Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](/[C:3](=[CH:9]\[C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:12][CH:11]=1)/[C:4]([O:6]CC)=O)#[N:2].[C:23]([NH2:31])(=[NH:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(OCC)(=O)C>CO>[O:6]=[C:4]1[NH:31][C:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[N:30][C:9]([C:10]2[CH:11]=[CH:12][C:13]([O:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:14][CH:15]=2)=[C:3]1[C:1]#[N:2]
Reactant: CCOC(=O)/C(C#N)=C/c1ccc(Oc2ccccc2)cc1
Reactant: N=C(N)c1ccccc1
Solvent: CO
Solvent: CCOC(C)=O
Product: N#Cc1c(-c2ccc(Oc3ccccc3)cc2)nc(-c2ccccc2)[nH]c1=O
Temperature: 25 °C
Reaction time: 15 h

Procedure:
A mixture of (E)-ethyl 2-cyano-3-(4-phenoxyphenyl)acrylate (100 mg, 0.341 mmol) and benzamidine (45.1 mg, 0.375 mmol) in methanol (1 mL) was stirred at room temperature for 15 h while opening to the air. The mixture was treated with ethyl acetate (30 mL), washed with water (5 mL), brine (5 mL), dried (MgSO4) and concentrated to give crude 6-oxo-4-(4-phenoxyphenyl)-2-phenyl-1,6-dihydropyrimidine-5-carbonitrile as tan solid. The crude material was taken to next reaction without purification. MS (ES+) m/z: 366 (M+H); LC retention time: 4.525 min (analytical HPLC Method B).
Reaction SMILES: [I:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([NH:11][S:12]([C:15]2[C:16]3[N:17]=[CH:18][CH:19]=[N:20][C:21]=3[CH:22]=[CH:23][CH:24]=2)(=[O:14])=[O:13])[CH:3]=1.Cl.[CH3:26][O:27][C:28](=[O:40])[C@@H:29]([NH2:39])[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([I:38])[CH:32]=1>>[CH3:26][O:27][C:28](=[O:40])[C@@H:29]([NH:39][C:6](=[O:7])[C:5]1[CH:9]=[CH:10][C:2]([I:1])=[CH:3][C:4]=1[NH:11][S:12]([C:15]1[C:16]2[N:17]=[CH:18][CH:19]=[N:20][C:21]=2[CH:22]=[CH:23][CH:24]=1)(=[O:14])=[O:13])[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([I:38])[CH:32]=1
Reactant: COC(=O)[C@@H](N)Cc1ccc(Cl)c(I)c1
Reactant: O=C(O)c1ccc(I)cc1NS(=O)(=O)c1cccc2nccnc12
Agent: Cl
Product: COC(=O)[C@H](Cc1ccc(Cl)c(I)c1)NC(=O)c1ccc(I)cc1NS(=O)(=O)c1cccc2nccnc12

Procedure:
4-Iodo-2-(quinoxaline-5-sulfonylamino)-benzoic acid was coupled to (S)-2-amino-3-(4-chloro-3-iodo-phenyl)-propionic acid methyl ester hydrochloride as in EXAMPLE 1, Part C, to afford title compound. HPLC: RT=10.61 min. MS (ESI+): mass calcd. for C25H19ClI2N4O5S, 776.77; m/z found, 777/779 [M+H]+. 1H NMR (400 MHz, CDCl3): 11.09 (s, 1H), 9.01-8.98 (m, 1H), 8.95-8.92 (m, 1H), 8.58 (d, J=7.3, 1H), 8.34 (d, J=8.5, 1H), 8.11 (d, J=1.5, 1H), 7.94-7.88 (m, 1H), 7.57 (d, J=1.9, 1H), 7.36-7.26 (m, 2H), 7.00-6.94 (m, 2H), 6.42 (d, J=6.3, 1H), 4.95-4.88 (m, 1H), 3.81 (s, 3H), 3.20-3.07 (m, 2H).
Reaction SMILES: [N+:1]([C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.[CH:20](N)([CH3:22])[CH3:21]>C1CCCCC1>[CH:20]([NH:1][C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([CH3:22])[CH3:21]
Reactant: CC(C)N
Reactant: O=C1c2ccccc2C(=O)c2c1cccc2[N+](=O)[O-]
Solvent: C1CCCCC1
Product: CC(C)Nc1cccc2c1C(=O)c1ccccc1C2=O
Yield: 93.5 %

Procedure:
63.3 g of 1-nitroanthraquinone (99% pure) in 320 ml of cyclohexane are reacted with 147.8 g of isopropylamine (molar ratio 10:1) for 70 minutes at a temperature of 160° C. and under a pressure of 50 bars. Working up analogously to Example 1 gives 62 g (94.5% of theory) of 97.6% pure 1-isopropylamino-anthraquinone.
Reaction SMILES: Br[C:2]1[C:3]([NH2:9])=[N:4][CH:5]=[C:6]([Br:8])[N:7]=1.[CH3:10][Si:11]([C:14]#[CH:15])([CH3:13])[CH3:12]>C1COCC1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:8][C:6]1[N:7]=[C:2]([C:15]#[C:14][Si:11]([CH3:13])([CH3:12])[CH3:10])[C:3]([NH2:9])=[N:4][CH:5]=1
Reactant: Nc1ncc(Br)nc1Br
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: C1CCOC1
Product: C[Si](C)(C)C#Cc1nc(Br)cnc1N
Temperature: -2.5 °C
Reaction time: 1.5 h
Yield: 97.6 %

Procedure:
To a solution of 3,5-dibromopyrazin-2-amine (125 g, 494 mmol), TEA (207.0 mL, 1483 mmol), and copper (I) iodide (0.941 g, 4.94 mmol) in THF (1255 mL) was added PdCl2(PPh3)2 (3.47 g, 4.94 mmol). The reaction mixture was cooled at about −5-0° C. and a solution of (trimethylsilyl)acetylene (65.0 mL, 470 mmol) in THF (157 mL) was added dropwise over about 15 min. The reaction mixture was stirred at about −5-0° C. for about 1.5 h and then allowed to warm to rt overnight. The reaction mixture was then filtered through a Celite® pad and washed with THF until no further product eluted. The filtrate was concd under reduced pressure to give a brown-orange solid. The solid was triturated and sonicated with warm petroleum ether (b.p. 30-60° C., 400 mL), cooled to rt, collected, washed with petroleum ether (b.p. 30-60° C.; 2×60 mL), and dried to give 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (124 g, 93%, 93% purity) as a brown solid: LC/MS (Table 1, Method b) Rt=2.51 min; MS m/z: 270, 272 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][P:4]([O-:8])[O:5]CC)[CH3:2].[C:9]([BH2:11])#[N:10].[Si](I)(C)(C)C.CCOC(C)=O>CC#N>[CH2:1]([O:3][P:4]([O-:8])[O-:5])[CH3:2].[C:9]([BH2:11])#[N:10]
Reactant: CCOP([O-])OCC
Agent: BC#N
Agent: C[Si](C)(C)I
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CCOP([O-])[O-]
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
Diethylphosphite-cyanoborane (7a) (1. 15 g) and Me3SiI (4 equivalents) were taken in anhydrous CH3CN and were heated at reflux in the dark for 2 days. The solvent and excess Me3SiI were removed under reduced pressure. The residue was taken in CH2Cl2 /water (1:1, v/v, 50 ml) and was stirred at room temperature for 1.5 hours. The aqueous layer was separated and washed with CH2Cl2 until the organic layer was colorless. The water was evaporated at room temperature by passing a stream of air over the solution. The residue was taken in EtOAc and filtered to remove a solid. The filtrate was dried and the solvent was removed under reduced pressure to give an oil. Often, the EtOAc solution became dark colored, which could not be removed by treatment with charcoal. To remove this color, the EtOAc was removed and the whole work-up was repeated. The yield of light yellow oil was 0.49 g, 50.72%.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[CH:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]1)#[N:2].[NH:20]1[C:28]2[C:23](=[C:24]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)[CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl>[CH3:12][N:8]1[C:9]2[CH:10]=[CH:11][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[C:6]([CH:13]2[CH2:18][CH2:17][CH:16]([N:32]3[CH2:33][CH2:34][N:29]([C:24]4[C:23]5[CH:22]=[CH:21][NH:20][C:28]=5[CH:27]=[CH:26][CH:25]=4)[CH2:30][CH2:31]3)[CH2:15][CH2:14]2)=[CH:7]1
Reactant: Cn1cc(C2CCC(=O)CC2)c2cc(C#N)ccc21
Reactant: c1cc(N2CCNCC2)c2cc[nH]c2c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCCl
Product: Cn1cc(C2CCC(N3CCN(c4cccc5[nH]ccc45)CC3)CC2)c2cc(C#N)ccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 55.6 %

Procedure:
A solution of 4-(5-cyano-1-methyl-3-indolyl)-cyclohexanone (0.75 g, 3 mmol), 1-(indol-4-yl)piperazine (0.6 g, 3 mmol), sodium triacetoxyborohydride (0.95 g, 4.5 mmol) and acetic acid (0.34 ml, 6 mmol) in 1,2-dichloroethane (20 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (3×60 ml) and washed with brine (3×60 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (10% methanol-ethyl acetate) afforded 0.73 g (56%) of product as a white solid: mp 274-275° C.
Reaction SMILES: Cl.[C:2]1([C:8]2([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:12]3[CH2:13][N:14]([C:17]([CH:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)=[O:18])[CH2:15][CH2:16][N:11]3[C:10](=[O:25])[O:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41]>O1CCCC1.O>[O:25]=[C:10]1[N:11]2[CH2:16][CH2:15][N:14]([C:17]([CH:19]3[CH2:24][CH2:23][N:22]([CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:21][CH2:20]3)=[O:18])[CH2:13][CH:12]2[C:8]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[O:9]1
Reactant: CCOC(=O)CBr
Reactant: O=C(C1CCNCC1)N1CCN2C(=O)OC(c3ccccc3)(c3ccccc3)C2C1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)CN1CCC(C(=O)N2CCN3C(=O)OC(c4ccccc4)(c4ccccc4)C3C2)CC1
Temperature: 0 °C
Reaction time: 20 h
Yield: 90.4 %

Procedure:
To a solution of hexahydro-1,1-diphenyl-7-[(4-piperidinyl)carbonyl]-3H-oxazolo[3,4-a]pyrazin-3-one hydrochloride (0.20 g, 0.45 mmol) and potassium carbonate (0.16 g, 1.2 mmol) in tetrahydrofuran (5 mL) was added ethyl bromoacetate (0.055 mL, 0.50 mmol) at 0° C., and the mixture was stirred at 0° C. for 2 hours and at room temperature for 20 hours. The reaction solution was diluted with water and then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. The solid was filtered off, and the filtrate was concentrated and dried to a solid. The residue was purified with silica gel column chromatography (ethyl acetate to ethyl acetate:methanol=9:1) to obtain the title compound (0.20 g, yield 90%).
Reaction SMILES: [NH:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=[O:4].[O:9]=C(CCC(O)=O)C(O)=O.O=C1O[C@H]([C@H](CO)O)C(O)=C1O>>[OH:9][C@H:7]1[CH2:8][NH:1][C@H:2]([C:3]([OH:5])=[O:4])[CH2:6]1
Reactant: O=C(O)[C@@H]1CCCN1
Reactant: O=C(O)CCC(=O)C(=O)O
Agent: O=C1O[C@H]([C@@H](O)CO)C(O)=C1O
Product: O=C(O)[C@@H]1C[C@@H](O)CN1
Temperature: 100 °C
Reaction time: 0.25 h

Procedure:
The reaction mixture was composed of 80 mM TES buffer (pH 7.5), 4 mM L-proline, 8 mM 2-ketoglutaric acid, 2 mM ferrous sulfate, 4 mM L-ascorbic acid, 2 mg/ml catalase and a pre-determined amount of the pure enzyme, the total volume being 500 μl. The reaction was initiated by addition of the enzyme and continued for 15 minutes at 30° C. The reaction was stopped by heating the reaction mixture at 100° C. for 2 minutes. The amount of trans-4-hydroxy-L-proline formed in the reaction mixture was determined by the pre-column derivatization method. One hundred microliter of 0.3M boric acid buffer (pH 10.7), 4 μl of aqueous solution of 10% (v/v) mercaptoethanol and 16 μl of ethanol solution of 5% (w/v) OPA were added to 100 μl of the reaction mixture, and the mixture was allowed to stand at 60° C. for 30 seconds. In addition, 50 μl of ethanol solution of 2% (W/V) NBD was added thereto and the mixture was allowed to stand at 60° C. for 40 minutes. The reaction was stopped by adding 30 μl of 1 N HCl to the reaction mixture, and the precipitates formed were removed therefrom by centrifugation and filtration. The trans-4-hydroxy-L-proline formed by the reaction was quantitatively determined by HPLC analysis.
Reaction SMILES: [NH:1]1C2(CCCCC2)[NH:4][CH2:3][C:2]1=[O:11].[O:12]1[CH2:22][CH:13]1[CH2:14][C:15]([O:17]CC(C)C)=O>C(O)(C)C.C(O)C>[CH2:14]1[C:15](=[O:17])[N:4]([CH2:3][C:2]([NH2:1])=[O:11])[CH2:22][CH:13]1[OH:12]
Reactant: O=C1CNC2(CCCCC2)N1
Reactant: CC(C)COC(=O)CC1CO1
Solvent: CCO
Solvent: CC(C)O
Product: NC(=O)CN1CC(O)CC1=O
Reaction time: 9 h

Procedure:
0.650 g 2,2-dimethyl-4-imidazolidinone ((5); R4 =R5 =CH3) (5.7 mmoles) is dissolved in 5 ml isopropanol. 1 g 2-methylpropyl 3,4-epoxybutanoate ((4); X=isobutyl) (6.32 mmoles) is added. The mixture is boiled for 9 h. A further 1 g of epoxyester is added and boiling is continued for a further 9 h. After cooling, the solvent is decanted and the dark mass obtained is taken up in ethanol. The solid obtained is filtered, to give oxiracetam, m.p. 167°-70° C.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:4]=[N:5][N:6]([CH2:8][C@@H:9]2[C@H:12]([NH:13][C:14](=[O:30])/[C:15](=[N:22]\[O:23][C:24]([CH3:29])([CH3:28])[C:25]([OH:27])=[O:26])/[C:16]3[N:17]=[C:18]([NH2:21])[S:19][CH:20]=3)[C:11](=[O:31])[N:10]2[S:32]([OH:35])(=[O:34])=[O:33])[N:7]=1.Cl.[N:37]1([C:42](N)=[NH:43])C=CC=N1.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:21][C:18]1[S:19][CH:20]=[C:16](/[C:15](=[N:22]/[O:23][C:24]([CH3:29])([CH3:28])[C:25]([OH:27])=[O:26])/[C:14]([NH:13][C@@H:12]2[C:11](=[O:31])[N:10]([S:32]([OH:35])(=[O:34])=[O:33])[C@@H:9]2[CH2:8][N:6]2[N:5]=[N:4][C:3]([CH2:2][NH:1][C:42]([NH2:43])=[NH:37])=[N:7]2)=[O:30])[N:17]=1
Reactant: CC(C)(O/N=C(\C(=O)N[C@@H]1C(=O)N(S(=O)(=O)O)[C@@H]1Cn1nnc(CN)n1)c1csc(N)n1)C(=O)O
Reactant: N=C(N)n1cccn1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(O/N=C(\C(=O)N[C@@H]1C(=O)N(S(=O)(=O)O)[C@@H]1Cn1nnc(CNC(=N)N)n1)c1csc(N)n1)C(=O)O
Temperature: 25 °C
Reaction time: 12 h
Yield: 50.4 %

Procedure:
To a solution of 2-(((Z)-(2-(((2R,3S)-2-((5-(aminomethyl)-2H-tetrazol-2-yl)methyl)-4-oxo-1-sulfoazetidin-3-yl)amino)-1-(2-aminothiazol-4-yl)-2-oxoethylidene)amino)oxy)-2-methylpropanoic acid (20 mg, 0.038 mmol) and pyrazole-1-carboxamidine hydrochloride (11.6 mg, 0.079 mmol). in DMF (376 μL) was added DIPEA (26.2 μL, 0.150 mmol). After stirring at rt for 12 h the solution was concentrated in vacuo. Toluene was added and it was reconcentrated (3×). The crude residue was purified by reverse phase prep HPLC (XSelect CSH, 19×100 mm, 5 μm, C18 column; ACN-water with 0.1% formic acid modifier, 24 mL/min), affording the title compound (11 mg, 45%) as a white powder. LCMS: Rt=0.31 min, m/z=575.2 (M+1) Method 2m_acidic; 1H NMR (500 MHz, DMSO-d6) δ 7.49-7.04 (m, 5H), 6.74 (br s, 1H), 5.26 (br s, 1H), 5.14-5.07 (m, 1H), 4.98-4.90 (m, 1H), 4.65 (br s, 2H), 4.59-4.52 (m, 1H), 1.36 (s, 3H), 1.34 (s, 3H).
Reaction SMILES: [CH3:1][CH:2]1[CH2:6][CH2:5][CH:4]([CH3:7])[NH:3]1.[CH:8]1([C:11]2[N:16]=[C:15]([C:17]([NH:19][C:20]3[CH:28]=[N:27][CH:26]=[CH:25][C:21]=3[C:22](O)=[O:23])=[O:18])[C:14]([NH:29][C:30]3[CH:31]=[N:32][CH:33]=[N:34][CH:35]=3)=[CH:13][CH:12]=2)[CH2:10][CH2:9]1>>[CH3:1][CH:2]1[CH2:6][CH2:5][CH:4]([CH3:7])[N:3]1[C:22]([C:21]1[CH:25]=[CH:26][N:27]=[CH:28][C:20]=1[NH:19][C:17]([C:15]1[C:14]([NH:29][C:30]2[CH:31]=[N:32][CH:33]=[N:34][CH:35]=2)=[CH:13][CH:12]=[C:11]([CH:8]2[CH2:10][CH2:9]2)[N:16]=1)=[O:18])=[O:23]
Reactant: CC1CCC(C)N1
Reactant: O=C(O)c1ccncc1NC(=O)c1nc(C2CC2)ccc1Nc1cncnc1
Product: CC1CCC(C)N1C(=O)c1ccncc1NC(=O)c1nc(C2CC2)ccc1Nc1cncnc1
Yield: 35 %

Procedure:
According to the general method described in step 3 of example 53, reaction of 2,5-dimethyl-pyrrolidine with 3-{[6-cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carbonyl]-amino}-isonicotinic acid provided the title compound (35%) as amorphous yellow solid.
Reaction SMILES: [Cl-].[Cl-].[Ca+2].[CH3:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=O)[CH:11]=[CH:12][NH:13]2)=[N:8][CH:7]=1.O=P(Cl)(Cl)[Cl:19]>CCOC(C)=O>[Cl:19][C:10]1[CH:11]=[CH:12][N:13]=[C:14]2[C:9]=1[N:8]=[CH:7][C:6]([O:5][CH3:4])=[CH:15]2
Reactant: COc1cnc2c(=O)cc[nH]c2c1
Reactant: O=P(Cl)(Cl)Cl
Agent: [Ca+2]
Agent: [Cl-]
Solvent: CCOC(C)=O
Product: COc1cnc2c(Cl)ccnc2c1
Temperature: 120 °C
Reaction time: 0.29 h

Procedure:
A two-necked round bottomed flask equipped with an air condenser (protected with CaCl2 guard tube) was charged with 7-Methoxy-1H-[1,5]naphthyridin-4-one (13 g) and POCl3 (65 mL). The reaction mixture was allowed to reflux at 120° C. for 12 h. The POCl3 was removed in vacuo and azeotroped twice with toluene. EtOAc (75 mL) was added and the reaction mixture was stirred at 50-60° C. for 15-20 min. EtOAc removed separated by decantation. The organic layers were combined and concentrated. The obtained crude was dissolved in EtOAc (50 ml) and a washed with satd. aqueous sodium bicarbonate. The organic layer was dried over Na2SO4 and concentrated. The resulting solids were suspended in hexane, stirred for 15 min, filtered and dried under vacuum.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:17][C:18]1[CH:25]=[CH:24][CH:23]=[C:22]([N+:26]([O-:28])=[O:27])[C:19]=1[C:20]#[N:21]>CN(C)C=O.N1C=CC=CC=1.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:17][C:18]2[CH:25]=[CH:24][CH:23]=[C:22]([N+:26]([O-:28])=[O:27])[C:19]=2[C:20]#[N:21])=[CH:5][CH:4]=1
Reactant: COc1ccc(O)cc1
Reactant: N#Cc1c(CBr)cccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: COc1ccc(OCc2cccc([N+](=O)[O-])c2C#N)cc1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 42.4 %

Procedure:
4-Methoxyphenol (0.1 g, 0.83 mmol) and potassium carbonate were added to a cooled (0° C.) and stirred solution of 2-bromomethyl-6-nitrobenzonitrile [W. T. Ashton and J. B. Hynes, J. Med. Chem, 16, 1233 (1973)] (0.2 g, 0.83 mmol) in dimethylformamide under nitrogen atmosphere. The reaction mixture was stirred at 0° C. for 1.5 hours, then diluted with pyridine (1.5 mL), water, stirred for 1 hour, filtered and dried. Purification by silica gel chromatography (50% hexanes in dichloromethane) yielded 100 mg of 2-(4-methoxyphenoxymethyl)-6-nitrobenzonitrile.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([NH2:41])[C:5]2[N:6]=[CH:7][N:8]([C:39]=2[N:40]=1)[C@@H:9]1[O:38][C@H:28]([CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[C@@H:19]([O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[C@H:10]1[O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].[S:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[CH2:47][CH2:48][OH:49].[H-].[Na+]>>[S:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[CH2:47][CH2:48][O:49][C:2]1[N:3]=[C:4]([NH2:41])[C:5]2[N:6]=[CH:7][N:8]([C:39]=2[N:40]=1)[C@@H:9]1[O:38][C@H:28]([CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[C@@H:19]([O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[C@H:10]1[O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]
Reactant: CC(C)(C)[Si](C)(C)OC[C@H]1O[C@@H](n2cnc3c(N)nc(Cl)nc32)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H]1O[Si](C)(C)C(C)(C)C
Reactant: OCCc1cccs1
Agent: [H-]
Agent: [Na+]
Product: CC(C)(C)[Si](C)(C)OC[C@H]1O[C@@H](n2cnc3c(N)nc(OCCc4cccs4)nc32)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H]1O[Si](C)(C)C(C)(C)C
Temperature: 50 °C

Procedure:
A mixture of 2-chloro-2′,3′,5′-tri-O-(tert-butyldimethylsilyl)adenosine) (Example 1, 1.0 g, 1.5 mmol) and 2-(thiophen-2-yl)ethyl alcohol (5 mL) was heated to 50° C. in a roundbottom flask under a nitrogen atmosphere. Sodium hydride (300 mg, 60% dispersion in mineral oil, 7.7 mmol) was added at a rate so as to control gas evolution. Once complete, the reaction was allowed to cool to room temperature and was carefully quenched with 10 mL of water, then extracted with ethyl acetate (3×20 ml). The combined organic phases were washed with 50 mL of brine, dried over MgSO4, and concentrated to give a brown oil that was purified by chromatography on silica gel eluting with a gradient of 0–10% methanol in CH2Cl2. This afforded 361 mg (33%) of 2-[2-(thiophen-2-yl)ethoxy]-2′,3′,5′-tri-O-(TERT-butyldimethylsilyl)adenosine as an off-white solid which was used without further purification
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][N:23]4[CH2:28][CH2:27][S:26][CH2:25][CH2:24]4)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(OO)=[O:32].OO>C(O)(C(F)(F)F)=O.C(Cl)Cl.[OH-].[Na+]>[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][N:23]4[CH2:24][CH2:25][S:26](=[O:32])[CH2:27][CH2:28]4)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: c1cc(C2(CN3CCSCC3)CCOCC2)ccc1OCCCN1CCCC1
Reactant: O=C(OO)C(F)(F)F
Agent: OO
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=S1CCN(CC2(c3ccc(OCCCN4CCCC4)cc3)CCOCC2)CC1
Temperature: 7.5 °C
Reaction time: 1 h
Yield: 79 %

Procedure:
To a solution of 4-{4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-thiomorpholine (200 mg, 0.494 mmol) in TFA (0.67 ml) at 5 to 10° C. was added dropwise a solution of trifluoro-peracetic acid [4M solution prepared by the addition of 27.5% H2O2 (0.94 ml) to TFA (1.56 ml)] and stirred at 5 to 10° C. for 1 hour. The reaction mixture was diluted with DCM (5 ml) and NaOH (5M solution, 4 ml) was added to attain pH14. The mixture was extracted with DCM ((2×5 ml), the combined DCM extracts were washed with saturated aqueous brine (10 ml), dried over MgSO4, filtered and concentrated in vacuo. The isolated yellow oil was purified by column chromatography on silica eluting with DCM(95):MeOH(4):NH3(I) to give the title compound as a yellow oil (165 mg, 79%). 1H NMR (400 MHz, CDCl3) δ 7.20 (d, 2H), 6.87 (d, 2H), 4.02 (t, 2H), 3.81-3.69 (m, 2H), 3.59-3.43 (m, 2H), 2.99-2.82 (m, 2H), 2.76-2.2.59 (m, 6H), 2.53 (br s, 4H), 2.46 (s, 2H), 2.31-1.73 (m, 12H).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.C([O-])([O-])=O.[K+].[K+].Br[CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CC(=O)CC.C(Cl)Cl>[C:20]1([CH2:19][CH2:18][O:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[CH:5]3)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: Oc1ccc2[nH]ccc2c1
Reactant: BrCCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CCC(C)=O
Product: c1ccc(CCOc2ccc3[nH]ccc3c2)cc1
Temperature: 25 °C
Yield: 46.6 %

Procedure:
A stirred mixture of 5-hydroxyindole (0.5 g, 3.8 mmol), anhydrous K2CO3 (1.58 g, 11.4 mmol), (2-bromoethyl) benzene (2.11 g, 11.4 mmol), and a catalytic amount of KI in 2-butanone (40 ml) was heated at reflux overnight under nitrogen. Once cooled to room temperature, the reaction mixture was filtered and the flitrate concentrated under reduced pressure to give an oil. The oil was taken up in CH2Cl2 (50 ml) and washed successively with 2N-NaOH (1×20 ml) and water (1×20 ml). The organic portion was dried (MgSO4) and the solvent was removed under reduced pressure to give an oil. The oil was purified by column chromatography using a solvent system of CH2Cl2 /Hexane (40:60) to give 0.42 g (47%) of 5-(2-phenylethyloxy)indole as an oil.