ccccc1
Agent: O=P(=O)[O-]
Agent: O=P(O)(O)O
Agent: [Ca+2]
Solvent: O=[N+]([O-])O
Product: O=[N+]([O-])c1ccccc1

Procedure:
British Pat. No. 586,732 discloses that the gas-phase nitration of benzene with HNO3 or NO2 is carried out with phosphates or a sintered product of phosphoric acid supported on a solid absorbent as catalyst. According to the example, nitrobenzene is obtained by the nitration of benzene with HNO3 with calcium metaphosphate as a catalyst, but the space time yield of nitrobenzene stays at such a low level as about 0.074 kg/liter catalyst.hour under a condition that the HNO3 /benzene molar ratio is 0.364, the temperature is 175° C. and WHSV is 0.176 kg/liter catalyst.hour. The above literature gives no examples with NO2 as a nitrating agent, so that the substantial embodiment of this invention is interpreted as nitration with nitric acid.
Reaction SMILES: C([O:3][C:4](=O)[C:5]([N:7]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[CH:14]=2)[CH2:9][CH2:8]1)=[O:6])C.Cl.[NH2:29][OH:30].[OH-].[K+].CO>CO>[CH:22]1([O:21][C:15]2[CH:14]=[C:13]([CH:10]3[CH2:11][CH2:12][N:7]([C:5](=[O:6])[C:4]([NH:29][OH:30])=[O:3])[CH2:8][CH2:9]3)[CH:18]=[CH:17][C:16]=2[O:19][CH3:20])[CH2:26][CH2:25][CH2:24][CH2:23]1
Reactant: NO
Reactant: CCOC(=O)C(=O)N1CCC(c2ccc(OC)c(OC3CCCC3)c2)CC1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: COc1ccc(C2CCN(C(=O)C(=O)NO)CC2)cc1OC1CCCC1
Reaction time: 8 h

Procedure:
To a stirred solution of 2-[4-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-1-yl]-2-oxo-acetic acid ethyl ester (5.3 mmol, 2.0 g) in methanol (55 mL) was added hydroxylamine hydrochloride (21.2 mmol, 1.5 g) followed by potassium hydroxide/methanol solution (5M; 5.3 mL) dropwise at room temperature. A white solid precipitated out of solution as this reaction stirred overnight. The reaction mixture was diluted with H2O (250 mL), acidified with 1N HCl (60 mL) and extracted with EtOAc (2×500 mL). Each organic phase was washed with H2O (250 mL) and the combined organics were dried (Na2SO4) and concentrated in vacuo to give a tan solid. The residue was purified by flash chromatography (SiO2 : 1) 80% EtOAc/hexane, 2) EtOAc) to afford the title compound as a white solid, mp=123.5°-124° C. (2.5 mmol, 0.920 g, 48%).
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C@@H:11]([O:13][C:14]3[C:15]4[O:23][CH:22]=[CH:21][C:16]=4[CH:17]=[N:18][C:19]=3[NH2:20])[CH3:12])=[N:9][N:10]=2)[N:7]=1.[CH3:24][N:25]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[N:26]1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>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.O>[CH3:24][N:25]1[CH:29]=[C:28]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([C@@H:11]([O:13][C:14]4[C:15]5[O:23][CH:22]=[CH:21][C:16]=5[CH:17]=[N:18][C:19]=4[NH2:20])[CH3:12])=[N:9][N:10]=3)[N:7]=2)[CH:27]=[N:26]1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: C[C@H](Oc1c(N)ncc2ccoc12)c1nnc2ccc(Cl)nn12
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: [K+]
Solvent: C1COCCO1
Solvent: O
Product: C[C@H](Oc1c(N)ncc2ccoc12)c1nnc2ccc(-c3cnn(C)c3)nn12

Procedure:
A mixture of 7-[(S)-1-(6-chloro[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethoxy]furo[3,2-c]pyridine-6-ylamine (15.0 mg, 0.045 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (18.9 mg, 0.091 mmol), Pd(PPh3)4 (5 mg, 0.004 mmol), potassium carbonate (18.8 mg, 0.136 mmol) and 4:1 dioxane:water (2 mL) was heated in a microwave reactor at 100° C. for 30 min. The solution was loaded into a SCX cartridge, washed with MeOH and ejected with 2M NH3 in MeOH. The filtrate was concentrated in vacuo, redissolved in MeOH (0.5 mL) and purified via HPLC. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=2.07 (d, J=6.6 Hz, 3H), 3.98 (s, 3H), 6.47 (q, J=6.6 Hz, 1H), 6.81 (d, J=1.8 Hz, 1H), 7.49 (d, J=9.9 Hz, 1H), 7.63 (d, J=2.0 Hz, 1H), 7.88 (s, 1H), 7.97 (s, 1H), 8.02 (s, 1H), 8.10 (d, J=9.6 Hz, 1H). MS (ES+): m/z 377.04 (100) [MH+]. HPLC: tR=1.95 min (ZQ3, polar—5 min).
Reaction SMILES: [N:1]([CH2:4][CH2:5][S:6][C:7]1[CH:8]=[C:9]([C:13]([C:15]2[N:16]=[CH:17][N:18]3[CH:22]=[CH:21][S:20][C:19]=23)=[O:14])[CH:10]=[N:11][CH:12]=1)=[N+:2]=[N-:3].[CH2:23]([Sn:27](Cl)([CH2:32][CH2:33][CH2:34][CH3:35])[CH2:28][CH2:29][CH2:30][CH3:31])[CH2:24][CH2:25][CH3:26].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1>>[N:1]([CH2:4][CH2:5][S:6][C:7]1[CH:8]=[C:9]([C:13]([C:15]2[N:16]=[CH:17][N:18]3[CH:22]=[C:21]([Sn:27]([CH2:28][CH2:29][CH2:30][CH3:31])([CH2:32][CH2:33][CH2:34][CH3:35])[CH2:23][CH2:24][CH2:25][CH3:26])[S:20][C:19]=23)=[O:14])[CH:10]=[N:11][CH:12]=1)=[N+:2]=[N-:3]
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: [N-]=[N+]=NCCSc1cncc(C(=O)c2ncn3ccsc23)c1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1cn2cnc(C(=O)c3cncc(SCCN=[N+]=[N-])c3)c2s1

Procedure:
The title compound (857 mg) was prepared in substantially the same manner as in step c) of Synthesis Example 1, except that 667 mg of 7-[5-(2-azidoethylthio)pyridin-3-yl]carbonylimidazo[5,1-b]-thiazole, 0.603 ml of tri-n-butylstannyl chloride, and 3.7 ml of a 1.0 N lithium bis(trimethylsilyl)amide/THF solution were used as the starting materials.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=1.Cl[C:19]1[C:24]([N+:25]([O-:27])=[O:26])=[CH:23][CH:22]=[CH:21][N:20]=1>CN1C(=O)CCC1.O>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:19]2[C:24]([N+:25]([O-:27])=[O:26])=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:13][CH:12]=1
Reactant: Nc1ccc(Nc2nc3ccccc3o2)cc1
Reactant: O=[N+]([O-])c1cccnc1Cl
Solvent: CN1CCCC1=O
Solvent: O
Product: O=[N+]([O-])c1cccnc1Nc1ccc(Nc2nc3ccccc3o2)cc1
Temperature: 140 °C
Reaction time: 1.5 h
Yield: 43.5 %

Procedure:
A mixture of N-(1,3-benzoxazol-2-yl)benzene-1,4-diamine (0.50 g) and 2-chloro-3-nitropyridine (0.352 g) in NMP (3.0 mL) was stirred at 140° C. for 1.5 h. After this time, the reaction mixture was cooled to ambient temperature, diluted with water (50 mL), and extracted with ethyl acetate (3×100 mL). The combined organic extracts were washed with brine (100 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue obtained was purified by chromatography (silica, methylene chloride to 1:9 ethyl acetate/methylene chloride) to afford N-(1,3-benzoxazol-2-yl)-N′-(3-nitropyridin-2-yl)benzene-1,4-diamine (0.335 g) as a red solid.
Reaction SMILES: [CH2:1]([CH:4]([CH2:15][CH:16]=[CH2:17])[CH2:5][O:6][SiH2:7][C:8]1[CH:13]=[CH:12][C:11](Br)=[CH:10][CH:9]=1)[CH:2]=[CH2:3].C([O-])([O-])=O.[K+].[K+].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=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.C1(C)C=CC=CC=1>[CH2:1]([CH:4]([CH2:15][CH:16]=[CH2:17])[CH2:5][O:6][SiH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:29]2[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=2)=[CH:10][CH:9]=1)[CH:2]=[CH2:3]
Reactant: C=CCC(CC=C)CO[SiH2]c1ccc(Br)cc1
Reactant: COc1ccc(B(O)O)cc1
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: [K+]
Solvent: Cc1ccccc1
Product: C=CCC(CC=C)CO[SiH2]c1ccc(-c2ccc(OC)cc2)cc1
Yield: 60 %

Procedure:
At first, a mixture of the 4-(diallylethoxysilyl)bromobenzene (191 mg, 0.61 mmol) obtained in Example 1, Pd(PPh3)4 (21.3 mg, 0.018 mmol), K2CO3 (127 mg, 0.92 mmol), and 4-methoxyphenyl boronic acid (112 mg, 0.74 mmol) was added with dist.toluene (5 mL). Subsequently, the resultant mixture was stirred under a nitrogen atmosphere at 80° C. for 13 hours to obtain a reaction mixture. Thereafter, a salt formed in the reaction mixture was removed by filtering with celite. The solvent was distilled from the organic layer with an evaporator to obtain a crude product. After that, the crude product thus obtained was separated and purified with PTLC (hexane/EtOAc=10/1), and thereby 4-(diallylethoxysilyl)-4′-methoxybiphenyl was obtained (125.4 mg, 60% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:28]([F:31])([F:30])[F:29])=[C:6]([CH:27]=1)[CH2:7][N:8]1[CH2:13][CH2:12][NH:11][C:10]2[N:14]=[CH:15][C:16]([C:18]3[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=3)=[CH:17][C:9]1=2.[F:32][C:33]1[CH:47]=[CH:46][C:36]2[C:37]([CH:40]3[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]3)=[N:38][O:39][C:35]=2[CH:34]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:28]([F:30])([F:29])[F:31])=[C:6]([CH:27]=1)[CH2:7][N:8]1[CH2:13][CH2:12][NH:11][C:10]2[N:14]=[CH:15][C:16]([C:18]3[CH:19]=[CH:20][C:21]([C:22]([N:43]4[CH2:42][CH2:41][CH:40]([C:37]5[C:36]6[CH:46]=[CH:47][C:33]([F:32])=[CH:34][C:35]=6[O:39][N:38]=5)[CH2:45][CH2:44]4)=[O:23])=[CH:25][CH:26]=3)=[CH:17][C:9]1=2
Reactant: O=C(O)c1ccc(-c2cnc3c(c2)N(Cc2cc(Cl)ccc2C(F)(F)F)CCN3)cc1
Reactant: Fc1ccc2c(C3CCNCC3)noc2c1
Product: O=C(c1ccc(-c2cnc3c(c2)N(Cc2cc(Cl)ccc2C(F)(F)F)CCN3)cc1)N1CCC(c2noc3cc(F)ccc23)CC1

Procedure:
4-{1-[5-chloro-2-(trifluoromethyl)benzyl]-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-7-yl}benzoic acid was reacted with 4-(6-fluorobenzo[d]isoxazol-3-yl)piperidine as in General Procedure 10 to give the title compound. LCMS: m/z=649.96 (M+H+); retention time=1.00 minutes.
Reaction SMILES: [C:1]([CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1)#[N:2].[O-]CC.[Na+].[Br:17][C:18]1[CH:19]=[N:20][CH:21]=[C:22]([CH:24]=O)[CH:23]=1>C(O)C>[Br:17][C:18]1[CH:23]=[C:22](/[CH:24]=[C:3](/[C:4]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[NH:6][CH:5]=2)\[C:1]#[N:2])[CH:21]=[N:20][CH:19]=1
Reactant: O=Cc1cncc(Br)c1
Reactant: N#CCc1c[nH]c2ccccc12
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: N#C/C(=C\c1cncc(Br)c1)c1c[nH]c2ccccc12
Reaction time: 1 h
Yield: 16 %

Procedure:
A solution of 3-cyanomethylindole (156 mg, 1.0 mmol) in anhydrous ethanol (1.5 mL) at room temperature was treated with 21% sodium ethoxide in ethanol (450 μL), stirred for 1 hour, treated with 3-bromopyridine-5-carboxaldehyde (J. Heterocycl. Chem., 1995, 32, 1801.) (187 mg, 1.0 mmol), stirred overnight, and concentrated. The residue was purified by flash column chromatography on silica gel with 2% methanol/dichloromethane to provide the desired product (52 mg, 16%). MS (DCI/NH3) m/e 325 (M+H)+.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:20](O)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]/[CH:28]=[CH:29]\[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37].C(Br)(Br)(Br)[Br:40]>ClCCl>[Br:40][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]
Reactant: BrC(Br)(Br)Br
Reactant: CCCCCCCC/C=C\CCCCCCCCO
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCCCCCCCC=CCCCCCCCCBr
Temperature: 25 °C
Yield: 87.8 %

Procedure:
This example is a method of synthesis for inventive compound no. 3508. Triphenylphosphine (5.24 g, 20 mmol) was added incrementally to a solution of oleyl alcohol (5.37 g, 20 mmol) and carbontetrabromide (6.63 g, 20 mmol) in 400 ml of dichloromethane, the resulting reaction mixture being stirred for an hour at room temperature. Removing the solvent under reduced pressure, left a residue, which was extracted with three 200 ml aliquots of hexane. Further purification by flash chromatography over silica gel using a hexane eluant produced 5.82 g of 1-bromo-9-octadecene (88% yield).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[C:7]([NH2:10])[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[Br:11][C:12]1[N:13]=[C:14](Br)[C:15]2[N:16]([CH:18]=[CH:19][N:20]=2)[CH:17]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:14]3[C:15]4[N:16]([CH:18]=[CH:19][N:20]=4)[CH:17]=[C:12]([Br:11])[N:13]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1
Reactant: Brc1cn2ccnc2c(Br)n1
Reactant: Nc1ccc2ncsc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Brc1cn2ccnc2c(Nc2ccc3ncsc3c2)n1

Procedure:
A quantity of 0.15 g (1 mmole) of benzothiazol-6-ylamine is treated with 0.27 g (1 mmole) of 6,8-Dibromo-imidazo[1,2-a]pyrazine in acetonitrile with 3 eq of K2CO3 at reflux for 16 hrs. The reaction mixture is cooled partitioned between ethyl acetate and water, the organic extracts are dried over anhydrous MgSO4 and evaporated in vacuo to afford Benzothiazol-6-yl-(6-bromo-imidazo[1,2-a]pyrazin-8-yl)-amine.
Reaction SMILES: [S:1](Cl)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[N-:12]=[N+:13]=[N-:14].[Na+]>CC(C)=O>[S:1]([N:12]=[N+:13]=[N-:14])([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CC(C)=O
Product: Cc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Reaction time: 2 h
Yield: 96.6 %

Procedure:
To a solution of tosyl chloride (4 g, 21 mmols) in acetone (60 ml) was added at 0-5 C a solution of sodium azide (1.37 g, 21 mmols) and the resulting solution was stirred at that temperature for 2 hours. Acetone was removed and the aqueous mixture was extracted with ether three times. The combined extracts were dried over MgSO4. Evaporation of solvents provided tosyl azide (4 g, 97%). (Eur. J. Org. Chem. 2003, 821-832.)