Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:9]1[C@@:13]2([CH3:31])[CH2:14][CH2:15][CH:16]3[C@@:21]4([CH3:30])[CH2:22][CH2:23][CH:24]([O:26][C:27](Cl)=[O:28])[CH2:25][C:20]4=[CH:19][CH2:18][CH:17]3[CH:12]2[CH2:11][CH2:10]1)[CH2:3][CH2:4][CH2:5][CH:6]([CH3:8])[CH3:7].[CH2:32]([CH2:37][O:38][CH2:39][CH2:40][NH2:41])[O:33][CH2:34][CH2:35][NH2:36]>ClCCl>[CH3:1][C@@H:2]([C@@H:9]1[C@:13]2([CH3:31])[C@H:12]([C@H:17]3[C@H:16]([CH2:15][CH2:14]2)[C@:21]2([CH3:30])[C:20]([CH2:25][C@@H:24]([O:26][C:27](=[O:28])[NH:36][CH2:35][CH2:34][O:33][CH2:32][CH2:37][O:38][CH2:39][CH2:40][NH2:41])[CH2:23][CH2:22]2)=[CH:19][CH2:18]3)[CH2:11][CH2:10]1)[CH2:3][CH2:4][CH2:5][CH:6]([CH3:8])[CH3:7]
Reactant: NCCOCCOCCN
Reactant: CC(C)CCC[C@@H](C)[C@H]1CCC2C3CC=C4CC(OC(=O)Cl)CC[C@]4(C)C3CC[C@@]21C
Solvent: ClCCl
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](OC(=O)NCCOCCOCCN)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of cholesteryl chloroformate (1 g, 2.23 mmol) in 25 mL dichloromethane was added dropwise under stirring to a solution of 2,2′-(ethylenedioxy)bis-(ethylamine) (495 mg, 3.34 mmol) in 75 mL dichloromethane. The reaction was stirred overnight at room temperature. The reaction was diluted with dichloromethane and extracted with water. The organic extract was dried over anhydrous MgSO4 dihydrate, filtered and evaporated. After purification on amino-modified silica gel (eluent: MeCl2→MeCl2/MeOH=975:25 v/v) the product (615 mg) was obtained as a white, waxy solid. MS (ISP): (M+H) 561.5
Reaction SMILES: C(O)(=O)C.C1COCC1.[Br:10][C:11]1[CH:16]=[C:15]([F:17])[C:14]([O:18][CH2:19][CH2:20][O:21][Si](C(C)(C)C)(C)C)=[CH:13][C:12]=1[CH2:29][C:30]([N:32]1[CH:37]=[CH:36][C:35](=[O:38])[CH2:34][CH:33]1[C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=1)=[O:31]>O>[Br:10][C:11]1[CH:16]=[C:15]([F:17])[C:14]([O:18][CH2:19][CH2:20][OH:21])=[CH:13][C:12]=1[CH2:29][C:30]([N:32]1[CH:37]=[CH:36][C:35](=[O:38])[CH2:34][C@H:33]1[C:39]1[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=1)=[O:31]
Reactant: CC(C)(C)[Si](C)(C)OCCOc1cc(CC(=O)N2C=CC(=O)CC2c2ccc(F)cc2)c(Br)cc1F
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: O
Product: O=C1C=CN(C(=O)Cc2cc(OCCO)c(F)cc2Br)[C@H](c2ccc(F)cc2)C1
Temperature: 25 °C
Reaction time: 16 h
Yield: 83.7 %

Procedure:
A mixture of acetic acid (4.5 ml), water (1.5 ml) and THF (1.5 ml) was added to a flask containing 1-(2-{2-bromo-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-4-fluoro-phenyl}-acetyl)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one (0.048 g, 0.082 mmol). The mixture was stirred at room temperature for 16 hours. Water was added and the product was extracted with EtOAc. The extract was washed with water and brine, dried over MgSO4, filtered and concentrated to dryness. Purification by flash chromatography (EtOAc) gave (S)-1-{2-[2-bromo-4-fluoro-5-(2-hydroxy-ethoxy)-phenyl]-acetyl}-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one (0.032 g) as a white foam.
Reaction SMILES: [C:1](#[N:3])C.[F:4][C:5]([F:15])([F:14])[CH:6]([C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)[CH3:7].C[Si](C#N)(C)C>C(N(CC)CC)C>[F:15][C:5]([F:4])([F:14])[CH:6]([C:8]1[CH:13]=[CH:12][N:11]=[C:10]([C:1]#[N:3])[CH:9]=1)[CH3:7]
Reactant: CC#N
Reactant: CC(c1ccncc1)C(F)(F)F
Agent: C[Si](C)(C)C#N
Solvent: CCN(CC)CC
Product: CC(c1ccnc(C#N)c1)C(F)(F)F
Temperature: 90 °C
Reaction time: 16 h

Procedure:
To 8 ml of acetonitrile were added 0.9 g of 4-(2,2,2-trifluoro-1-methyl-ethyl)pyridine=N-oxide, 1.31 ml of triethylamine and 1.4 g of trimethylsilyl cyanide, and the mixture was stirred at 90° C. for 16 hours. Thereafter, the reaction solution was allowed to cool to temperature, and concentrated. The residue was subjected to silica gel column chromatography to obtain 0.7 g of 4-(2,2,2-trifluoro-1-methyl-ethyl)pyridine-2-carbonitrile.
Reaction SMILES: O.[OH-].[Li+].[CH2:4]([N:7]([CH2:22][CH2:23][CH3:24])[C:8]([C:10]1[CH:11]=[C:12]([CH:17]=[C:18]([CH2:20][CH3:21])[CH:19]=1)[C:13]([O:15]C)=[O:14])=[O:9])[CH2:5][CH3:6]>C1COCC1.CO.O.O.Cl>[CH2:22]([N:7]([CH2:4][CH2:5][CH3:6])[C:8]([C:10]1[CH:11]=[C:12]([CH:17]=[C:18]([CH2:20][CH3:21])[CH:19]=1)[C:13]([OH:15])=[O:14])=[O:9])[CH2:23][CH3:24]
Reactant: CCCN(CCC)C(=O)c1cc(CC)cc(C(=O)OC)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: CCCN(CCC)C(=O)c1cc(CC)cc(C(=O)O)c1
Temperature: 22.5 °C
Reaction time: 3 h

Procedure:
Lithium hydroxide monohydrate (0.0680 g, 1.6 mmol) is added to a mixture of methyl 3-[(dipropylamino)carbonyl]-5-ethylbenzoate (PREPARATION 20, 0.450 g, 1.6 mmol) in a mixture of THF/methanol/water (2/1/1, 8 mL). The mixture is stirred at 20-25 degrees C. for 3 hours. The mixture is then diluted with water (20 mL) and hydrochloric acid (1 N) is added to bring the pH to less than 3. The aqueous mixture is extracted with ethyl acetate. The organic phase is separated and washed with saline, dried over anhydrous magnesium sulfate, filtered and concentrated to give the title compound, MS (ESI+) for C16H23NO3 m/z (M+H)+=278.2.
Reaction SMILES: S[C:2]1N=CN=C2C=1NC=N2.[NH2:11][C:12]1[N:20]=[C:19]2[C:15]([NH:16][CH:17]=[N:18]2)=[C:14]([SH:21])[N:13]=1>>[NH2:11][C:12]1[N:20]=[C:19]2[C:15]([NH:16][CH:17]=[N:18]2)=[C:14]([S:21][CH3:2])[N:13]=1
Reactant: Sc1ncnc2nc[nH]c12
Reactant: Nc1nc(S)c2[nH]cnc2n1
Product: CSc1nc(N)nc2nc[nH]c12

Procedure:
By repeating this procedure but replacing the above 6-mercaptopurine compound with the corresponding 2-amino-6-mercaptopurine compound there is obtained the corresponding 2-amino-6-methylthiopurine compound.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6]([N:9]=[C:10]=[O:11])=[CH:5][CH:4]=1.[N:14]([Si](C)(C)C)=[N+:15]=[N-:16].CCCCCC>C(OCC)(=O)C>[F:1][C:2]([F:12])([F:13])[C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:10](=[O:11])[NH:16][N:15]=[N:14]2)=[CH:7][CH:8]=1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Reactant: O=C=Nc1ccc(C(F)(F)F)cc1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: O=c1[nH]nnn1-c1ccc(C(F)(F)F)cc1
Temperature: 110 °C
Yield: 78.3 %

Procedure:
To 4-trifluoromethylphenyl isocyanate (2.89 ml, 20.2 mmol) was added 5.36 ml of azidotrimethylsilane (39.9 mmol), and the mixture was stirred at 110° C. for twenty-four hours. After cooling, the mixture was subjected to column chromatography using silicagel (eluate; ethyl acetate:hexane=1:1 to 2:1 to ethyl acetate) to collect a desired fraction to be concentrated. The crystals obtained were recrystallized from ethyl acetate-hexane to give 3.64 g of 1-(4-trifluoromethylphenyl)-5(1H,4H)-tetrazolone (78%) as colorless needles.
Reaction SMILES: C(O[C:4]([C:6]1[C:7]([OH:26])=[C:8]2[CH:16]=[CH:15][N:14]([CH2:17][C:18]3[CH:23]=[CH:22][C:21](OC)=[CH:20]C=3)[C:9]2=[C:10]([C:12]#[N:13])[N:11]=1)=[O:5])C.[NH2:27][CH2:28][C:29]([OH:31])=[O:30].[CH3:32][O-:33].[Na+].CO>>[C:12]([C:10]1[N:11]=[C:6]([C:4]([NH:27][CH2:28][C:29]([OH:31])=[O:30])=[O:5])[C:7]([OH:26])=[C:8]2[CH:16]=[CH:15][N:14]([C:17]3[CH:18]=[CH:23][C:22]([O:33][CH3:32])=[CH:21][CH:20]=3)[C:9]=12)#[N:13]
Reactant: NCC(=O)O
Reactant: CCOC(=O)c1nc(C#N)c2c(ccn2Cc2ccc(OC)cc2)c1O
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1ccc(-n2ccc3c(O)c(C(=O)NCC(=O)O)nc(C#N)c32)cc1

Procedure:
Prepared in analogy to that of Example 1(e) from 7-cyano-4-hydroxy-1-(4-methoxy-benzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester, glycine and NaOMe/HOMe. The title compound, ESI MS (m/z): 367 (M+H)+.
Reaction SMILES: [C:1]([CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[CH2:9][S:10][C:11]1[CH:12]=[C:13]([CH:17]([CH3:23])[C:18]([O:20]CC)=[O:19])[CH:14]=[CH:15][CH:16]=1)#N.[OH-:24].[K+].Cl.[OH2:27]>C(O)COCCO>[C:1]([CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[CH2:9][S:10][C:11]1[CH:12]=[C:13]([CH:17]([CH3:23])[C:18]([OH:20])=[O:19])[CH:14]=[CH:15][CH:16]=1)([OH:27])=[O:24]
Reactant: CCOC(=O)C(C)c1cccc(SCC2CCCCC2C#N)c1
Reactant: [OH-]
Reactant: O
Agent: Cl
Agent: [K+]
Solvent: OCCOCCO
Product: CC(C(=O)O)c1cccc(SCC2CCCCC2C(=O)O)c1
Temperature: 250 °C
Reaction time: 5.5 h

Procedure:
The above ester compound (2.6 g) was added to a solution of potassium hydroxide (2.6 g) in water (5 ml) and diethylene glycol (8 ml) and the mixture was heated with stirring for 5.5 hours in an oil bath maintained at 250° C. The reaction mixture was poured into water, acidified with hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layers were washed with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure to give the title compound (2.5 g) as an oil. IRνmaxfilm cm-1 : 1700 (C=O). MS m/e: 322 (M+).
Reaction SMILES: C(O[C:4]1[C:5](=[O:12])[C:6](=[O:11])[C:7]=1[O:8][CH2:9][CH3:10])C.[NH2:13][C:14]1[C:15]([OH:28])=[C:16]([S:21]([N:24]([O:26][CH3:27])[CH3:25])(=[O:23])=[O:22])[C:17]([Cl:20])=[CH:18][CH:19]=1>C(O)C>[Cl:20][C:17]1[C:16]([S:21]([N:24]([O:26][CH3:27])[CH3:25])(=[O:22])=[O:23])=[C:15]([OH:28])[C:14]([NH:13][C:4]2[C:5](=[O:12])[C:6](=[O:11])[C:7]=2[O:8][CH2:9][CH3:10])=[CH:19][CH:18]=1
Reactant: CON(C)S(=O)(=O)c1c(Cl)ccc(N)c1O
Reactant: CCOc1c(OCC)c(=O)c1=O
Solvent: CCO
Product: CCOc1c(Nc2ccc(Cl)c(S(=O)(=O)N(C)OC)c2O)c(=O)c1=O
Temperature: 45 °C
Reaction time: 1 h

Procedure:
A solution of 3,4-diethoxy-3-cyclobutene-1,2-dione (2.83 g, 1.2 equiv) in ethanol (30 ml) was treated with TEA (1.54 g, 1.1 equiv) and the reaction mixture was heated to 45° C. 3-Amino-6-chloro-2-hydroxy-N-methoxy-N-methyl-benzenesulfonamide (3.7 g, 1 equiv) was added portion wise over 30 minutes, with vigorous stirring, maintaining the reaction mixture at 45° C. The reaction mixture was stirred at 45° C. for 1 hour and then allowed to cool to RT. The solvent was removed in vacuo and the residue was partitioned between EtOAc (600 ml) and water (2×200 ml). The aqueous portion was separated and extracted with EtOAc (3×200 ml) and the combined organic extracts were washed with water (3×200 ml) and allowed to stand over night. The resulting solid was collected by filtration and dried in vacuo to afford the title compound. The mother liquor was evaporated to give a yellow/brown oily solid which was triturated with ethanol (100 ml). The solid was collected by filtration, washed with EtOH and dried in vacuo to afford the title compound; [M+H]+ 390.
Reaction SMILES: [C:1]1([C:7]([NH:20][CH:21]2[C:41](=[O:42])[N:23]3[CH:24]([C:29](Cl)=[N:30][CH2:31][C:32]4[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=4)[C:25]([CH3:28])([CH3:27])[S:26][C@H:22]23)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)C.[NH3:46]>C(Cl)(Cl)Cl>[C:1]1([C:7]([NH:20][CH:21]2[C:41](=[O:42])[N:23]3[CH:24]([C:29](=[N:30][CH2:31][C:32]4[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=4)[NH2:46])[C:25]([CH3:28])([CH3:27])[S:26][C@H:22]23)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COc1ccc(CN=C(Cl)C2N3C(=O)C(NC(c4ccccc4)(c4ccccc4)c4ccccc4)[C@H]3SC2(C)C)cc1
Reactant: N
Solvent: CCO
Solvent: ClC(Cl)Cl
Product: COc1ccc(CN=C(N)C2N3C(=O)C(NC(c4ccccc4)(c4ccccc4)c4ccccc4)[C@H]3SC2(C)C)cc1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
To a 0° C. solution of 13.1 g. (22 mmoles) of 6-(triphenylmethylamino)-2,2-dimethyl-3-{chloro-[N-(4-methoxybenzyl)imino]methyl}penam in 45 ml. of ethanol-free chloroform, a 1.33 N ammonia solution in chloroform is added all at once. The resulting mixture is stirred 5 minutes at 0° C. and then for 45 minutes at 25° C. The mixture is then filtered, and the filtrate rotoevaporated to an amber oil. Addition of ether (100 ml.) affords a precipitate which is filtered and then taken up in 150 ml. chloroform. The chloroform solution is washed first with 100 ml. 0.5N NaOH; and then with three 150 ml. portions of water. It is then dried over anhydrous sodium sulfate and rotoevaporated to afford the title compound as an orange foam. Rotoevaporation of the filtrate obtained after the ether precipitation procedure affords more of the title compound, as an orange foam. Total yield= 12.05 g. (95%). 1H--NHR (CDCl3 ) ppm (δ) 1.33 (3H, s, 2--CH3); 1.60 (3H, s, 2--CH3); 3.81 (3H, s, --OCH3); 4.17-4.68 (3H, m; 3-, 5- and 6-H); 4.24 (2H, s, --CH2 --), 4H, AB with Ha within 7.2-7.68 multiplet; Hb centered at 6.89, J= 9 HZ. (CH3O--C6H4 --), 7.2-7.68 (15H, m, C6H5). Infrared (CH2Cl2) λmax (μ) 5.62 (s, strong); 5.75-5.83 (broad s, strong); 5.97 (broad s, strong).
Reaction SMILES: [O:1]1[CH:5]2[CH2:6][O:7][CH2:8][CH:4]2[O:3]S1(=O)=O.[Br:11][C:12]1[CH:24]=[C:23]2[C:15]([C:16]3[C:17](=[O:32])[C:18]4[CH:30]=[CH:29][C:28](O)=[CH:27][C:19]=4[C:20]([CH3:26])([CH3:25])[C:21]=3[NH:22]2)=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+].S(=O)(=O)(O)O>CN(C=O)C.O.C1COCC1>[Br:11][C:12]1[CH:24]=[C:23]2[C:15]([C:16]3[C:17](=[O:32])[C:18]4[CH:30]=[CH:29][C:28]([O:3][CH:4]5[CH:5]([OH:1])[CH2:6][O:7][CH2:8]5)=[CH:27][C:19]=4[C:20]([CH3:25])([CH3:26])[C:21]=3[NH:22]2)=[CH:14][CH:13]=1
Reactant: O=S1(=O)OC2COCC2O1
Reactant: CC1(C)c2cc(O)ccc2C(=O)c2c1[nH]c1cc(Br)ccc21
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [Cs+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: O
Product: CC1(C)c2cc(OC3COCC3O)ccc2C(=O)c2c1[nH]c1cc(Br)ccc21
Temperature: 80 °C
Reaction time: 15 h
Yield: 72.2 %

Procedure:
Under nitrogen atmosphere, tetrahydro-furo[3,4-d][1,3,2]dioxathiol 2,2-dioxide (71.5 mg, 0.420 mmol) was dissolved in DMF (1.40 mL), added with 3-bromo-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound A5-1, 50.0 mg, 0.140 mmol) and cesium carbonate (228 mg, 0.700 mmol), and stirred at 80° C. for 15 hr. Subsequently, sulfuric acid (0.10 mL, 18 M), THF (3.00 mL) and water (0.50 mL) were added to the mixture, which was then stirred at room temperature for 24 hr and further at 60° C. for 24 hr. The reaction solution was added to water, extracted with ethyl acetate, washed with water, saturated aqueous solution of sodium bicarbonate, and saturated brine, and dried over sodium sulfate. After filtering and concentration under reduced pressure, the resulting residues were washed with dichloromethane and purified by NH silica gel column chromatography (ethyl acetate/THF) to obtain the target compound (44.7 mg, 72%).
Reaction SMILES: [CH2:1]([NH:4][C:5]1[CH:6]=[C:7]([CH2:11][C:12]([OH:14])=O)[CH:8]=[CH:9][CH:10]=1)[CH:2]=[CH2:3].C(Cl)(Cl)[Cl:16].C(=O)([O-])[O-].[Na+].[Na+].[C:25](Cl)([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>O>[C:25]([N:4]([CH2:1][CH:2]=[CH2:3])[C:5]1[CH:6]=[C:7]([CH2:11][C:12]([Cl:16])=[O:14])[CH:8]=[CH:9][CH:10]=1)([O:27][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:26]
Reactant: ClC(Cl)Cl
Reactant: O=C(Cl)OCc1ccccc1
Reactant: C=CCNc1cccc(CC(=O)O)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: C=CCN(C(=O)OCc1ccccc1)c1cccc(CC(=O)Cl)c1
Temperature: 40 °C
Reaction time: 2 h

Procedure:
To 15 g. 3-(allylamino)phenylacetic acid in 200 ml. warm chloroform is added a solution of 12 g. sodium carbonate in 150 ml. water. To the vigorously stirred solution is added 10 g. carbobenzyloxy chloride. After 2 hours stirring at 40° C., the layers are separated, washed three times with 1 N hydrochloric acid, dried, and evaorated to an oil. The oil is dissolved in 300 ml. toluene, treated with 15 ml. thionyl chloride and the solution is refluxed for 5 hours. The solvents are evaporated and the residue is dissolved three times in toluene, evaporating each time ultimately to yield 3-(N-carbobenzyloxy-allylamino)phenylacetyl chloride as a viscous, orange oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C@H:20]3[C@H:15]([CH2:16][CH:17]=[CH:18][CH2:19]3)[C:14](=[O:21])[N:13]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]Br)[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[C:29]1(=[O:39])[NH:33][C:32](=[O:34])[C:31]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:30]12.C(=O)([O-])[O-].[K+].[K+].C[N:47](C=O)C>O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C@H:20]3[C@H:15]([CH2:16][CH:17]=[CH:18][CH2:19]3)[C:14](=[O:21])[N:13]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][NH:33][C:29](=[O:39])[C:30]3[C:31](=[CH:35][CH:36]=[CH:37][CH:38]=3)[C:32]([NH2:47])=[O:34])[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: CN(C)C=O
Reactant: O=C1NC(=O)c2ccccc21
Reactant: COc1ccc(C2=NN(CCCCCCBr)C(=O)[C@H]3CC=CC[C@@H]23)cc1OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: COc1ccc(C2=NN(CCCCCCNC(=O)c3ccccc3C(N)=O)C(=O)[C@H]3CC=CC[C@@H]23)cc1OC

Procedure:
A mixture of 10 g of compound 117, 10 g of phthalimide and 10 g of potassium carbonate was heated for 5 h at 100° C. in DMF. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and evaporated. The residue was purified by chromatography (dichloromethane) and crystallized from ethyl acetate/ether. M.p. 104°-105° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[CH:25]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]2=3)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[Br:32]Br.O.[Cl-].[Na+]>C(O)(=O)C.C(OCC)(=O)C>[Br:32][C:16]1[CH:15]=[CH:14][C:13]2[N:12]([S:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)(=[O:10])=[O:11])[CH:25]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]=2[CH:17]=1
Reactant: BrBr
Reactant: COc1ccc(S(=O)(=O)N2c3ccccc3-c3ccccc3C2c2ccccc2)cc1
Agent: [Cl-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: O
Product: COc1ccc(S(=O)(=O)N2c3ccc(Br)cc3-c3ccccc3C2c2ccccc2)cc1
Temperature: 25 °C
Yield: 27.6 %

Procedure:
A stirred suspension of 5-[(4-methoxyphenyl)sulfonyl]-6-phenyl-5,6-dihydrophenanthridine (4.27 g, 10 mmol) was heated to 50° C. in glacial acetic acid (20 mL) and treated drop-wise over three hours with excess bromine (8.0 g, 50 mmol). After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, and the precipitate filtered. The organic phase filtrate was washed sequentially with a saturated, aqueous, sodium thiosulfate solution, a 1 N hydrochloric acid solution, and water. The organic phase was further washed sequentially with a 2.5 N aqueous sodium hydroxide solution until a basic extract was obtained, water, and a saturated, aqueous, sodium chloride solution. The organic phase was dried over anhydrous sodium sulfate, filtered through a short column of silica gel, and the solvent removed in vacuo to afford a crude yellow solid (4.0 g, 7.9 mmol, 79%). The crude solid was purified by repetitive preparative chromatography on a Biotage® 40 Mi column of pre-packed silica gel (90 g), eluting with dichloromethane at a flow rate of 25 mL/min; to afford, after evaporation of the appropriate fractions, a monobromo compound and a dibromo compound, both as solids. Crystallization of the monobromo compound from a mixture of dichloromethane-diethyl ether-hexane yielded the title compound (1.4 g, 2.76 mmol, 28%) as a homogeneous, colorless, crystalline solid, m.p. 209-211° C.;
Reaction SMILES: [P:1]([O:13]C[C@H]1O[C@@H](N2C3N=CN=C(N)C=3N=C2)[C@H](O)[C@@H]1O)([O:4][P:5]([O:8]P(O)(O)=O)([OH:7])=[O:6])(=[O:3])[OH:2].S([O-])([O-])(=O)=O.C1S/C(=C2/N=C3C(S/2)=CC(=O)C=C3)/N[C@H]1[C:52]([OH:54])=[O:53]>>[O-:3][P:1]([O:4][P:5]([O-:8])([O-:7])=[O:6])(=[O:2])[O-:13].[C:52](=[O:54])=[O:53]
Reactant: Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]1O
Reactant: O=C1C=Cc2n/c(=C3\N[C@@H](C(=O)O)CS3)sc2=C1
Agent: O=S(=O)([O-])[O-]
Product: O=C=O
Product: O=P([O-])([O-])OP(=O)([O-])[O-]

Procedure:
combining the ATP and sulfate containing feedstock with luciferin and an ATP-dependent luciferase in the presence of oxygen such that the ATP is consumed to produce AMP, inorganic pyrophosphate, carbon dioxide and light; and
Reaction SMILES: [CH3:1][C:2]([CH3:9])([CH2:7][OH:8])[C:3]([O:5][CH3:6])=[O:4].N1C=CN=C1.[C:15]([Si:19]([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)Cl)([CH3:18])([CH3:17])[CH3:16]>CN(C=O)C>[CH3:6][O:5][C:3](=[O:4])[C:2]([CH3:9])([CH3:1])[CH2:7][O:8][Si:19]([C:15]([CH3:18])([CH3:17])[CH3:16])([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: COC(=O)C(C)(C)CO
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: COC(=O)C(C)(C)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 22 h
Yield: 113.7 %

Procedure:
A solution of methyl 2,2-dimethyl-3-hydroxypropionate (5.0 g, 37.8 mmol) in DMF (75 mL) was cooled to 0° C. and treated with imidazole (3.86 g, 56.7 mmol) then tert-butyl diphenylchlorosilane (11.8 mL, 45.4 mmol). The mixture was stirred at RT for 22 h then concentrated in vacuo. The residue was partitioned between EtOAc and water. The phases were separated and the aqueous layer was extracted with EtOAc (×2). The combined organic phase was washed with 10% aqueous citric acid solution, saturated aqueous sodium bicarbonate solution and brine, dried (Na2SO4) and concentrated in vacuo to give the title compound as a golden oil (15.93 g, quant.). LCMS (Method 3): Rt 5.32 min, m/z 393.3 [M+Na+].
Reaction SMILES: Cl.[CH3:2][NH:3][C:4]([C:6]1[CH:7]=[CH:8][C:9]([CH2:12][CH2:13][C:14]([OH:16])=O)=[N:10][CH:11]=1)=[O:5].C(N(C(C)C)C(C)C)C.[NH2:26][CH2:27][C:28]([N:30]([C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[C:34]([CH2:39][O:40][C:41]2[C:49]3[N:48]=[C:47]([O:50][CH3:51])[N:46]([CH2:52][C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=4)[C:45]=3[CH:44]=[CH:43][CH:42]=2)[C:33]=1[Cl:59])[CH3:31])=[O:29].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>ClCCl>[NH4+:3].[Cl:59][C:33]1[C:34]([CH2:39][O:40][C:41]2[C:49]3[N:48]=[C:47]([O:50][CH3:51])[N:46]([CH2:52][C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=4)[C:45]=3[CH:44]=[CH:43][CH:42]=2)=[C:35]([Cl:38])[CH:36]=[CH:37][C:32]=1[N:30]([CH3:31])[C:28](=[O:29])[CH2:27][NH:26][C:14](=[O:16])[CH2:13][CH2:12][C:9]1[CH:8]=[CH:7][C:6]([C:4]([NH:3][CH3:2])=[O:5])=[CH:11][N:10]=1
Reactant: COc1nc2c(OCc3c(Cl)ccc(N(C)C(=O)CN)c3Cl)cccc2n1Cc1ccccn1
Reactant: CNC(=O)c1ccc(CCC(=O)O)nc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CNC(=O)c1ccc(CCC(=O)NCC(=O)N(C)c2ccc(Cl)c(COc3cccc4c3nc(OC)n4Cc3ccccn3)c2Cl)nc1
Product: [NH4+]
Reaction time: 0.08 h
Yield: 5 %

Procedure:
To a suspension of 3(5-methylcarbamoyl-pyridin-2-yl)propionic acid hydrochloride (0.26 g, 1.06 mmol) in dichloromethane (20 mL) was added ethyldiisopropylamine (0.74 mL, 4.26 mmol), the solution was stirred for 5 min, and then 2-amino-N-(2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)-N-methylacetamide (0.5 g, 1.0 mmol) was added followed by HOBT (0.135 g, 1.0 mmol) and EDCI (0.28 mL, 1.59 mmol). The reaction mixture was then stirred overnight at room temperature and partitioned in dichloromethane (100 mL) and a saturated solution of NaHCO3 (100 mL). Organic layer was separated, dried (MgSO4) and concentrated to give oil, which was purified by flash chromatography using a mixture of dichloromethane- and a 5% ammonium solution in methanol (9:1) to give 6-(3-((2-((2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)(methyl)amino)-2-oxoethyl)amino)-3-oxopropyl)-N-methylnicotinamide as foam. LCMS (APCI) 690 (M+); 1HNMR (400 MHz, MeOD) δ 2.60 (t, 2H), 3.07 (s, 3H), 3.19 (t, 2H), 3.20 (s, 3H), 3.32-3.69 (dd, 2H), 4.01 (s, 3H), 5.19 (s, 2H), 5.46 (dd, 2H), 6.71-8.74 (m, 12H)