Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]1[C:20]2[CH:19]=[CH:18][CH:17]=[C:16]([OH:21])[C:15]=2[C:14]2[C:9]1=[C:10]([F:22])[CH:11]=[CH:12][CH:13]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:24]([N:26]([CH2:30][CH3:31])[CH2:27][CH2:28]Cl)[CH3:25].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CN(C=O)C>[CH2:1]([N:8]1[C:20]2[CH:19]=[CH:18][CH:17]=[C:16]([O:21][CH2:25][CH2:24][N:26]([CH2:30][CH3:31])[CH2:27][CH3:28])[C:15]=2[C:14]2[C:9]1=[C:10]([F:22])[CH:11]=[CH:12][CH:13]=2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Oc1cccc2c1c1cccc(F)c1n2Cc1ccccc1
Reactant: CCN(CC)CCCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CN(C)C=O
Product: CCN(CC)CCOc1cccc2c1c1cccc(F)c1n2Cc1ccccc1
Yield: 56.1 %

Procedure:
9-Benzyl-8-fluoro-9H-carbazol-4-ol (0.0273 g, 0.0940 mmol), 2-diethylaminoethylchloride hydrochloride (0.0237 g, 0.14 mmol), potassium carbonate (0.0396 g, 0.29 mmol), sodium iodide (0.0013 g, 0.0087 mmol) and DMF (1 mL) are heated at 80° C. for 3 h. After the mixture had cooled, it is partitioned between water and ethyl acetate. The organic layer is dried over magnesium sulfate and concentrated to an oil. The oil is chromatographed on silica gel (20 mL) using methanol/dichloromethane (1/99 to 2/98 to 3/97) to give 0.0206 g (56%) of the title compound; mp 60-60.5° C.; MS (ESI+) for C25H27FN2O m/z 391.3 (M+H)+; 1H NMR (CDCl3) δ1.17, 2.79, 3.17, 4.39, 5.53, 6.73, 7.02, 7.13, 7.25, 7.38, 8.15. Anal. Calcd for C25H27FN2O: C, 76.89; H, 6.97; N, 7.17. Found: C, 76.33; H, 7.18; N, 7.13.
Reaction SMILES: [O:1]=[C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[S:5][C:4]([C:12]2[N:17]=[C:16]([C:18]([OH:20])=O)[CH:15]=[CH:14][CH:13]=2)=[N:3]1.[NH2:21][CH2:22][CH2:23][OH:24].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.O.C(OCC)(=O)C>[OH:24][CH2:23][CH2:22][NH:21][C:18]([C:16]1[CH:15]=[CH:14][CH:13]=[C:12]([C:4]2[S:5][C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[C:2](=[O:1])[N:3]=2)[N:17]=1)=[O:20]
Reactant: NCCO
Reactant: O=C(O)c1cccc(-c2nc(=O)c3ccccc3s2)n1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C(NCCO)c1cccc(-c2nc(=O)c3ccccc3s2)n1
Temperature: 80 °C
Reaction time: 6 h
Yield: 10.5 %

Procedure:
6-(4-Oxo-4H-1,3-benzothiazin-2-yl)-2-pyridinecarboxylic acid (1.00 g, 3.5 mmol) was dissolved in DMF (20 ml). 2-Aminoethanol (0.51 g, 8.3 mmol), WSC (1.34 g, 7.0 mmol) and HOBt (0.95 g, 7.0 mmol) were added thereto, and the mixture was stirred at 80° C. for 6 hrs. The reaction mixture was combined with ethyl acetate and water. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was subjected to a silica gel column chromatography. The fractions eluted with ethyl acetate-methanol (4:1, v/v) were collected, concentrated and recrystallized from diisopropyl ether-methanol to give the titled compound (0.12 g, 10%) as pale yellow crystals.
Reaction SMILES: [CH3:1][N:2]([CH3:35])[C:3]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:8][CH2:7][C:6]([CH2:10][CH2:11][CH2:12][C:13]2[C:17]3[CH:18]=[N:19][CH:20]=[CH:21][C:16]=3[NH:15][C:14]=2[Si](CC)(CC)CC)([OH:9])[CH2:5][CH2:4]1.O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[CH3:35][N:2]([CH3:1])[C:3]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:8][CH2:7][C:6]([CH2:10][CH2:11][CH2:12][C:13]2[C:17]3[CH:18]=[N:19][CH:20]=[CH:21][C:16]=3[NH:15][CH:14]=2)([OH:9])[CH2:5][CH2:4]1
Reactant: CC[Si](CC)(CC)c1[nH]c2ccncc2c1CCCC1(O)CCC(c2ccccc2)(N(C)C)CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: CN(C)C1(c2ccccc2)CCC(O)(CCCc2c[nH]c3ccncc23)CC1

Procedure:
A solution of 4-dimethylamino-4-phenyl-1-[3-(2-triethylsilanyl-1H-pyrrolo[3,2-c]pyridin-3-yl)propyl]cyclohexanol (410 mg, 0.83 mmol) in anhydrous tetrahydrofuran (25 mL) was mixed with tetra-n-butyl ammonium fluoride trihydrate (1.05 g, 3.32 mmol) and boiled with reflux for 6 h. The reaction mixture was then concentrated to low volume in a vacuum and the raw product purified by means of flash chromatography (38 g, 20×2.5 cm) with ethyl acetate/methanol (2:1). The product was taken up in dichloromethane (40 mL), the solution dried with sodium sulphate and concentrated to low volume in a vacuum.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([NH2:19])[C:7]([C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=2)=[CH:8][CH:9]=1)([O-:3])=[O:2].N([O-])=O.[Na+].NC(N)=O.[N-:28]=[N+:29]=[N-].[Na+]>C(O)(=O)C.S(=O)(=O)(O)O.O>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][C:13]([N+:16]([O-:18])=[O:17])=[CH:14][CH:15]=2)=[C:6]([N:19]=[N+:28]=[N-:29])[CH:5]=1)([O-:3])=[O:2]
Reactant: [N-]=[N+]=[N-]
Reactant: Nc1cc([N+](=O)[O-])ccc1-c1ccc([N+](=O)[O-])cc1
Agent: NC(N)=O
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(=O)O
Product: [N-]=[N+]=Nc1cc([N+](=O)[O-])ccc1-c1ccc([N+](=O)[O-])cc1
Reaction time: 0.33 h
Yield: 66.9 %

Procedure:
To a solution of 10.0 g (38.6 mmol) of 4,4′-dinitro-2-biphenylamine in a mixture of 200 mL of acetic acid and 40 mL of sulfuric acid at 0° C. was added dropwise 5.32 g (77.2 mmol, Aldrich Co.) of sodium nitrite. The mixture was stirred at 5-10° C. for 2 h after 5.00 g of urea (to destroy the excess nitrous acid), 500 mL of ice-water and 5 g of activated carbon was added. The cold suspension was stirred again for 20 min and filtrated rapidly through a Büchner funnel into a flask immersed in an ice bath. A solution of 5.07 g (77.2 mmol, Aldrich Co.) of sodium azide in 100 mL of water was added dropwise to the yellow clear filtrate. The resulting solution was stirred at 0° C. for 1 h and at room temperature for 24 h. The mixture was quenched with 500 mL of a solution of NaHCO3 in water and extracted three times with ethyl acetate. The organic layer was dried over magnesium sulfate and the solvent was removed under vacuum. Recristallization in ethanol afforded 7.37 g of the title product as a yellow solid. M.P. 171-172° C. (Yield: 72%).
Reaction SMILES: [CH3:1][C:2]1[C:6]([CH:7]([CH3:10])[CH2:8][OH:9])=[CH:5][N:4]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[N:3]=1.C(P(CCCC)CCCC)CCC.[CH3:34][O:35][C:36](=[O:49])[CH2:37][C:38]1[C:46]2[C:41](=[CH:42][C:43](O)=[CH:44][CH:45]=2)[N:40]([CH3:48])[CH:39]=1>C1(C)C=CC=CC=1>[CH3:34][O:35][C:36](=[O:49])[CH2:37][C:38]1[C:46]2[C:41](=[CH:42][C:43]([O:9][CH2:8][CH:7]([C:6]3[C:2]([CH3:1])=[N:3][N:4]([C:11]4[CH:16]=[CH:15][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:13][CH:12]=4)[CH:5]=3)[CH3:10])=[CH:44][CH:45]=2)[N:40]([CH3:48])[CH:39]=1
Reactant: COC(=O)Cc1cn(C)c2cc(O)ccc12
Reactant: Cc1nn(-c2ccc(C(F)(F)F)cc2)cc1C(C)CO
Agent: CCCCP(CCCC)CCCC
Solvent: Cc1ccccc1
Product: COC(=O)Cc1cn(C)c2cc(OCC(C)c3cn(-c4ccc(C(F)(F)F)cc4)nc3C)ccc12
Temperature: 0 °C
Yield: 58.6 %

Procedure:
2-[3-Methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-propan-1-ol (150 mg, 0.5276 mmol) is dissolved into anhydrous toluene (2 mL) and cooled in an ice bath to 0° C. with stirring under nitrogen. Tributyl phosphine (200 uL, 0.7914 mmol) is added by syringe followed by 1-1′-azodicarbonyl-dipiperidine (200 mg, 0.7914 mmol). Finally, (6-Hydroxy-1-methyl-1H-indol-3-yl)-acetic acid methyl ester (145 mg, 0.6596 mmol) is then added. The reaction is allowed to stir under nitrogen at 0° C. for 1 hour, then room temperature and monitored by TLC and HPLC. Upon completion, the reaction is diluted with hexanes and allowed to stir vigorously for 10 min. The resulting white precipitate is then filtered away and the solution is concentrated under vacuum. The residue is further purified using either EtOAc/Hexanes (1:9) or Acetone/Hexanes (1:9) gradients on silica gel chromatography to yield (1-Methyl-6-{2-[3-methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-propoxy}-1H-indol-3-yl)-acetic acid methyl ester (150 mg, 0.309 mmol) or 59%.
Reaction SMILES: [Br:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17]Cl)=[CH:13][CH:12]=1.C([O-])([O-])=O.[K+].[K+].CN(C=O)C>O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH2:17][C:14]2[CH:15]=[CH:16][C:11]([O:10][CH3:9])=[CH:12][CH:13]=2)=[CH:6][N:7]=1
Reactant: COc1ccc(CCl)cc1
Reactant: Oc1ccc(Br)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(COc2ccc(Br)nc2)cc1

Procedure:
To a round-bottomed flask was added 6-bromopyridin-3-ol (5.0 g), PMBCl (4.95 g), K2CO3 (7.93 g) and DMF (20 mL). The resultant mixture was stirred at r.t. overnight. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (50 mL×2). The combined organic layers was washed with water (20 mL×2), brine (20 mL×2), and dried over anhydrous Na2SO4. After filtration and evaporation of the solvent, the residue was recrystallized from ethyl acetate and petroleum ether to provide the subtitle compound. MS ESI+: m/z=294 [M+H]+.
Reaction SMILES: Cl.[CH:2]([N:5]1[C:9]([C:10]2[N:19]=[C:18]3[N:12]([CH2:13][CH2:14][O:15][C:16]4[CH:23]=[C:22]([C@@H:24]5[CH2:29][CH2:28][NH:27][CH2:26][C@H:25]5[OH:30])[CH:21]=[CH:20][C:17]=43)[CH:11]=2)=[N:8][CH:7]=[N:6]1)([CH3:4])[CH3:3].[CH3:31][N:32]([CH3:37])[C:33](=[O:36])[CH2:34]Cl>>[OH:30][C@H:25]1[C@H:24]([C:22]2[CH:21]=[CH:20][C:17]3[C:18]4[N:12]([CH:11]=[C:10]([C:9]5[N:5]([CH:2]([CH3:4])[CH3:3])[N:6]=[CH:7][N:8]=5)[N:19]=4)[CH2:13][CH2:14][O:15][C:16]=3[CH:23]=2)[CH2:29][CH2:28][N:27]([CH2:34][C:33]([N:32]([CH3:37])[CH3:31])=[O:36])[CH2:26]1
Reactant: CC(C)n1ncnc1-c1cn2c(n1)-c1ccc([C@@H]3CCNC[C@H]3O)cc1OCC2
Reactant: CN(C)C(=O)CCl
Agent: Cl
Product: CC(C)n1ncnc1-c1cn2c(n1)-c1ccc([C@@H]3CCN(CC(=O)N(C)C)C[C@H]3O)cc1OCC2
Yield: 80.4 %

Procedure:
Following the procedure for Example 330, trans-racemic-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-piperidin-3-ol hydrochloride (0.15 g, 0.35 mmol) was reacted with N,N-dimethyl-2-chloroacetamide (46 mg, 0.38 mmol) to give 304 (135 mg, 80%). LCMS: RT=2.50 min, [M+H]+=480. 1H NMR 400 MHz (CDCl3) δ: 8.40 (1H, d, J=8.26 Hz), 7.86 (1H, s), 7.43 (1H, s), 7.08-7.03 (1H, m), 6.82 (1H, d, J=1.72 Hz), 6.02 (1H, m), 4.38 (4H, m), 4.10 (1H, br, m), 3.38 (2H, m), 3.31 (2H, m), 3.09 (3H, s), 3.00 (1H, m), 2.98 (3H, s), 2.47 (2H, m), 1.86 (2H, m), 1.60 (6H, dd, J=6.59, 2.76 Hz)
Reaction SMILES: Cl.[CH:2]1[C:14]2[CH:13]([CH2:15][O:16][C:17]([NH:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)=[O:18])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[NH:41]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[C@@H:42]([C:51](O)=[O:52])[CH2:43][C:44]1[CH:49]=[CH:48][C:47]([Cl:50])=[CH:46][CH:45]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[Cl:50][C:47]1[CH:48]=[CH:49][C:44]([CH2:43][C@@H:42]([NH:41][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[C:51]([N:29]2[CH2:28][CH2:27][CH:26]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[NH:19][C:17]([O:16][CH2:15][CH:13]3[C:12]4[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=4[C:6]4[C:14]3=[CH:2][CH:3]=[CH:4][CH:5]=4)=[O:18])[CH2:31][CH2:30]2)=[O:52])=[CH:45][CH:46]=1
Reactant: O=C(Nc1ccccc1C1CCNCC1)OCC1c2ccccc2-c2ccccc21
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)O
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Product: CC(C)(C)OC(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCC(c2ccccc2NC(=O)OCC2c3ccccc3-c3ccccc32)CC1
Yield: 67.3 %

Procedure:
The title compound was prepared according to the procedure described in Example 1 (Step f) from (fluoren-9-ylmethoxy)-N-(2-(4-piperidyl)phenyl)-carboxamide hydrochloride (Step b) (6.51 g, 15 mmol), DIEA (2.7 mL, 15 mmol), Boc-p-Cl-D-PheOH (PepTech Corporation) (6.8 g, 22.5 mmol), HOAT (Aldrich) (3.1 g, 22.5 mmol) and EDC (Aldrich) (4.32 g, 22.5 mmol) in DMF (25 mL). Purification by silica gel chromatography (3:1 hexane:EtOAc) provided the title compound as a white foam (6.87 g). MS (ESI, pos. ion) m/z: 680 (M+1); MS (ESI, neg. ion) m/z: 678 (M−1). Calc'd for C40H42ClN3O5: 679.28.
Reaction SMILES: [S:1]1[C:9]2[CH2:8][CH2:7][NH:6][CH2:5][C:4]=2[CH:3]=[CH:2]1.[C:10]([N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][CH2:24]I)[CH2:19][CH2:18]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].[OH-].[Na+]>C(Cl)Cl>[C:10]([N:17]1[CH2:18][CH2:19][CH:20]([CH2:23][CH2:24][N:6]2[CH2:7][CH2:8][C:9]3[S:1][CH:2]=[CH:3][C:4]=3[CH2:5]2)[CH2:21][CH2:22]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11]
Reactant: c1cc2c(s1)CCNC2
Reactant: CC(C)(C)OC(=O)N1CCC(CCI)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(CCN2CCc3sccc3C2)CC1
Reaction time: 20 h

Procedure:
A suspension of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine.HCL (2-1) (1.76 g, 0.01 moles) in CH2Cl2 (15 ml) was treated with 2-(N-BOC-4-piperidinyl)ethyl iodide (2--2) (3.73 g, 0.011 moles) followed by 20% NaOH (10 ml) and Aliquot-336 (Aldrich). After stirring for 20 hours the reaction mixture was diluted with CH2Cl2 and the organic phase was separated, washed with brine, dried (Na2SO4) and concentrated. The residue was purified by flash chromatography on silica gel eluting with CHCl3 (98)/MeOH(2) to give pure 2-3.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N+:11]([O-])=O)=[C:7]([CH:10]=1)[CH:8]=[O:9].CC([O-])=O.[Na+].CCN(C(C)C)C(C)C.[C:28]([O:31][CH2:32][C:33](Cl)=[O:34])(=[O:30])[CH3:29]>CCOC(C)=O.O=[Pt]=O>[C:28]([O:31][CH2:32][C:33]([NH:11][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:10][C:7]=1[CH:8]=[O:9])=[O:34])(=[O:30])[CH3:29]
Reactant: CC(=O)OCC(=O)Cl
Reactant: COc1ccc([N+](=O)[O-])c(C=O)c1
Agent: O=[Pt]=O
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(NC(=O)COC(C)=O)c(C=O)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 6.8 %

Procedure:
To the solution of 5-methoxy-2-nitrobenzaldehyde (6 g, 0.33 mol) in EtOAc (100 mL) was added 20% PtO2/C (1.2 g, 20%) and NaOAc (1.2 g, 20%). The reaction was stirred under hydrogen at room temperature for 0.5 h. The mixture was filtered through a Celite pad, and the filtrate was dried over anhydrous Na2SO4. After filtration, the solution was cooled to −78° C., and to which was added DIPEA (6.4 g, 0.5 mol, 1.5 eq) and 2-chloro-2-oxoethyl acetate (4.5 g, 0.33 mol, 1.0 eq). The resulting mixture was gradually warmed up to room temperature and stirred overnight. The reaction mixture was washed with water twice, dried over Na2SO4 and evaporated most of the solvent in vacuum. Then the solid separating out was collected by filtration to give 2-(2-formyl-4-methoxyphenylamino)-2-oxoethyl acetate (5.6 g, yield: 71%) as a light yellow solid.
Reaction SMILES: C1C2NC3C(=CC=CC=3)SC=2C=CC=1.[CH3:15][O:16][CH:17]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=[CH:18]1>>[CH3:15][O:16][C:17]1[CH:18]=[CH:19][CH2:20][CH:21]=[CH:22][CH:23]=1
Reactant: COC1C=CC=CC=C1
Agent: c1ccc2c(c1)Nc1ccccc1S2
Product: COC1=CC=CCC=C1
Temperature: 150 °C

Procedure:
Phenothiazine (1.4 gm=0.1% by weight of 7-methoxycycloheptatriene) was dissolved in 1381.9 gm of distilled 7-methoxycycloheptatriene. The solution was then heated under nitroen at ambient pressure for 2 hours at 150° C., during which time low-boiling materials were removed by a condenser set for downward distillation. Upon cooling, the residual material weighed 1345.2 grams, representing a crude yield of 97.3% (based on initial 7-methoxy isomer). NMR analysis indicated a product composition of 76 mole % 3-methoxycyclohepta-1,3,5-triene, 12 mole % 1-methoxycyclohepta-1,3,5-triene and 4 mole % unconverted 7-methoxy isomer. The product was of sufficiently good quality to be utilized for conversion to 1-methoxycycloheptatriene without prior distillation.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.C(=O)([O-])[O-].[K+].[K+].Br[CH2:18][C:19]#[N:20]>C(#N)C>[NH:9]1[C:10]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2[O:1][CH2:18][C:19]#[N:20])[CH:7]=[CH:8]1
Reactant: N#CCBr
Reactant: Oc1cccc2cc[nH]c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: N#CCOc1cccc2cc[nH]c12
Temperature: 0 °C
Reaction time: 3 h

Procedure:
In a 100 mL roundbottom flask equipped with a magnetic stirrer and rubber septum, 7-hydroxy-1H-indole (1.66 g., 12.48 mmol) was dissolved 50 mL anhydrous acetonitrile. The flask was charged with potassium carbonate (6.88 g., 49.9 mmol) and cooled to 0° C. While stirring, bromoacetonitrile (1.64 g., 13.73 mmol) was added dropwise over two minutes. The reaction mixture was allowed to warm to ambient temperature and stirring was continued for three hours. The solution was washed with water (2×30 mL) and brine (1×30 mL), dried over MgSO4 and concentrated in vacuo. The resulting oily brown residue was purified by flash chromatography (95:5 ethyl acetate:hexanes to 85:15 ethyl acetate:hexanes over minutes) to give (1H-Indol-7-yloxy)-acetonitrile as a crystalline solid (0.244-g.) ms: (M−H)−=171.2.
Reaction SMILES: [CH:1]([N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:20][CH2:21][CH2:22][CH2:23][S:24](Cl)(=[O:26])=[O:25].C(Cl)(Cl)Cl>ClCCl>[C:2]1([CH:1]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:14]2[CH2:19][CH2:18][N:17]([S:24]([CH2:23][CH2:22][CH2:21][Cl:20])(=[O:26])=[O:25])[CH2:16][CH2:15]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: c1ccc(C(c2ccccc2)N2CCNCC2)cc1
Reactant: O=S(=O)(Cl)CCCCl
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: O=S(=O)(CCCCl)N1CCN(C(c2ccccc2)c2ccccc2)CC1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
39.2 g (155 mmol) benzhydrylpiperazine and 19.7 ml (141 mmol) TEA are present in 100 ml absolute dichloromethane and cooled to ca. 0° C. under moisture exclusion. 25 g (141 mmol) 3-chloropropanesulfonyl chloride are dissolved in 70 ml absolute dichloromethane and added dropwise. The mixture is stirred for two hours under cooling and subsequently mixed with chloroform and washed with saturated NaCl solution. The organic phase is dried over sodium sulfate and concentrated under vacuum until dry. The solid is further processed without further purification: yield 59.2 g.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]([C:13]([F:16])([F:15])[F:14])=[C:4]([F:12])[C:5]([F:11])([F:10])[C:6]([F:9])([F:8])[F:7].II>>[F:7][C:6]([F:8])([F:9])[C:5]([F:10])([F:11])[CH:4]([F:12])[CH:3]([C:13]([F:15])([F:14])[F:16])[C:2]([F:18])([F:17])[F:1]
Reactant: FC(=C(C(F)(F)F)C(F)(F)F)C(F)(F)C(F)(F)F
Agent: II
Product: FC(C(C(F)(F)F)C(F)(F)F)C(F)(F)C(F)(F)F
Temperature: -78 °C
Reaction time: 15 h
Yield: 45.7 %

Procedure:
Perfluoro-2-methylpent-2-ene (3 g) and iodine (1.25 g) were sealed in a 10 mL pressure tube. The tube was cooled to -78° C., evacuated, and charged with 1500 psi of hydrogen at room temperature. The tube was then heated at 240° C. for 1 h, and 260° C. for 15 h. The tube was cooled, vented, and opened. The liquid was washed with water, giving 1,1,1,2,2,3,5,5,5-nonafluoro-4-trifluoromethylpentane (1.38 g) which was 99.5% pure by GC analysis. GC/IR 3000 cm-1, w (C-H); 1288 cm-1, vs (C-F); 1228 cm-1, vs (C-F); 691 cm-1, m. 19FNMR (CCl3F as internal standard): -62 ppm, c, 3F; -67.5 ppm, c, 3F; -83.9 ppm, t, 3F; -122-133 ppm, AB, 2F; -212.2 ppm, c, 1 F. 1HNMR (CHCl3 as internal standard): 5.27 ppm, dd, 1H; 3.55 ppm, c, 1H. The boiling point of this product was 67° C.
Reaction SMILES: Cl[C:2]1[C:3]2[C:10]([C:11]([OH:13])=[O:12])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[NH2:14][C:15]1[CH:16]=[C:17]([C:21]#[CH:22])[CH:18]=[CH:19][CH:20]=1>CO>[C:21]([C:17]1[CH:16]=[C:15]([NH:14][C:2]2[C:3]3[C:10]([C:11]([OH:13])=[O:12])=[CH:9][NH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:20]=[CH:19][CH:18]=1)#[CH:22]
Reactant: C#Cc1cccc(N)c1
Reactant: O=C(O)c1c[nH]c2ncnc(Cl)c12
Solvent: CO
Product: C#Cc1cccc(Nc2ncnc3[nH]cc(C(=O)O)c23)c1
Temperature: 125 °C
Yield: 56.7 %

Procedure:
To 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid (0.38 g, 1.9 mmol) in dry methanol (4ml) was added m-aminophenyl acetylene (0.47 g, 4.0 mmol). The suspension was heated in a sealed pressure tube at 125° C. for 18 hours. The reaction mixture was cooled to ambient temperature, filtered with methylene chloride washes and dried in vacuo to afford the title compound as a tan powder (0.30 g, 54%). TS-MS: 278 (MH+); anal. RP18-HPLC RT: min.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.Br[CH2:18][C:19]([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)=[O:20].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH:11]2[CH2:16][CH2:15][N:14]([CH2:18][C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[O:20])[CH2:13][CH2:12]2)(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: O=S(=O)(c1ccc(Br)cc1)C1CCNCC1
Reactant: O=C(CBr)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: O=C(CN1CCC(S(=O)(=O)c2ccc(Br)cc2)CC1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 17 h
Yield: 37.9 %

Procedure:
4-(4-Bromophenylsulphonyl)piperidine (Example 1 Step d, 0.9 g, 0.003 mol) was added to a mixture of 2-bromo-4′-fluoroacetophenone (0.7 g, 0.0033 mol) and potassium carbonate (0.84 g, 0.006 mol) in acetonitrile (5 ml) and the resulting slurry stirred at room temperature for 17 h. The insolubles were removed by filtration and the solvent evaporated to give a gum which was purified by column chromatography (SiO2, CH2Cl2:MeOH 97:3) to give 0.5 g (36% yield) of product as a colourless solid. δH (400 MHz, CDCl3) 1.75-1.90 (2H, m), 2.05-2.13 (2H, m), 2.25-2.40 (2H, m), 2.85-3.00 (1H, m), 3.04-3.20 (2H, m), 3.75-3.85 (2H, m), 7.12 (1H, t, 8 Hz), 7.24 (4H, s), 7.98-8.02 (2H, m).
Reaction SMILES: C[C@@H]1[O:7][C@@H:6](OC[C@H]2O[C@@H](OC3C(=O)C4C(O)=CC(O)=CC=4OC=3C3C=CC(O)=C(O)C=3)[C@H](O)[C@@H](O)[C@@H]2O)[C@H](O)[C@H](O)[C@H]1O.CC1OC(OCC2OC(O[C:60]3[C:69](=[O:70])[C:68]4[C:63](=[CH:64][C:65]([OH:72])=[CH:66][C:67]=4[OH:71])[O:62][C:61]=3[C:73]3[CH:78]=[CH:77][C:76](O)=[C:75]([OH:80])[CH:74]=3)C(O)C(O)C2O)C(O)C(O)C1O.C1[C@H]2C3N(C[C@@H]1CNC2)C(=O)C=CC=3>>[CH3:6][O:7][C:76]1[CH:77]=[CH:78][C:73]([C@H:61]2[O:62][C:63]3[CH:64]=[C:65]([OH:72])[CH:66]=[C:67]([OH:71])[C:68]=3[C:69](=[O:70])[CH2:60]2)=[CH:74][C:75]=1[OH:80]
Reactant: CC1OC(OCC2OC(Oc3c(-c4ccc(O)c(O)c4)oc4cc(O)cc(O)c4c3=O)C(O)C(O)C2O)C(O)C(O)C1O
Reactant: C[C@@H]1O[C@@H](OC[C@H]2O[C@@H](Oc3c(-c4ccc(O)c(O)c4)oc4cc(O)cc(O)c4c3=O)[C@H](O)[C@@H](O)[C@@H]2O)[C@H](O)[C@H](O)[C@H]1O
Agent: O=c1cccc2n1C[C@@H]1CNC[C@H]2C1
Product: COc1ccc([C@@H]2CC(=O)c3c(O)cc(O)cc3O2)cc1O

Procedure:
rutin, 3-[[6-O-(6-Deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl]oxy]-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one; rutoside; quercetin-3-rutinoside; 3,3′,4′,5,7-pentahydroxyflavone-3-rutinoside; melin; phytomelin; eldrin; ilixathin; sophorin; globularicitrin; paliuroside; osyritrin; osyritin; myrticolorin; violaquercitrin; Birutan; Rutabion; Rutozyd; Tanrutin;