Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: NN.[F:3][CH2:4][C:5]1[CH:6]=[C:7]([N:11]([CH2:13][C:14]([O:16]C)=O)[NH2:12])[CH:8]=[CH:9][CH:10]=1.[O-:18][C:19]#[N:20].[Na+].FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[F:3][CH2:4][C:5]1[CH:6]=[C:7]([N:11]2[CH2:13][C:14](=[O:16])[NH:20][C:19](=[O:18])[NH:12]2)[CH:8]=[CH:9][CH:10]=1
Reactant: N#C[O-]
Reactant: COC(=O)CN(N)c1cccc(CF)c1
Agent: NN
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: Cc1ccccc1
Product: O=C1CN(c2cccc(CF)c2)NC(=O)N1
Reaction time: 2.25 h
Yield: 78 %

Procedure:
The hydrazine (Intermediate 55, 1.5 g, 7.1 mmol) was dissolved in dry toluene (30 ml) under nitrogen at room temperature. Sodium cyanate (1.6 g, 24.6 mmol) was added followed by trifluoroacetic acid (1.7 ml, 22,1 mmol). The reaction was stirred for 2.25 h after which the reaction was poured into saturated sodium bicarbonate solution (100 ml) and extracted with ethyl acetate (4×(100 ml). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give a white solid. The crude material was triturated with ether (2×100 ml) to give the title compound (Intermediate 56, 1.41 g, 78%) as a colourless powder, m.p. 169°-70°.
Reaction SMILES: [CH:1]1([OH:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N12CCN(CC1)CC2.[S:16](Cl)([C:19]1[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=1)(=[O:18])=[O:17]>C(OCC)(=O)C>[CH:1]1([O:7][S:16]([C:19]2[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=2)(=[O:18])=[O:17])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: OC1CCCCC1
Agent: C1CN2CCN1CC2
Solvent: CCOC(C)=O
Product: Cc1ccc(S(=O)(=O)OC2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 96 h
Yield: 90.4 %

Procedure:
5.0 g (0.05 mol) cyclohexanol and 11.2 g (0.1 mol) 1,4-diazabicyclo[2.2.2]octane are added to 50 mL ethyl acetate. This solution is cooled in an ice bath and 14.3 g (0.075 mol) tosyl chloride in 30 ml ethyl acetate is added drop-wise over 15 minutes. The ice bath is removed and the mixture is allowed to stir at room temperature for 4 days. After this time the solid precipitate is filtered and washed. The ethyl acetate filtrate and washings are then combined and washed successively with 10% HCl, saturated aq NaHCO3 and brine. The ethyl acetate is then evaporated and the resulting oil is purified by column chromatography to yield 11.5 g (90%) of cyclohexyl-p-toluenesulfonate.
Reaction SMILES: [Br-].[F:2][CH2:3][CH2:4][CH2:5][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC([O-])(C)C.[K+].[F:31][C:32]1[CH:33]=[C:34]([C@H:39]2[CH2:44][CH2:43][C@H:42]([C@H:45]3[CH2:50][CH2:49][C@H:48]([CH:51]=O)[CH2:47][CH2:46]3)[CH2:41][CH2:40]2)[CH:35]=[CH:36][C:37]=1[F:38]>C1COCC1>[F:2][CH2:3][CH2:4][CH:5]=[CH:51][C@H:48]1[CH2:49][CH2:50][C@H:45]([C@H:42]2[CH2:43][CH2:44][C@H:39]([C:34]3[CH:35]=[CH:36][C:37]([F:38])=[C:32]([F:31])[CH:33]=3)[CH2:40][CH2:41]2)[CH2:46][CH2:47]1
Reactant: FCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=C[C@H]1CC[C@H]([C@H]2CC[C@H](c3ccc(F)c(F)c3)CC2)CC1
Agent: CC(C)(C)[O-]
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Product: FCCC=C[C@H]1CC[C@H]([C@H]2CC[C@H](c3ccc(F)c(F)c3)CC2)CC1
Temperature: -20 °C
Reaction time: 1 h

Procedure:
A mixture of (3-fluoropropyl)triphenylphosphonium bromide (13.8 g, 34.1 millimols) with THF (60 ml) was cooled down to -20° C., followed by adding t-BuOK (3.5 g, 34.1 millimols) to the mixture, stirring for one hour, dropwise adding to the mixture, a THF (120 ml) solution of trans-4-(trans-4-(3,4-difluorophenyl)cyclohexyl)cyclohexanecarbaldehyde (9.5 g, 31.0 millimols) so as to keep the temperature at -20° C. or lower, stirring the mixture at the same temperature for 2 hours, and treating the reaction product in the same manner as in Example 2, to obtain raw (trans-4-(trans-4-(4-fluorobutenyl)cyclohexyl)cyclohexyl)-3,4-difluorobenzene (9.2 g).
Reaction SMILES: C(O[C:4]([C:6]1[CH:11]=[C:10]([C:12]2[CH:13]=[N:14][CH:15]=[C:16]([F:18])[CH:17]=2)[CH:9]=[C:8]([CH3:19])[N:7]=1)=[O:5])C.[CH3:20][O:21][CH2:22][C:23]1[N:24]=[C:25]([NH2:28])[S:26][CH:27]=1>>[CH3:20][O:21][CH2:22][C:23]1[N:24]=[C:25]([NH:28][C:4]([C:6]2[CH:11]=[C:10]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([F:18])[CH:17]=3)[CH:9]=[C:8]([CH3:19])[N:7]=2)=[O:5])[S:26][CH:27]=1
Reactant: CCOC(=O)c1cc(-c2cncc(F)c2)cc(C)n1
Reactant: COCc1csc(N)n1
Product: COCc1csc(NC(=O)c2cc(-c3cncc(F)c3)cc(C)n2)n1

Procedure:
The title compound, was prepared from 5-Fluoro-6′-methyl-[3,4′]bipyridinyl-2′-carboxylic acid ethyl ester in accordance with the general method of example 26, step 6 using 4-Methoxymethyl-thiazol-2-ylamine instead of 3-Chloroaniline to yield the final compound as a off-white solid, MS (ISP): m/e=359.1 (M+H)+.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[S:16][CH:17]=[CH:18][C:19]=3[NH:20][S:21]([CH:24]([CH3:26])[CH3:25])(=[O:23])=[O:22])=[CH:11][CH:10]=2)O1.[CH3:28][O:29][C:30](=[O:41])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([N+:37]([O-:39])=[O:38])[C:32]=1Br.C([O-])([O-])=O.[Na+].[Na+].O1CCOCC1>C(OCC)C.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>[CH3:28][O:29][C:30]([C:31]1[C:32]([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[S:16][CH:17]=[CH:18][C:19]=3[NH:20][S:21]([CH:24]([CH3:25])[CH3:26])(=[O:22])=[O:23])=[CH:13][CH:14]=2)=[C:33]([N+:37]([O-:39])=[O:38])[CH:34]=[CH:35][CH:36]=1)=[O:41]
Reactant: CC(C)S(=O)(=O)Nc1ccsc1-c1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Reactant: COC(=O)c1cccc([N+](=O)[O-])c1Br
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: CCOCC
Solvent: C1COCCO1
Product: COC(=O)c1cccc([N+](=O)[O-])c1-c1ccc(-c2sccc2NS(=O)(=O)C(C)C)cc1
Temperature: 25 °C
Yield: 36.2 %

Procedure:
Heat the mixture of propane-2-sulfonic acid {2-[4-{4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-thiophen-3-yl}-amide(662 mg, 1.65 mmol), 2-bromo-3-nitro-benzoic acid methyl ester (390 mg, 1.5 mmol), Na2CO3(2M, 2.2 mL, 4.5 mmol) and Pd(PPh3)4 (260 mg, 0.26 mmol) and 15 ml of 1,4 dioxane under N2 to 80° C. overnight. After cooling to room temperature, dilute with diethyl ether (200 mL). Wash with water, saturated aq. sodium chloride, and dry over MgSO4. Remove solvent and purify by flash chromatography (Silica gel-hexane/EtOAc) to provide 6-nitro-4′-[3-(propane-2-sulfonylamino)-thiophen-2-yl]-biphenyl-2-carboxylic acid methyl ester (250 mg). MS (m/e): 478.7(M+1).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](N)=[O:10])=[CH:4][C:3]=1[CH3:12].Cl.[CH2:14]([OH:16])[CH3:15]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:16][CH2:14][CH3:15])=[O:10])=[CH:4][C:3]=1[CH3:12]
Reactant: CCO
Reactant: Cc1cc(CC(N)=O)ccc1F
Agent: Cl
Product: CCOC(=O)Cc1ccc(F)c(C)c1
Temperature: 85 °C
Reaction time: 10 h

Procedure:
2-(4-Fluoro-3-methylphenyl)acetamide (863 mg) was dissolved in saturated hydrochloric acid/ethanol (20 ml), and the reaction solution was stirred at 85° C. for 10 hours. The reaction solution was concentrated under reduced pressure and then diluted with ethyl acetate, followed by separation with water. The organic layer was washed with saturated aqueous sodium bicarbonate and brine and then dried over magnesium sulfate. 919 mg of the title compound was obtained by concentration under reduced pressure. The property values of the compound are as follows.
Reaction SMILES: [F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][NH:7][C:8]([C:10]2([CH2:23][CH2:24][CH2:25][CH2:26]Br)[C:22]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:16]3[C:11]2=[CH:12][CH:13]=[CH:14][CH:15]=3)=[O:9])=[CH:4][CH:3]=1.[N:30]1([C:36]2[CH:45]=[N:44][C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[N:37]=2)[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1>>[F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][NH:7][C:8]([C:10]2([CH2:23][CH2:24][CH2:25][CH2:26][N:33]3[CH2:34][CH2:35][N:30]([C:36]4[CH:45]=[N:44][C:43]5[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=5)[N:37]=4)[CH2:31][CH2:32]3)[C:22]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:16]3[C:11]2=[CH:12][CH:13]=[CH:14][CH:15]=3)=[O:9])=[CH:4][CH:3]=1
Reactant: c1ccc2nc(N3CCNCC3)cnc2c1
Reactant: O=C(NCc1ccc(F)cc1)C1(CCCCBr)c2ccccc2-c2ccccc21
Product: O=C(NCc1ccc(F)cc1)C1(CCCCN2CCN(c3cnc4ccccc4n3)CC2)c2ccccc2-c2ccccc21

Procedure:
Prepared analogously to Example 1 from 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid-4-fluoro-benzylamide and 2-piperazin-1-yl-quinoxaline.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20](Cl)(Cl)([Cl:22])[Cl:21].[Cl:25][C:26]1[CH:47]=[C:46]([O:48][CH2:49][CH:50]=[C:51]([Cl:53])[Cl:52])[CH:45]=[C:44]([Cl:54])[C:27]=1[O:28][CH2:29][C:30](=O)[CH2:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][CH:34]=1>C(#N)C>[Cl:25][C:26]1[CH:47]=[C:46]([O:48][CH2:49][CH:50]=[C:51]([Cl:52])[Cl:53])[CH:45]=[C:44]([Cl:54])[C:27]=1[O:28][CH2:29][C:30]([CH2:31][O:32][C:33]1[CH:34]=[CH:35][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:37][CH:38]=1)=[C:20]([Cl:22])[Cl:21]
Reactant: ClC(Cl)(Cl)Cl
Reactant: O=C(COc1ccc(C(F)(F)F)cc1)COc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Product: FC(F)(F)c1ccc(OCC(COc2c(Cl)cc(OCC=C(Cl)Cl)cc2Cl)=C(Cl)Cl)cc1

Procedure:
312 mg of triphenylphosphine, 183 mg of carbon tetrachloride and 200 mg of 1-[2,6-dichloro-4-(3,3-dichloro-allyloxy)-phenoxy]-3-(4-trifluoromethyl-phenoxy)-propan-2-one are stirred in 3 ml of acetonitrile for 24 hours at 55° C. The reaction mixture is concentrated and the residue is purified over silica gel. The title compound is obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([O:13]C)=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.Br.C(OCC)C>C(O)(=O)C>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1
Reactant: COc1ccc(Oc2ccc(Cl)cc2)cc1
Agent: Br
Solvent: CC(=O)O
Solvent: CCOCC
Product: Oc1ccc(Oc2ccc(Cl)cc2)cc1

Procedure:
The 4-(4'-chlorophenoxy)anisol was demethylated by refluxing it with an excess of 48% HBr in glacial acetic acid for 24 hours. The crude product, obtained after hydrolysis and extraction with diethyl ether, was recrystallized from hexane to yield 4-(4'-chlorophenoxy)phenol as a white solid, bp 83°-85° C., 24.5 g (91.4%).
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[CH:16]=[CH:15][CH:14]=[CH:13][C:4]=1[CH:5](O)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.P(Br)(Br)[Br:20].[Br-]>C(OCC)C>[F:1][C:2]([F:18])([F:17])[C:3]1[CH:16]=[CH:15][CH:14]=[CH:13][C:4]=1[CH:5]([Br:20])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: OC(c1ccccc1)c1ccccc1C(F)(F)F
Reactant: BrP(Br)Br
Agent: [Br-]
Solvent: CCOCC
Product: FC(F)(F)c1ccccc1C(Br)c1ccccc1
Reaction time: 16 h

Procedure:
2-(Trifluoromethyl)benzhydrol (20.2 g, 79.9 mmol) was dissolved in ethyl ether (195 mL), and cooled in an ice-H2O bath, under N2. To the resulting solution was added, dropwise, a solution of PBr3 (3.80 mL, 40.0 mmol) in ethyl ether (95 mL). After addition was complete, the reaction mixture was brought to room temperature and stirred for 16 hours. The reaction mixture was cooled in an ice-H2O bath and quenched with H2O (200 mL). The aqueous layer was extracted with ethyl ether (2×200 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated to dryness at low heat to give a quantitative yield of product bromide as a pale yellow oil. 300 MHz 1H NMR (CDCl3): δ6.69 (s, 1H, (Ph)2CH. MS: 235 (M+ -Br).
Reaction SMILES: [N:1]1([C:7]2[N:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.NC1C=CC(N2CCC(O)C2)=NC=1.ClC1C=CC([N+]([O-])=O)=CN=1.N1CC[C@H](O)C1>>[NH2:13][C:10]1[CH:9]=[CH:8][C:7]([N:1]2[CH2:6][CH2:5][C@H:3]([OH:4])[CH2:2]2)=[N:12][CH:11]=1
Reactant: Nc1ccc(N2CCOCC2)nc1
Agent: Nc1ccc(N2CCC(O)C2)nc1
Agent: O=[N+]([O-])c1ccc(Cl)nc1
Agent: O[C@H]1CCNC1
Product: Nc1ccc(N2CC[C@H](O)C2)nc1

Procedure:
With a method similar to that used for the preparation of 6-morpholin-4-yl-pyridin-3-ylamine above, 1-(5-amino-pyridin-2-yl)-pyrrolidin-3-ol was prepared from 2-chloro-5-nitro-pyridine and (S)-pyrrolidin-3-ol. LCMS calcd for C9H13N3O (m/e) 179, obsd 180 (M+H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]2[CH2:23][C@@H:22]([C:24]3[CH:35]=[CH:34][C:27]4[O:28][C:29]([CH3:33])([CH3:32])[O:30][CH2:31][C:26]=4[CH:25]=3)[O:21][C:20]2=[O:36])[CH:5]=[CH:6][CH:7]=1.[N+:37]([C:40]1[CH:41]=[C:42]([N:46]=[C:47]=[O:48])[CH:43]=[CH:44][CH:45]=1)([O-:39])=[O:38].C(O)(C)C>ClCCl>[CH3:33][C:29]1([CH3:32])[O:28][C:27]2[CH:34]=[CH:35][C:24]([C@H:22]3[O:21][C:20](=[O:36])[N:19]([CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][O:12][CH2:11][CH2:10][O:9][CH2:8][C:4]4[CH:3]=[C:2]([NH:1][C:47]([NH:46][C:42]5[CH:43]=[CH:44][CH:45]=[C:40]([N+:37]([O-:39])=[O:38])[CH:41]=5)=[O:48])[CH:7]=[CH:6][CH:5]=4)[CH2:23]3)=[CH:25][C:26]=2[CH2:31][O:30]1
Reactant: O=C=Nc1cccc([N+](=O)[O-])c1
Reactant: CC1(C)OCc2cc([C@@H]3CN(CCCCCCOCCOCc4cccc(N)c4)C(=O)O3)ccc2O1
Solvent: ClCCl
Solvent: CC(C)O
Product: CC1(C)OCc2cc([C@@H]3CN(CCCCCCOCCOCc4cccc(NC(=O)Nc5cccc([N+](=O)[O-])c5)c4)C(=O)O3)ccc2O1
Reaction time: 4 h
Yield: 85 %

Procedure:
A solution of (5R)-3-{6-[2-{(3-aminophenyl)methoxy}ethoxy]hexyl}-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one (1.00 g) in anhydrous dichloromethane (15 ml) was treated under nitrogen at 20° with 3-nitrophenyl isocyanate (0.43 g) and the mixture stirred for 4 h. Isopropanol (20 ml) was added and the mixture stirred for 17 h before the solvent was removed in vacuo to give a residue that was purified by Biotage. Elution with dichloromethane-EtOH-ammonia (325:8:1) followed by solvent evaporation in vacuo gave the title compound (1.13 g). LCMS RT=3.85 min, ES+ve 663 (MH)+.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:11]2[C:16]([OH:17])=[CH:15][CH:14]=[CH:13][N:12]=2)O)=[CH:5][CH:4]=1)[CH3:2]>[OH-].[OH-].[Pd+2].C(O)(=O)C>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:11]2[C:16]([OH:17])=[CH:15][CH:14]=[CH:13][N:12]=2)=[CH:5][CH:4]=1)[CH3:2]
Reactant: CCc1ccc(C(O)c2ncccc2O)cc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CC(=O)O
Product: CCc1ccc(Cc2ncccc2O)cc1
Reaction time: 76 h
Yield: 82.3 %

Procedure:
A mixture of 4-ethylphenyl-3-hydroxypyridin-2-yl-methanol (0.60 g, 2.62 mmol), 20% palladium hydroxide/carbon (300 mg) and acetic acid (8 mL) was stirred under a hydrogen atmosphere for 76 hours. After filtration to remove the insoluble materials, the filtrate was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give 2-(4-ethylbenzyl)-3-hydroxypyridine (0.46 g, 82%) as a colorless powder.
Reaction SMILES: [CH3:1][N:2]([CH2:14][C:15]([OH:17])=O)[NH:3][C:4](=[O:13])[NH:5][CH2:6][C:7]1[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=1.[NH2:18][C@@H:19]([CH2:43][C:44]1[CH:49]=[CH:48][C:47]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:46][CH:45]=1)[C:20]([N:22]([C@@H:34]([CH3:42])[CH:35]([O:39][CH2:40][CH3:41])[O:36][CH2:37][CH3:38])[CH2:23][C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][CH:25]=1)=[O:21]>>[C:51]([O:50][C:47]1[CH:46]=[CH:45][C:44]([CH2:43][C@H:19]([NH:18][C:15](=[O:17])[CH2:14][N:2]([CH3:1])[NH:3][C:4]([NH:5][CH2:6][C:7]2[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=2)=[O:13])[C:20]([N:22]([C@@H:34]([CH3:42])[CH:35]([O:39][CH2:40][CH3:41])[O:36][CH2:37][CH3:38])[CH2:23][C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=[CH:26][CH:25]=2)=[O:21])=[CH:49][CH:48]=1)([CH3:54])([CH3:52])[CH3:53]
Reactant: CN(CC(=O)O)NC(=O)NCc1ccncc1
Reactant: CCOC(OCC)[C@H](C)N(Cc1cccc2ccccc12)C(=O)[C@@H](N)Cc1ccc(OC(C)(C)C)cc1
Product: CCOC(OCC)[C@H](C)N(Cc1cccc2ccccc12)C(=O)[C@H](Cc1ccc(OC(C)(C)C)cc1)NC(=O)CN(C)NC(=O)NCc1ccncc1

Procedure:
According to the procedure described in the synthesis method of Compound II-15, 2-(1-methyl-2-(pyridin-4-ylmethylcarbamoyl)hydrazinyl)acetic acid (Compound VI-6) 71 mg (0.30 mmol) was coupled with (S)-2-amino-3-(4-tert-butoxyphenyl)-N—((S)-1,1-diethoxy-propan-2-yl)-N-(naphthalen-1-ylmethyl)propanamide (Compound IV-2) 100 mg (0.20 mmol) to obtain the title compound.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]([C:11]1[C:12]2[CH:13]=[CH:14][NH:15][C:16]=2[CH:17]=[CH:18][CH:19]=1)=[O:10].C(=O)([O-])[O-].[K+].[K+].[CH2:26]([CH:28]1[O:30][CH2:29]1)Cl>CC(C)=O>[O:30]1[CH2:29][CH:28]1[CH2:26][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]([C:11]1[C:12]2[CH:13]=[CH:14][NH:15][C:16]=2[CH:17]=[CH:18][CH:19]=1)=[O:10]
Reactant: ClCC1CO1
Reactant: O=C(Nc1ccccc1O)c1cccc2[nH]ccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: O=C(Nc1ccccc1OCC1CO1)c1cccc2[nH]ccc12

Procedure:
Under an inert atmosphere, a solution of 3 g of N-(2-hydroxyphenyl)-1H-indol-4-carboxamide and 1.65 g of potassium carbonate in 100 ml of acetone was refluxed for 24 hours with 4.7 ml of epichlorhydrin and after purifying by chromatography over silica (eluent: ethyl acetate--triethylamine, 9-1) and evaporating to dryness, the residue was triturated in pentane, then filtered and dried under reduced pressure at 60° C. to obtain 2.8 g of N-[2-[(2-oxiranyl)methoxy]phenyl]-1H-indol-4-carboxamide melting at 122° C.
Reaction SMILES: CC[C@@H]([C@H](NC([C@@H](N[C:149]([C@@H:151]([NH2:159])[CH2:152][CH2:153][CH2:154][NH:155][C:156]([NH2:158])=[NH:157])=[O:150])CCC(N)=O)=O)C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(O)=O)CCCCN)=O)CCCCN)=O)CC1C2C(=CC=CC=2)NC=1)=O)CCCCN)=O)CCSC)=O)CCCNC(N)=N)=O)CCCNC(N)=N)=O)CC(N)=O)=O)CCC(N)=O)=O)CC1C=CC=CC=1)=O)CC1C2C(=CC=CC=2)NC=1)=O)[C@H](CC)C)=O)CCCCN)=O)C.N[C@H](C(O)=[O:170])CCCNC(=N)N.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC(C(O)=O)=C(C2C3C=CC(O)=CC=3OC3C=2C=CC(C=3)=O)C=1.NC(CCCC)C(O)=O.C1C(N=C=S)=CC2C(OC3(C4C=CC(O)=CC=4OC4C=C(O)C=CC3=4)C=2C=1)=O.CCN(C(C)C)C(C)C.C(O)(C(F)(F)F)=O.C([SiH](C(C)C)C(C)C)(C)C>CN(C=O)C>[NH2:159][C@@H:151]([C:149]([OH:170])=[O:150])[CH2:152][CH2:153][CH2:154][NH:155][C:156](=[NH:157])[NH2:158]
Reactant: N=C(N)NCCC[C@H](N)C(=O)O
Reactant: CC[C@H](C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(=N)N)[C@@H](C)CC)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O
Agent: CC(C)[SiH](C(C)C)C(C)C
Agent: CCCCC(N)C(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Solvent: CN(C)C=O
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: N=C(N)NCCC[C@@H](N)C(=O)O

Procedure:
General Procedure for Peptide Synthesis. Tat49-57 (RKKRRQRRR; SEQ ID NO:28), truncated and alanine-substituted peptides derived from Tat49-57, Antennapedia43-58 (RQIKIWFQNRRMKWKK; SEQ ID NO:29), and homopolymers of arginine (R5–R9; SEQ ID NO:1–5) and d-arginine (r5-r9) were prepared with an automated peptide synthesizer (ABI433) using standard solid-phase Fmoc chemistry (35) with HATU as the peptide coupling reagent. The fluorescein moiety was attached via a aminohexanoic acid spacer by treating a resin-bound peptide (1.0 mmol) with fluorescein isothiocyanate (1.0 mmol) and DIEA (5 mmol) in DMF (10 mL) for 12 h. Cleavage from the resin was achieved using 95:5 TFA/triisopropylsilane. Removal of the solvent in vacuo gave a crude oil which was triturated with cold ether. The crude mixture thus obtained was centrifuged, the ether was removed by decantation, and the resulting orange solid was purified by reverse-phase HPLC (H2O/CH3CN in 0.1% TFA). The products were isolated by lyophilization and characterized by electrospray mass spectrometry. Purity of the peptides was >95% as determined by analytical reverse-phase HPLC (H2O/CH3CN in 0.1% TFA).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:10]2[N:11]=[CH:12][N:13]=[C:14](Cl)[C:9]=2[NH:8][CH:7]=1)=[O:5])[CH3:2].[CH:16]1([CH2:19][O:20][C:21]2[CH:26]=[C:25]([O:27][CH3:28])[C:24]([F:29])=[CH:23][C:22]=2B2OC(C)(C)C(C)(C)O2)[CH2:18][CH2:17]1>>[CH2:1]([O:3][C:4]([C:6]1[C:10]2[N:11]=[CH:12][N:13]=[C:14]([C:22]3[CH:23]=[C:24]([F:29])[C:25]([O:27][CH3:28])=[CH:26][C:21]=3[O:20][CH2:19][CH:16]3[CH2:18][CH2:17]3)[C:9]=2[NH:8][CH:7]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1c[nH]c2c(Cl)ncnc12
Reactant: COc1cc(OCC2CC2)c(B2OC(C)(C)C(C)(C)O2)cc1F
Product: CCOC(=O)c1c[nH]c2c(-c3cc(F)c(OC)cc3OCC3CC3)ncnc12

Procedure:
Starting from 4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester and 2-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (example A42) the title compound is obtained as pale yellow solid.
Reaction SMILES: C[O-].[Na+].[CH3:4][Si:5]([CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23](=[O:25])[CH3:24])=[CH:18][CH:17]=1)([CH3:13])[C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1.[N:26](OCCC(C)C)=[O:27].C(O)(=O)C>CO>[CH3:4][Si:5]([CH2:14][O:15][C:16]1[CH:17]=[CH:18][C:19]([C:22](=[N:26][OH:27])[C:23](=[O:25])[CH3:24])=[CH:20][CH:21]=1)([CH3:13])[C:6]1[CH:7]=[CH:8][C:9]([F:12])=[CH:10][CH:11]=1
Reactant: CC(C)CCON=O
Reactant: CC(=O)Cc1ccc(OC[Si](C)(C)c2ccc(F)cc2)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CC(=O)C(=NO)c1ccc(OC[Si](C)(C)c2ccc(F)cc2)cc1

Procedure:
28 ml of a 30% solution of sodium methanolate in methanol are added at room temperature to 31.6 g of 1-(4-[{dimethyl-(4-fluorophenyl)-silyl}methoxy]phenyl)-propan-2-one in 300 ml of methanol, and 27 ml of isopentyl nitrite are then added dropwise. The reaction mixture is stirred for a further hour and rendered neutral with acetic acid; the solvent is evaporated off in vacuo. 200 ml of ethyl acetate are added to the residue; the organic phase is washed with water and saturated sodium chloride solution and dried over sodium sulfate; the solvent is evaporated off in vacuo. Recrystallisation from diethyl ether/hexane yields the title product having a melting point of 115-117° C.
Reaction SMILES: [CH:1]([C:3](O)([CH2:8][CH2:9][CH2:10][CH3:11])[CH2:4][CH2:5][CH2:6][CH3:7])=[CH2:2]>C1(C)C=CC=CC=1>[CH:1]([C:3]([CH2:8][CH2:9][CH2:10][CH3:11])=[CH:4][CH2:5][CH2:6][CH3:7])=[CH2:2]
Reactant: C=CC(O)(CCCC)CCCC
Solvent: Cc1ccccc1
Product: C=CC(=CCCC)CCCC
Yield: 55.9 %

Procedure:
A solution of 5.1 grams of 5-vinyl-5-nonanol in 25 ml of toluene containing 38 mg of MTO was refluxed overnight, cooled, washed with aq. potassium carbonate, dried, stripped, and the residue distilled at 25 mm Hg to give 2.55 g (56%) of 5-vinyl-4-nonene as a cis/trans mixture, identified by NMR spectroscopy.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([OH:11])[CH3:10])[CH:5]=[CH:4][N:3]=1.[C:18]([N:26]=C=O)(=[O:25])C1C=CC=CC=1.C(O)C.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[OH:11][C:9]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)([CH3:10])[CH2:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:18]([NH2:26])=[O:25])[CH:7]=1
Reactant: O=C=NC(=O)c1ccccc1
Reactant: CC(O)(Cc1ccnc(N)c1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: ClCCl
Product: CC(O)(Cc1ccnc(NC(N)=O)c1)c1ccccc1
Temperature: 50 °C
Yield: 47 %

Procedure:
The crude 1-(2-Amino-pyridin-4-yl)-2-phenyl-propan-2-ol (120 mg) is dissolved in methylene chloride (4 mL). Then benzoyl isocynate (155 mg, 1.1 mmol) is added. The reaction mixture is sealed and heated at 50° C. for 16 hour. The solvent is then carefully removed and to the residue are added ethanol (5 mL) and potassium carbonate (73 mg, 0.53 mmol). The resulting mixture is heated at 85° C. for 2 hrs. Then solvent is removed to give the crude product which is purified by silica flash column chromatography using MeOH in DCM (gradient from 0% to 10%) to give 67 mg of the titled product.