Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=1.[F:23][C:24]([F:35])([F:34])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.O.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>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][C:14]([C:15]1[CH:20]=[CH:19][C:18]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[C:24]([F:35])([F:34])[F:23])=[CH:17][CH:16]=1)=[O:22]
Reactant: O=C(NCCc1c[nH]c2ccc(Cl)cc12)c1ccc(I)cc1
Reactant: OB(O)c1ccccc1C(F)(F)F
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: [Na+]
Solvent: COCCOC
Solvent: O
Product: O=C(NCCc1c[nH]c2ccc(Cl)cc12)c1ccc(-c2ccccc2C(F)(F)F)cc1
Yield: 39.8 %

Procedure:
N-(2-(5-chloro-1H-indol-3-yl)ethyl)-2′-(trifluoromethyl)biphenyl-4-carboxamide was prepared according to method B with N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4-iodobenzamide (0.075 g; 0.176 mmol), 2-(trifluoromethyl)phenylboronic acid (0.035 g; 0.180 mmol), tetrakis(triphenylphosphine)palladium (0.010 g; 0.009 mmol), sodium carbonate (0.037 g; 0.353 mmol), in dimethoxyethane (3 mL) and water (1 mL), irradiated in a microwave oven at 180° C. for 5 minutes. Flash chromatography on silica gel (eluent 10 to 80% ethyl acetate in heptane) furnished 0.031 g (40%) of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-2′-(trifluoromethyl)biphenyl-4-carboxamide as a white solid.
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH:26][C@@H:27]2[C@@H:32]3[CH2:33][C@@H:29]([CH:30]=[CH:31]3)[C@@H:28]2[C:34]([NH2:36])=[O:35])=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([CH2:17][N:18]4[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]4)=[CH:13][C:12]=3[O:24][CH3:25])[NH:8][C:5]2=[N:6][CH:7]=1.[CH2:37]1[O:40][C@H:38]1[CH3:39]>CO>[Cl:1][C:2]1[C:3]([NH:26][C@@H:27]2[C@@H:32]3[CH2:33][C@@H:29]([CH:30]=[CH:31]3)[C@@H:28]2[C:34]([NH2:36])=[O:35])=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([CH2:17][N:18]4[CH2:23][CH2:22][N:21]([CH2:37][C@@H:38]([OH:40])[CH3:39])[CH2:20][CH2:19]4)=[CH:13][C:12]=3[O:24][CH3:25])[NH:8][C:5]2=[N:6][CH:7]=1
Reactant: C[C@H]1CO1
Reactant: COc1cc(CN2CCNCC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1
Solvent: CO
Product: COc1cc(CN2CCN(C[C@H](C)O)CC2)ccc1-c1nc2c(N[C@H]3[C@@H](C(N)=O)[C@@H]4C=C[C@H]3C4)c(Cl)cnc2[nH]1

Procedure:
(1S,2S,3R,4R)-3-[6-Chloro-2-(2-methoxy-4-piperazin-1-ylmethyl-phenyl)-3H-imidazo[4,5-b]pyridine-7-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (Compound XLII above) (45 mg, 0.088 mmol) was reacted with (S)-(−)-propylene oxide (7.7 mg, 0.13 mmol) in methanol (5 mL) at 60° C. in a sealed tube for six hours. The reaction was concentrated to afford the title compound as a rust colored solid (14 mg, 28%). Mp 142-6° C. 1H NMR (d-chloroform): 10.76 (br s, 1H), 8.34 (d, J=9 Hz, 1H), 8.04 (s, 1H), 7.12 (m, 2H), 6.37 (m, 3H), 5.57 (d, J=9 Hz, 1H), 5.19 (m, 2H), 4.08 (s, 3H), 3.84 (m, 1H), 3.58 (s, 2H), 3.49 (m, 1H), 3.18 (s, 1H), 2.92 (s 1H), 2.87 (d, J=9 Hz, 1H), 2.72 (m, 2H), 2.62-2.39 (m, 2H), 2.35 (d, J=0 Hz, 1H), 2.26 (m, 1H), 1.76 (d, J=7 Hz, 1H), 1.31 (m, 1H), 1.15 (d, J=9 Hz, 3H). MS: 566.21 (M+H). HPLC retention time: 1.71 minutes (G Method).
Reaction SMILES: Cl[C:2](=[O:16])[CH2:3][CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:6]1.CC1C=CC=C(C)N=1.[H][H]>[Pd].O1CCCC1>[O:16]=[CH:2][CH2:3][CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:6]1
Reactant: CCOC(=O)N1CCC(CCC(=O)Cl)CC1
Reactant: [H][H]
Agent: [Pd]
Solvent: Cc1cccc(C)n1
Solvent: C1CCOC1
Product: CCOC(=O)N1CCC(CCC=O)CC1
Yield: 81 %

Procedure:
A mixture of 102 parts of ethyl 4-(3-chloro-3-oxopropyl)-1-piperidinecarboxylate, 45 parts of 2,6-dimethylpyridine and 630 parts of tetrahydrofuran was hydrogenated at normal pressure and at room temperature with 5 parts of palladium-on-charcoal catalyst 10%. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated. The residue was dissolved in 650 parts of dichloromethane. The solution was washed twice with 100 parts of a hydrochloric acid solution 5% and twice with 100 parts of water, dried, filtered and evaporated. The residue was distilled, yielding 71.1 parts (81%) of ethyl 4-(3-oxopropyl)-1-piperidinecarboxylate; bp. 130°-135° C. at 133 Pa (int. 46).
Reaction SMILES: [NH:1]([C:3]1[S:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1)[NH2:2].N[C:13](N)=[O:14].N>>[N:1]1[N:2]=[C:13]([OH:14])[N:7]2[C:6]3[CH:8]=[CH:9][CH:10]=[CH:11][C:5]=3[S:4][C:3]=12
Reactant: NNc1nc2ccccc2s1
Reactant: NC(N)=O
Agent: N
Product: Oc1nnc2sc3ccccc3n12

Procedure:
2-Hydrazinobenzothiazole (100 grams) and urea (100 grams) were fused on an oil bath at about 180° C. for about an hour, by which time the molten material had solidified and evolution of ammonia had ceased. The solid thus obtained, the desired s-triazolo(3,4-b)benzothiazol-3-ol, was recrystallized twice from methanol, m.p., 235° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:27])[C:4]1[C:9]([NH:10][CH:11]([CH:14]=[O:15])[CH2:12][CH3:13])=[CH:8][C:7]([CH3:16])=[N:6][C:5]=1[O:17][C:18]1[C:23]([CH3:24])=[CH:22][C:21]([Cl:25])=[CH:20][C:19]=1[CH3:26].CC(=CC)C.[O-:33]Cl=O.[Na+]>>[CH3:1][O:2][C:3](=[O:27])[C:4]1[C:9]([NH:10][CH:11]([C:14]([OH:33])=[O:15])[CH2:12][CH3:13])=[CH:8][C:7]([CH3:16])=[N:6][C:5]=1[O:17][C:18]1[C:19]([CH3:26])=[CH:20][C:21]([Cl:25])=[CH:22][C:23]=1[CH3:24]
Reactant: [O-][Cl+][O-]
Reactant: CCC(C=O)Nc1cc(C)nc(Oc2c(C)cc(Cl)cc2C)c1C(=O)OC
Agent: CC=C(C)C
Agent: [Na+]
Product: CCC(Nc1cc(C)nc(Oc2c(C)cc(Cl)cc2C)c1C(=O)OC)C(=O)O
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A mixture of 2-(4-chloro-2,6-dimethyl-phenoxy)-4-(1-formyl-propylamino)-6-methyl-nicotinic acid methyl ester, 2-methyl-2-butene, excess NaClO2, and NaH2PO4 was stirred at rt for 15 min. The mixture was quenched with sat. sodium bicarbonate and extracted with hexane. The aqueous layer was acidified to pH 4 and extracted twice with diethyl ether. The organic layer was separated, dried and concentrated to give the title compound. The crude material was purified by silica gel column chromatography to give the desired product as a white crystal after recrystallization. Anal. For C20H23N2O5Cl calc., C, 59.04; H, 5.70; N, 6.89; found C, 59.29; H, 5.73; N, 6.83.
Reaction SMILES: I([O-])(=O)(=O)=[O:2].[Na+].[NH2:7][C:8]1[C:9]2[C:16]([C:17]3[CH:22]=[CH:21][C:20]([S:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:19][CH:18]=3)=[CH:15][N:14]([C:30]([CH3:33])([CH3:32])[CH3:31])[C:10]=2[N:11]=[CH:12][N:13]=1>O.C(O)(=O)C>[C:30]([N:14]1[C:10]2[N:11]=[CH:12][N:13]=[C:8]([NH2:7])[C:9]=2[C:16]([C:17]2[CH:18]=[CH:19][C:20]([S:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:2])=[CH:21][CH:22]=2)=[CH:15]1)([CH3:33])([CH3:32])[CH3:31]
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: CC(C)(C)n1cc(-c2ccc(Sc3ccccc3)cc2)c2c(N)ncnc21
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: CC(C)(C)n1cc(-c2ccc(S(=O)c3ccccc3)cc2)c2c(N)ncnc21

Procedure:
A solution of sodium periodate (0.60 g) dissolved in water (16 ml) was added to a solution of 4-amino-5-[4-(phenylthio)phenyl]-7-(tert-butyl)pyrrolo[2,3-d]pyrimidine (1.0 g) in glacial acetic acid (30 ml) with stirring whilst keeping the temperature below 5° C. The mixture was stirred for 66 hours at ambient temperature. The mixture was filtered and the filtrate was added to water (300 ml). This mixture was basified with solid sodium bicarbonate, filtered to remove a small amount of solid which was discarded and the filtrate extracted with ethyl acetate to give a residue which was purified by flash column chromatography on silica using ethyl acetate/triethylamine (9:1) as the mobile phase, to give a solid which was rechromatographed under the same conditions to give 7-tert-butyl-5-(4-phenylsulphinylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine, m.p. 180-182° C.
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([CH3:9])[C:5]([NH2:8])=[N:6][CH:7]=1.[F:10][C:11]1[CH:12]=[C:13]([C:26]2[C:27]([S:32]([NH:35][CH3:36])(=[O:34])=[O:33])=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:14]=[CH:15][C:16]=1B1OC(C)(C)C(C)(C)O1>>[NH2:8][C:5]1[N:6]=[CH:7][C:2]([C:16]2[CH:15]=[CH:14][C:13]([C:26]3[C:27]([S:32]([NH:35][CH3:36])(=[O:33])=[O:34])=[CH:28][CH:29]=[CH:30][CH:31]=3)=[CH:12][C:11]=2[F:10])=[N:3][C:4]=1[CH3:9]
Reactant: Cc1nc(Br)cnc1N
Reactant: CNS(=O)(=O)c1ccccc1-c1ccc(B2OC(C)(C)C(C)(C)O2)c(F)c1
Product: CNS(=O)(=O)c1ccccc1-c1ccc(-c2cnc(N)c(C)n2)c(F)c1

Procedure:
The title compound was prepared in a manner similar to that described in Example 427 using 5-bromo-3-methylpyrazin-2-amine and 3′-fluoro-N-methyl-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide. MS (ESI): mass calcd. for C18H17FN4O2S, 372.11; m/z found, 373.1 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 8.27 (s, 1H), 8.09-8.00 (d, J=7.9, 1H), 7.96-7.87 (m, 1H), 7.71-7.63 (m, 1H), 7.63-7.55 (m, 1H), 7.44-7.38 (d, J=7.5, 1H), 7.34-7.21 (m, 2H), 2.46 (s, 3H), 2.44 (s, 3H).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([O:16][S:17]([CH3:20])(=[O:19])=[O:18])[CH2:13][C@H:12]1[CH:21]=[CH:22][C:23]1[N:24]([CH3:28])[CH:25]=[CH:26][N:27]=1)=[O:10])[C:2]1C=CC=C[CH:3]=1.Cl.[H][H]>[Pd].CO.C(OCC)(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([O:16][S:17]([CH3:20])(=[O:18])=[O:19])[CH2:13][C@H:12]1[CH2:21][CH2:22][C:23]1[N:24]([CH3:28])[CH:25]=[CH:26][N:27]=1)=[O:10])[CH:2]=[CH2:3]
Reactant: Cn1ccnc1C=C[C@@H]1C[C@@H](OS(C)(=O)=O)CN1C(=O)OCc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CO
Product: C=CCOC(=O)N1C[C@H](OS(C)(=O)=O)C[C@H]1CCc1nccn1C
Reaction time: 1 h
Yield: 113.2 %

Procedure:
A solution of (2S,4R)-1-benzyloxycarbonyl-4-methanesulfonyloxy-2-[2-(1-methylimidazol-2-yl)vinyl]pyrrolidine (5.70 g), conc. hydrochloric acid (2.34 ml) and 10% palladium on carbon (50% wet) (3.0 g) in methanol (120 ml) was stirred under atmospheric pressure of hydrogen at ambient temperature for 4 hours. The catalyst was filtered off and the filtrate was concentrated in vacuo. The resulting residue was dissolved in a mixture of tetrahydrofuran (60 ml) and water (60 ml). To solution was added dropwise a solution of allyloxycarbonyl chloride (1.94 ml) in tetrahydrofuran (5 ml) keeping the pH 8-10 with 4N sodium hydroxide under ice-cooling and then the mixture was stirred at the same temperature for 1 hour. The reaction mixture was concentrated in vacuo to give a residue. The residue was dissolved in ethyl acetate (100 ml) and then the solution was washed twice with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated in vacuo. The resulting residue was chromatographed on silica gel (150 g) eluting with chloroform and methanol (19:1, V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2R,4R)-1-allyloxycarbonyl-2-[2-(1-methylimidazol-2-yl)ethyl]-4-methanesulfonyloxypyrrolidine (5.69 g).
Reaction SMILES: [Cl:1][C:2]1[CH:34]=[CH:33][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:15](=[O:17])(=[O:16])[N:14]([CH3:18])[C:13]3[S:19][C:20]([C:22]#[C:23][CH2:24][O:25]C4CCCCO4)=[CH:21][C:12]=3[C:11]=2[OH:32])=[O:9])=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:1][C:2]1[CH:34]=[CH:33][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:15](=[O:16])(=[O:17])[N:14]([CH3:18])[C:13]3[S:19][C:20]([C:22]#[C:23][CH2:24][OH:25])=[CH:21][C:12]=3[C:11]=2[OH:32])=[O:9])=[CH:4][CH:3]=1
Reactant: CN1c2sc(C#CCOC3CCCCO3)cc2C(O)=C(C(=O)NCc2ccc(Cl)cc2)S1(=O)=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: CN1c2sc(C#CCO)cc2C(O)=C(C(=O)NCc2ccc(Cl)cc2)S1(=O)=O
Temperature: 60 °C
Yield: 51.8 %

Procedure:
To a stirring suspension of N-(4-chlorobenzyl)-4-hydroxy-1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)prop-1-ynyl)-1H-thieno[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide (Preparation 36, 0.20 g) in MeOH (20 mL) at ambient temperature is added p-toluenesulfonic acid monohydrate (0.030 g). The resulting solution is heated at 60° C. for 45 min. The mixture is cooled to 0° C. and the resulting solid is filtered to afford 0.087 g (52%) of the title compound as a white solid. Physical characteristics; 1H NMR (DMSO-d6) δ3.44, 4.30, 4.48, 7.35, 7.37, 8.50; IR (diffuse reflectance) 3354, 1618, 1570, 1538, 1493, 1436, 1367, 1351, 1304, 1291, 1189, 1151, 1092, 1015, 815 cm−1; MS (EI) m/z 438 (M+). Anal. Found: C, 49.23; H, 3.49; N, 6.38.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH2:9][OH:10].[NH:11]1[CH:15]=[CH:14][N:13]=[N:12]1>>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([N:12]2[N:13]=[CH:14][CH:15]=[N:11]2)=[C:3]([CH2:9][OH:10])[CH:4]=1
Reactant: c1c[nH]nn1
Reactant: Cc1ccc(I)c(CO)c1
Product: Cc1ccc(-n2nccn2)c(CO)c1

Procedure:
The title compound was synthesized in analogy to the procedure described for building block K11 from (2-iodo-5-methylphenyl)methanol [220991-50-4] and 1H-1,2,3-triazole.
Reaction SMILES: [CH:1]1([C:5]2[N:9]3[CH:10]=[CH:11][N:12]=[C:13]([NH2:14])[C:8]3=[C:7](I)[N:6]=2)[CH2:4][CH2:3][CH2:2]1.N#N.C(N(CC)CC)C.[C:25]1([C:31]#[CH:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C)C=O.[Cu]I>[CH:1]1([C:5]2[N:9]3[CH:10]=[CH:11][N:12]=[C:13]([NH2:14])[C:8]3=[C:7]([C:32]#[C:31][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:6]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: Nc1nccn2c(C3CCC3)nc(I)c12
Reactant: C#Cc1ccccc1
Agent: [Cu]I
Agent: N#N
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Nc1nccn2c(C3CCC3)nc(C#Cc3ccccc3)c12
Temperature: 25 °C
Reaction time: 16 h
Yield: 28.4 %

Procedure:
A solution of 3-cyclobutyl-1-iodoimidazo[1,5-a]pyrazin-8-amine (50 mg, 0.159 mmol) in N,N-dimethylformamide (6 mL) and evacuated and charged with N2 three times, then treated with triethylamine (0.044 mL, 0.318 mmol), phenylacetylene (0.175 mL, 1.59 mmol), and copper (I) iodide (3.0 mg, 0.0159 mmol). The mixture re-evacuated and charged with N2 twice more, then charged with tetrakis(triphenylphoshine)palladium (0) (20.2 mg, 0.0175 mmol) and evacuated and charged with N2 a final two times. The reaction mixture was stirred at rt for 16 h, then concentrated in vacuo, dissolved in MeOH/CH3CN (1:1)(4 mL) and was filtered through a 0.45 fritted μM autovial prior to purification via mass directed preparative HPLC that afforded 13 mg of the title compound. 1H NMR (DMSO-d6, 400 MHz) δ 1.87-1.99 (m, 1H), 2.01-2.15 (m, 1H), 2.32-2.47 (m, 4H), 3.87-3.99 (m, 1H), 6.66 (brs, 2H), 7.08 (brs, 1H), 7.40-7.51 (m, 4H), 7.59-7.67 (m, 2H); MS (ES+): m/z 289.13 [MH+].
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14](Br)[CH:15]=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:18][C:19]1[CH:24]=[C:23]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:22]=[CH:21][N:20]=1>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:20]3[CH:21]=[CH:22][C:23]([C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:24][C:19]3=[N:18][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1ccnc(N)c1
Reactant: CC(C)(C)OC(=O)N1CCC(C(Br)C=O)CC1
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCC(c2cnc3cc(C(C)(C)C)ccn23)CC1
Yield: 23.7 %

Procedure:
The title compound was prepared from 470 mg of 1-(t-butoxycarbonyl)-4-(1-bromo-2-oxoethyl)piperidine (from Procedure 23, Step C) and 277 mg of 2-amino-4-t-butyl pyridine (from Step A) in 12 mL ethanol using a procedure analogous to that described in Example 235, Step A to provide 130 mg of the title compound as a solid.
Reaction SMILES: Cl.[NH2:2][C:3]([NH2:5])=[NH:4].[Na].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][C:17](=O)[C:16](=[CH:21]N(C)C)[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]>C(O)C>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][C:17]2[N:4]=[C:3]([NH2:5])[N:2]=[CH:21][C:16]=2[CH2:15]1)=[O:13])([CH3:10])([CH3:8])[CH3:9]
Reactant: CN(C)C=C1CN(C(=O)OC(C)(C)C)CCC1=O
Reactant: N=C(N)N
Agent: Cl
Agent: [Na]
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCc2nc(N)ncc2C1
Reaction time: 2 h
Yield: 43 %

Procedure:
Guanidine hydrochloride 7.07 g (74 mmol) was added at 0° C. to a solution of sodium 1.65 g (74 mmol) in absolute ethanol and stirring was performed for 2 h at RT under nitrogen as inert gas. 60 ml (60 mmol) of this reaction mixture were added to the solution of 3-dimethylaminomethylene-4-oxo-piperidine-1-carboxylic acid tert-butyl ester in 100 ml of absolute ethanol and refluxing was performed for 5 h. After removal of the solvent and purification by means of column chromatography, 2-amino-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 5.72 g (43% of theoretical) was obtained.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[C:12](=[O:17])C(F)(F)F.C([OH:20])C.[OH-].[Na+]>O>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[C:12]([OH:17])=[O:20]
Reactant: CCO
Reactant: O=C(c1cccn1Cc1ccco1)C(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)c1cccn1Cc1ccco1

Procedure:
1-Furfurylpyrrole (2.3 g, 15.6 mMol), 15 ml of trifluoroacetic anhydride (22.35 g, 106 mmol), 50 ml of nitromethane and 25 ml anhydrous diethylether were combined in a 100 ml round bottom flask. The mixture was stirred overnight under positive argon. The reaction was heated and the excess solvents distilled off. The mixture was evaporated to dryness under reduced pressure to give 3.9 g of a dark oil. The oil was distilled in a Kugel-rohr apparatus. The fraction collected at 80° C. to 90° C. at 0.2 mm Hg pressure gave 3.0 g of the colorless oil. 1-(2-furanylmethyl)-2-trifluoroacetyl-1H-pyrrole. This oil was combined with 50 ml ethylalcohol in a 100 ml round bottom flask equipped with a reflux condenser. The mixture was heated to reflux. Sodium hydroxide, 3.0 g in 15 ml of water, was added, and the reaction mixture was refluxed for 3 hours. The ethanol was distilled off and 50 ml of water was added. The mixture was cooled and acidified by addition of 5.0 g malonic acid. A precipitate formed which was collected by filtration. The solid precipitate was recrystallized from acetonitrile to give the title compound a white powder, mp=117° C. to 118° C., infrared spectrum absorption at 3400 cm-1, 1675 cm-1, 1530 cm-1, 1440 cm-1, 750 cm-1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6](Cl)=[O:7].[N:14]1([CH:20]([CH3:33])[CH2:21][CH2:22][NH:23][C:24]2[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=2)[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6]([N:23]([CH2:22][CH2:21][CH:20]([N:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1)[CH3:33])[C:24]1[CH:25]=[CH:26][C:27]([N+:30]([O-:32])=[O:31])=[CH:28][CH:29]=1)=[O:7]
Reactant: COc1ccc(C(=O)Cl)cc1OC
Reactant: CC(CCNc1ccc([N+](=O)[O-])cc1)N1CCOCC1
Product: COc1ccc(C(=O)N(CCC(C)N2CCOCC2)c2ccc([N+](=O)[O-])cc2)cc1OC

Procedure:
In a manner similar to Preparation 16, react 3,4-dimethoxybenzoyl chloride with N-[3-(morpholin-4-yl)butyl]-4-nitrobenzenamine to obtain the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([NH:14][C:15](=[O:19])OCC)=[N:5]2.[N:20]1[CH:25]=[CH:24][CH:23]=[N:22][C:21]=1[N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([NH:14][C:15]([N:29]1[CH2:30][CH2:31][N:26]([C:21]3[N:20]=[CH:25][CH:24]=[CH:23][N:22]=3)[CH2:27][CH2:28]1)=[O:19])=[N:5]2
Reactant: c1cnc(N2CCNCC2)nc1
Reactant: CCOC(=O)Nc1nc2cc(Cl)ccc2nc1OC
Product: COc1nc2ccc(Cl)cc2nc1NC(=O)N1CCN(c2ncccn2)CC1
Yield: 90 %

Procedure:
Ethyl N-(6-chloro-2-methoxyquinoxalin-3-yl)carbamate and 1-(2-pyrimidyl)piperazine were reacted by the same way with the example 22 to obtain the titled compound (yield, 90%). 1H NMR (300 MHz, CDCl3): δ 3.71 (s, 4H), 3.99 (s, 3H), 4.15 (s, 4H), 6.55 (s, 1H), 7.27-7.43 (m, 2H), 7.66 (s, 1H), 7.80 (s, 1H), 8.35 (s, 2H).
Reaction SMILES: [OH-].[K+].O.[CH3:4][C:5]1[NH:10][C:9](=[S:11])[NH:8][C:7](=[O:12])[CH:6]=1.[Cl-].Cl[CH2:15][C:16]1[C:21]([CH3:22])=[C:20]([O:23][CH3:24])[C:19]([CH3:25])=[CH:18][NH+:17]=1>C(O)C>[CH3:22][C:21]1[C:16]([CH2:15][S:11][C:9]2[NH:8][C:7](=[O:12])[CH:6]=[C:5]([CH3:4])[N:10]=2)=[N:17][CH:18]=[C:19]([CH3:25])[C:20]=1[O:23][CH3:24]
Reactant: Cc1cc(=O)[nH]c(=S)[nH]1
Reactant: COc1c(C)c[nH+]c(CCl)c1C
Agent: [Cl-]
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: COc1c(C)cnc(CSc2nc(C)cc(=O)[nH]2)c1C
Temperature: 25 °C
Reaction time: 20 h
Yield: 36 %

Procedure:
After dissolving 0.22 g (4.0 mmol) of potassium hydroxide in the mixture of 15 ml of ethanol and 3 ml of water, first 0.28 g (2.0 mmol) of 6-methyl-2-thiouracil, then a solution of 0.44 g (2.0 mmol) of 2-chloromethyl-3,5-dimethyl-4-methoxypyridinium chloride (m.p.: 127°-128° C.) in 15 ml of ethanol are added. The reaction mixture is stirred at room temperature for 20 hours, then ethanol is evaporated under reduced pressure, 10 ml of water are added to the residue and the product is extracted 3 times with 5 ml of chloroform each. The combined organic phase is washed with water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue is recrystallized from 2-propanol to obtain 0.21 g (36%) of the title compound as a white crystalline product, m.p.: 231°-233° C.
Reaction SMILES: [CH2:1]([C:5]([CH3:7])=[O:6])[CH:2]([CH3:4])[CH3:3].[CH3:8][C:9]([CH3:11])=O>>[CH3:3][CH:2]([CH2:1][C:5]([CH2:7][CH:9]([CH3:11])[CH3:8])=[O:6])[CH3:4]
Reactant: CC(C)=O
Reactant: CC(=O)CC(C)C
Product: CC(C)CC(=O)CC(C)C

Procedure:
DIBK is generally produced at the same time as methyl isobutyl ketone (MIBK) in a condensation reaction of acetone. However, the conversion and the selectivity for DIBK are very low and wholly insufficient.
Reaction SMILES: [CH3:1][CH:2]([CH3:32])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24](=O)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:14][CH2:13]2)[CH:7]=1)=[O:4].Cl.[C:34]1([N:40]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)N)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>>[C:34]1([N:40]2[C:42]3[C:47](=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:23]([CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][N:15]3[CH2:16][CH2:17][CH:12]([C:8]4[CH:7]=[C:6]([NH:5][C:3](=[O:4])[CH:2]([CH3:1])[CH3:32])[CH:11]=[CH:10][CH:9]=4)[CH2:13][CH2:14]3)=[C:24]2[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCCCCC(=O)c3ccccc3)CC2)c1
Reactant: NN(c1ccccc1)c1ccccc1
Agent: Cl
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCCCc3c(-c4ccccc4)n(-c4ccccc4)c4ccccc34)CC2)c1

Procedure:
Prepared by Procedure E and Scheme M using 2-methyl-N-{3-[1-(7-oxo-7-phenylheptyl)-4-piperidinyl]phenyl}propanamide and 1,1-diphenylhydrazine hydrochloride: ESMS m/e: 584.3 (M+H)+.