Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:4]1[S:8][C:7]([CH2:9][NH:10][C:11](=[O:25])[C:12]2[CH:17]=[CH:16][CH:15]=[N:14][C:13]=2[O:18][C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>C(Cl)Cl.O1CCCC1>[OH:3][CH:1]([C:4]1[S:8][C:7]([CH2:9][NH:10][C:11](=[O:25])[C:12]2[CH:17]=[CH:16][CH:15]=[N:14][C:13]=2[O:18][C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)=[CH:6][CH:5]=1)[CH3:2]
Reactant: CC(=O)c1ccc(CNC(=O)c2cccnc2Oc2cccnc2)s1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClCCl
Product: CC(O)c1ccc(CNC(=O)c2cccnc2Oc2cccnc2)s1
Reaction time: 2 h

Procedure:
To a stirred suspension of N-(5-Acetyl-thiophen-2-ylmethyl)-2-(pyridin-3-yloxy)-nicotinamide (0.300 grams, 0.85 mmole) in methylene chloride (25 ml) and tetrahydrofuran (25 ml) at room temperature was added sodium borohydride (0.035 grams, 0.93 mmole) and stirred for 2 hours. The mixture was quenched with saturated NH4Cl (˜1 ml) and concentrated under reduced pressure to about 15 ml. This mixture was poured into water and extracted with ethyl acetate. The combined organics were washed with water and brine, dried over MgSO4, filtered and concentrated to give an oil that was purified by chromatography on silica eluting with 5% methanol/methylene chloride. Recrystalization from ethyl acetate/hexane gave a white solid. (0.207 g). M.P. 92-94° C.; Anal. calcd. for C18H17N3O3S: C, 60.83;H, 4.82; N, 11.82. Found: C, 60.68; H, 4.77; N, 11.89.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[C:11](=O)[CH:10]([CH2:14][CH:15]=O)[CH2:9][CH2:8]2.[C:17]([NH:20][CH2:21][CH2:22][NH2:23])(=[O:19])[CH3:18]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[C:12]2[C:11]3[N:23]([CH2:22][CH2:21][NH:20][C:17](=[O:19])[CH3:18])[CH:15]=[CH:14][C:10]=3[CH2:9][CH2:8][C:7]=2[CH:6]=[CH:5][CH:4]=1
Reactant: CC(=O)NCCN
Reactant: COc1cccc2c1C(=O)C(CC=O)CC2
Solvent: Cc1ccccc1
Product: COc1cccc2c1-c1c(ccn1CCNC(C)=O)CC2
Yield: 53.7 %

Procedure:
400 mg of 8-methoxy-2-(2-oxoethyl)-1-tetralone were heated to reflux for 15 minutes under argon with 205 mg of N-acetyl-ethylenediamine in 8 ml of toluene. The solvent was removed in a vacuum and the residue was chromatographed on 40 g of silica gel with hexane/ethyl acetate 1:1 and then with ethyl acetate. 280 mg (54%) of N-[2-(4,5-dihydro-9-methoxy-1H-benz[g]indol-1-yl)ethyl]-acetamide were obtained as yellowish crystals with m.p. 132°-133°.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH2:7][NH2:8])([O-:3])=[O:2].[Cl:12][C:13]1[N:14]=[C:15](Cl)[C:16]2[CH:21]=[C:20]([CH3:22])[S:19][C:17]=2[N:18]=1>>[Cl:12][C:13]1[N:14]=[C:15]([NH:8][CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[C:16]2[CH:21]=[C:20]([CH3:22])[S:19][C:17]=2[N:18]=1
Reactant: NCc1cccc([N+](=O)[O-])c1
Reactant: Cc1cc2c(Cl)nc(Cl)nc2s1
Product: Cc1cc2c(NCc3cccc([N+](=O)[O-])c3)nc(Cl)nc2s1

Procedure:
Following the procedure of Example 1, the reaction of 3-nitrobenzylamine with 2,4-dichloro-6-methyl-thieno-[2,3-d]-pyrimidine yields 2-chloro-6-methyl-4-(3-nitrobenzylamino)-thieno-[2,3-d]-pyrimidine
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2([CH2:14][CH2:15][N:16]3[C@H:21]4[CH2:22][CH2:23][C@@H:17]3[CH2:18][CH:19]([N:24]3[C:28]5[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=5[N:26]=[C:25]3[CH3:33])[CH2:20]4)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[Cl:34][C:35]1[CH:43]=[C:42]([F:44])[C:41]([S:45]([NH:48][CH:49]([CH3:51])[CH3:50])(=[O:47])=[O:46])=[CH:40][C:36]=1[C:37](O)=[O:38].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>>[Cl:34][C:35]1[C:36]([C:37]([N:11]2[CH2:10][CH2:9][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)([CH2:14][CH2:15][N:16]3[C@H:21]4[CH2:22][CH2:23][C@@H:17]3[CH2:18][CH:19]([N:24]3[C:28]5[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=5[N:26]=[C:25]3[CH3:33])[CH2:20]4)[CH2:13][CH2:12]2)=[O:38])=[CH:40][C:41]([S:45]([NH:48][CH:49]([CH3:50])[CH3:51])(=[O:46])=[O:47])=[C:42]([F:44])[CH:43]=1
Reactant: CC(C)NS(=O)(=O)c1cc(C(=O)O)c(Cl)cc1F
Reactant: Cc1nc2ccccc2n1C1C[C@H]2CC[C@@H](C1)N2CCC1(c2cccc(F)c2)CCNCC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Product: Cc1nc2ccccc2n1C1C[C@H]2CC[C@@H](C1)N2CCC1(c2cccc(F)c2)CCN(C(=O)c2cc(S(=O)(=O)NC(C)C)c(F)cc2Cl)CC1
Yield: 42 %

Procedure:
0.290 g (0.65 mmol) 1-((1R,5S)-8-{2-[4-(3-fluorophenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole and 0.288 g (0.975 mmol) 2-chloro-4-fluoro-5-[(isopropylamino)sulfonyl]benzoic acid were combined following the HATU general procedure in Example 5. This compound was purified by reverse phase chromatography on a 0-100% gradient of 0.1% TFA in water in acetonitrile. 0.196 g obtained (42% yield). 1H NMR (300 MHz, DMSO-d6) δ 8.09-8.19 (m, 1H), 7.76-7.99 (m, 2H), 7.38-7.55 (m, 4H), 7.25-7.31 (m, 1H), 7.07-7.20 (m, 3H), 4.52-4.62 (m, 1H), 3.92-4.01 (m, 1H), 3.29-3.43 (m, 6H), 3.01-3.11 (m, 1H), 2.76 (s, 1H), 2.47-2.51 (m, 2H), 2.36-2.45 (m, 1H), 1.78-2.04 (m, 12H), 1.25-1.32 (m, 3H), 0.99-1.07 (m, 6H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([NH:11][CH2:12][C:13]1[O:14][CH:15]=[C:16]([OH:20])[C:17](=[O:19])[CH:18]=1)(=[O:10])=[O:9].[OH:21][C:22]1C(=O)C=C(CNS(C2C=CC=CC=2)(=O)=O)OC=1CO>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([NH:11][CH2:12][C:13]1[O:14][C:15]([CH2:22][OH:21])=[C:16]([OH:20])[C:17](=[O:19])[CH:18]=1)(=[O:9])=[O:10]
Reactant: O=c1cc(CNS(=O)(=O)c2ccccc2Cl)occ1O
Reactant: O=c1cc(CNS(=O)(=O)c2ccccc2)oc(CO)c1O
Product: O=c1cc(CNS(=O)(=O)c2ccccc2Cl)oc(CO)c1O
Yield: 48.59 %

Procedure:
2-Chloro-N-(5-hydroxy-6-hydroxymethyl-4-oxo-4H-pyran-2-ylmethyl)-benzenesulfonamide (9-03) (8.0 g, 48.59%) was synthesized as a white solid from 2-chloro-N-(5-hydroxy-4-oxo-4H-pyran-2-ylmethyl)-benzenesulfonamide (8-03) (15.0 g, 47.61 mmol) following the procedure described for N-(5-hydroxy-6-hydroxymethyl-4-oxo-4H-pyran-2-ylmethyl)-benzenesulfonamide (9-01).
Reaction SMILES: [CH3:1][C:2]([CH3:20])([O:4][C:5]([NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17](O)=[O:18])=[CH:11][CH:10]=1)=[O:6])[CH3:3].C(=O)([O-])[O-].[NH4+:25].[NH4+]>>[CH3:1][C:2]([CH3:20])([O:4][C:5]([NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]([NH2:25])=[O:18])=[CH:11][CH:10]=1)=[O:6])[CH3:3]
Reactant: CC(C)(C)OC(=O)NCc1ccc(CCC(=O)O)cc1
Reactant: [NH4+]
Agent: O=C([O-])[O-]
Product: CC(C)(C)OC(=O)NCc1ccc(CCC(N)=O)cc1
Yield: 84 %

Procedure:
Prepared analogously to Example 63a) from 4-[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]benzene propanoic acid, N,N'-carbonyldiimidazole and ammonium carbonate in a yield of 84% of theory. Colourless crystals, which were used in the following step without purification.
Reaction SMILES: [CH:1]12[O:6][CH:2]1[CH2:3][CH2:4][CH2:5]2.[CH2:7]([NH2:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>CCOC(C)=O.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH2:7]([NH:14][C@@H:2]1[CH2:3][CH2:4][CH2:5][C@H:1]1[OH:6])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: NCc1ccccc1
Reactant: C1CC2OC2C1
Agent: [Ti+4]
Agent: CC(C)[O-]
Solvent: CCOC(C)=O
Product: O[C@@H]1CCC[C@H]1NCc1ccccc1

Procedure:
Cyclopentene oxide (5.0 g, 59.1 mmol), benzylamine (7.0 g, 65.3 mmol) and titanium isopropoxide (3.40 g, 12.0 mmol) were taken in a microwave vial and microwaved at 150° C. for 3 hours. The reaction mixture was then cooled and diluted with EtOAc (100 mL). The organic layer was washed with water and dried over anhydrous Na2SO4. Evaporation of the solvent in vacuo and purification on a silica gel column (0 to 20% MeOH/CH2Cl2) afforded trans-2-(benzylamino)cyclopentanol. MS APCI calc'd for C12H17NO [M+H]+ 192. found 192.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[N:11][OH:12])[CH2:6][CH2:5]2.[C:13]([C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1)#[N:14]>>[OH:12]/[N:11]=[C:7]1\[CH2:6][CH2:5][C:4]2[C:8]\1=[CH:9][CH:10]=[C:2]([C:18]1[CH:19]=[CH:20][C:15]([C:13]#[N:14])=[CH:16][CH:17]=1)[CH:3]=2
Reactant: N#Cc1ccc(B(O)O)cc1
Reactant: ON=C1CCc2cc(Br)ccc21
Product: N#Cc1ccc(-c2ccc3c(c2)CC/C3=N\O)cc1

Procedure:
The title compound was prepared from 5-bromoindan-1-one oxime and 4-cyanophenyl boronic acid according to the procedure described in example 6. MS (ESI) m/z 249; HRMS: calcd for C16H12N2O+H+, 249.10224; found (ESI, [M+H]+), 249.1021.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([CH:9]=1)[CH2:7][OH:8].C(=O)([O-])[O-].[K+].[K+].[CH2:19](Br)[CH2:20][CH2:21][CH3:22]>CN(C)C(=O)C>[CH2:19]([O:1][C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([CH:9]=1)[CH2:7][OH:8])[CH2:20][CH2:21][CH3:22]
Reactant: O=[N+]([O-])c1ccc(O)cc1CO
Reactant: CCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: CCCCOc1ccc([N+](=O)[O-])c(CO)c1
Temperature: 20 °C
Reaction time: 2 h

Procedure:
5.1 g (30 mmol) of 5-hydroxy-2-nitrobenzyl alcohol were stirred with 2.5 g (18 mmol) of potassium carbonate and 25 ml of N,N-dimethylacetamide at 70°-80° C. for 30 minutes. After cooling to 20° C., 3.9 ml (36 mmol) of 1-butylbromide were added dropwise and the mixture was stirred at 90° C. for 2 hours. After cooling, the reaction mixture was concentrated in vacuo, the residue was treated with water and the pH was brought to 7 with 2N HCl. The oil obtained crystallizes after about 30 minutes; the product was filtered off with suction, washed with water and dried; 6 g, melting point 47°-49° C.
Reaction SMILES: [CH3:1][C:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])=[C:7]([O:21][CH3:22])[CH:6]=1)([OH:4])[CH3:3].[C:23](OC(=O)C)(=[O:25])[CH3:24]>C(Cl)Cl.C(N(CC)CC)C>[CH3:3][C:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]([S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])[C:23](=[O:25])[CH3:24])=[C:7]([O:21][CH3:22])[CH:6]=1)([OH:4])[CH3:1]
Reactant: CC(=O)OC(C)=O
Reactant: COc1cc(C(C)(C)O)ccc1NS(=O)(=O)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1cc(C(C)(C)O)ccc1N(C(C)=O)S(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 1-methyl-1-(4-phenylsulfonylamino-3-methoxyphenyl)-ethanol (2.65 g; prepared in Reference Example 38.) in methylene chloride (15 ml), acetic anhydride (3.05 ml) and triethylamine (4.60 ml) were added. The mixture was stirred overnight at room temperature. The solvent was distilled off. The residue was purified on silica gel column chromatography (hexane:AcOEt=3:4) to give the title compound (2.33 g) having the following physical data.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([C:12]([OH:14])=O)[S:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:15]1([C:21]2[N:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=2)[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1>>[N:15]1([C:21]2[N:26]=[CH:25][C:24]([NH:27][C:12]([C:9]3[S:10][CH:11]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[N:8]=3)=[O:14])=[CH:23][CH:22]=2)[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1
Reactant: O=C(O)c1nc(-c2ccccc2)cs1
Reactant: Nc1ccc(N2CCOCC2)nc1
Product: O=C(Nc1ccc(N2CCOCC2)nc1)c1nc(-c2ccccc2)cs1

Procedure:
With a procedure similar to example 1 above, 4-phenyl-thiazole-2-carboxylic acid (6-morpholin-4-yl-pyridin-3-yl)-amide was prepared from 4-phenyl-thiazole-2-carboxylic acid and 6-morpholin-4-yl-pyridin-3-ylamine. LCMS calcd for C19H18N4O2S (m/e) 366, obsd 367 (M+H).
Reaction SMILES: CCN(CC)CC.II.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:29]([O:33][C:34](=[O:63])[NH:35][CH2:36][C:37]1([C:40]([NH:42][NH:43][C:44]([CH:46]2[CH2:52][CH2:51][C@@H:50]3[CH2:53][N:47]2[C:48](=[O:62])[N:49]3[O:54][CH2:55][C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)=O)=[O:41])[CH2:39][CH2:38]1)([CH3:32])([CH3:31])[CH3:30]>C(Cl)Cl>[CH2:55]([O:54][N:49]1[C:48](=[O:62])[N:47]2[CH2:53][C@H:50]1[CH2:51][CH2:52][CH:46]2[C:44]1[O:41][C:40]([C:37]2([CH2:36][NH:35][C:34](=[O:63])[O:33][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:38][CH2:39]2)=[N:42][N:43]=1)[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1
Reactant: CC(C)(C)OC(=O)NCC1(C(=O)NNC(=O)C2CC[C@@H]3CN2C(=O)N3OCc2ccccc2)CC1
Agent: II
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCC1(c2nnc(C3CC[C@@H]4CN3C(=O)N4OCc3ccccc3)o2)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 83.1 %

Procedure:
Et3N (8.3 g, 0.082 mol) was added to a 0° C. solution of I2 (10.43 g, 0.041 mol), PPh3 (10.76 g, 0.041 mol) in CH2Cl2 (250 mL). The mixture was allowed to warm to rt. After stirring at rt for 0.5 hr, tert-butyl(1-(2-((5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)hydrazinecarbonyl)cyclopropyl)methylcarbamate (10 g, 0.0205 mol) was added. The mixture was stirred at rt for another 1 hr. The mixture was concentrated, EtOAc (250 mL) was added, and the mixture was filtered to remove Ph3PO. The filtrate was concentrated and the residue was purified by silica gel column chromatography (gradient elution 33˜50% EtOAc/petroleum ether) to afford tert-butyl (1-(5-((5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,3,4-oxadiazol-2-yl)cyclopropyl)methylcarbamate (8 g, 83%) as a white solid. ESI-MS (EI+, m/z): 470.3 [M+H]+.
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:7][C@H:6]1[N:19]1[CH:24]=[CH:23][C:22](=[O:25])[NH:21][C:20]1=[O:26])(=[O:3])[CH3:2].[I:27]I.C(OCC)(=O)C.S(=O)(=O)(O)[O-].[Na+]>C(#N)C>[C:1]([O:4][C@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:7][C@H:6]1[N:19]1[CH:24]=[C:23]([I:27])[C:22](=[O:25])[NH:21][C:20]1=[O:26])(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@H]1O[C@@H](n2ccc(=O)[nH]c2=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: II
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CC(=O)OC[C@H]1O[C@@H](n2cc(I)c(=O)[nH]c2=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 80 °C

Procedure:
454 mg (1.23 mmol) of the above product 4 as starting material, 420 mg (1.66 mmol, 1.3 eq) of iodine and 700 mg (1.27 mmol, 1 eq) of ceric ammonium nitrate are dissolved in 15 mL of anhydrous acetonitrile and heated to 80° C. After the starting material disappears, 100 mL of ethyl acetate and 30 mL (5%) of sodium bisulfate are added in turns. 30 mL of saturated saline is used to wash. After collection and combination with an organic phase, the solution is concentrated by reduced pressure. After purified by rapid column chromatography (acetone/n-hexane=2:3), a white powder product (1-(2′,3′,5′-Tri-O-acetyl-β-D-arabinofuranosyl)-5-iodopyrimidin-2,4(3H)-dione) 5 is obtained. Its weight and yield are 425 mg and 70% respectively.
Reaction SMILES: S([O-])(O)(=O)=O.[Na+].[CH2:7]([O:11][CH2:12][CH2:13][CH2:14][CH2:15]OC=C)[CH:8]1[O:10][CH2:9]1.C(=O)([O-])[OH:20].[Na+]>O>[CH2:7]([O:11][CH:12]([OH:20])[CH2:13][CH2:14][CH3:15])[CH:8]1[O:10][CH2:9]1
Reactant: C=COCCCCOCC1CO1
Reactant: O=C([O-])O
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: O
Product: CCCC(O)OCC1CO1
Yield: 94 %

Procedure:
A 1-L four-necked separable flask was charged with 5.0 g of sodium hydrogen sulfate and 140 g of pure water and then provided with a stirrer, a thermometer, an air-introducing tube, and a vacuum pump with a cooling trap. With stirring, 500 g of vinyloxybutyl glycidyl ether synthesized as described above was gradually added to the flask while the liquid temperature was controlled to be kept at 40° C. After the addition was completed, the pressure was reduced to 20 kPa. The mixture was continuously stirred for 1 hour while dry air was introduced at 100 ml/minute. The reaction liquid was then analyzed by gas chromatography. As a result, no peak was observed for vinyloxybutyl glycidyl ether, and thus, the reaction was completed. After 2.1 g of sodium hydrogen carbonate was added to neutralize the completed reaction liquid, the liquid was concentrated by removing water from the system by distillation using a rotary evaporator. After it was checked that the content of water in the system was 800 ppm or less, the liquid concentrate was filtered and then subjected to distillation (0.4 kPa, distillation temperature 82° C.) using a reduced-pressure distillation apparatus with a Vigreux column, so that butanediol glycidyl ether was obtained with a purity of 99% and a yield of 94%.
Reaction SMILES: N1C=CC=CC=1.[NH2:7][C:8]1[CH:9]=[C:10]([CH:20]=[CH:21][C:22]=1[O:23][CH3:24])[C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:12].[S:25](Cl)([C:28]1[C:40]2[CH:39]=[CH:38][CH:37]=[C:33]([N:34]([CH3:36])[CH3:35])[C:32]=2[CH:31]=[CH:30][CH:29]=1)(=[O:27])=[O:26]>O>[CH3:35][N:34]([CH3:36])[C:33]1[CH:37]=[CH:38][CH:39]=[C:40]2[C:32]=1[CH:31]=[CH:30][CH:29]=[C:28]2[S:25]([NH:7][C:8]1[CH:9]=[C:10]([CH:20]=[CH:21][C:22]=1[O:23][CH3:24])[C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:12])(=[O:27])=[O:26]
Reactant: COc1ccc(C(=O)Nc2ccccc2)cc1N
Reactant: CN(C)c1cccc2c(S(=O)(=O)Cl)cccc12
Solvent: c1ccncc1
Solvent: O
Product: COc1ccc(C(=O)Nc2ccccc2)cc1NS(=O)(=O)c1cccc2c(N(C)C)cccc12
Temperature: 25 °C
Reaction time: 20 h
Yield: 91.1 %

Procedure:
Pyridine (5 mL) was added to a mixture of 3-amino-4-methoxy-N-phenyl-benzamide (0.73 g, 3.0 mmol) and dansyl chloride (0.81 g, 3.0 mmol) and stirred under an inert atmosphere at room temperature. After 20 hours, the mixture was diluted with water (50 mL) and extracted with ethyl acetate (2×50 mL). The combined extracts were washed with water then saturated brine, then dried over MgSO4 and stripped of solvent under reduced pressure to afford the product (1.3 g); m.p. 231-232° C.
Reaction SMILES: O[C:2]1[C:7]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:9])=[CH:6][N:5]=[C:4]2[N:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:17]=[CH:18][C:3]=12.P(Cl)(Cl)([Cl:27])=O.[OH-].[Na+]>>[Cl:27][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:9])=[CH:6][N:5]=[C:4]2[N:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:17]=[CH:18][C:3]=12
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=C(c1ccccc1)c1cnc2c(cnn2-c2ccccc2)c1O
Agent: [Na+]
Agent: [OH-]
Product: O=C(c1ccccc1)c1cnc2c(cnn2-c2ccccc2)c1Cl
Temperature: 110 °C
Reaction time: 1.5 h
Yield: 66 %

Procedure:
A mixture of (4-hydroxy-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)(phenyl)methanone (0.38 g, 1.2 mmol) and phosphorus oxychloride (1.3 mL) was stirred at 110° C. for 1.5 hr. The mixture was cooled, poured onto ice, basified with sodium hydroxide aqueous solution to pH=8, and extracted with ethyl acetate. Combined extracts were dried (Na2SO4) and concentrated. Flash chromatography gave (4-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)(phenyl)methanone (0.26 g, 0.79 mmol, 66% yield) as a yellow solid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.[C:14](Cl)(=[O:23])[CH:15]=[CH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([CH2:9][C:10]([O:12][CH3:13])=[O:11])[C:14](=[O:23])/[CH:15]=[CH:16]/[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:6][CH:7]=1
Reactant: O=C(Cl)C=Cc1ccccc1
Reactant: COC(=O)CNc1ccc(Br)cc1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: COC(=O)CN(C(=O)/C=C/c1ccccc1)c1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 97.5 %

Procedure:
(4-Bromophenylamino)acetic acid, methyl ester (8.74 g, 0.036 mol) was treated with cinnamoyl chloride (11.99 g, 0.072 mol) in pyridine (50 mL) in the presence of 4-dimethylaminopyridine (0.489 g, 0.004 mol). The reaction mixture was stirred at room temperature for 2 h. The crude product was purified by flash column chromatography on silica gel, eluting with ethyl acetate/dichloromethane (1:20), to give the title compound as a white crystalline solid (13.13 g, 98%). 1HNMR (300 MHz) (CDCl3) δ 3.67 (3H, s), 4.42 (2H, s), 6.28 (1H, d, J=16 Hz), 7.19 (2H, d), 7.2-7.3 (5H, m), 7.51 (2H, d) and 7.66 (1H, d, J=16 Hz).
Reaction SMILES: CS[C:3](SC)=[CH:4][N+:5]([O-:7])=[O:6].[O:10]1[CH2:14][CH2:13][CH:12]([CH2:15][NH:16][CH2:17][CH2:18][NH2:19])[CH2:11]1>C(O)C>[N+:5]([CH:4]=[C:3]1[NH:19][CH2:18][CH2:17][N:16]1[CH2:15][CH:12]1[CH2:13][CH2:14][O:10][CH2:11]1)([O-:7])=[O:6]
Reactant: CSC(=C[N+](=O)[O-])SC
Reactant: NCCNCC1CCOC1
Solvent: CCO
Product: O=[N+]([O-])C=C1NCCN1CC1CCOC1
Temperature: 85 °C
Yield: 81 %

Procedure:
2.5 g (0.0178 mol) of 1,1-dimethylthio-2-nitroethene, 2.56 g (0.0178 mol) of N1-((tetrahydrofuran-3-yl)methyl)ethane-1,2-diamine were added to 50 ml of ethanol. The resulting mixture was heated under reflux for 8 hours at 80-90 ° C. The mixture was then cooled to educe solid, concentrated, filtrated and dried to give a light yellow powder in 81% yield.
Reaction SMILES: [Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH2:13][CH2:14][CH3:15])[NH:6]2.Cl[CH2:17][C:18]1[N:22]=[C:21]([C:23]2[C:24]([CH3:29])=[N:25][O:26][C:27]=2[CH3:28])[O:20][N:19]=1>>[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH2:13][CH2:14][CH3:15])[N:6]2[CH2:17][C:18]1[N:22]=[C:21]([C:23]2[C:24]([CH3:29])=[N:25][O:26][C:27]=2[CH3:28])[O:20][N:19]=1
Reactant: Cc1noc(C)c1-c1nc(CCl)no1
Reactant: CCCc1cc2c(Cl)c(C#N)ccc2[nH]1
Product: CCCc1cc2c(Cl)c(C#N)ccc2n1Cc1noc(-c2c(C)noc2C)n1

Procedure:
Synthesized as described in Example 4 from 4-chloro-2-propyl-1H-indole-5-carbonitrile and 3-(chloromethyl)-5-(3,5-dimethyl-4-isoxazolyl)-1,2,4-oxadiazole
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:17][CH:18]=[CH2:19])[CH3:16])[CH:5]=[CH:4][C:3]=1[C:20]([C:22]1[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][CH:23]=1)=O.[CH:29]([NH2:31])=O>C(O)=O>[CH2:17]([N:15]([CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][O:8][C:6]1[CH:7]=[C:2]2[C:3]([C:20]([C:22]3[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][CH:23]=3)=[N:31][CH:29]=[N:1]2)=[CH:4][CH:5]=1)[CH3:16])[CH:18]=[CH2:19]
Reactant: NC=O
Reactant: C=CCN(C)CCCCCCOc1ccc(C(=O)c2ccc(Br)cc2)c(N)c1
Solvent: O=CO
Product: C=CCN(C)CCCCCCOc1ccc2c(-c3ccc(Br)cc3)ncnc2c1

Procedure:
A solution of 230 mg of [2-amino-4-[6-(allyl-methyl-amino)-hexyloxy]-phenyl]-(4-bromo-phenyl)-methanone in 0.5 ml of formic acid and 2 ml of formamide is boiled at 165° C. for 25 min., then concentrated and converted into the free amine (title compound) with methylene chloride/saturated sodium bicarbonate solution. After purification (silica gel, methylene chloride/methanol 2.5% to 10%) the residue is dissolved in methylene chloride/ether and treated with 23.7 mg of fumaric acid. After stirring and filtration there are obtained 30 mg of allyl-[6-[4-(4-bromo-phenyl)-quinazolin-7-yloxy]-hexyl]-methyl-amine.fumarate (1:1), m.p 90°-95° C., MS: m/e 454 (M+H+, 1 Br).
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[CH:5][C:6]=1[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].Br[C:16]1[S:25][C:19]2[S:20][C:21](Br)=[C:22]([CH3:23])[C:18]=2[C:17]=1[CH3:26]>C1COCC1.[Zn]>[CH2:7]([C:6]1[CH:5]=[CH:4][S:3][C:2]=1[C:16]1[S:25][C:19]2[S:20][C:21]([C:2]3[S:3][CH:4]=[CH:5][C:6]=3[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])=[C:22]([CH3:23])[C:18]=2[C:17]=1[CH3:26])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: Cc1c(Br)sc2sc(Br)c(C)c12
Reactant: CCCCCCCCc1ccsc1Br
Agent: [Zn]
Solvent: C1CCOC1
Product: CCCCCCCCc1ccsc1-c1sc2sc(-c3sccc3CCCCCCCC)c(C)c2c1C
Temperature: 25 °C
Reaction time: 16 h
Yield: 71.8 %

Procedure:
To a solution of 2-bromo-3-octylthiophene (4.0 g, 14.5 mmol) in dry THF (20 ml) under nitrogen was added a solution of Rieke zinc (Aldrich, 1.1 g 20 ml of THF, 17 mmol) at −78° C. The solution was allowed to warm to RT and stirred for 16 h. Stirring was stopped and the solution allowed to settle for 2 h. The resultant solution was transferred by cannula into a flask containing 2,5-dibromo-3,4-dimethylthieno[2,3-b]thiophene (1.28 g, 3.9 mmol), degassed THF (50 ml) and [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (64 mg, 2 mol %) at 0° C. The reaction was warmed to RT over 30 min, and then refluxed for 24 h. The reaction was cooled and quenched with 5% HCL. The resultant mixture was extracted with ethyl acetate (3×50 ml), and the combined organics were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography over silica (eluent: petrol), followed by reverse phase chromatography (eluent: CH3CN/THF 2:1) to afford the product as a colourless oil (1.56 g, 72%). M/Z 556 (M+). Found C, 69.1%, H, 7.6%. Calc. for C32H44S4 C, 69.0; H 8.0. NMR gave the expected signals.