Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:11]([C:12]([O:14][CH3:15])=[O:13])=[N:10][C:9]2[NH:8][C:7](=[O:16])[CH2:6][S:5][C:4]=2[CH:3]=1.[CH2:17]([Sn](CC)(CC)CC)[CH3:18]>CN(C)C=O.CO.C(OCC)(=O)C.[Pd].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>[CH2:17]([C:2]1[C:11]([C:12]([O:14][CH3:15])=[O:13])=[N:10][C:9]2[NH:8][C:7](=[O:16])[CH2:6][S:5][C:4]=2[CH:3]=1)[CH3:18]
Reactant: COC(=O)c1nc2c(cc1Br)SCC(=O)N2
Reactant: CC[Sn](CC)(CC)CC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Pd]
Solvent: CO
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCc1cc2c(nc1C(=O)OC)NC(=O)CS2
Yield: 16.8 %

Procedure:
Methyl 7-bromo-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxylate (Example 304b) (2.00 g, 6.6 mmol), tetraethyltin (3.17 mL, 16 mmol) and bis(triphenylphosphine)palladium(II) chloride (1.12 g, 1.6 mmol) in dimethylformamide (40 mL) were heated at 120° C. for 24 h. The mixture was filtered through Kieselguhr, washed through with ethyl acetate and evaporated. Chromatography on silica gel (20-50% ethyl acetate/petroleum ether) gave a mixture of the 7-ethyl and 7-vinyl compounds (0.29 g). This mixture was hydrogenated in methanol/ethyl acetate (2:1, 60 mL) over 10% palladium on carbon (60 mg) (1 atmosphere, room temperature) for 24 h. Filtration and evaporation of solvent gave the product (0.28 g).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl.[OH2:16].[OH-].[Na+].[C:19]1([CH3:25])C=CC=C[CH:20]=1>>[C:9]1([C:25]2[CH:19]=[C:20]([OH:16])[C:7]3[C:2](=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:1]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: Nc1ccccc1
Reactant: O
Reactant: Cc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Oc1cc(-c2ccccc2)nc2ccccc12
Temperature: 135 °C
Yield: 20 %

Procedure:
This amide (250 mg, 1.53 mmol) was refluxed using a Dean-Stark apparatus with aniline (143 mg, 1.53 mmol) and aniline •HCl (10 mg, 0.08 mmol) in toluene (10 mL) for 16 h. The solution was concentrated to afford a brown oil that was mixed with polyphosphoric acid (2 g) and heated at 135° C. for 20 min. The reaction mixture was poured into water and adjusted to pH 8 with 5 M NaOH. The aqueous suspension was extracted twice with ethyl acetate. The organic layers were combined, washed with brine, dried over MgSO4, filtered and concentrated. The residue was flash chromatographed on silica gel, eluting with 3% MeOH in ethyl acetate, to give 2-phenyl-4-hydroxyquinoline (2), 67 mg, 20% yield.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:21]([N+:22]([O-])=O)=[CH:20][C:19]([Br:25])=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.O.[Sn](Cl)Cl.C(=O)(O)[O-].[Na+]>C(O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:21]([NH2:22])=[CH:20][C:19]([Br:25])=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])c1cc(Br)cnc1Nc1ccc(OCc2ccccc2)cc1
Agent: Cl[Sn]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: Nc1cc(Br)cnc1Nc1ccc(OCc2ccccc2)cc1
Temperature: 70 °C

Procedure:
N-[4-(benzyloxy)phenyl]-5-bromo-3-nitropyridin-2-amine (28.5 g, 0.071 mmol) and tin (II) chloride dihydrate (160.67 g, 0.712 mmol) were dissolved in 500 mL ethanol under N2 and the reaction mixture heated at reflux (70° C.) for 30 min. Sodium bicarbonate was then added to the cooled mixture until the pH was greater than 9.5, and then the mixture was filtered through celite which was washed with methanol. The combined organic phases were concentrated in vacuo before being re-constituted in CH2Cl2, drying over Na2SO4, and concentration in vacuo to yield N2-[4-(benzyloxy)phenyl]-5-bromopyridine-2,3-diamine. 1H NMR (400 MHz, CDCl3) δ 3.44 (bs, 2H), 5.07 (s, 2H), 6.02 (bs, 1H), 6.97 (dt, 2H, J=5.6, 3.6 Hz), 7.12 (d, 1H, J=2.0 Hz), 7.32 (dt, 2H, J=4.8, 0.4 Hz), 7.34-7.48 (m, 5H), 7.84 (d, 1H, J=2 Hz); MS (ES+): m/z 371 [MH+], 372 (35) [MH2+]
Reaction SMILES: [CH2:1]([S:3][CH2:4][C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:18]([C:23]([OH:25])=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:13][CH:12]=2)[C:8]2[CH:26]=[CH:27][CH:28]=[CH:29][C:7]=2[N:6]=1)[CH3:2].[OH:30]O>C(O)(=O)C>[CH2:1]([S:3]([CH2:4][C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[C:18]([C:23]([OH:25])=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:15][CH:16]=2)[C:8]2[CH:26]=[CH:27][CH:28]=[CH:29][C:7]=2[N:6]=1)=[O:30])[CH3:2]
Reactant: OO
Reactant: CCSCc1nc2ccccc2n1Cc1ccc(-c2ccccc2C(=O)O)cc1
Solvent: CC(=O)O
Product: CCS(=O)Cc1nc2ccccc2n1Cc1ccc(-c2ccccc2C(=O)O)cc1
Reaction time: 24 h

Procedure:
2.01 g (5.0 mmol) of 4'-[(2-ethylthiomethyl-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylic acid are dissolved in 25 ml of glacial acetic acid and treated with 0.51 ml of 30% strength hydrogen peroxide. The solution is allowed to stand for 24 hours at ambient temperature and is then evaporated to dryness. The residue is purified over a silica gel column (grain size: 40-63 μm, eluting agent: methylene chloride/ethanol/glacial acetic acid=50/1/0.15). The homogeneous fractions are combined, the solvents are distilled off, the residue is dissolved in methylene chloride and washed three times using water. The organic phase is dried using magnesium sulphate and evaporated to dryness. The crystalline residue is mixed with diethylether, the mixture is filtered under suction and the crystals are dried at 75° C. in vacuum.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1)#[N:2].[CH3:10][C:11]1[CH:12]=CC(C)=[CH:15][CH:16]=1.O1CCOC1.N1C=CC=CC=1>C(OCC)(=O)C>[CH3:10][C:11]1([CH3:12])[CH:16]=[CH:15][C:5]2[CH:4]=[C:3]([C:1]#[N:2])[CH:8]=[CH:7][C:6]=2[O:9]1
Reactant: Cc1ccc(C)cc1
Reactant: N#Cc1ccc(O)cc1
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Solvent: C1COCO1
Product: CC1(C)C=Cc2cc(C#N)ccc2O1
Temperature: 140 °C
Reaction time: 24 h
Yield: 30 %

Procedure:
Under an argon atmosphere, 4-cyanophenol (0.186 g, 1.56 mmole), p-xylene (1 mL), the dioxolane prepared above (0.2 g, 1.56 mmole), and pyridine (0.12 mL, 1.56 mmole) were combined in that order. The mixture was heated to 140° C. (internal temperature). After 24 hours, the reaction mixture was diluted with ethyl acetate (3 mL) and washed with 10% hydrochloric acid. The organic layers were collected, washed with 1N sodium hydroxide, brine, dried over magnesium sulfate, and concentrated in vacuo to give the title compound as a dark brown oil (0.085 g, 30% yield).
Reaction SMILES: [F:1][C:2]([F:29])([F:28])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([OH:25])=[O:24])=[CH:21][CH:20]=1.[OH-].[Na+].I[CH2:33][CH:34]([OH:37])[CH2:35][OH:36].CN(C)P(N(C)C)(N(C)C)=O>O.CCOCC>[F:1][C:2]([F:28])([F:29])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([O:25][CH2:33][CH:34]([OH:37])[CH2:35][OH:36])=[O:24])=[CH:21][CH:20]=1
Reactant: OCC(O)CI
Reactant: O=C(O)c1ccc(NCCCCCCCCCCCCCCCC(F)(F)F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: O
Product: O=C(OCC(O)CO)c1ccc(NCCCCCCCCCCCCCCCC(F)(F)F)cc1

Procedure:
A solution of 7.34 g. of 4-[15-(trifluoromethyl)pentadecylamino]benzoic acid, 4.80 g. of 25% aqueous sodium hydroxide, and 12.6 g. of 3-iodo-1,2-propanediol in 50 ml. of hexamethylphosphoramide is stirred for 24 hours at ambient temperature, diluted with 100 ml. of ether and stirred for 5 days at ambient temperature. The mixture is treated with water and extracted with ether. The dried extracts are evaporated to yield the product as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.C[O-].[Na+].[Cl-].[NH4+:14]>CO>[ClH:1].[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]([NH2:14])=[NH:7])=[CH:4][CH:3]=1
Reactant: N#Cc1ccc(Cl)cc1
Reactant: [NH4+]
Agent: C[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Product: Cl
Product: N=C(N)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 104.3 %

Procedure:
To a solution of 4-chlorobenzonitrile (5.0 g) in methanol (40 ml) was added sodium methoxide (0.20 g) and the reaction was stirred at room temperature for 3 days. Ammonium chloride (1.94 g) was added and the reaction was stirred overnight. The reaction was filtered and the filtrate concentrated to an oil. After the addition of ether the off-white precipitate was collected and dried to give the title compound (3.62 g). Electrospray MS m/z 155 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2([C:26]([N:28]3[CH2:33][CH2:32][CH2:31][CH:30]([CH2:34]OS(C)(=O)=O)[CH2:29]3)=[O:27])[CH2:25][CH2:24][CH2:23]2)=[CH:18][CH:17]=1.O1C2C=CC(OCC3CCCN(C(C4(C5C=CC(Cl)=CC=5)CCC4)=O)C3)=CC=2OC1>>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2([C:26]([N:28]3[CH2:33][CH2:32][CH2:31][CH:30]([CH2:34][O:8][C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[CH2:29]3)=[O:27])[CH2:25][CH2:24][CH2:23]2)=[CH:18][CH:17]=1
Reactant: Oc1ccc(F)cc1
Reactant: CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1
Agent: O=C(N1CCCC(COc2ccc3c(c2)OCO3)C1)C1(c2ccc(Cl)cc2)CCC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: O=C(N1CCCC(COc2ccc(F)cc2)C1)C1(c2ccc(Cl)cc2)CCC1
Yield: 57.4 %

Procedure:
Compound 84 was synthesized from 4-fluorophenol (0.29 g, 2.60 mmol), cesium carbonate (1.27 g, 3.89 mmol) and compound 43 (1.0 g, 2.60 mmol), using the method described for the synthesis of compound 44 to give 0.60 g of the desired product 84. C23H25ClFNO2, LRMS (m/z)=402 (MH+).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7](Br)[C:8]#[C:9][CH3:10].CN(C)C=O.[Cl:17][C:18]1[NH:28][C:21]2[CH:22]=[N:23][N:24]([CH3:27])[C:25](=[O:26])[C:20]=2[N:19]=1>C(OCC)(=O)C>[CH2:7]([N:19]1[C:20]2[C:25](=[O:26])[N:24]([CH3:27])[N:23]=[CH:22][C:21]=2[N:28]=[C:18]1[Cl:17])[C:8]#[C:9][CH3:10]
Reactant: Cn1ncc2[nH]c(Cl)nc2c1=O
Reactant: CC#CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC#CCn1c(Cl)nc2cnn(C)c(=O)c21
Temperature: 25 °C
Reaction time: 18 h

Procedure:
0.166 g of potassium carbonate and 0.106 μl of 2-butynyl bromide were added to a 10 ml N,N-dimethylformamide solution of 0.184 g of 2-chloro-5-methyl-1,5-dihydroimidazo[4,5-d]pyridazin-4-one, and the mixture was stirred at room temperature for 18 hours. 50 ml of ethyl acetate was added to the solution, and the mixture was washed three times with 20 ml of water and then with 20 ml of a saturated sodium chloride solution. The organic liquid was dried over magnesium sulfate, and concentrated under reduced pressure. Then, the residue was purified by silica gel column chromatography. Thus, 0.175 g of 3-(2-butynyl)-2-chloro-5-methyl-3,5-dihydroimidazo[4,5-d]pyridazin-4-one was obtained from the fraction eluted with hexane-ethyl acetate (4:1), and 0.033 g of 1-(2-butynyl)-2-chloro-5-methyl-1,5-dihydroimidazo[4,5-d]pyridazin-4-one was obtained from the fraction eluted with hexane-ethyl acetate (2:3).
Reaction SMILES: [CH2:1]([SH:5])[CH:2]([CH3:4])[CH3:3].C[O-].[Na+].[NH2:9][C:10]1[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][C:17]2[C:12](=[CH:13][C:14](Cl)=[CH:15][CH:16]=2)[CH:11]=1.O>CO>[NH2:9][C:10]1[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][C:17]2[C:12](=[CH:13][C:14]([S:5][CH2:1][CH:2]([CH3:4])[CH3:3])=[CH:15][CH:16]=2)[CH:11]=1
Reactant: Nc1cc2cc(Cl)ccc2cc1[N+](=O)[O-]
Reactant: CC(C)CS
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CC(C)CSc1ccc2cc([N+](=O)[O-])c(N)cc2c1
Reaction time: 0.17 h

Procedure:
To 1 mole of isobutylmercaptan in 500 ml of methanol stirring at room temperature is added 1.1 mol of sodium methoxide. The mixture is stirred for 10 minutes and the solvent is evaporated under vacuum. The residue is taken up in 500 ml of dimethylformamide. To this mixture, stirring at room temperature, is added 1 mole of 2-amino-7-chloro-3-nitronaphthalene. The mixture is refluxed for 2 hours, then cooled and poured into 2 liters of water. After stirring for 30 minutes the resulting precipitate is filtered off and recrystallized from methanol or ethanol to yield the title compound.
Reaction SMILES: [CH2:1]([Mg]Br)[CH2:2][CH3:3].[C:6]1([C:12]2[CH:24]=[CH:23][C:15]([C:16]([C:18]([O:20]CC)=O)=[O:17])=[CH:14][CH:13]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[OH:25][C:26]1[C:27](=O)[O:28][C:29](C)([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)C=1O.C(Cl)(Cl)Cl>C1COCC1>[C:12]1([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:13]=[CH:14][C:15]([C:16]2([CH2:1][CH2:2][CH3:3])[O:17][C:26](=[O:25])[C:27]([O:28][CH2:29][C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)=[C:18]2[OH:20])=[CH:23][CH:24]=1
Reactant: CCOC(=O)C(=O)c1ccc(-c2ccccc2)cc1
Reactant: CCC[Mg]Br
Reactant: CC1(c2ccccc2)OC(=O)C(O)=C1O
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: CCCC1(c2ccc(-c3ccccc3)cc2)OC(=O)C(OCc2ccccc2)=C1O
Yield: 8 %

Procedure:
A total of 5.2 mL (10.4 mmol) of 2.0 M n-propylmagnesium bromide was added to a solution of 2.4 g (10 mmol) of ethyl 4-phenylbenzoylformate in THF in an analogous manner as described for the synthesis of 3,4-dihydroxy-5-methyl-5-phenyl-2(5H)-furanone to give prior to hydrogenolysis 0.30 g (8% yield) of 5-[(1,1′-biphenyl)-4-yl]-4-hydroxy-3-phenylmethoxy-5-propyl-2(5H)-furanone as an off white solid after crystallization from CHCl3 and hexanes.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[Cl:11][CH2:12][CH2:13][CH2:14]O>S(=O)(=O)(O)O>[OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([O:7][CH2:14][CH2:13][CH2:12][Cl:11])=[O:6]
Reactant: OCCCCl
Reactant: O=C(O)c1cccc(O)c1
Agent: O=S(=O)(O)O
Product: O=C(OCCCCl)c1cccc(O)c1
Yield: 93.9 %

Procedure:
A solution of 3-hydroxybenzoic acid (16.0 g, 0.115 mol) in 3-chloropropanol (76 g, 0.81 mol) and 0.5 mL of concentrated sulfuric acid was refluxed overnight. The excess alcohol was removed by vacuum distillation. The brown viscous residue was dissolved in ethyl acetate (60 mL) and washed with water (2×15 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The brown viscous residue was purified by column chromatography (ethyl acetate/hexane, 30:70) to give the product as a white solid (23.3 g, 0.108 mol, 93.7%): 1H NMR (CDCl3) δ2.19-2.28 (m, 2H), 3.69 (t, 2H, J=6.3 Hz), 4.48 (t, 2H, J=6Hz), 5.92 (s, 1H), 7.05-7.64 (m, 4H); MS exact mass: calcd. 214,0396, found 214.0400.
Reaction SMILES: C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[Cl:25][C:26]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][CH2:37][N:38](C(OC(C)(C)C)=O)[CH2:39][CH2:40][NH:41][CH2:42]C(OC(C)(C)C)=O)=[CH:31][C:27]=1[C:28]([OH:30])=O.[C:57]12([CH2:67][NH2:68])[CH2:66][CH:61]3[CH2:62][CH:63]([CH2:65][CH:59]([CH2:60]3)[CH2:58]1)[CH2:64]2.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[ClH:25].[ClH:25].[ClH:25].[Cl:25][C:26]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][CH2:37][NH:38][CH2:39][CH2:40][NH:41][CH3:42])=[CH:31][C:27]=1[C:28]([NH:68][CH2:67][C:57]12[CH2:66][CH:61]3[CH2:60][CH:59]([CH2:65][CH:63]([CH2:62]3)[CH2:64]1)[CH2:58]2)=[O:30]
Reactant: CC(C)(C)OC(=O)CNCCN(CCCc1ccc(Cl)c(C(=O)O)c1)C(=O)OC(C)(C)C
Reactant: NCC12CC3CC(CC(C3)C1)C2
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CNCCNCCCc1ccc(Cl)c(C(=O)NCC23CC4CC(CC(C4)C2)C3)c1
Product: Cl

Procedure:
PyBrOP (0.2 g) was added to a solution of 2-chloro-5-[3-[[(1,1-dimethylethoxy)carbonyl][2-[[(1,1-dimethylethoxy)carbonyl]methylamino]ethyl]-amino]propyl]-benzoic acid (0.2 g, Example 13b), adamantanemethylamine (0. 1 ml) and triethylamine (0.15 ml) in N,N-dimethylformamide (10 ml). After 1 h the reaction mixture was diluted with ethyl acetate and washed with water, then washed twice with ammonium is chloride solution, twice with saturated sodium hydrogencarbonate solution and once with brine. The organic extracts were dried over magnesium sulfate, filtered, evaporated and purified by chromatography on silica (eluting with dichloromethane: methanol/2-10%). The product was redissolved in dichloromethane: methanol/1:1 (15 ml) and 4M hydrochloric acid in dioxane (2 ml) added. The mixture was stirred until deprotection was complete then purified by prep RP-HPLC (acetonitrile/0.1% aqueous trifluoroacetic acid). Conversion to the hydrochloride salt by treatment with 4M hydrochloric acid in 1,4-dioxane/methanol gave the title compound (0.055 g).
Reaction SMILES: [C:1]1([CH:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)N2CCN(CCCN)CC2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1([N:30]2[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][CH2:38][NH2:39])[CH2:32][CH2:31]2)C=CC=CC=1.[N:40]([C:43]([CH3:50])([CH3:49])[CH2:44][C:45]([O:47][CH3:48])=[O:46])=[C:41]=[O:42]>C1(C)C=CC=CC=1>[C:1]1([CH:7]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:40]([C:43]([CH3:50])([CH3:49])[CH2:44][C:45]([O:47][CH3:48])=[O:46])[C:41]([NH:39][CH2:38][CH2:37][CH2:36][N:33]2[CH2:32][CH2:31][NH:30][CH2:35][CH2:34]2)=[O:42])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)CC(C)(C)N=C=O
Reactant: NCCCN1CCN(c2ccccc2)CC1
Reactant: NCCCN1CCN(C(c2ccccc2)c2ccccc2)CC1
Solvent: Cc1ccccc1
Product: COC(=O)CC(C)(C)N(C(=O)NCCCN1CCNCC1)C(c1ccccc1)c1ccccc1

Procedure:
9.0 g (0.029 mol) of 1-diphenylmethyl-4-(3-aminopropyl)-piperazine are dissolved in 30 ml of toluene and according to process alternative (a) mixed with stirring with a mixture of 4.6 g (0.029 mol) of methyl 3-isocyanatoisovalerate and 20 ml of toluene. The mixture is heated for 30 minutes to approximately 70° C., evaporated to dryness under reduced pressure and the oily residue rubbed after the addition of diethyl ether. The methyl 3-(1-diphenylmethylpiperazin-4-ylpropylureido)-isovalerate thus obtained is pure according to its thin-layer chromatogram. ##STR20## Yield: 9.8 g (72% of theory).
Reaction SMILES: C1(S[C@H:8]2[CH2:13][CH2:12][C@H:11]([C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][C:15]=3[OH:21])[CH2:10][CH2:9]2)C=CC=CC=1.Cl[C:23]1[CH:28]=[CH:27][CH:26]=[C:25](C(OO)=O)[CH:24]=1.[S:33]([O-:37])([O-])(=[O:35])=S.[Na+].[Na+]>ClCCl>[C:23]1([S:33]([C@H:8]2[CH2:13][CH2:12][C@H:11]([C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][C:15]=3[OH:21])[CH2:10][CH2:9]2)(=[O:37])=[O:35])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=S([O-])([O-])=S
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Oc1ccc([C@H]2CC[C@H](Sc3ccccc3)CC2)c(O)c1
Agent: [Na+]
Solvent: ClCCl
Product: O=S(=O)(c1ccccc1)[C@H]1CC[C@H](c2ccc(O)cc2O)CC1
Temperature: 0 °C

Procedure:
A round bottom flask containing trans-4-[4-(phenylsulfanyl)cyclohexyl]-1,3-benzenediol (18 mg, 0.06 mmol) and dichloromethane (2 ml) was cooled to 0° C. and meta-chloroperbenzoic acid (50-60%, 41 mg, 0.24 mmol) was added with stirring. After 30 min at this temperature the reaction mixture was poured into saturated sodium thiosulfate solution (5 ml) and partitioned between saturated aqueous sodium hydrogen carbonate (10 ml) and dichloromethane (10 ml). The aqueous phase was further extracted with dichloromethane (2×10 ml) and the combined organic extracts were washed with brine, dried over magnesium sulfate and concentrated in vacuo. Purification via flash column chromatography (SiO2, ethyl acetate/petrol, 30:70) afforded the title compound (6 mg, 30%) as an off-white solid. δH (d4-MeOH) 1.40-1.62 (4H, m), 1.88-1.95 (2H, m), 2.05-2.13 (2H, m), 2.72 (1H, m), 3.18 (1H, m), 6.08-6.13 (2H, m), 6.82 (1H, d), 7.64 (2H, m), 7.75 (1H, m), 7.90 (2H, m); m/z (ES+) 333 (M+H)+.
Reaction SMILES: C([O:8][C@@H:9]1[C@@H:13]([CH2:14][O:15][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[S:12][CH:11]([N:33]2[CH:41]=[N:40][C:39]3[C:34]2=[N:35][C:36]([Cl:43])=[N:37][C:38]=3Cl)[C@H:10]1[F:44])C1C=CC=CC=1.ClB(Cl)Cl.CO.C(=O)([O-])O.[Na+].[NH3:56].C(O)C>C(Cl)Cl>[F:44][C@H:10]1[C@H:9]([OH:8])[C@@H:13]([CH2:14][OH:15])[S:12][C@H:11]1[N:33]1[CH:41]=[N:40][C:39]2[C:34]1=[N:35][C:36]([Cl:43])=[N:37][C:38]=2[NH2:56]
Reactant: N
Reactant: CC(C)(C)[Si](OC[C@H]1SC(n2cnc3c(Cl)nc(Cl)nc32)[C@@H](F)[C@@H]1OCc1ccccc1)(c1ccccc1)c1ccccc1
Agent: ClB(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: ClCCl
Solvent: CO
Product: Nc1nc(Cl)nc2c1ncn2[C@@H]1S[C@H](CO)[C@@H](O)[C@@H]1F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 31 %

Procedure:
360 mg of the 9-(3-O-benzyl-5-O-t-butyldiphenylsilyl-2-deoxy-2-fluoro-4-thio-D-arabinofuranosyl)-2,6-dichloropurine was dissolved in 11 ml of methylene chloride. To this solution, 2.70 ml of 1 M trichloroboran was added dropwise at -78° C. under a stream of argon. The mixture was allowed to warm up to room temperature, and then stirred for 30 minutes. To this was added 1.0 ml of methanol at -78° C. The resulting mixture was stirred for a further 30 minutes, and then allowed to warm up to room temperature. To this mixture was added a saturated aqueous solution of sodium hydrogencarbonate. The solvent was distilled off, and the residue was azeotropically distilled with methanol three times. The residue was then separated into the alpha-anomer and the beta-anomer by silica gel column chromatography. 115 mg of the beta-anomer obtained was dissolved in 20 ml of a saturated ammonia/ethanol solution, and allowed to react in a sealed tube at 80° C. for 7 hours. The solvent was distilled off, and the residue was dissolved in 5 ml of DMF. To this solution was added 137 mg of ammonium fluoride, and the mixture was stirred at room temperature overnight. The solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 51 mg (yield 31%) of the title compound.
Reaction SMILES: [CH3:1][N:2]([CH3:27])[S:3]([N:6]1[CH:10]=[C:9]([CH:11]([OH:19])[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:8]=[C:7]1[Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])(=[O:5])=[O:4].[H-].[Na+].[CH3:30]I>C1COCC1.CCOC(C)=O>[CH3:27][N:2]([CH3:1])[S:3]([N:6]1[CH:10]=[C:9]([CH:11]([O:19][CH3:30])[CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:8]=[C:7]1[Si:20]([C:23]([CH3:24])([CH3:26])[CH3:25])([CH3:21])[CH3:22])(=[O:4])=[O:5]
Reactant: CI
Reactant: CN(C)S(=O)(=O)n1cc(C(O)Cc2ccccc2)nc1[Si](C)(C)C(C)(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COC(Cc1ccccc1)c1cn(S(=O)(=O)N(C)C)c([Si](C)(C)C(C)(C)C)n1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 2-(tert-butyl-dimethyl-silanyl)-4-(1-hydroxy-2-phenyl-ethyl)-imidazole-1-sulfonic acid dimethylamide (160 mg) at r.t. in THF (5 ml) under an argon atmosphere was added NaH (18 mg; 55% dispersion in mineral oil) in one portion. After 1 hour stirring at r.t., MeI (0.04 ml) was added and stirring at r.t. was continued overnight. The mixture was diluted with EtOAc and washed with H2O. The aqueous phase was back extracted with EtOAc. The combined organics were washed with H2O and brine, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel; gradient: cyclohexane→cyclohexane/EtOAc 65:35) to give 2-(tert-butyl-dimethyl-silanyl)-4-(1-methoxy-2-phenyl-ethyl)-imidazole-1-sulfonic acid dimethylamide (111 mg) as light yellow viscous oil. MS (ISP): 424.3 ([M+H]+)