Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([OH:8])=[O:7].C([O-])([O-])=O.[K+].[K+].Br[CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]>CC(C)=O>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([O:8][CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:7]
Reactant: O=C(O)c1cccs1
Reactant: CC(C)(C)OC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C)(C)OC(=O)COC(=O)c1cccs1
Temperature: 50 °C
Reaction time: 0.08 h
Yield: 100 %

Procedure:
To a solution of thiophene-2-carboxylic acid (500 mg, 3.90 mmol) in acetone (20 ml), K2CO3 (593 mg, 4.29 mmol) was added, and mixture was stirred for 5 minutes, then KI (64.8 mg, 0.390 mmol) was added, followed by dropwise addition of tert-butyl 2-bromoacetate (0.634 ml, 4.29 mmol). The mixture was heated at 50° C. overnight. The solid residue was filtered out and washed with DCM; the solvent was evaporated and 2-tert-butoxy-2-oxoethyl thiophene-2-carboxylate was obtained as a clear oil (945 mg, 3.90 mmol, 100% yield, MS/ESI+ 264.9 [MNa]+) and used in the following reaction without further purification.
Reaction SMILES: Br[C:2]1[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:17][CH3:18])=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][CH:6]=1.C([Li])CCC.CCCCCC.[C:35]([CH2:39][C:40](Cl)=[O:41])([CH3:38])([CH3:37])[CH3:36].O>O1CCCC1>[CH3:16][O:15][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][C:11]=1[O:17][CH3:18])[N:8]=[CH:7][CH:6]=[C:5]2[O:4][C:3]1[CH:19]=[CH:20][C:21]([CH3:23])=[CH:22][C:2]=1[C:40](=[O:41])[CH2:39][C:35]([CH3:38])([CH3:37])[CH3:36]
Reactant: CC(C)(C)CC(=O)Cl
Reactant: COc1cc2nccc(Oc3ccc(C)cc3Br)c2cc1OC
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: O
Product: COc1cc2nccc(Oc3ccc(C)cc3C(=O)CC(C)(C)C)c2cc1OC
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 14 %

Procedure:
4-(2-Bromo-4-methylphenoxy)-6,7-dimethoxyquinoline (100 mg) was dissolved in tetrahydrofuran (6 ml) to prepare a solution which was then cooled to −78° C. A 1.59 M n-butyllithium/hexane solution (0.4 ml) was added thereto, and the mixture was stirred at −78° C. for 20 min. Tert-butylacetyl chloride (0.2 ml) was added to the reaction solution, and the mixture was stirred at room temperature overnight. Further, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using acetone-chloroform to give the title compound (15 mg, yield 14%).
Reaction SMILES: [C:1](#[N:3])[CH3:2].C([Li])CCC.[C:9]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.Cl>O1CCCC1.CCCCCC>[OH:16][C:9]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:2][C:1]#[N:3]
Reactant: O=C(c1ccccc1)c1ccccc1
Reactant: CC#N
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: N#CCC(O)(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
The solution of 8.2 g of acetonitrile in 200 ml of tetrahydrofuran is added dropwise to the solution of 14.08 g of butyl lithium in 125 ml of tetrahydrofuran and 125 ml of n-hexane while stirring at -70° under nitrogen and stirring is continued for 1 hour. Thereupon the solution of 36.4 g benzophenone in 200 ml of tetrahydrofuran is added dropwise and the mixture stirred for 20 minutes at room temperature. It is poured onto 300 g of ice and 100 ml of 3N hydrochloric acid, the organic layer separated and the aqueous phase extracted three times with 50 ml of diethyl ether. The combined organic solutions are dried, evaporated and the residue recrystallized from ethanol, to yield the β-hydroxy-β,β-diphenyl-propionitrile melting at 136°-138°.
Reaction SMILES: Br.Br[CH2:3][C:4]([C:6]12[CH2:13][N:10]([CH2:11][CH2:12]1)[CH2:9][CH2:8][CH2:7]2)=[O:5].[N-:14]=[N+:15]=[N-:16].[Na+]>CN(C)C=O>[N:14]([CH2:3][C:4]([C:6]12[CH2:13][N:10]([CH2:11][CH2:12]1)[CH2:9][CH2:8][CH2:7]2)=[O:5])=[N+:15]=[N-:16]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C(CBr)C12CCCN(CC1)C2
Agent: Br
Agent: [Na+]
Solvent: CN(C)C=O
Product: [N-]=[N+]=NCC(=O)C12CCCN(CC1)C2
Temperature: 25 °C
Reaction time: 21 h

Procedure:
A solution of 5-(α-bromoacetyl)-1-azabicyclo[3.2.1]octane hydrobromide (D27) (1.8 g; 5.8 mmole) in dry N,N-dimethylformamide (25 ml) was treated with sodium azide (0.41 g; 6.3 mmole) and stirred in the dark at room temperature for 21h. The reaction mixture was concentrated in vacuo and the residue was treated with a saturated potassium carbonate solution (25 ml) and extracted into chloroform (4×25 ml). The dried (sodium sulphate) organic layers were concentrated in vacuo to give the title compound (D28) as an orange oil (0.75 g; 67%) which was used in the next stage without purification.
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([CH3:14])=[CH:11][C:12]#[N:13])[CH:6]=[CH:7][CH:8]=1.[CH:17]([C:19]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=1)=O.[C:27](#[N:31])[CH2:28][C:29]#[N:30].N1CCCCC1>C(O)C>[NH2:31][C:27]1[N:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:15])([F:16])[F:1])[CH:4]=2)[C:10]([CH3:14])=[C:11]([C:12]#[N:13])[CH:17]([C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=2)[C:28]=1[C:29]#[N:30]
Reactant: CC(=CC#N)Nc1cccc(C(F)(F)F)c1
Reactant: N#Cc1ccc(C=O)cc1
Reactant: N#CCC#N
Solvent: CCO
Solvent: C1CCNCC1
Product: CC1=C(C#N)C(c2ccc(C#N)cc2)C(C#N)=C(N)N1c1cccc(C(F)(F)F)c1

Procedure:
Under argon, 750 mg (3.32 mmol) of the compound of Example 2A, 434.79 mg (3.32 mmol) 4-formylbenzonitrile and 219.04 mg (3.32 mmol) malononitrile are dissolved in 5 ml ethanol. 28.23 mg (33 μl, 0.33 mmol) piperidine are added, and the mixture is stirred at reflux overnight. The product is crystallised from the reaction mixture at 0° C. The formed crystals are filtered, washed twice with cold ethanol and dried.
Reaction SMILES: [CH2:1]([C:5]1[N:6]=[C:7]([CH3:27])[NH:8][C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC.[S:59]1[CH:63]=[CH:62][N:61]=[C:60]1[CH2:64]O>O1CCCC1>[CH2:1]([C:5]1[N:6]=[C:7]([CH3:27])[N:8]([CH2:64][C:60]2[S:59][CH:63]=[CH:62][N:61]=2)[C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc(C)[nH]c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: OCc1nccs1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Product: CCCCc1nc(C)n(Cc2nccs2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 75.5 %

Procedure:
A mixture of 4′-[(4-butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (1 g), 1,1′-(azodicarbonyl)dipiperidine (1.41 g), tributylphosphine (1.74 mL), 1,3-thiazol-2-ylmethanol (0.48 g) and tetrahydrofuran (50 mL) was stirred at room temperature for 4 hr. The reaction mixture was concentrated. The residue was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.96 g, 75%).
Reaction SMILES: [F:1][C:2]1([F:25])[CH2:7][CH2:6][C:5]([CH2:9][NH:10][C:11]([C:13]2[C:14]3[CH:15]=[CH:16][C:17](Cl)=[N:18][C:19]=3[CH:20]=[CH:21][C:22]=2[Cl:23])=[O:12])([OH:8])[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.[F:35][C@H:36]1[CH2:40][CH2:39][NH:38][CH2:37]1>>[F:1][C:2]1([F:25])[CH2:7][CH2:6][C:5]([CH2:9][NH:10][C:11]([C:13]2[C:14]3[CH:15]=[CH:16][C:17]([N:38]4[CH2:39][CH2:40][C@H:36]([F:35])[CH2:37]4)=[N:18][C:19]=3[CH:20]=[CH:21][C:22]=2[Cl:23])=[O:12])([OH:8])[CH2:4][CH2:3]1
Reactant: F[C@H]1CCNC1
Reactant: O=C(NCC1(O)CCC(F)(F)CC1)c1c(Cl)ccc2nc(Cl)ccc12
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NCC1(O)CCC(F)(F)CC1)c1c(Cl)ccc2nc(N3CC[C@H](F)C3)ccc12

Procedure:
The title compound was synthesized according to the procedure described in example 1 using 2,6-dichloro-quinoline-5-carboxylic acid (4,4-difluoro-1-hydroxy-cyclohexylmethyl)-amide, DIPEA and (S)-3-fluoro-pyrrolidine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.75 (1H), 7.85 (m, 1H), 7.58 (2H), 7.05 (1H), 5.43-5.56 (1H), 4.56 (s, 1H), 3.89 (m, 2H), 3.70 (m, 1H), 3.55 (m, 1H), 3.26 (m, 2H), 2.44 (m, 2H), 2.06 (m, 2H), 1.85 (m, 2H), 1.74-1.76 (m, 5H), 1.27-1.32 (m, 2H). m/z: 442 [M+H]
Reaction SMILES: C([O:3][C:4]([C:6]1[O:7][C:8]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:20][CH2:19][N:18]([CH2:21][C:22]4[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=4[Cl:29])[CH2:17][CH2:16]3)=[C:11]([CH3:30])[C:9]=2[CH:10]=1)=[O:5])C.[OH-].[Li+]>C1COCC1.O.CO>[Cl:28][C:27]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:29])[C:22]=1[CH2:21][N:18]1[CH2:17][CH2:16][N:15]([C:12]2[CH:13]=[CH:14][C:8]3[O:7][C:6]([C:4]([OH:5])=[O:3])=[CH:10][C:9]=3[C:11]=2[CH3:30])[CH2:20][CH2:19]1
Reactant: CCOC(=O)c1cc2c(C)c(N3CCN(Cc4c(Cl)cccc4Cl)CC3)ccc2o1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: Cc1c(N2CCN(Cc3c(Cl)cccc3Cl)CC2)ccc2oc(C(=O)O)cc12
Reaction time: 2 h
Yield: 166.9 %

Procedure:
To a solution of 5-[4-(2,6-Dichloro benzyl)-piperazine-1-yl]-4-methyl-benzofuran-2-carboxylic acid ethyl ester (0.08 g, 0.0001 mol) in THF:Water:Methanol (3:2:1) mixture (19 ml) was added lithium hydroxide (0.02 g, 0.0005 mol) at 0° C. The reaction mixture was stirred for 2 hours. The completion of the reaction was confirmed by TLC. Solvent was concentrated under reduced pressure added ice water. The pH of the mixture was made acidic with 1N HCl and the solid separated was filtered. After drying under vacuum, isolated 5-[4-(2,6-Dichloro benzyl)-piperazine-1-yl]-4-methyl-benzofuran-2-carboxylic acid (70 mg, 94%).
Reaction SMILES: [CH:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[S:6][C:5]=2[CH:4]=[C:3]([C:16](O)=[O:17])[CH:2]=1.B#B>O1CCCC1.O>[OH:17][CH2:16][C:3]1[CH:2]=[CH:1][C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[S:6][C:5]=2[CH:4]=1
Reactant: O=C(O)c1ccc2c(c1)Sc1ccccc1CC2
Agent: B#B
Solvent: O
Solvent: C1CCOC1
Product: OCc1ccc2c(c1)Sc1ccccc1CC2

Procedure:
Dissolve 7.5 gm. of 10,11-dihydrodibenzo[b,f]-thiepin-3-carboxylic acid in 140 ml. of tetrahydrofuran. With stirring, add 90 ml. of 1 N diborane in tetrahydrofuran. Stir at room temperature for 2 hours and dilute the reaction mixture with water. Extract into ether, and evaporate the ether extract to dryness. Stir the residue with hexane and filter to obtain the title product (m.p., 82°-84° C.).
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].[CH3:9][C:10]1[N:11]=[CH:12][S:13][CH:14]=1.[CH3:15][C:16]([S:19]([N:21]=[C:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)=[O:20])([CH3:18])[CH3:17].C[Al](C)C.CCCCCCC>C1COCC1.C1(C)C=CC=CC=1>[CH3:18][C:16]([S:19]([NH:21][C:22]1([C:12]2[S:13][CH:14]=[C:10]([CH3:9])[N:11]=2)[CH2:23][CH2:24][O:25][CH2:26][CH2:27]1)=[O:20])([CH3:15])[CH3:17]
Reactant: Cc1cscn1
Reactant: CC(C)(C)S(=O)N=C1CCOCC1
Agent: CC(C)[N-]C(C)C
Agent: C[Al](C)C
Agent: [Li+]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Solvent: CCCCCCC
Product: Cc1csc(C2(NS(=O)C(C)(C)C)CCOCC2)n1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 68.5 %

Procedure:
A 2.0M solution of lithium diisopropylamide in THF (492 μl, 984 μmol) was added dropwise to a solution of 4-methylthiazole (97.5 mg, 984 μmol) in dry THF (0.3 ml) cooled to −78° C. and once the addition was complete the reaction was stirred for 30 minutes at −78° C. followed by addition of dry toluene (0.6 ml). To a solution of 2-methyl-N-(2H-pyran-4(3H,5H,6H)-ylidene)propane-2-sulfinamide (CAN 861857-62-7, 100 mg, 492 μmol) in dry toluene (1 mL) was added a 2.0M solution of trimethylaluminum in heptane (271 μl, 541 μmol). The former solution was then added to the reaction mixture cooled at −78° C. The reaction was allowed to warm up to room temperature overnight. The reaction was quenched by the addition of a saturated aqueous solution of ammonium chloride and was then diluted with ethyl acetate. The bi-phasic mixture was poured into a separatory funnel and extracted. The organic phase was collected, dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a dichloromethane/methanol gradient to yield the title compound (102 mg, 69%). MS (ESI, m/z): 303.5 (M+H+).
Reaction SMILES: C(O[C:4]1[CH2:9][CH:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH3:22])[CH2:7][C:6](=[O:23])[CH:5]=1)C.[CH2:24]([Li])[CH3:25].O>C1C=CC=CC=1>[CH2:24]([C:4]1[CH2:9][CH:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH3:22])[CH2:7][C:6](=[O:23])[CH:5]=1)[CH3:25]
Reactant: CCOC1=CC(=O)CC(c2ccccc2OCOCCOC)C1
Reactant: [Li]CC
Solvent: c1ccccc1
Solvent: O
Product: CCC1=CC(=O)CC(c2ccccc2OCOCCOC)C1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A solution of 3-ethoxy-5-(2-methoxyethoxymethoxyphenyl)-2-cyclohexenone (2.0 g) in benzene (60 ml) was added dropwise with stirring in an atmosphere of dry nitrogen to an ice-cooled 1.5 M solution of ethyllithium in benzene (20.8 ml). When the addition was complete, water was added and the mixture was allowed to stand overnight at room temperature. The benzene layer was separated and the aqueous layer was extracted with ether. The organic solutions were combined, dried and the solvents were evaporated under reduced pressure. The residue was purified by preparative-layer chromatography on silica gel using a mixture of ethyl acetate and petroleum ether (b.p. 60°-80°) for elution to afford the title compound (0.65 g) as a pale yellow oil. (Found: C, 70.9; H, 7.7. C18H24O4 requires C, 71.0; H, 7.9%.)
Reaction SMILES: [CH3:1][O:2][C:3](/[C:5](=[CH:10]/[C:11]1[O:12][C:13]([CH3:16])=[CH:14][CH:15]=1)/[CH2:6][C:7]([OH:9])=O)=[O:4].[C:17]([O-])(=[O:19])[CH3:18].[K+].O.C(OCC)(=O)C>C(OC(=O)C)(=O)C>[CH3:16][C:13]1[O:12][C:11]2[CH:10]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:6]=[C:7]([O:9][C:17](=[O:19])[CH3:18])[C:15]=2[CH:14]=1
Reactant: COC(=O)/C(=C/c1ccc(C)o1)CC(=O)O
Reactant: CC(=O)[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC(=O)OC(C)=O
Product: COC(=O)c1cc(OC(C)=O)c2cc(C)oc2c1
Temperature: 140 °C

Procedure:
A mixture of E-3-methoxycarbonyl-4-(5-methylfur-2-yl)-but-3-enoic acid (Method 15; 1.39 g, 6.2 mmol) and potassium acetate (620 mg, 6.3 mmol) in acetic anhydride (12.5 ml) was heated at 140° C. for 15 mins. The reaction mixture was cooled and poured on to a water/ethyl acetate mixture; the aqueous layer was separated and the organic layer washed sequentially with saturated sodium bicarbonate solution and brine, dried (MgSO4) and evaporated in vacuo to yield the crude product as a dark crystalline mass. This was chromatographed (50 g Bondelut, eluting with hexane containing ethyl acetate, 0-100%) to give the title compound as a pale yellow solid, 1.42 g (92%). NMR: 2.36 (s, 3H), 3.34 (s, 3H), 3.87 (s, 3H), 6.68 (s, 1H), 7.56 (s, 1H), 7.96 (s, 1H); m/z 247 (M−H)−, 97.1% by LC-MS.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([NH:20][C:21](=[O:30])[C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[C:6]([NH:9][C:10](=[O:19])[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)=[CH:7][CH:8]=1)#[N:2].Cl.[NH2:32][OH:33].C(N(CC)C(C)C)(C)C>>[NH2:2][C:1](=[N:32][OH:33])[C:3]1[CH:4]=[C:5]([NH:20][C:21](=[O:30])[C:22]2[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=2)[C:6]([NH:9][C:10](=[O:19])[C:11]2[CH:12]=[CH:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=2)=[CH:7][CH:8]=1
Reactant: NO
Reactant: COc1ccc(C(=O)Nc2ccc(C#N)cc2NC(=O)c2ccc(OC)cc2)cc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(C(=O)Nc2ccc(C(N)=NO)cc2NC(=O)c2ccc(OC)cc2)cc1
Yield: 93.3 %

Procedure:
To a stirred solution of 4-cyano-N1,N2-bis(4-methoxybenzoyl)-1,2-benzenediamine (750 mg, 1.9 mmol) was added hydroxylamine hydrochloride (130 mg, 1.9 mmol) and N,N-diisopropylethylamine (0.30 mL, 1.9 mmol). After heating at reflux for 12 h, the solution was cooled and the solvent was removed in vacuo. The residue was suspended in ethyl acetate and water, stirred vigorously, filtered, and dried in vacuo to give 770 mg (95%) of the title product as a white solid.
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:10]([C:19]2[CH:24]=[CH:23][C:22]([CH:25](C(OC(C)(C)C)=O)[C:26]([O:28]C(C)(C)C)=[O:27])=[C:21]([N+:40]([O-:42])=[O:41])[CH:20]=2)=[N:11][CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1>ClCCl>[Cl:8][C:9]1[C:10]([C:19]2[CH:24]=[CH:23][C:22]([CH2:25][C:26]([OH:28])=[O:27])=[C:21]([N+:40]([O-:42])=[O:41])[CH:20]=2)=[N:11][CH:12]=[C:13]([C:15]([F:17])([F:16])[F:18])[CH:14]=1
Reactant: CC(C)(C)OC(=O)C(C(=O)OC(C)(C)C)c1ccc(-c2ncc(C(F)(F)F)cc2Cl)cc1[N+](=O)[O-]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(O)Cc1ccc(-c2ncc(C(F)(F)F)cc2Cl)cc1[N+](=O)[O-]
Temperature: 23 °C
Reaction time: 65 h

Procedure:
16 ml of trifluoroacetic acid were added dropwise to a solution of 10.2 g of 3-chloro-2-[4-(bis-[1,1-dimethylethoxycarbonyl]-methyl)-3-nitrophenyl]-5-trifluoromethylpyridine in 100 ml of anhydrous dichloromethane. After stirring at 23° C. for 65 hours, the methylene chloride was removed by distillation. The residue was dissolved in 100 ml of ether, after which the ether phase was extracted three times with 50 ml of water each time, dried over sodium sulfate and concentrated. The crude product was stirred with n-hexane/ether (9:1). Yield: 5.1 g (72%) of colorless crystals.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]([C:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([C:19]4[C:27]5[O:26][CH2:25][O:24][C:23]=5[CH:22]=[CH:21][C:20]=4[O:28][CH2:29][CH2:30][CH3:31])[C:13]=3[NH:12][CH:11]=2)=[O:9])[CH2:3][CH2:2]1.Cl[C:33]([O:35][CH2:36][CH3:37])=[O:34]>>[CH2:36]([O:35][C:33]([N:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]([C:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([C:19]4[C:27]5[O:26][CH2:25][O:24][C:23]=5[CH:22]=[CH:21][C:20]=4[O:28][CH2:29][CH2:30][CH3:31])[C:13]=3[NH:12][CH:11]=2)=[O:9])[CH2:3][CH2:2]1)=[O:34])[CH3:37]
Reactant: CCCOc1ccc2c(c1-c1ncnc3c(C(=O)NC4CCNCC4)c[nH]c13)OCO2
Reactant: CCOC(=O)Cl
Product: CCCOc1ccc2c(c1-c1ncnc3c(C(=O)NC4CCN(C(=O)OCC)CC4)c[nH]c13)OCO2

Procedure:
Starting from 4-(5-propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid piperidin-4-ylamide (example A177) and ethyl chloroformate the title compound was obtained as colorless solid.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[Mg].Br[CH2:12][CH2:13][CH:14]=[CH2:15].[Cl-].[NH4+]>CCOCC>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]([OH:7])[CH2:15][CH2:14][CH:13]=[CH2:12])=[CH:4][CH:3]=1
Reactant: C=CCCBr
Reactant: O=Cc1ccc(Cl)cc1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: CCOCC
Product: C=CCCC(O)c1ccc(Cl)cc1
Yield: 50.8 %

Procedure:
A solution of 70 g (0.5 mole) of 4-chlorobenzaldehyde in 100 ml of absolute ether is added dropwise to a Grignard solution of 12.2 g (0.5 mole) of magnesium and 67.5 g (0.5 mole) of 4-bromo-1-butene in 350 ml of absolute ether, with stirring, and, when the addition has ended, the mixture is heated at the reflux temperature for 2 hours. The cooled reaction mixture is poured into a mixture of 1 liter of saturated ammonium chloride solution and ice, the organic phase is separated off, washed twice with water, dried over sodium sulphate and concentrated in vacuo and the residue is then distilled under a high vacuum. 50 g (58% of theory) of 5-(4-chlorophenyl)-pent-1-en-5-ol of boiling point 100° C.-105° C./0.13 mbar are obtained.
Reaction SMILES: OO.[C@@H:3]1([N:12]2[CH:19]=[N:18][C:16]([NH2:17])=[N:15][C:13]2=[O:14])[O:11][C@H:8]([CH2:9][OH:10])[C@@H:6]([OH:7])[C@H:4]1O.[C:20]([O-:25])(=O)CCC.[Na+].C(O)[C:28]([NH2:33])(CO)CO.Cl>>[O:25]=[C:20]1[N:33]=[C:28]2[C:19](=[N:18][C:16]([NH2:17])=[N:15][C:13]2=[O:14])[N:12]1[C@@H:3]1[O:11][C@H:8]([CH2:9][OH:10])[C@@H:6]([OH:7])[CH2:4]1
Reactant: NC(CO)(CO)CO
Reactant: CCCC(=O)[O-]
Reactant: Nc1ncn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)n1
Agent: Cl
Agent: OO
Agent: [Na+]
Product: NC1=NC(=O)C2=NC(=O)N([C@H]3C[C@H](O)[C@@H](CO)O3)C2=N1
Reaction time: 0.67 h

Procedure:
The H2O2-UV irradiated slides or slides produced with cells grown in presence of either Cd+Cr+H2O2 or 5-azacytidine, or sodium butyrate are incubated overnight at 4° C. in the presence of 30 μl of an anti-8-oxo-dG mouse monoclonal antibody (Gentaur) diluted 1/100 in 10 mM Tris-HCl, pH 7.5, 10% Foetal Bovine Serum. The slides are washed once in PBS and then incubated for 40 minutes in the presence of a goat anti-mouse IgG1 antibody (southern Biotechnology Associates, Inc) diluted at a concentration of 0.1 μg/1×106 cells in PBS.
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:11].[C:12]([O-])([O-])=O.[K+].[K+].CI.O>CN(C=O)C>[CH3:12][O:11][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]=1[NH2:1]
Reactant: O=C([O-])[O-]
Reactant: Nc1c(O)cccc1[N+](=O)[O-]
Agent: [K+]
Solvent: O
Solvent: CI
Solvent: CN(C)C=O
Product: COc1cccc([N+](=O)[O-])c1N
Yield: 90.5 %

Procedure:
To a mixture of 2-amino-3-nitrophenol (19.25 g) and K2CO3 (19 g) in DMF (100 mL) was added MeI (11 mL) at room temperature and the mixture was stirred over night and then poured into water. The resulting precipitate was collected by filtration and the solid was washed with water to afford the desired product (19 g, 90%). 1H NMR (300 MHz, CDCl3) δ ppm 3.92 (s, 1H), 6.43 (br s, 1H), 6.61 (dd, 1H, J=7.5, 9.0 Hz), 6.89 (dd, 1H, J=0.9, 7.5 Hz), 7.73 (dd, 1H, J=0.9, 9.0 Hz); LC-MS: m/e=169 [M+1]+
Reaction SMILES: [C:1]([Cl:4])(Cl)=[O:2].[CH3:5][CH:6]([CH2:11][NH:12][CH3:13])[C:7]([O:9][CH3:10])=[O:8]>C1(C)C=CC=CC=1>[CH3:13][N:12]([CH2:11][CH:6]([C:7]([O:9][CH3:10])=[O:8])[CH3:5])[C:1]([Cl:4])=[O:2]
Reactant: O=C(Cl)Cl
Reactant: CNCC(C)C(=O)OC
Solvent: Cc1ccccc1
Product: COC(=O)C(C)CN(C)C(=O)Cl
Temperature: 20 °C

Procedure:
To a solution of 16 g of phosgene in 70 ml of toluene, a solution of 17.4 g of methyl 2-methyl-3-methylaminopropionate in 30 ml of toluene was added dropwise with stirring at 20° C. The mixture was stirred at room temperature for 4 hours and evaporated to dryness. The residue was stirred for 10 min. with 100 ml of ethyl ether, filtered, the filtrates are evaporated to dryness and the residue was distilled at high vacuum to give the N-methyl-N-(2-methoxycarbonylpropyl)carbamoyl chloride, bp. 97°-100°/1 mm Hg.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[CH2:16](O)[CH2:17][OH:18].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[C:9]1([C:8]2([C:5]3[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=3)[O:18][CH2:17][CH2:16][O:15]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: O=C(c1ccccc1)c1ccc(Br)cc1
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: Brc1ccc(C2(c3ccccc3)OCCO2)cc1

Procedure:
In 1300 milliliters of toluene in a flask equipped with a Dean-Stark tube are dissolved 100 grams of p-bromobenzophenone; and to this solution is added 150 grams of ethyleneglycol and 4.4 grams of p-toluenesulphonic acid. This mixture is refluxed until no further water collects in the Dean-Stark tube. After distilling off the toluene and recrystallization from methanol one obtains 2-phenyl-2-(p-bromophenyl)-1,3-dioxolane.