Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][CH:10]([C:13](Cl)=[O:14])[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.[Br:16][C:17]1[CH:29]=[CH:28][C:20]([O:21][CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:19][CH:18]=1.C(N(CC)CC)C>ClCCl>[Br:16][C:17]1[CH:29]=[CH:28][C:20]([O:21][CH:22]2[CH2:23][CH2:24][N:25]([C:13]([CH:10]3[CH2:11][CH2:12][N:7]([C:4]4[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=4)[CH2:8][CH2:9]3)=[O:14])[CH2:26][CH2:27]2)=[CH:19][CH:18]=1
Reactant: Brc1ccc(OC2CCNCC2)cc1
Reactant: O=C(Cl)C1CCN(c2ccncc2)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(C1CCN(c2ccncc2)CC1)N1CCC(Oc2ccc(Br)cc2)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 33.4 %

Procedure:
A suspension of 1-(4-pyridyl)piperidine-4-carbonyl chloride (0.94 g) in dichloromethane (20 ml) was added slowly to a stirred solution of 4-(4-bromophenoxy)piperidine (1.0 g) and triethylamine (1.09 ml) in dichloromethane (10 ml) at 5° C. under an atmosphere of argon. The mixture was stirred at ambient temperature for 16 hours, and then the solvent was removed by evaporation. The residue was triturated with water. The resulting solid was collected by filtration and recrystallised from ethanol (10 ml) to give 4-(4-bromophenoxy)-1-[1-[4-pyridyl]piperidin-4-ylcarbonyl]piperidine (0.58 g) as an off-white solid, m.p. 127-130° C.;
Reaction SMILES: C[O:2][CH:3]1[CH2:8][CH2:7][CH:6]([C:9]2[NH:13][C:12]3[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=3[N:10]=2)[CH2:5][CH2:4]1>I.O>[NH:10]1[C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[N:13]=[C:9]1[CH:6]1[CH2:7][CH2:8][CH:3]([OH:2])[CH2:4][CH2:5]1
Reactant: COC1CCC(c2nc3ccccc3[nH]2)CC1
Agent: I
Solvent: O
Product: OC1CCC(c2nc3ccccc3[nH]2)CC1
Yield: 85.3 %

Procedure:
A solution of 2-(4-methoxy-cyclohexyl)-1H-benzoimidazole (500 mg, 2.17 mmol) in HI (35%) (5 mL) was heated to 90° C. for 1 h. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2×10 mL); the organic layers was combined and washed with brine (2×10 mL), dried over Na2SO4, and concentrated to give the desired product (400 mg, 1.85 mmol, 85% yield) as brown solid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][C:9]=1[NH2:19])([CH3:4])([CH3:3])[CH3:2].C([O:25][C:26](=O)[CH2:27][C:28](=[O:40])[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([N:35]2[CH:39]=[CH:38][CH:37]=[N:36]2)[CH:30]=1)(C)(C)C>>[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][C:9]=1[NH:19][C:26](=[O:25])[CH2:27][C:28](=[O:40])[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([N:35]2[CH:39]=[CH:38][CH:37]=[N:36]2)[CH:30]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1cc(NC(=O)OC(C)(C)C)c(N)cc1C(F)(F)F
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(-n2cccn2)c1
Product: Cc1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-n3cccn3)c2)cc1C(F)(F)F

Procedure:
The title compound was prepared (2-amino-5-methyl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J15) (290 mg, 1.0 mmol) and 3-oxo-3-(3-pyrazol-1-yl-phenyl)-propionic acid tert-butyl ester (Example K12) (286 mg, 1.0 mmol) according to the general procedure M. Obtained as a white solid (370 mg, 74%).
Reaction SMILES: Br[C:2]1[S:3][C:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][N:6]=1.[CH3:12][NH:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1COCC1>[CH3:12][N:13]([CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:2]1[S:3][C:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][N:6]=1
Reactant: CCOC(=O)c1cnc(Br)s1
Reactant: CNCCc1ccccc1
Solvent: C1CCOC1
Product: CCOC(=O)c1cnc(N(C)CCc2ccccc2)s1
Temperature: 100 °C

Procedure:
To a solution of ethyl 2-bromo-1,3-thiazole-5-carboxylate (0.5 g, 2.1 mmol) in THF (2 mL) was added N-methylphenethylamine (0.86 g, 6.4 mmol). The reaction was heated to 100° C. via microwave for 30 minutes. The reaction was partitioned between water and ethyl acetate. The organics were dried over sodium sulfate, filtered and evaporated. Purification by flash chromatography (15-50% ethyl acetate/hexanes) gave ethyl 2-[methyl(2-phenylethyl)amino]-1,3-thiazole-5-carboxylate. 1H NMR (600 MHz, DMSO-d6) δ 7.81 (s, 1H), 7.22 (m, 5H), 4.17 (q, J=7.34 Hz, 2H), 3.70 (t, J=7.33 Hz, 2H), 3.00 (s, 3H), 2.87 (t, J=7.63 Hz, 2H), 1.21 (t, J=7.01 Hz, 3H); ESIMS calcd 291.1 (M++H), found 291.0 (M++F).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11](OS(C)(=O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:19]([O-:22])(=[S:21])[CH3:20].[K+]>CN(C)C=O.C(OCC)(=O)C>[C:19]([S:21][CH:11]1[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]1)(=[O:22])[CH3:20]
Reactant: CC([O-])=S
Reactant: CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(=O)SC1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 105 °C
Reaction time: 4 h
Yield: 905.4 %

Procedure:
In 40 ml of dimethylformamide were dissolved 4.12 g (14.7 mmol) of 1-(tert-butoxycarbonyl)-4-(methanesulfonyloxy)piperidine, and 2.53 g (2.21 mmol) of potassium thioacetate were added to the solution, followed by stirring of the resulting mixture at 105° C. for 4 hours under nitrogen atmosphere. After cooling, the reaction mixture was diluted with ethyl acetate and washed with water and then a saturated aqueous NaCl solution, followed by evaporation of the solvent. The thus obtained residue was subjected to silica gel column chromatography and the fractions eluted with a mixed solvent of hexane-ethyl acetate (5:1) were collected to obtain 5.19 g (yield: 81%) of the title compound as an oil.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][CH:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][CH2:16][C:15]1=[O:24].Br[CH2:26][CH2:27][CH:28]1[CH2:30][CH2:29]1>O1CCCC1.CN(C)P(=O)(N(C)C)N(C)C>[CH:28]1([CH2:27][CH2:26][C:14]2([CH3:13])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:17][CH2:16][C:15]2=[O:24])[CH2:30][CH2:29]1
Reactant: CC1C(=O)CCc2ccccc21
Reactant: BrCCC1CC1
Agent: [Li]CCCC
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CC1(CCC2CC2)C(=O)CCc2ccccc21
Temperature: -30 °C
Reaction time: 2 h
Yield: 63 %

Procedure:
To a stirring solution of diisopropylamine (4.81 mL, 34.3 mmol) in 50 mL of tetrahydrofuran cooled to 0° C. in an ice bath was added dropwise 1.6M n-butyl lithium in tetrahydrofuran (21.45 mL, 34.3 mmol) over 30 minutes. The solution was cooled to −30° C. and 1-methyl-2-tetralone (5.0 g, 31.2 mmol) in 10 mL of tetrahydrofuran added. The resulting reaction mixture was placed in an ice bath for 2 hour. Cool the solution to −78° C., and added hexamethylphosphoric triamide 20 mL followed by the dropwise addition of (2-Bromo-ethyl)-cyclopropane (6.97 g, 46.8 mmol). The reaction was stirred at rt for 48 hours. Partition the reaction mixture between ethyl acetate and saturated aqueous NH4Cl, extract the aqueous layer 3 times with ethyl acetate. The combined organic layers were washed sequentially with saturated sodium bicarbonate, brine, and then dried over MgSO4. The product was purified by flash chromatography on SiO2, eluting with a 0-10% diethyl ether/hexane gradient yielding the product (4.488 g, 63% yield). 1H NMR (300 MHz, CDCl3): δ ppm 0.01 (m, 2H) 0.47 (m, 2H) 0.67 (m, 1H) 0.98 (m, 2H) 1.55 (s, 3H) 1.95 (td, J=12.78, 4.60 Hz, 1H) 2.37 (ddd, J=13.60, 12.13, 4.78 Hz, 1H) 2.80 (m, 2H) 3.19 (m, 2H) 7.31 (m, 2H) 7.44 (m, 2H). MS (ESI+) m/z=229 (M+H)+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:28][C:17]3=[CH:18][N:19]=[C:20]([N:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:29]1([S:32](Cl)(=[O:34])=[O:33])[CH2:31][CH2:30]1.C(N(CC)CC)C>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:28][C:17]3=[CH:18][N:19]=[C:20]([N:22]4[CH2:23][CH2:24][N:25]([S:32]([CH:29]5[CH2:31][CH2:30]5)(=[O:34])=[O:33])[CH2:26][CH2:27]4)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=S(=O)(Cl)C1CC1
Reactant: CC(C)(C)OC(=O)N1CCC(C2Cc3cc(N4CCNCC4)ncc3O2)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(C2Cc3cc(N4CCN(S(=O)(=O)C5CC5)CC4)ncc3O2)CC1

Procedure:
The title compound is prepared by treatment of 4-(5-piperazin-1-yl-2,3-dihydro-furo[2,3-c]pyridin-2-yl)-piperidine-1-carboxylic acid tert-butyl ester with cyclopropylsulfonyl chloride in dichloromethane in the presence of triethylamine. LC (method 10): tR=1.47 min; Mass spectrum (ESI+): m/z=493 [M+H]+.
Reaction SMILES: Br[C:2]1SC=C2C=1NC(=O)N2.[Br:11][C:12]1[CH:13]=[CH:14][C:15]2[NH:16][C:17]3[C:22]([C:23]=2[CH:24]=1)=[CH:21][C:20]([Br:25])=[CH:19][CH:18]=3.[H-].[Na+].CI.[Cl-].[NH4+]>O.O1CCCC1>[Br:25][C:20]1[CH:19]=[CH:18][C:17]2[N:16]([CH3:2])[C:15]3[C:23]([C:22]=2[CH:21]=1)=[CH:24][C:12]([Br:11])=[CH:13][CH:14]=3
Reactant: Brc1ccc2[nH]c3ccc(Br)cc3c2c1
Reactant: O=c1[nH]c2csc(Br)c2[nH]1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CI
Solvent: C1CCOC1
Solvent: O
Product: Cn1c2ccc(Br)cc2c2cc(Br)ccc21
Reaction time: 4 h

Procedure:
4-Bromo-1H-thieno[3,4-d]imidazol-2(3H)-one represented by formula (5a) was obtained in the same manner as in Example 1. In 3 ml/mmol of tetrahydrofuran to 3,6-dibromo-9H-carbazole, it was reacted with 1.1 equivalents of sodium hydride for 1 hour under argon gas atmosphere while being kept at 0° C. in an ice bath, and then 1.2 equivalents of methyl iodide was added and a reaction was further continued for 4 hours at room temperature. The reaction was stopped by adding an excessive amount of a mixed aqueous solution of ion-exchange water:ammonium chloride=3:1. The product was extracted from the resulting reaction liquid to an organic layer using diethyl ether and dried over sodium sulfate and then the solvent was evaporated, followed by a purification step by column separation using an ethyl acetate/hexane solvent, so that 3,6-dibromo-9-methyl-9H-carbazole was obtained.
Reaction SMILES: [OH:1][C:2]1[CH:12]=[CH:11][C:5]([CH:6]=[CH:7][C:8]([OH:10])=[O:9])=[CH:4][CH:3]=1.[H][H]>CO.[Pd]>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][C:8]([OH:10])=[O:9])=[CH:11][CH:12]=1
Reactant: O=C(O)C=Cc1ccc(O)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: O=C(O)CCc1ccc(O)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 94.2 %

Procedure:
10% Pd/C (60 mg) was added to a stirred solution of 4-hydroxycinnamic acid (325 mg, 1.98 mmol) in MeOH (15 mL) under an inert atmosphere. Hydrogen gas was then passed through the reaction mixture by means of a hydrogen filled bladder and the mixture was stirred at room temperature for 2 hrs. The reaction mixture was filtered over celite and the celite was washed with MeOH. The filtrate was collected and concentrated under reduced pressure to afford 310 mg (94.5% yield) of 3-[4-hydroxy phenyl]propionic acid as a white solid. 1H NMR (DMSO): δ 7.0 (d, 2H), 6.6 (d, 2H), 2.35 (t, 2H), 2.25 (t, 2H), LC-MS purity: 96.55%.
Reaction SMILES: C([O:3][C:4](=[O:17])[CH2:5][NH:6][C:7]([C:9]1[C:13]([CH3:14])=[C:12]([CH:15]=O)[NH:11][CH:10]=1)=[O:8])C.[OH-].[Na+].[CH3:20][NH:21][S:22]([C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29](=[O:34])[CH2:28]2)(=[O:24])=[O:23].N1CCCCC1>CO.C(O)C>[CH3:14][C:13]1[C:9]([C:7]([NH:6][CH2:5][C:4]([OH:3])=[O:17])=[O:8])=[CH:10][NH:11][C:12]=1[CH:15]=[C:28]1[C:27]2[C:31](=[CH:32][CH:33]=[C:25]([S:22](=[O:23])(=[O:24])[NH:21][CH3:20])[CH:26]=2)[NH:30][C:29]1=[O:34]
Reactant: CCOC(=O)CNC(=O)c1c[nH]c(C=O)c1C
Reactant: CNS(=O)(=O)c1ccc2c(c1)CC(=O)N2
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCNCC1
Solvent: CO
Solvent: CCO
Product: CNS(=O)(=O)c1ccc2c(c1)C(=Cc1[nH]cc(C(=O)NCC(=O)O)c1C)C(=O)N2
Temperature: 25 °C
Reaction time: 1 h
Yield: 54.8 %

Procedure:
A mixture of [(5-formyl-4-methyl-1H-pyrrole-3-carbonyl)-amino]-acetic acid ethyl ester (0.142 g, 0.59 mmol) and 1N NaOH (1.2 mL) in methanol (10 mL) was stirred at room temperature for 1 hr. The reaction was concentrated and the residue was condensed with 5-methylaminosulfonyl-2-oxindole (0.13 g, 0.48 mmol) and piperidine (0.12 mL) in ethanol (12 mL) to give 0.11 g (52%) of the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([CH2:27][CH3:28])=[C:12]([C:14]3[C:15](=[O:26])[N:16]([CH3:25])[N:17]=[C:18]([CH3:24])[C:19]=3S(C)(=O)=O)[CH:13]=2)=[CH:4][CH:3]=1.CN1CCCC1=[O:35].[OH-].[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([CH2:27][CH3:28])=[C:12]([C:14]3[C:15](=[O:26])[N:16]([CH3:25])[N:17]=[C:18]([CH3:24])[C:19]=3[OH:35])[CH:13]=2)=[CH:4][CH:3]=1
Reactant: CN1CCCC1=O
Reactant: CCc1ccc(-c2ccc(Cl)cc2)cc1-c1c(S(C)(=O)=O)c(C)nn(C)c1=O
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: CCc1ccc(-c2ccc(Cl)cc2)cc1-c1c(O)c(C)nn(C)c1=O
Temperature: 70 °C
Reaction time: 3 h
Yield: 63.6 %

Procedure:
To a 25 ml volume three-necked flask, 4-[5-(4-chlorophenyl)-2-ethylphenyl]-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone ((2-34)-(1)-67) (290 mg), N-methyl-2-pyrrolidone (890 mg), and aqueous sodium hydroxide solution (410 mg) were added under a nitrogen atmosphere, and stirred at 70° C. for 3 hours. After the reaction mixture was cooled to room temperature, toluene was added and washed. The organic layer was removed. To the resulting aqueous layer, 10 wt % of hydrochloric acid was added to adjust pH to less than 1, and extracted with ethyl acetate 3 times. The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to column chromatography (hexane: ethyl acetate=2:1) to give 157 mg of 4-[5-(4-chlorophenyl)-2-ethylphenyl]-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone ((1-4)-(1)-67).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][CH:27]=1)[O:5][C:6]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])[C:7]=1[C:8]([NH2:10])=[O:9].[CH:28]([S:31](Cl)(=[O:33])=[O:32])([CH3:30])[CH3:29].S(Cl)(Cl)(=O)=O>N1C=CC=CC=1.C(OCC)(=O)C>[F:15][C:13]1[CH:14]=[C:6]([O:5][C:4]2[CH:25]=[CH:26][CH:27]=[C:2]([NH:1][S:31]([CH:28]([CH3:30])[CH3:29])(=[O:33])=[O:32])[CH:3]=2)[C:7]([C:8]([NH2:10])=[O:9])=[C:11]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])[CH:12]=1
Reactant: NC(=O)c1c(Nc2ccc(I)cc2F)cc(F)cc1Oc1cccc(N)c1
Reactant: CC(C)S(=O)(=O)Cl
Solvent: O=S(=O)(Cl)Cl
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CC(C)S(=O)(=O)Nc1cccc(Oc2cc(F)cc(Nc3ccc(I)cc3F)c2C(N)=O)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 46.5 %

Procedure:
In analogy to GP 6b, 144 mg of 2-(3-amino-phenoxy)-4-fluoro-6-(2-fluoro-4-iodo-phenylamino)-benzamide (Intermediate 1.4; 0.3 mmol, 1 eq.) were dissolved in 1.5 mL pyridine and treated with 51 mg iso-propylsulfonyl chloride (0.36 mmol, 1.2 eq., dissolved in 0.5 mL pyridine). The reaction mixture was stirred at rt overnight, treated with another 0.5 eq. sulfonylchloride (in 0.2 mL pyridine) and stirring was continued at rt overnight. After addition of further 0.5 eq. sulfonylchloride (in 0.2 mL pyridine) and further stirring at rt overnight, the resulting mixture diluted with ethyl acetate, washed with water and the organic layers dried. Concentration in vacuo followed by HPLC purification provided 82 mg (46% yield) of the desired compound, which includes substoichiometric amounts of formic acid.
Reaction SMILES: F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(C(C)C)CC)(C)C.[NH:34]1[C:42]2[C:37](=[CH:38][CH:39]=[C:40]([C:43]([OH:45])=O)[CH:41]=2)[CH:36]=[CH:35]1.[CH3:46][O:47][C:48](=[O:57])[C:49]1[CH:54]=[CH:53][C:52]([NH2:55])=[CH:51][C:50]=1[Cl:56]>O1CCCC1>[CH3:46][O:47][C:48](=[O:57])[C:49]1[CH:54]=[CH:53][C:52]([NH:55][C:43]([C:40]2[CH:41]=[C:42]3[C:37]([CH:36]=[CH:35][NH:34]3)=[CH:38][CH:39]=2)=[O:45])=[CH:51][C:50]=1[Cl:56]
Reactant: O=C(O)c1ccc2cc[nH]c2c1
Reactant: COC(=O)c1ccc(N)cc1Cl
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc(NC(=O)c2ccc3cc[nH]c3c2)cc1Cl
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 26 %

Procedure:
Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (8.3 g, 17.8 mmol, 1.1 equiv.) and diisopropyl ethyl amine (4.4 ml, 33.9 mmol, 2.1 equiv.) were added to 1H-indole-6-carboxylic acid (2.6 g, 16.2 mmol, 1 equiv.) in tetrahydrofuran (30 mL) and the mixture was shaken for 5 minutes at room temperature. 4-Amino-2-chlorobenzoic acid methyl ester (3.3 g, 17.9 mmol, 1.1 equiv.) was added and the resultant mixture was shaken at room temperature for 16 hours. The solvent was removed under vacuum and the residue triturated with dichloromethane (10 mL). The solid was filtered to afford 2-chloro-4-[(1H-indole-6-carbonyl)-amino]-benzoic acid methyl ester, 1.4 g (26% yield). LC @215 nm; Rt 1.36: 90%, m/z (ES+): 329 (M+H+.); δH (400 MHz; d6-DMSO) 11.65 (1H, s), 10.59 (1H, s), 8.16 (1H, s), 8.10 (1H, s), 7.93 (2H, m), 7.65 (2H, s), 7.59 (1H, m), 6.62 (1H, s), 3.85 (3H, s).
Reaction SMILES: [O:1]=[C:2]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]([C-:10]1[CH:14]=[CH:13][CH:12]=[CH:11]1)=O.[CH-:21]1[CH:25]=[CH:24][CH:23]=[CH:22]1.[Fe+2:26].O>OS(O)(=O)=O.C(O)(=O)C>[C:2]([CH:3]1[CH2:4][CH2:5][CH2:6][CH:7]=[C:8]1[C-:10]1[CH:14]=[CH:13][CH:12]=[CH:11]1)(=[O:1])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH-:21]1[CH:25]=[CH:24][CH:23]=[CH:22]1.[Fe+2:26]
Reactant: O=C(CCCCCC(=O)[c-]1cccc1)c1ccccc1
Agent: [Fe+2]
Agent: O=S(=O)(O)O
Agent: c1cc[cH-]c1
Solvent: O
Solvent: CC(=O)O
Product: O=C(c1ccccc1)C1CCCC=C1[c-]1cccc1
Reaction time: 8 h
Yield: 36.2 %

Procedure:
7-Oxo-7-phenylheptanoylferrocene (1.94g; 5 mmole) was dissolved in 5% H2SO4 /acetic acid (40 ml; excess) at room temperature. The solution was stirred overnight and then poured into water (400 ml) and extracted with chloroform (3 × 200 ml). The organic layers were extracted with water, saturated aqueous sodium bicarbonate, and water, and dried (Na2SO4) to yield a brown oil. The crude occurrence product was suspended in hot petroleum ether (bp 40°-60° C.) and filtered. The filtrate was submitted to preparative thin layer chromatography on silica. The main yellow band was eluted with petroleum ether/ethyl acetate (10:1) and gave 670 mg (36.2%) of pure 3-benzoyl-2-ferrocenylcyclohexene mp 127°-129° C. EXAMPLE 8
Reaction SMILES: [CH:1]1([N:7]([CH2:17][CH:18]2[CH2:20][CH2:19]2)[C:8]2[N:13]=[CH:12][N:11]=[C:10]([C:14]([OH:16])=O)[CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:21][C:22]1[CH:27]=[CH:26][C:25]([S:28]([NH:31][CH2:32][CH:33]([OH:36])[CH2:34][OH:35])(=[O:30])=[O:29])=[CH:24][CH:23]=1>>[CH:1]1([N:7]([CH2:17][CH:18]2[CH2:20][CH2:19]2)[C:8]2[N:13]=[CH:12][N:11]=[C:10]([C:14]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([S:28]([NH:31][CH2:32][CH:33]([OH:36])[CH2:34][OH:35])(=[O:30])=[O:29])=[CH:24][CH:23]=3)=[O:16])[CH:9]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=C(O)c1cc(N(CC2CC2)C2CCCCC2)ncn1
Reactant: Nc1ccc(S(=O)(=O)NCC(O)CO)cc1
Product: O=C(Nc1ccc(S(=O)(=O)NCC(O)CO)cc1)c1cc(N(CC2CC2)C2CCCCC2)ncn1

Procedure:
Following the general method as outlined in Example 1, starting from 6-[cyclohexyl(cyclopropylmethyl)amino]pyrimidine-4-carboxylic acid (Intermediate 13) and 4-amino-N-(2,3-dihydroxypropyl)benzenesulfonamide (Intermediate 15), the title compound was obtained as a brown solid after purification by column chromatography (silica) eluting with cyclohexane containing increasing amounts of EtOAc.
Reaction SMILES: [N+](=[C:3]1[C@H:7]([OH:8])[C@@H:6]([CH2:9][OH:10])[O:5][C@H:4]1[N:11]1[CH:18]=[CH:17][C:15](=[O:16])[NH:14][C:12]1=[O:13])=[N-].[N-:19]=[N+:20]=[N-:21].[Na+]>>[N:19]([C:17]1[C:15](=[O:16])[NH:14][C:12](=[O:13])[N:11]([CH:18]=1)[C@@H:4]1[O:5][C@H:6]([CH2:9][OH:10])[C@@H:7]([OH:8])[CH2:3]1)=[N+:20]=[N-:21]
Reactant: [N-]=[N+]=C1[C@H](n2ccc(=O)[nH]c2=O)O[C@H](CO)[C@H]1O
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Product: [N-]=[N+]=Nc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O

Procedure:
5-azido-2-'-deoxyuridine nucleoside and nucleotide compounds and a method of producing them. The method involves reacting a 5'-deoxyuridine compound with nitrosonium tetrafluoroborate to produce a 5-nitro-deoxyuridine compound. The 5-nitro-deoxyuridine compound is reduced to a 5-amino-deoxyuridine compound in the presence of metallic zinc. The 5-amino-deoxyuridine compound is acidified and reacted with sodium nitrite to produce a 5-diazo-deoxyuridine compound. The diazo-deoxyuridine compound is then reacted with sodium azide to produce a 5-azido-deoxyuridine compound. The latter, in the monophosphate form, is further reacted with diphenylchlorophosphate to produce the photoactive triphosphate, 5-azido-2'-deoxyuridine-5'-triphosphate or 5-azido-dUTP. The photoactive compound, when added to DNA in an in vitro synthesis reaction, produces photoactive DNA.
Reaction SMILES: [Na].[O:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]3[C:12]([O:35][CH2:36][CH:37]4[CH2:39][CH2:38]4)=[N:13][N:14]([CH3:34])[C:15]=3[NH:16][S:17]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([CH3:33])([CH3:32])[C:27]([O:29]CC)=[O:28])=[CH:22][CH:21]=3)(=[O:19])=[O:18])=[CH:10][C:5]=2[O:4][CH2:3]1>CO.O.O1CCCC1>[O:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]3[C:12]([O:35][CH2:36][CH:37]4[CH2:39][CH2:38]4)=[N:13][N:14]([CH3:34])[C:15]=3[NH:16][S:17]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([CH3:33])([CH3:32])[C:27]([OH:29])=[O:28])=[CH:22][CH:21]=3)(=[O:18])=[O:19])=[CH:10][C:5]=2[O:4][CH2:3]1
Reactant: CCOC(=O)C(C)(C)c1ccc(S(=O)(=O)Nc2c(-c3ccc4c(c3)OCO4)c(OCC3CC3)nn2C)cc1
Agent: [Na]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: Cn1nc(OCC2CC2)c(-c2ccc3c(c2)OCO3)c1NS(=O)(=O)c1ccc(C(C)(C)C(=O)O)cc1
Reaction time: 24 h
Yield: 36.6 %

Procedure:
An aqueous solution of sodium hydroxyde (2N, 1 ml) was slowly added to a solution of ethyl 2-{4-[([4-(1,3-benzodioxol-5-yl)-3-(cyclopropylmethoxy)-1-methyl-1H-pyrazol-5-yl]amino)sulfonyl]phenyl}-2-methylpropanoate (Example 75) (83 mg) in a mixture of methanol:water:tetrahydrofuran (1:1:1) (6 ml) and the reaction was heated to 50 C. for 24 h. The reaction was quenched by the addition of a saturated aqueous solution of ammonium chloride (8 ml) and extracted with dichloromethane (3×8 ml). The organic fraction was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative TLC eluted with dichloromethane:methanol (9:1) yielding the title compound as a white solid (28.8 mg).
Reaction SMILES: [CH3:1][C:2]1[C:10]2[CH2:9][O:8][C:7](=[O:11])[C:6]=2[CH:5]=[CH:4][C:3]=1[CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][NH:17][CH2:16][C:15]1=[O:20].[CH3:21][C:22]1[C:30]2[CH2:29][O:28][C:27](=[O:31])[C:26]=2[CH:25]=[CH:24][C:23]=1[C@@H:32]1[CH2:34][O:33]1>CCO>[OH:33][C@H:32]([C:23]1[CH:24]=[CH:25][C:26]2[C:27](=[O:31])[O:28][CH2:29][C:30]=2[C:22]=1[CH3:21])[CH2:34][N:17]1[CH2:18][CH2:19][N:14]([CH2:13][CH2:12][C:3]2[CH:4]=[CH:5][C:6]3[C:7](=[O:11])[O:8][CH2:9][C:10]=3[C:2]=2[CH3:1])[C:15](=[O:20])[CH2:16]1
Reactant: Cc1c([C@@H]2CO2)ccc2c1COC2=O
Reactant: Cc1c(CCN2CCNCC2=O)ccc2c1COC2=O
Solvent: CCO
Product: Cc1c(CCN2CCN(C[C@H](O)c3ccc4c(c3C)COC4=O)CC2=O)ccc2c1COC2=O
Temperature: 100 °C

Procedure:
A sealed tube containing 1-[2-(4-Methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-2-one (60 mg, 0.19 mmol) and 4-methyl-5-[(2R)-oxiran-2-yl]-2-benzofuran-1(3H)-one dissolved in 1 mL of EtOH was heated to 100° C. overnight. After 16 hrs the solvent was removed and the material purified via flash chromatography to give the title product. LC-MS (IE, m/z): 465 [M+1]+.