Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[C:23]([N+:25]([O-])=O)[CH:22]=[CH:21][C:3]=1[O:4][CH2:5][CH2:6][N:7]([CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)[CH3:8].[O-]S(S([O-])=O)=O.[Na+].[Na+].O>C(O)C>[NH2:25][C:23]1[CH:22]=[CH:21][C:3]([O:4][CH2:5][CH2:6][N:7]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=2)[CH3:8])=[C:2]([Cl:1])[CH:24]=1
Reactant: COc1ccc(CCN(C)CCOc2ccc([N+](=O)[O-])cc2Cl)cc1OC
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: COc1ccc(CCN(C)CCOc2ccc(N)cc2Cl)cc1OC
Yield: 32.8 %

Procedure:
A portion (15.63 g, 0.040 mol) of the 1-(2-chloro-4-nitrophenoxy)-2-[N-(3,4-dimethoxyphenethyl)-N-methylamino]ethane produced in (2) above was dissolved in hot ethanol (500 ml) and, thereafter, a solution consisting of a mixture of Na2S2O4 (27.56 g) and water (125 ml) was added to the resulting solution, thereby forming a precipitate. The mixture was heated at the reflux temperature for 20 min. Thereafter, the solvent was evaporated and the residue was diluted with water, followed by extraction with ethyl acetate. An aqueous solution of sodium carbonate was added to the aqueous layer such that it became basic up to a pH of about 9, followed by three extractions with ethyl acetate. The organic extracts were combined, dried with magnesium sulfate, and the solvent was evaporated; thereafter, the residue was purified by being subjected to column chromatography on silica gel using, as an eluent, ethyl acetate containing methanol (10%). The fractions containing the end compound were combined and the solvent was evaporated to yield the end compound 1-(4-amino-2-chlorophenoxy)-2-[N-(3,4-dimethoxyphenethyl)-N-methylamino]ethane (4.78 g) as a yellow oil.
Reaction SMILES: [CH2:1]([C:4]1[N:5]([CH2:17][CH2:18][C:19]([O:21]CC)=O)[C:6]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:16]=1)[CH2:2][CH3:3].C([O-])(=O)C.[NH4+:28]>>[CH2:1]([C:4]1[N:5]([CH2:17][CH2:18][C:19]([NH2:28])=[O:21])[C:6]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:16]=1)[CH2:2][CH3:3]
Reactant: CCCc1nc2cnc3ccccc3c2n1CCC(=O)OCC
Reactant: [NH4+]
Agent: CC(=O)[O-]
Product: CCCc1nc2cnc3ccccc3c2n1CCC(N)=O
Yield: 86.3 %

Procedure:
Ethyl 3-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propanoate (5.0 g, 16 mmol) was treated with ammonium acetate (25.0 g) according to the method described in Part B of Example 9 to provide 3.9 g of 3-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propanamide, which was used without purification.
Reaction SMILES: FC(F)(F)C(O)=O.[O:8]=[C:9]1[N:13](C(OC(C)(C)C)=O)[CH:12]([CH2:21][CH2:22][C:23]([F:26])([F:25])[F:24])[CH2:11][N:10]1C(OC(C)(C)C)=O>ClCCl>[F:26][C:23]([F:24])([F:25])[CH2:22][CH2:21][CH:12]1[CH2:11][NH:10][C:9](=[O:8])[NH:13]1
Reactant: CC(C)(C)OC(=O)N1CC(CCC(F)(F)F)N(C(=O)OC(C)(C)C)C1=O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1NCC(CCC(F)(F)F)N1
Yield: 131 %

Procedure:
Trifluoroacetic acid (6.05 g, 53.04 mmol, 3 eq) in dichloromethane (50 ml) is added to a solution of di-tert-butyl 2-oxo-4-(3,3,3-trifluoropropyl)imidazolidine-1,3-dicarboxylate a7 (6.76 g, 17.68 mmol, 1 eq) in dichloromethane (60 ml) at room temperature overnight. The reaction mixture is condensed under reduced pressure to afford 4.22 g of 4-(3,3,3-trifluoropropyl)imidazolidin-2-one a10 as a yellow oil.
Reaction SMILES: [NH2:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH:8]=2)=[CH:4][CH:3]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]=[C:28]=[O:29])=[CH:23][CH:22]=1>O1CCCC1>[CH2:14]([NH:13][C:9]1[CH:8]=[C:7]([O:6][C:5]2[CH:18]=[CH:19][C:2]([NH:1][C:28]([NH:27][C:24]3[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=3)=[O:29])=[CH:3][CH:4]=2)[CH:12]=[CH:11][N:10]=1)[CH2:15][CH2:16][CH3:17]
Reactant: O=C=Nc1ccc(F)cc1
Reactant: CCCCNc1cc(Oc2ccc(N)cc2)ccn1
Solvent: C1CCOC1
Product: CCCCNc1cc(Oc2ccc(NC(=O)Nc3ccc(F)cc3)cc2)ccn1

Procedure:
4-(4-Aminophenoxy)-2-butylaminopyridine (54 mg), p-fluorophenyl isocyanate (34.5 mg) and tetrahydrofuran (5 ml) were stirred at room temperature for 2.5 hours. After adding NH type silica gel to the reaction solution, the solvent was distilled off under reduced pressure, and the reaction product was adsorbed onto the silica gel. The silica gel was charged into a dry column packed with NH type silica gel, and column purification was performed (hexane:ethyl acetate=1:1, followed by ethyl acetate). The solvent was distilled off under reduced pressure and the residue was solidified with ethyl acetate-hexane to obtain 15 mg of the target substance as a light yellow powder.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]2[N:9]=[C:10]([NH2:12])[N:11]=[C:7]2[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:5][CH:4]=1.[Br:19][C:20]1[CH:21]=[C:22]([C:26](Cl)=[O:27])[CH:23]=[CH:24][CH:25]=1>>[Br:19][C:20]1[CH:21]=[C:22]([CH:23]=[CH:24][CH:25]=1)[C:26]([NH:12][C:10]1[N:11]=[C:7]2[C:6]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[N:8]2[N:9]=1)=[O:27]
Reactant: O=C(Cl)c1cccc(Br)c1
Reactant: COc1ccc(-c2ccccc2)c2nc(N)nn12
Product: COc1ccc(-c2ccccc2)c2nc(NC(=O)c3cccc(Br)c3)nn12

Procedure:
According to example 6, the title compound was synthesized from 5-methoxy-8-phenyl-[1,2,4]triazolo[1,5-a]pyridin-2-y-lamine and 3-bromo-phenyl carboxylic acid chloride (MS m/e (%): 423.3 (M+H+, 100).
Reaction SMILES: [F:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:22]=[C:21]3[C:17]([N:18]([CH:24]([CH3:26])[CH3:25])[C:19](=[O:23])[NH:20]3)=[C:16](I)[N:15]=2)=[N:6]1.[H][H]>CN(C)C=O.[Pd]>[F:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:22]=[C:21]3[C:17]([N:18]([CH:24]([CH3:26])[CH3:25])[C:19](=[O:23])[NH:20]3)=[CH:16][N:15]=2)=[N:6]1
Reactant: CC(C)n1c(=O)[nH]c2nc(-c3nn(Cc4ccccc4F)c4ncccc34)nc(I)c21
Reactant: [H][H]
Agent: [Pd]
Solvent: CN(C)C=O
Product: CC(C)n1c(=O)[nH]c2nc(-c3nn(Cc4ccccc4F)c4ncccc34)ncc21
Reaction time: 8 h

Procedure:
330 mg (0.57 mmol) of the compound from example 116 were initially charged in dimethylformamide (10.0 ml), then 66 mg of palladium (10% w/w on charcoal) were added and the mixture was hydrogenated at standard hydrogen pressure for two days. Subsequently, another 66 mg of palladium (10% w/w on charcoal) were added and hydrogenation was continued overnight.
Reaction SMILES: [CH2:1]([N:8]1[C:12]2=[C:13]([N:20]3[CH2:29][CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:21]3)[N:14]=[C:15]([C:17](O)=[O:18])[CH:16]=[C:11]2[C:10]([CH3:30])=[C:9]1[CH3:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O>O1CCCC1>[CH2:1]([N:8]1[C:12]2=[C:13]([N:20]3[CH2:29][CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:21]3)[N:14]=[C:15]([CH2:17][OH:18])[CH:16]=[C:11]2[C:10]([CH3:30])=[C:9]1[CH3:31])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1c(C)n(Cc2ccccc2)c2c(N3CCc4ccccc4C3)nc(C(=O)O)cc12
Solvent: O
Solvent: C1CCOC1
Product: Cc1c(C)n(Cc2ccccc2)c2c(N3CCc4ccccc4C3)nc(CO)cc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 95.6 %

Procedure:
Hydroborane tetrahydrofuran complex (1.0M in tetrahydrofuran solution; 1 ml, 1.0 mmol) was added at 0° C. to a solution of 1-benzyl-7-(3,4-dihydro-1H-isoquinolin-2-yl)-2,3-dimethyl-1H-pyrrolo[2,3-c]pyridin-5-carboxylic acid (20 mg, 0.05 mmol) prepared in Example 733 in anhydrous tetrahydrofuran (1 ml). The reaction mixture was stirred overnight at room temperature. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was dried on anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (ethyl acetate/n-hexane=1/1, v/v) to give 19 mg of the titled compound as a white solid.
Reaction SMILES: [C:1]1([N:7]2[N:11]3[C:12](=[O:22])[CH:13]=[C:14]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[N:15]=[C:10]3[CH:9]=[CH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(OC2C=CC=CC=2)C=CC=CC=1>>[C:1]1([N:7]2[CH:8]=[C:9]3[C:10]([N:15]=[C:14]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH:13]=[C:12]3[OH:22])=[N:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=c1cc(-c2ccccc2)nc2ccn(-c3ccccc3)n12
Solvent: c1ccc(Oc2ccccc2)cc1
Product: Oc1cc(-c2ccccc2)nc2nn(-c3ccccc3)cc12
Reaction time: 8 h

Procedure:
6.5 g. of 1,5-diphenylpyrazolo[1,5-a]pyrimidin-7(1H)-one (0.0226 mol.) and 18 g. of diphenyl ether are heated at 250°-260° for 90 minutes. After standing overnight, the crystallized 2,6-diphenyl-2H-pyrazolo[3,4-b]pyridin-4-ol is filtered off, washed with ethanol and dried at 80°, yield: 6.1 g. (94%); m.p. 280°-281°.
Reaction SMILES: [BH4-].[Na+].[CH3:3][C:4]1[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[C:18]([CH3:24])[C:5]=1[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14](=[O:17])[CH2:15][CH3:16])=[CH:10][CH:9]=1>C1COCC1.CCO>[CH3:3][C:4]1[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[C:18]([CH3:24])[C:5]=1[CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([CH:14]([OH:17])[CH2:15][CH3:16])=[CH:12][CH:13]=1
Reactant: CCC(=O)c1ccc(OCc2c(C)c(C)cc(C)c2C)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: C1CCOC1
Product: CCC(O)c1ccc(OCc2c(C)c(C)cc(C)c2C)cc1
Reaction time: 2 h
Yield: 99.3 %

Procedure:
NaBH4 (616 mg, 16.2 mmol) is added to the solution of 1-[4-(2,3,5,6-Tetramethyl-benzyloxy)-phenyl]-propan-1-one (4.0 g, 13.5 mmol) in THF (30 mL) and EtOH (5 mL). After stirring for 2 h, the reaction is quenched by water and extracted with ethyl acetate. The solvent is removed to afford the titled compound as a white solid (4.0 g).
Reaction SMILES: [OH:1][CH:2]([CH2:14][OH:15])[CH2:3][N:4]([CH2:9][CH:10]([OH:13])[CH2:11][OH:12])[CH2:5][CH2:6][CH2:7][NH2:8].[CH2:16]1[O:18][CH:17]1[CH2:19][OH:20]>CO>[OH:1][CH:2]([CH2:14][OH:15])[CH2:3][N:4]([CH2:9][CH:10]([OH:13])[CH2:11][OH:12])[CH2:5][CH2:6][CH2:7][NH:8][CH2:16][CH:17]([OH:18])[CH2:19][OH:20]
Reactant: OCC1CO1
Reactant: NCCCN(CC(O)CO)CC(O)CO
Solvent: CO
Product: OCC(O)CNCCCN(CC(O)CO)CC(O)CO

Procedure:
N,N-di-(2,3-dihydroxypropyl)trimethylenediamine (11.1 g., 0.05 mole) was dissolved in 125 ml. of methanol and heated under reflux with agitation. Glycidol (3.7 g., 0.05 mole) was added dropwise over a period of 1.5 hour and the solution mixed an additional hour at 60° C.-80° C. The methyl alcohol and other volatiles were removed by stripping under reduced pressure to leave the product suitable for use in the next steps.
Reaction SMILES: C[N:2]([C:8]1[C:13](=[O:14])[C:12]2[CH:15]=[C:16]([CH2:19][CH2:20][CH2:21][CH3:22])[CH:17]=[CH:18][C:11]=2[S:10][CH:9]=1)[C:3]([C:5](N)=[O:6])=[O:4].[OH-:23].[Na+]>C(O)C.O>[CH2:19]([C:16]1[CH:17]=[CH:18][C:11]2[S:10][CH:9]=[C:8]([NH:2][C:3](=[O:4])[C:5]([OH:6])=[O:23])[C:13](=[O:14])[C:12]=2[CH:15]=1)[CH2:20][CH2:21][CH3:22]
Reactant: [OH-]
Reactant: CCCCc1ccc2scc(N(C)C(=O)C(N)=O)c(=O)c2c1
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCCCc1ccc2scc(NC(=O)C(=O)O)c(=O)c2c1

Procedure:
6.15 g (0.0193 mol) of N-[6-(n-butyl)-4H-1-benzothiopyran-4-on-3-yl]-oxamide methyl ester are stirred with a solution of 22.6 ml of 1N sodium hydroxide solution in 147 ml of ethanol and 970 ml of water for 2 hours at 70°. A small degree of cloudiness is then removed by filtration and the filtrate is acidified with hydrochloric acid, a crystalline product being precipitated. After cooling, the crystals are filtered with suction and washed first with water, then with ethanol and subsequently with ether. After drying there is obtained N-[6-(n-butyl)-4H-1-benzothiopyran-4-on-3-yl)-oxalic acid monoamide having a melting point of 208° (decomposition).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21][CH2:22][N:23]4[C:32](=[O:33])[C:31]5[C:26](=[CH:27][C:28]([OH:34])=[CH:29][CH:30]=5)[NH:25][C:24]4=[O:35])[CH2:15][CH2:14]3)OCCO2)=[CH:4][CH:3]=1.Cl.N>C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH:13]2[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21][CH2:22][N:23]3[C:32](=[O:33])[C:31]4[C:26](=[CH:27][C:28]([OH:34])=[CH:29][CH:30]=4)[NH:25][C:24]3=[O:35])[CH2:15][CH2:14]2)=[CH:6][CH:7]=1
Reactant: O=c1[nH]c2cc(O)ccc2c(=O)n1CCCCN1CCC(C2(c3ccc(F)cc3)OCCO2)CC1
Agent: Cl
Agent: N
Solvent: CCO
Product: O=c1[nH]c2cc(O)ccc2c(=O)n1CCCCN1CCC(Cc2ccc(F)cc2)CC1
Reaction time: 4 h
Yield: 28 %

Procedure:
A mixture of 1.9 parts of 3-[4-[4-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]-1-piperidinyl]butyl]-7-hydroxy-2,4(1H,3H)-quinazolinedione, 10 parts of a hydrochloric acid solution 6N and 20 parts of ethanol was stirred for 4 hours at reflux temperature. The base was liberated with ammonia. The product was filtered off and purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated, yielding 0.5 parts (28%) of 3-[4-[4-(4-fluorobenzyl)-1-piperidinyl]butyl]-7-hydroxy-2,4(1H,3H)-quinazolinedione; mp. 207.9° C. (27).
Reaction SMILES: Cl[S:2]([C:5]1[S:9][C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:16])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[NH2:17][C:18]1[O:22][N:21]=[C:20]([CH3:23])[C:19]=1[Br:24]>>[Br:24][C:19]1[C:20]([CH3:23])=[N:21][O:22][C:18]=1[NH:17][S:2]([C:5]1[S:9][C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:16])=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: Cc1noc(N)c1Br
Reactant: Cc1ccccc1-c1ccc(S(=O)(=O)Cl)s1
Product: Cc1ccccc1-c1ccc(S(=O)(=O)Nc2onc(C)c2Br)s1

Procedure:
N-(4-bromo-3-methyl-5-isoxazolyl)-5-(2-tolyl)thiophene-2-sulfonamide was prepared in the same manner as described in Example 2. Reaction of 5-chlorosulfonyl-2-(2-tolyl)thiophene with 5-amino-4-bromo-3-methylisoxazole gave the crude product which was purified by column chromatography giving the pure product (gum). This gum was dissolved in 5 ml of NH4OH, concentrated and dried under high vacuum to get the ammonium salt of N-(4-bromo-3-methyl-5-isoxazolyl)-5-(2-tolyl)thiophene-2-sulfonamide in 67% yield, m.p. 180°-184° C. (NH3+ salt).
Reaction SMILES: [CH3:1][N:2]([CH3:12])[CH2:3][CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1.[ClH:13].[CH2:14]([O:16][C:17]1[CH:18]=[C:19]([C:26]2[C@@H:35]3[C@@H:30]([CH2:31][CH:32]=[CH:33][CH2:34]3)[C:29](=[O:36])[N:28]([C:37]3[CH:42]=[CH:41][C:40]([C:43](N4CCN(C5C=CC=CC=5)CC4)=[O:44])=[CH:39][CH:38]=3)[N:27]=2)[CH:20]=[CH:21][C:22]=1[O:23][CH2:24][CH3:25])[CH3:15]>C(OCC)C>[ClH:13].[ClH:13].[CH2:14]([O:16][C:17]1[CH:18]=[C:19]([C:26]2[C@@H:35]3[C@@H:30]([CH2:31][CH:32]=[CH:33][CH2:34]3)[C:29](=[O:36])[N:28]([C:37]3[CH:38]=[CH:39][C:40]([C:43]([N:9]4[CH2:8][CH2:7][N:6]([CH2:5][CH2:4][CH2:3][N:2]([CH3:1])[CH3:12])[CH2:11][CH2:10]4)=[O:44])=[CH:41][CH:42]=3)[N:27]=2)[CH:20]=[CH:21][C:22]=1[O:23][CH2:24][CH3:25])[CH3:15]
Reactant: CCOc1ccc(C2=NN(c3ccc(C(=O)N4CCN(c5ccccc5)CC4)cc3)C(=O)[C@@H]3CC=CC[C@H]23)cc1OCC
Reactant: CN(C)CCCN1CCNCC1
Agent: Cl
Solvent: CCOCC
Product: CCOc1ccc(C2=NN(c3ccc(C(=O)N4CCN(CCCN(C)C)CC4)cc3)C(=O)[C@@H]3CC=CC[C@H]23)cc1OCC

Procedure:
Prepared from intermediate product A1 and 1-(3-dimethylaminopropyl)piperazine as described for compound 1. Cystallised from diethyl ether as the free base. M.p. 248° C. (with decomposition).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:10]([CH3:11])=[N:9][N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[C:5]2=[N:6][CH:7]=1.[C:21]([NH:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1)(=[O:24])[CH:22]=[CH2:23].C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][N:8]2[C:5]3=[N:6][CH:7]=[C:2]([C:28]4[CH:27]=[C:26]([NH:25][C:21](=[O:24])[CH:22]=[CH2:23])[CH:31]=[CH:30][CH:29]=4)[CH:3]=[C:4]3[C:10]([CH3:11])=[N:9]2)=[CH:14][CH:15]=1
Reactant: C=CC(=O)Nc1cccc(B(O)O)c1
Reactant: COc1ccc(Cn2nc(C)c3cc(Br)cnc32)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: COCCOC
Product: C=CC(=O)Nc1cccc(-c2cnc3c(c2)c(C)nn3Cc2ccc(OC)cc2)c1
Temperature: 100 °C

Procedure:
The starting material 5-bromo-1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine (7) (134 mg, 0.402 mmol, 1 eq) and (3-acrylamidophenyl)boronic acid (153) (100 mg, 0.366 mmol, 1 eq) in DME (10 mL) was degassed and purged under argon atmosphere for 10 min. To this reaction mixture was charged Cs2CO3 (233 mg, 0.732 mmol, 2 eq) followed by addition of Pd(PPh3)4 (0.016 mg, 0.03 mmol) and degassing and purging under argon for additional 10 min. The reaction mixture was heated at 100° C. for 16 h in a sealed tube. After completion of the reaction, the solvents were removed and reaction mixtures were extracted into EtOAc, dried over Na2SO4 and the solvents distilled off. The crude material was submitted for flash column purification using 40% EtOAc in hexane to obtain off-white solid compound N-(3-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)acrylamide 154. MS m/z 397.2 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH3:23])[C:5]2[N:11]=[C:10]([NH:12][NH2:13])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][C:17]([S:20][CH3:21])=[CH:16][CH:15]=3)[C:6]=2[CH:22]=1.[Br:24][CH2:25][C:26](Br)=O.C([O-])(=O)C.[Na+]>>[CH3:1][C:2]1[CH:3]=[C:4]([CH3:23])[C:5]2[N:11]3[C:26]([CH2:25][Br:24])=[N:13][N:12]=[C:10]3[CH2:9][N:8]=[C:7]([C:14]3[CH:15]=[CH:16][C:17]([S:20][CH3:21])=[CH:18][CH:19]=3)[C:6]=2[CH:22]=1
Reactant: CSc1ccc(C2=NCC(NN)=Nc3c(C)cc(C)cc32)cc1
Reactant: O=C(Br)CBr
Agent: CC(=O)[O-]
Agent: [Na+]
Product: CSc1ccc(C2=NCc3nnc(CBr)n3-c3c(C)cc(C)cc32)cc1

Procedure:
In the manner given in Preparation 2, 7,9-dimethyl-5-[p-(methylthio)phenyl]-3H-1,4-benzodiazepin-2-yl hydrazine was reacted with bromoacetyl bromide and after 1.5 hours with sodium acetate, than the mixture was refluxed to give 8,10-dimethyl-1-(bromomethyl)-6-[p-(methylthio)phenyl]-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C@@:13]3([CH3:27])[CH2:17][O:16]C(C)(C)[N:14]3C(OC(C)(C)C)=O)=[N:10][N:9]=2)=[CH:4][C:3]=1[C:28]([F:31])([F:30])[F:29].[C:32](#N)[CH3:33].O>>[NH2:14][C@@:13]([C:11]1[S:12][C:8]([C:5]2[CH:6]=[CH:7][C:2]([O:1][CH2:6][CH2:7][CH2:2][CH2:3][CH2:4][CH2:5][CH2:8][CH2:32][CH3:33])=[C:3]([C:28]([F:31])([F:30])[F:29])[CH:4]=2)=[N:9][N:10]=1)([CH3:27])[CH2:17][OH:16]
Reactant: CC(C)(C)OC(=O)N1C(C)(C)OC[C@]1(C)c1nnc(-c2ccc(O)c(C(F)(F)F)c2)s1
Reactant: CC#N
Solvent: O
Product: CCCCCCCCCOc1ccc(-c2nnc([C@@](C)(N)CO)s2)cc1C(F)(F)F

Procedure:
The title compound was prepared from protected phenyl-thiadiazole 6a in 90% (579 mg) yield. HPLC retention time on a C8(2) column (30×50 mm, 3 μL) is 1.68 min with gradient 50-98% acetonitrile-H2O (0.1% TFA) in 3.5 min as mobile phase. MS (ESI, M+H+)=446.2; 1H NMR (400 MHz, DMSO-d6) δ 8.21 (dd, 1H, J=9.0 Hz, J=2.0 Hz), 8.15 (d, 1H, J=2.0 Hz), 7.45 (d, 1H, J=8.4), 4.21 (t, 2H, J=6.2 Hz), 3.74-3.85 (m, 3H), 1.68-1.77 (m, 5H), 1.25-1.45 (m, 12H), 0.849 (t, 3H, J=6.4).
Reaction SMILES: [C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[C:3]([NH2:7])[CH:2]=1.C(N(CC)CC)C.[CH3:16][Si:17]([CH3:20])([CH3:19])Cl>C1(C)C=CC=CC=1>[CH3:16][Si:17]([NH:7][C:3]1[CH:4]=[CH:5][CH:6]=[C:1]([NH:8][Si:17]([CH3:20])([CH3:19])[CH3:16])[CH:2]=1)([CH3:20])[CH3:19]
Reactant: Nc1cccc(N)c1
Reactant: C[Si](C)(C)Cl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: C[Si](C)(C)Nc1cccc(N[Si](C)(C)C)c1
Yield: 95.8 %

Procedure:
m-Phenylenediamine (10.8 g; 0.1 mole) and triethylamine (20.2 g; 0.2 mole) in dry toluene (100 ml) were stirred and treated with trimethylchlorosilane (21.7 g; 0.2 mole) which was added dropwise over 1 hour. Stirring was continued for a further hour, and the mixture was then heated under reflux for 1 hour. After cooling and filtering the product, the solvent was evaporated to leave 24.2 g of m-bis(trimethylsilylamino)benzene, which is hereinafter referred to as Silamine II. This product has a theoretical amino-hydrogen equivalent weight of 63, i.e., its theoretical amino-hydrogen content is 15.87 equivalents/kg.
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([C:16](=[NH:21])[O:17][CH2:18][CH2:19][CH3:20])[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[F:22][C:23]1[CH:31]=[CH:30][C:26]([C:27](Cl)=[O:28])=[CH:25][CH:24]=1>>[F:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([N:21]=[C:16]([N:7]2[CH2:6][C:5]3[CH:4]=[CH:3][CH:2]=[CH:1][C:11]=3[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8]2)[O:17][CH2:18][CH2:19][CH3:20])=[O:28])=[CH:25][CH:24]=1
Reactant: O=C(Cl)c1ccc(F)cc1
Reactant: CCCOC(=N)N1Cc2ccccc2-c2ccccc2C1
Product: CCCOC(=NC(=O)c1ccc(F)cc1)N1Cc2ccccc2-c2ccccc2C1

Procedure:
starting from propyl 5,7-dihydro-6H-dibenz[c,e]-azepine-6-carboximidate and p-fluorobenzoyl chloride, there is obtained propyl N-(p-fluorobenzoyl)-5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate as a solid, mass spectrum m/e: M+ 402 (5), 359 (14), 194 (100), 123 (51);
Reaction SMILES: [CH2:1]([O:5][CH:6]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:7][NH:8][CH2:9][CH:10]1[O:14][CH:13]([CH3:15])[CH:12]([CH3:16])[O:11]1)[CH2:2][CH2:3][CH3:4].C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:34][CH2:35][C:36](Cl)=[O:37]>O>[CH2:18]([O:17][CH:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])[CH2:7][N:8]([CH2:9][CH:10]1[O:14][CH:13]([CH3:15])[CH:12]([CH3:16])[O:11]1)[C:36](=[O:37])[CH2:35][Cl:34])[CH2:19][CH2:20][CH3:21]
Reactant: O=C(Cl)CCl
Reactant: CCCCOC(CNCC1OC(C)C(C)O1)OCCCC
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: O
Product: CCCCOC(CN(CC1OC(C)C(C)O1)C(=O)CCl)OCCCC

Procedure:
N-(2,2-Dibutoxyethyl)-N-(4,5-dimethyl-1,3-dioxolan-2-ylmethyl)amine (0.05 mole), benzene (100 ml), water (100 ml) and sodium carbonate (2 grams) are charged into a glass reaction vessel equipped with a mechanical stirrer and thermometer. The reaction mixture is cooled to a temperature of from 5° to 10° C and chloroacetyl chloride (0.05 mole) is added dropwise with stirring. After the addition is completed stirring is continued until the reaction mixture has reached room temperature. After this time the organic phase is separated from the aqueous phase and is washed with water. The washed solution is then dried over anhydrous magnesium sulfate, filtered and stripped of solvent under reduced pressure to yield the desired product N-(2,2-dibutoxyethyl)-N-(4,5-dimethyl-1,3-dioxolan-2-ylmethyl)-α-chloroacetamide as the residue.