Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:5]=[C:4]([N+:14]([O-])=O)[C:3]=1[NH2:17].[Cl:18][C:19]1[C:20]([CH:29]=O)=[C:21]([O:27][CH3:28])[N:22]=[N:23][C:24]=1[O:25][CH3:26]>CO.[Pd]>[Cl:18][C:19]1[C:20]([C:29]2[NH:14][C:4]3[CH:5]=[C:6]([N:8]4[CH2:13][CH2:12][O:11][CH2:10][CH2:9]4)[CH:7]=[C:2]([CH3:1])[C:3]=3[N:17]=2)=[C:21]([O:27][CH3:28])[N:22]=[N:23][C:24]=1[O:25][CH3:26]
Reactant: Cc1cc(N2CCOCC2)cc([N+](=O)[O-])c1N
Reactant: COc1nnc(OC)c(C=O)c1Cl
Agent: [Pd]
Solvent: CO
Product: COc1nnc(OC)c(-c2nc3c(C)cc(N4CCOCC4)cc3[nH]2)c1Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of 2-methyl-4-morpholin-4-yl-6-nitro-phenylamine (0.252 g, 1.06 mmol) in methanol (15 mL) was added 10% palladium on carbon (25 mg) and the suspension flushed well with nitrogen, followed by hydrogen. The resulting suspension was stirred 8 hours at room temperature under an atmosphere of hydrogen (ca. 1 atm). The resulting suspension was filtered under nitrogen through a pad of Celite and washed with methanol (25 mL). This solution was cooled down to 0° C., the 5-chloro-3,6-dimethoxy-pyridazine-4-carbaldehyde (0.225 g, 1.12 mmol) in methanol (10 mL) was added and the reaction mixture was stirred exposed to air at 23° C. for 18 hours. MeOH was evaporated in vacuo and the crude material was purified by preparative HPLC (see method below) to give the title compound as a yellow solid. (0.265 g, 64%) HPLC: 99% (220 nm), LCMS (+ESI, M+H+) m/z 390, IR (KBr, cm−1) 3421, 2956, 2852, 1625, 1470, 1362; 1H NMR (400 MHz, CDCl3) δ 9.99 (s, 1H), 7.17 (s, 0.3H) 6.88 (s, 0.3H), 6.80 (s, 0.7H), 6.74 (s, 0.7H), 4.14 (s, 0.9H), 4.13 (s, 0.9H), 4.12 (s, 2.2H), 4.11 (s,2.2H), 3.83 (m, 4H), 3.13 (m, 4H), 2.62 (s, 2.2H), 2.48 (s, 0.9H). Procedure for the Preparation of 2-(4-chloro-2,6-dimethoxy-pyrimidin-5-yl)-4-methyl-6-morpholin-4-yl-1H-benzimidazole
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:6](=[O:19])[NH:7][N:8]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH:10]=1)=[O:4].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[CH2:20]([N:7]1[C:6](=[O:19])[C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:10][C:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)=[N:8]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: BrCc1ccccc1
Reactant: COC(=O)c1cc(-c2ccc(OC)cc2)n[nH]c1=O
Product: COC(=O)c1cc(-c2ccc(OC)cc2)nn(Cc2ccccc2)c1=O
Yield: 96.9 %

Procedure:
Using 4-methoxycarbonyl-6-(4-methoxyphenyl)-2H-pyridazin-3-one and benzyl bromide as starting materials, the procedures of Example 1 were repeated likewise, whereby the title compound was obtained in a yield of 96.9%.
Reaction SMILES: C1(=O)OC(=O)C=C1.[C:8]([OH:15])(=[O:14])/[CH:9]=[CH:10]\[C:11]([OH:13])=[O:12].[OH-].[Na+:17].[O-2].[La+3].[O-2].[O-2].[La+3].[N+]([O-])(O)=O.CN(CCO)CCO.S(=O)(=O)(O)O>O>[C:8]([O-:15])(=[O:14])/[CH:9]=[CH:10]\[C:11]([O-:13])=[O:12].[Na+:17].[Na+:17]
Reactant: O=C(O)/C=C\C(=O)O
Agent: CN(CCO)CCO
Agent: O=C1C=CC(=O)O1
Agent: O=S(=O)(O)O
Solvent: O
Solvent: O=[N+]([O-])O
Product: O=C([O-])/C=C\C(=O)[O-]
Temperature: 80 °C
Reaction time: 70 h

Procedure:
A disodium maleate solution was prepared by dissolving 19.6 g (0.2 mol) of maleic anhydride in 50 ml of water and by adding the resulting maleic acid solution to 33.3 g of a 48% lye solution (0.4 mol NaOH). During the addition the temperature of the reaction mixture was maintained at 70-90° C. Lanthanum(III)oxide, La2O3, (8.15 g, 0.025 mol) was dissolved in 65% nitric acid (16.8 g, 0.173 mol) and in 12 ml of water and added to the reaction mixture together with N-methyl diethanol-amine (11.9 g, 0.1 mol). The reaction mixture was stirred at 85° C. under a reflux condenser for 70 hours. The reaction mixture was cooled and rendered acidic (pH 1-2) by addition of sulfuric acid. The formed La(III)sulfate precipitate was removed by filtration. The remaining sodium sulfate was precipitated by addition of acetone. After filtration and concentration the remaining solution (7.2 g), which contained water 67.6 w-%, the organic compounds were analyzed as silyl or methyl ester derivatives by means of 13C NMR spectra and by GC-MS (table 1, entry 3, and table 2, entry 3, respectively).
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:11]2[S:12][C:13]3[C:14](Cl)=[N:15][CH:16]=[CH:17][C:18]=3[N:19]=2)=[C:4]([CH:7]=[C:8]([F:10])[CH:9]=1)[C:5]#[N:6].[Br:21][Si](C)(C)C.C(=O)(O)[O-].[Na+]>C(#N)CC>[Br:21][C:14]1[C:13]2[S:12][C:11]([C:3]3[C:2]([Cl:1])=[CH:9][C:8]([F:10])=[CH:7][C:4]=3[C:5]#[N:6])=[N:19][C:18]=2[CH:17]=[CH:16][N:15]=1
Reactant: C[Si](C)(C)Br
Reactant: N#Cc1cc(F)cc(Cl)c1-c1nc2ccnc(Cl)c2s1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCC#N
Product: N#Cc1cc(F)cc(Cl)c1-c1nc2ccnc(Br)c2s1
Temperature: 50 °C
Yield: 100.2 %

Procedure:
To a suspension of 3-chloro-2-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-5-fluorobenzonitrile (118 mg, 0.36 mmol) in propionitrile (3.5 mL) was added bromotrimethylsilane (0.15 mL, 1.1 mmol) and the reaction mixture was heated at 50° C. for 7 hours. The cooled mixture was treated with aqueous sodium bicarbonate and extracted three times with DCM. The combined organic washings were dried (Na2SO4), filtered and concentrated in vacuo to give the title compound as a yellow solid (133 mg, 100%). 1H NMR (300 MHz, CDCl3): δ 8.53 (d, J=5.6 Hz, 1H), 8.04 (d, J=5.6 Hz, 1H), 7.59 (dd, J=7.7, 2.5 Hz, 1H), 7.55 (dd, J=7.3, 2.5 Hz, 1H). LCMS (Method D): RT=3.88, m/z: 368 [M+H+].
Reaction SMILES: [Cl:1]C(Cl)(Cl)C(Cl)(Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[CH3:35][Si:36]([CH3:48])([CH3:47])[NH:37][S:38]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)(=O)=[O:39]>>[CH3:35][Si:36]([CH3:48])([CH3:47])[N:37]=[S:38]([Cl:1])([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:39]
Reactant: C[Si](C)(C)NS(=O)(=O)c1ccccc1
Reactant: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: C[Si](C)(C)N=S(=O)(Cl)c1ccccc1

Procedure:
The reactants used in the general procedure were hexachloroethane (0.1353 mol, 32.68 g), triphenylphosphine (0.1367 mol, 36.22 g), triethylamine (0.1353 mol, 19.2 ml), and N-trimethylsilyl-sulfonamide (3b) (0.1353 mol, 31.0 g).
Reaction SMILES: C1(O[C:8](=[O:22])[NH:9][C:10]2[N:11]([O:20][CH3:21])[CH2:12][C:13]3[CH2:14][CH2:15][CH2:16][CH2:17][C:18]=3[CH:19]=2)C=CC=CC=1.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1>>[CH3:21][O:20][N:11]1[C:10]([NH:9][C:8]([N:34]2[CH2:33][CH2:32][N:31]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[O:24][CH3:23])[CH2:36][CH2:35]2)=[O:22])=[CH:19][C:18]2[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=2[CH2:12]1
Reactant: CON1CC2=C(C=C1NC(=O)Oc1ccccc1)CCCC2
Reactant: COc1ccccc1N1CCNCC1
Product: COc1ccccc1N1CCN(C(=O)NC2=CC3=C(CCCC3)CN2OC)CC1
Yield: 64 %

Procedure:
Phenyl-N-(2-methoxy-5,6,7,8-tetrahydroisoquinolin-3-yl)carbamate and 1-(2-methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[S:15][C:14]3[C:13](=[O:16])[NH:12][C:11]4([CH2:21][CH2:20][NH:19][CH2:18][CH2:17]4)[NH:10][C:9]=3[CH:8]=2)=[CH:3][CH:2]=1.CN(C=O)C.[C:27](O[BH-](OC(=O)C)OC(=O)C)(=O)[CH3:28].[Na+]>C(=O)C>[CH2:27]([N:19]1[CH2:20][CH2:21][C:11]2([NH:10][C:9]3[CH:8]=[C:7]([C:4]4[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=4)[S:15][C:14]=3[C:13](=[O:16])[NH:12]2)[CH2:17][CH2:18]1)[CH3:28]
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: O=C1NC2(CCNCC2)Nc2cc(-c3ccncc3)sc21
Agent: CC=O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCN1CCC2(CC1)NC(=O)c1sc(-c3ccncc3)cc1N2
Yield: 9.1 %

Procedure:
A mixture of 6′-(pyridin-4-yl)-1′H-spiro[piperidine-4,2′-thieno[3,2-d]pyrimidin]-4′(3′H)-one in DMF (0.16 M, 0.50 mL, 0.080 mmol), acetaldehyde in DMF (0.20 M, 1 mL, 0.20 mmol) and sodium triacetoxyborohydride (40 mg, 0.19 mmol) was stirred for 16 h at room temperature. The reaction mixture was extracted with EtOAc (3.5 mL) and 2% aqueous sodium hydrogen carbonate (1 mL). After evaporating the organic solvent, the crude product was chromatographed on preparative HPLC (YMC CombiPrep. Hydrosphere C18, 10 mM NH4HCO3 in water/MeCN) to afford the title compound (2.4 mg, 9.1%):
Reaction SMILES: Cl[C:2]1[C:3]2[C:8]([N:9]=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[CH2:16]([N:18]1[CH2:23][CH2:22][CH:21]([NH2:24])[CH2:20][CH2:19]1)[CH3:17]>>[CH2:16]([N:18]1[CH2:23][CH2:22][CH:21]([NH:24][C:2]2[C:3]3[C:8]([N:9]=[C:10]4[C:15]=2[CH:14]=[CH:13][CH:12]=[CH:11]4)=[CH:7][CH:6]=[CH:5][CH:4]=3)[CH2:20][CH2:19]1)[CH3:17]
Reactant: CCN1CCC(N)CC1
Reactant: Clc1c2ccccc2nc2ccccc12
Product: CCN1CCC(Nc2c3ccccc3nc3ccccc23)CC1

Procedure:
Following the general procedure of Example 1 and making non-critical variations but using 9-chloroacridine and 1-ethylpiperidin-4-amine, the title compound was obtained; MS (Found M+1=306).
Reaction SMILES: [N:1]1([CH2:7][CH:8]([C:19]2([OH:23])[CH2:22][CH2:21][CH2:20]2)[C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH2:24]=O.O.[OH-].[Na+]>C(O)=O>[CH3:24][N:4]1[CH2:5][CH2:6][N:1]([CH2:7][CH:8]([C:19]2([OH:23])[CH2:22][CH2:21][CH2:20]2)[C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:16])[F:17])[CH:10]=2)[CH2:2][CH2:3]1
Reactant: OC1(C(CN2CCNCC2)c2cccc(C(F)(F)F)c2)CCC1
Reactant: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: O=CO
Product: CN1CCN(CC(c2cccc(C(F)(F)F)c2)C2(O)CCC2)CC1
Temperature: 70 °C

Procedure:
A solution of 1-{2-piperazin-1-yl-1-[3-(trifluoromethyl)phenyl]ethyl}cyclobutanol (60 mg, 0.17 mmol), see Example 14, in formic acid (0.33 mL) at 50° C, was treated with an aqueous solution of formaldehyde (37% in water, 0.14 mL, 0.21 mmol). The reaction was heated at 70° C. for 1.5 h, after which time the reaction was poured into water (5 mL) and basified to pH=10 with the addition of a 2 N aqueous solution of sodium hydroxide. The product was then extracted with ethyl acetate (3×4 mL), and the combined organic extracts were dried over magnesium sulfate and concentrated to yield 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl}cyclobutanol as a colorless oil. The product was dissolved in methanol (0.5 mL) and the resulting solution was treated with a saturated methanolic solution of hydrochloric acid (0.5 mL) followed by diethyl ether (2 mL). The solution was stored in the refrigerator for 16 h. The resulting precipitate was filtered and washed with diethyl ether to yield 52 mg (69%) 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl}cyclobutanol dihydrochloride as a white solid. MS (ESI) m/z 343 ([M+H]+); HRMS: calcd for C18H25F3N2O.2.00 HCl, 414.1453; found (ESI), 343.2007.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:42]([OH:43])[C@@H:41]([O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C@@H:40]([CH2:52][O:53][C:54](=[O:59])[C:55]([CH3:58])([CH3:57])[CH3:56])[O:39][C@H:10]1[O:11][CH2:12][CH:13]([CH2:15][CH2:16][CH2:17][C@H:18]([C@@H:20]1[C@:37]2([CH3:38])[C@H:23]([C@H:24]3[C@H:34]([CH2:35][CH2:36]2)[C@:32]2([CH3:33])[CH:27]([CH2:28][CH2:29][CH2:30][CH2:31]2)[CH2:26][CH2:25]3)[CH2:22][CH2:21]1)[CH3:19])[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:60](OC(=O)C)(=[O:62])[CH3:61].C1(C)C=CC=CC=1>N1C=CC=CC=1>[C:60]([O:43][C@H:42]1[C@@H:41]([O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C@@H:40]([CH2:52][O:53][C:54](=[O:59])[C:55]([CH3:57])([CH3:56])[CH3:58])[O:39][C@@H:10]([O:11][CH2:12][CH:13]([CH2:15][CH2:16][CH2:17][C@H:18]([C@@H:20]2[C@:37]3([CH3:38])[C@H:23]([C@H:24]4[C@H:34]([CH2:35][CH2:36]3)[C@:32]3([CH3:33])[CH:27]([CH2:28][CH2:29][CH2:30][CH2:31]3)[CH2:26][CH2:25]4)[CH2:22][CH2:21]2)[CH3:19])[CH3:14])[C@@H:9]1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)(=[O:62])[CH3:61]
Reactant: CC(CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CCC4CCCC[C@]4(C)[C@H]3CC[C@]12C)CO[C@@H]1O[C@H](COC(=O)C(C)(C)C)[C@H](OCc2ccccc2)[C@H](O)[C@H]1OCc1ccccc1
Reactant: CC(=O)OC(C)=O
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CC(=O)O[C@H]1[C@@H](OCc2ccccc2)[C@@H](COC(=O)C(C)(C)C)O[C@@H](OCC(C)CCC[C@@H](C)[C@H]2CC[C@H]3[C@@H]4CCC5CCCC[C@]5(C)[C@H]4CC[C@]23C)[C@@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 85.4 %

Procedure:
Compound 27 (10 mg, 12.3 μmol) was dissolved in pyridine (1 mL). To the solution, acetic anhydride (0.5 mL) was added, and the mixture was stirred at the room temperature for 1 hour. The solvent was subjected to azeotropy with toluene, and the residue was purified with Sephadex LH-20 (CHCl3:MeOH=1:2) to obtain Compound 28 (9 mg, 85.4%).
Reaction SMILES: [OH:1][CH:2]1[C:7]([O:10][CH3:11])([O:8][CH3:9])[CH2:6][CH2:5][N:4]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:3]1.O1CCC[CH2:20]1.CC(C)([O-])C.[K+].S(OC)(OC)(=O)=O>C(OCC)(=O)C.O>[CH3:20][O:1][CH:2]1[C:7]([O:8][CH3:9])([O:10][CH3:11])[CH2:6][CH2:5][N:4]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:3]1
Reactant: COC1(OC)CCN(C(=O)OC(C)(C)C)CC1O
Reactant: C1CCOC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: COS(=O)(=O)OC
Solvent: CCOC(C)=O
Solvent: O
Product: COC1CN(C(=O)OC(C)(C)C)CCC1(OC)OC
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
The title compound was prepared by taking tert-butyl 3-hydroxy-4,4-dimethoxypiperidine-1-carboxylate (702 mg, 0.00269 mol) in Tetrahydrofuran (10 mL, 0.1 mol) at 0° C. and adding in Potassium tert-butoxide (15 mL, 0.015 mol). The reaction was stirred for 20 min and then Dimethyl sulfate (0.56 mL, 0.006 mol) was added and the temperature raised to ambient temperature. After stirring overnight the reaction mixture was poured into water and ethyl acetate. The organic layers were separated, dried and concentrated in vacuo to afford an oil which was used as-is (424 mg, 99%) MS calculated for C13H25NO5: (M+H) 276; found 276.1.
Reaction SMILES: [Cl:1][C:2]1[C:7]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:6][C:5]([N:12]2[C:17](=[O:18])[C:16]3[CH2:19][CH2:20][CH2:21][C:15]=3[NH:14][C:13]2=[O:22])=[C:4]([F:23])[CH:3]=1.[CH3:24]I>C[O-].[Na+].CO>[Cl:1][C:2]1[C:7]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:6][C:5]([N:12]2[C:17](=[O:18])[C:16]3[CH2:19][CH2:20][CH2:21][C:15]=3[N:14]([CH3:24])[C:13]2=[O:22])=[C:4]([F:23])[CH:3]=1
Reactant: CC(C)Oc1cc(-n2c(=O)[nH]c3c(c2=O)CCC3)c(F)cc1Cl
Reactant: CI
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: CC(C)Oc1cc(-n2c(=O)c3c(n(C)c2=O)CCC3)c(F)cc1Cl

Procedure:
using 3-(4-chloro-2-fluoro-5-isopropoxyphenyl)-1,5,6,7-tetrahydro-2H-cyclopenta[d]pyrimidine-2,4(3H)dione in sodium methylate/methanol with methyl iodide there is obtained 3-(4-chloro-2-fluoro-5-isopropoxyphenyl)-1,5,6,7-tetrahydro-1-methyl-2H-cyclopenta[d]-pyrimidine-2,4(3H)-dione, m.p. 125°-127° C.;
Reaction SMILES: [Cl:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[CH:5][CH:4]=1.S(Cl)([Cl:15])=O.[Cl-]>>[Cl:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([Cl:15])=[O:12])=[CH:5][CH:4]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)Cc1ccc(CCl)cc1
Agent: [Cl-]
Product: O=C(Cl)Cc1ccc(CCl)cc1

Procedure:
A mixture of 1 g of p-chloromethylphenylacetic acid and 6 ml of thionylchloride is stirred at room temperature for 25 hours after which the excessthionyl chloride is removed under vacuum to yield p-chloromethylphenylacetyl chloride.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[CH3:5][O:6][C:7]([C:9]1[S:10][CH:11]=[CH:12][C:13]=1[OH:14])=[O:8].C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH3:5][O:6][C:7]([CH:9]1[CH:13]([O:14][C:1](=[O:3])[CH3:2])[CH:12]=[CH:11][S:10]1)=[O:8]
Reactant: CC(=O)Cl
Reactant: COC(=O)c1sccc1O
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: COC(=O)C1SC=CC1OC(C)=O
Temperature: 0 °C
Reaction time: 4 h
Yield: 96 %

Procedure:
8.6 parts of acetyl chloride are added in the course of 10 minutes to a solution, cooled to 0° C., of 16 parts of 3-hydroxy-thiophene-2-carboxylic acid methyl ester and 15.3 parts by volume of triethylamine in 100 parts by volume of chloroform. The solution is stirred for 4 hours at 0° C. After the reaction, the mixture was poured into 100 parts by volume of ice water and the organic phase is separated off, dried and concentrated. The residue is distilled. 19.4 parts (96% of theory) of 3-acetoxydihydrothiophene-2-carboxylic acid methyl ester of boiling point 82°-84° C./0.08 mbar are obtained.
Reaction SMILES: [H-].[Na+].[OH:3][CH:4]([C:14]1[CH:15]=[C:16]([Si:19]([CH3:22])([CH3:21])[CH3:20])[O:17][CH:18]=1)[CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.I[CH3:24]>O1CCCC1>[CH3:24][O:3][CH:4]([C:14]1[CH:15]=[C:16]([Si:19]([CH3:22])([CH3:21])[CH3:20])[O:17][CH:18]=1)[CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CI
Reactant: C[Si](C)(C)c1cc(C(O)CCCc2ccccc2)co1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(CCCc1ccccc1)c1coc([Si](C)(C)C)c1
Temperature: 25 °C

Procedure:
To a stirred suspension of sodium hydride (0.063 g., 1.05 mmol) in 10 ml tetrahydrofuran at 0° under argon, was added dropwise via syringe 4-(1-hydroxy-4-phenylbutyl)-2-trimethylsilylfuran (0.274 g., 0.951 mmol). This was followed by the addition of iodomethane (0.352 g., 2.48 mmol) and warming of the reaction mixture to room temperature. Several more equivalents of sodium hydride and iodomethane were subsequently added in increments over 2.5 hours until TLC indicated that no starting material remained. The reaction mixture was carefully filtered through celite and partitioned between ethyl ether and 5% hydrochloric acid. The organic portion was washed with 5% sodium bicarbonate, water, saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated to give an oil. Purification by flash chromatography (silica, hexane to 5% ethyl ether/hexane) yielded the desired methyl ether.
Reaction SMILES: [NH2:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([Cl:9])=[CH:4][N:3]=1.[CH2:10]([NH:17][C:18](=[O:21])[CH2:19]Cl)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[NH2:1][C:2]1[C:7]([O:8][CH2:19][C:18]([NH:17][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:21])=[CH:6][C:5]([Cl:9])=[CH:4][N:3]=1
Reactant: O=C(CCl)NCc1ccccc1
Reactant: Nc1ncc(Cl)cc1O
Product: Nc1ncc(Cl)cc1OCC(=O)NCc1ccccc1

Procedure:
The title compound was prepared by the method of P. Nedenskov, N. Clauson-Kaas, J. Lei, H.-N. Heide, G. Olsen and G. Jansen (Acta Chemica Scandinavica, 1969, 23, 1791) from 2-amino-5-chloro-3-pyridinol (G. Mattern, Helv. Chimica Acta, 1977, 60, 2062) and N-benzyl-α-chloroacetamide. Sand coloured solid:
Reaction SMILES: [CH3:1][N:2]1[C:10]2[N:9]=[CH:8][N:7]([CH3:11])[C:6]=2[C:5](=[O:12])[NH:4][C:3]1=[O:13].Cl[CH2:15][CH2:16][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:1][N:2]1[C:10]2[N:9]=[CH:8][N:7]([CH3:11])[C:6]=2[C:5](=[O:12])[N:4]([CH2:15][CH2:16][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20])[C:3]1=[O:13]
Reactant: Cn1cnc2c1c(=O)[nH]c(=O)n2C
Reactant: CC(C)=CCCCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)=CCCCn1c(=O)c2c(ncn2C)n(C)c1=O

Procedure:
9.0 g (0.05 mol) of 3,7-dimethylxanthine, 8.0 g (0.06 mol) of 1-chloro-5-methyl-4-hexene and 8.3 g (0.06 mol) of potassium carbonate are stirred in 200 ml of dimethylformamide at 110° C. for 22 hours. After the solvent has been removed in vacuo, 100 ml of 1N sodium hydroxide solution are added and the mixture is extracted thoroughly with methylene chloride. The extract is extracted again by shaking with dilute sodium hydroxide solution, washed with water until neutral, dried and evaporated under reduced pressure and the residue is recrystallized from diisopropyl ether.
Reaction SMILES: [CH3:1][N:2]1[C:7]([C:8]([O:10]C)=O)=[C:6]([OH:12])[C:5]2[S:13][C:14]3[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=3[C:4]=2[S:3]1(=[O:22])=[O:21].[NH2:23][C:24]1[CH:29]=[N:28][CH:27]=[CH:26][N:25]=1>>[CH3:1][N:2]1[C:7]([C:8]([NH:23][C:24]2[CH:29]=[N:28][CH:27]=[CH:26][N:25]=2)=[O:10])=[C:6]([OH:12])[C:5]2[S:13][C:14]3[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=3[C:4]=2[S:3]1(=[O:22])=[O:21]
Reactant: COC(=O)C1=C(O)c2sc3cc(C)ccc3c2S(=O)(=O)N1C
Reactant: Nc1cnccn1
Product: Cc1ccc2c3c(sc2c1)C(O)=C(C(=O)Nc1cnccn1)N(C)S3(=O)=O
Yield: 39 %

Procedure:
Prepared analogous to Example 1 from methyl 2,7-dimethyl-4-hydroxy-2H-[1] benzothieno [2,3-e]-1,2-thiazine-3-carboxylate-1,1-dioxide and amino-pyrazine with a yield of 39% of theory.
Reaction SMILES: Cl.[CH3:2][C:3]1([CH3:22])[C:7]([CH3:9])([CH3:8])[O:6][B:5]([C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[O:4]1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:29](Cl)(=[O:31])[CH3:30]>C1COCC1>[CH3:9][C:7]1([CH3:8])[C:3]([CH3:22])([CH3:2])[O:4][B:5]([C:10]2[CH:11]=[CH:12][C:13]([N:16]3[CH2:17][CH2:18][N:19]([C:29](=[O:31])[CH3:30])[CH2:20][CH2:21]3)=[CH:14][CH:15]=2)[O:6]1
Reactant: CC1(C)OB(c2ccc(N3CCNCC3)cc2)OC1(C)C
Reactant: CC(=O)Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1CCOC1
Product: CC(=O)N1CCN(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl) piperazine hydrochloride (419 mg, 1.29 mmol) and cesiumcarbonate (1.27 g, 3.9 mmol) in THF (30 mL) was added acetyl chloride (0.5 mL, 6.5 mmol). Then the mixture was stirred at room temperature overnight, extracted with EA, washed with NaHCO3 solution and brine. The organic solution was concentrated and purified by flash column chromatography, eluting with PE/EA, to give product as a white solid. MS (m/z): 331 (M+H)+.
Reaction SMILES: [CH2:1]([C:3]1[S:4][CH:5]=[C:6](/[CH:8]=[CH:9]/[C:10]2[C:11]([O:22]COC)=[N:12][N:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[CH3:21])[CH:14]=2)[N:7]=1)[CH3:2].Cl>CO>[CH2:1]([C:3]1[S:4][CH:5]=[C:6](/[CH:8]=[CH:9]/[C:10]2[C:11]([OH:22])=[N:12][N:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[CH3:21])[CH:14]=2)[N:7]=1)[CH3:2]
Reactant: CCc1nc(/C=C/c2cn(-c3ccccc3C)nc2OCOC)cs1
Agent: Cl
Solvent: CO
Product: CCc1nc(/C=C/c2cn(-c3ccccc3C)nc2O)cs1
Temperature: 50 °C
Reaction time: 1 h
Yield: 85.5 %

Procedure:
To a solution of 2-ethyl-4-{(E)-2-[3-(methoxymethoxy)-1-(2-methylphenyl)-1H-pyrazol-4-yl]ethenyl}-1,3-thiazole (0.81 g) in methanol (20 mL) was added concentrated hydrochloric acid (0.42 mL) at room temperature, and the mixture was stirred at 50° C. for 1 hr. The reaction mixture was evaporated under reduced pressure, saturated aqueous sodium hydrogen carbonate was added to the residue, and the mixture was extracted with ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. Recrystallization of the residue from tetrahydrofuran-hexane gave 4-[(E)-2-(2-ethyl-1,3-thiazol-4-yl)ethenyl]-1-(2-methylphenyl)-1H-pyrazol-3-ol (0.607 g, yield 86%) as colorless prism crystals. melting point: 174-176° C.