Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.Cl.C[Al](C)C.C[O:19][C:20]([C:22]1[N:23]=[C:24]([CH2:68][CH2:69][CH3:70])[N:25]([CH2:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[C:44]3[N:48]([C:49]([C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=4)([C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)[C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[N:47]=[N:46][N:45]=3)=[CH:34][CH:33]=2)[C:26]=1[C:27]([O:29][CH3:30])=[O:28])=O>CCOCC.C1(C)C=CC=CC=1>[CH3:30][O:29][C:27]([C:26]1[N:25]([CH2:31][C:32]2[CH:33]=[CH:34][C:35]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[C:44]3[N:48]([C:49]([C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=4)([C:56]4[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=4)[C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[N:47]=[N:46][N:45]=3)=[CH:36][CH:37]=2)[C:24]([CH2:68][CH2:69][CH3:70])=[N:23][C:22]=1[C:20]([N:10]1[CH2:9][CH2:8][N:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH2:12][CH2:11]1)=[O:19])=[O:28]
Reactant: CCCc1nc(C(=O)OC)c(C(=O)OC)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: c1ccc(N2CCNCC2)nc1
Agent: C[Al](C)C
Agent: Cl
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: CCCc1nc(C(=O)N2CCN(c3ccccn3)CC2)c(C(=O)OC)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Temperature: 10 °C
Reaction time: 0.25 h
Yield: 70.7 %

Procedure:
To a solution of 0.72 g (4.4 mmol) of 1-(2-pyridyl)piperazine in 10 mL of anhydrous CH2C12 under N2 was added 4.4 mL (4.4 mmol) of a 1 N solution of HCl in ether. After 15 min., the suspension was cooled to 10° C. and treated with 2.2 mL (4.4 mmol) of 2.0 M Me3Al in toluene. Slow gas evolution was noted. After 30 min., a solution of 2.81 g (4.00 mmol) of 4,5-bis(methoxycarbonyl)-2-propyl-1-[(2'-(N-trityltetrazol-5-yl)biphen-4-yl)methyl]imidazole in 12 mL of CH2C12 was added. The reaction mixture was allowed to warm to room temperature and stir for 2 h, then partitioned between EtOAc and H2O. The water layer was washed with EtOAc and the combined organic extracts were washed with water and brine, then dried over MgSO4. After removal of solvents at reduced pressure, the residual tan foam (4.08 g) was purified using flash chromatography (eluent: 50/50 EtOAc-hexane to 1% MeOH-EtOAc) to give 2.36 g (71%)of the title compound as a white foam. 1H NMR (300 MHz, CDCl3): δ0.88 (t, J=7.5 Hz, 3H, CH3); 1.70 (sextet, J=7.5 Hz, 2H, CH2); 2.52 (t, J=7.5 Hz, 2H, CH2); 3.45 (m, 2H, piperazine); 3.54 (m, 2H, piperazine); 3.63 (m, 2H, piperazine); 3.71 (s, 3H, CO2CH3); 3.93 (m, 2H, piperazine); 5.46 (s, 2H, benzyl); 6.67 (m, 2H, aromatic); 6.82 (d, J=8.0 Hz, 2H, p-disubstituted aromatic); 6.94 (d, J=7.5 Hz, 6H, trityl); 7.11 (d, J=8.0 Hz, 2H, p-disubstituted aromatic); 7.2-7.4 (m, 10H, aromatic); 7.4-7.5 (m, 3H, aromatic); 7.91 (dd, J=7.0, 6.0 Hz, 1H, tetrazolyl-phenyl); 8.19 (approx. dd, J=5.5, 2.0 Hz, 1H, pyridyl).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([CH2:27][CH3:28])[S:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19]C(OC(C)(C)C)=O)[CH:14]=2)[CH:5]=[CH:6][CH:7]=1.[Cu](C#N)[C:30]#[N:31].O.N>CN(C)C=O>[C:30]([C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([CH2:27][CH3:28])[S:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[CH:14]=2)[CH:5]=[CH:6][CH:7]=1)#[N:31]
Reactant: N#C[Cu]C#N
Reactant: CCc1nc(-c2cccc(Br)c2)c(-c2ccnc(NC(=O)OC(C)(C)C)c2)s1
Agent: N
Solvent: CN(C)C=O
Solvent: O
Product: CCc1nc(-c2cccc(C#N)c2)c(-c2ccnc(N)c2)s1
Temperature: 150 °C
Reaction time: 20 h
Yield: 56.4 %

Procedure:
To a solution of 4-(3-bromophenyl)-5-[2-(tert-butoxycarbonylamino)-4-pyridyl]-2-ethyl-1,3-thiazole (0.5 g, 1.1 mmol) in N,N-dimethylformamide (10 mL) was added copper cyanide (0.25 g, 1.6 mmol), and the mixture was stirred for 20 hours at 150° C. under argon atmosphere. Into the reaction mixture was poured ammonia water, and the deposit was removed, then, extracted with ethyl acetate. The extracts were washed with water, then, dried and concentrated. The residue was purified by silica gel column chromatography (hexane-ethyl acetate=4:1) to obtain a crystal. This crystal was washed with hexane-ethyl acetate to obtain a title compound (0.19 g, yield 57%).
Reaction SMILES: C(O[C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]=1[CH:17]=[O:18])CC(C)C.[OH:19][C:20]1[C:29]2[C:24](=[CH:25]C=CC=2)[C:23](C=O)=CC=1.BrCCC(C)C>>[CH2:20]([O:19][C:15]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([CH:17]=[O:18])=[CH:7][CH:16]=1)[CH2:29][CH:24]([CH3:25])[CH3:23]
Reactant: CC(C)CCOc1ccc2ccccc2c1C=O
Reactant: O=Cc1ccc(O)c2ccccc12
Solvent: CC(C)CCBr
Product: CC(C)CCOc1ccc(C=O)c2ccccc12

Procedure:
Prepared according to the Procedure for 2-(isopentyloxy)-1-naphthaldehyde using 4-hydroxy-1-naphthaldehyde and 1-bromo-3-methylbutane.
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[O:7][C:6](=[O:8])[CH2:5][C:4](=[O:9])[O:3]1.N1C=CC=CC=1.[N:17]([CH2:20][CH2:21][CH2:22][C:23](Cl)=[O:24])=[N+:18]=[N-:19]>C(Cl)Cl>[N:17]([CH2:20][CH2:21][CH2:22][C:23]([CH:5]1[C:6](=[O:8])[O:7][C:2]([CH3:10])([CH3:1])[O:3][C:4]1=[O:9])=[O:24])=[N+:18]=[N-:19]
Reactant: CC1(C)OC(=O)CC(=O)O1
Reactant: [N-]=[N+]=NCCCC(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC1(C)OC(=O)C(C(=O)CCCN=[N+]=[N-])C(=O)O1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To the solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (3.82 g, 26.5 mmol) and pyridine (4.20 g, 53.0 mmol) in 150 ml of CH2Cl2 was added dropwise a solution of crude 4-azidobutyric chloride (3.90 g, 26.5 mmol) in 30 ml of CH2Cl2 at 0° C. The mixture was stirred at 0° C. for 1 hr then at room temperature for 1 hr. The solution was, washed with 0.5N aqueous HCl (60 ml), water (60 ml) followed by brine (60 ml) and dried. After evaporation of solvent, 5-(4-azidobutanoyl)-2,2-dimethyl-1,3-dioxane-4,6-dione was obtained as a light pink oil (6.20 g, 92%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:9]=1[NH:10][CH3:11])[C:7]#[N:8].[H-].[Na+].Br[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17].CO>CN(C=O)C>[CH2:19]([O:18][C:16]([C:15]1[N:10]([CH3:11])[C:9]2[C:2]([F:1])=[CH:3][N:4]=[CH:5][C:6]=2[C:7]=1[NH2:8])=[O:17])[CH3:20]
Reactant: CNc1c(F)cncc1C#N
Reactant: CCOC(=O)CBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CO
Product: CCOC(=O)c1c(N)c2cncc(F)c2n1C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 52 %

Procedure:
5-Fluoro-4-methylamino-nicotinonitrile (2.35 g, 15 mmol) was dissolved in DMF (50 mL) and the solution cooled in an ice-bath. This solution was treated portionwise with sodium hydride (900 mg, 60% in oil, 22.5 mmol). The mixture was allowed to warm to room temperature and stirring continued for 15 minutes at room temperature. Ethyl bromoacetate (2.49 ml, 22.5 mmol) was added and the mixture stirred for 30 minutes at room temperature The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was isolated, dried (Na2SO4) and evaporated to give a solid. Trituration of the resultant solid with methanol gave the title compound (1.85 g, 52%) as a yellow solid. LCMS (method B): RT=2.09 min, M+H+ 238.
Reaction SMILES: [CH3:1][NH:2][C:3](SC)=[CH:4][N+:5]([O-:7])=[O:6].[CH3:10][N:11]([CH2:13][C:14]1[O:18][C:17]([CH2:19][S:20][CH2:21][CH2:22][NH2:23])=[CH:16][CH:15]=1)[CH3:12].CC(C)CC(=O)C>O>[CH3:12][N:11]([CH2:13][C:14]1[O:18][C:17]([CH2:19][S:20][CH2:21][CH2:22][NH:23][C:3]([NH:2][CH3:1])=[CH:4][N+:5]([O-:7])=[O:6])=[CH:16][CH:15]=1)[CH3:10]
Reactant: CNC(=C[N+](=O)[O-])SC
Reactant: CN(C)Cc1ccc(CSCCN)o1
Solvent: O
Solvent: CC(=O)CC(C)C
Product: CNC(=C[N+](=O)[O-])NCCSCc1ccc(CN(C)C)o1

Procedure:
N-Methyl-1-(methylthio)-2-nitroetheneamine (230 g) in water (400 ml) was stirred and heated at 45°-50°. 2-[[[5-(Dimethylamino) methyl-2-furanyl]methyl]thio]ethanamine (321 g) was added dropwise over 4 hr and the resultant solution stirred for a further 31/2 hr. The solution was then heated at reflux for 1/2 hr., cooled to 70° and 4-methylpentan-2-one (2 liters) added. The water was removed by azeotropic distillation under reduced pressure (260 torr) and the resultant solution treated with charcoal (10 g) at 50°. The solution was filtered and cooled to 10°. N-[2-[[[5-(dimethylamino)methyl-2-furanyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine (380 g) was filtered off and dried m.p. 69°-70°.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:17])[CH:5]=[C:6]([O:8][C:9]1[CH:14]=[C:13]([CH3:15])[CH:12]=[CH:11][C:10]=1[F:16])[CH3:7])[CH3:2].[Br:18]N1C(=O)CCC1=O>ClCCl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:17])/[CH:5]=[C:6](/[O:8][C:9]1[CH:14]=[C:13]([CH3:15])[CH:12]=[CH:11][C:10]=1[F:16])\[CH2:7][Br:18])[CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)C=C(C)Oc1cc(C)ccc1F
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClCCl
Product: CCOC(=O)/C=C(\CBr)Oc1cc(C)ccc1F
Temperature: 75 °C
Yield: 88.8 %

Procedure:
A solution of 3-(2-fluoro-5-methyl-phenoxy)-but-2-enoic acid ethyl ester (1.11 g, 4.65 mmol) in dichloromethane (18.9 mL) was treated with N-bromosuccinimide (0.87 g, 4.89 mmol) and benzoyl peroxide (90 mg, 0.37 mmol). The reaction was then heated to 75° C. overnight. At this time, the reaction was cooled to 25° C. and then concentrated in vacuo. Purification by Analogix flash chromatography (40 g, 2% ethyl acetate/hexanes) afforded (E)-4-bromo-3-(2-fluoro-5-methyl-phenoxy)-but-2-enoic acid ethyl ester (1.31 g, 89%) as a light yellow oil: HR-ES-MS m/z calculated for C13H14O3FBr [M+H]+ 317.0183, observed 317.0182; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.15 (t, J=7.2 Hz, 3H), 2.31 (s, 3H), 4.07 (q, J=7.2 Hz, 2H), 4.78 (s, 2H), 4.81 (s, 1H), 7.11 (dd, J=7.8, 1.8 Hz, 1H), 7.14-7.22 (m, 1H), 7.33 (dd, J=10.6, 8.5 Hz, 1H): and (Z)-4-bromo-3-(2-fluoro-5-methyl-phenoxy)-but-2-enoic acid ethyl ester (0.13 g, 9%) as a golden yellow oil: HR-ES-MS m/z calculated for C13H14O3FBr [M+H]+ 317.0183, observed 317.0182; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.09 (t, J=7.1 Hz, 3H), 2.26 (s, 3H), 3.97 (q, J=7.1 Hz, 2H), 4.29 (s, 2H), 5.98 (s, 1H), 6.97 (m, 2H), 7.20 (dd, J=10.7, 8.9 Hz, 1H).
Reaction SMILES: [NH:1]([CH2:3][C:4]([OH:6])=[O:5])[CH3:2].[C:7]([O:15][CH2:16][CH2:17][O:18][C:19](ON1C(=O)CCC1=O)=[O:20])(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>>[CH3:2][N:1]([C:19]([O:18][CH2:17][CH2:16][O:15][C:7]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:14])=[O:20])[CH2:3][C:4]([OH:6])=[O:5]
Reactant: O=C(OCCOC(=O)c1ccccc1)ON1C(=O)CCC1=O
Reactant: CNCC(=O)O
Product: CN(CC(=O)O)C(=O)OCCOC(=O)c1ccccc1
Yield: 44.4 %

Procedure:
Following the general procedure for the synthesis of acyloxyalkyl carbamates, sarcosine (0.104 g, 1.17 mmol) and (2,5-dioxoazolidinyloxycarbonyloxy)ethyl benzoate (0.3 g, 0.976 mmol) were reacted to provide 122 mg (44% yield) of the title compound (40) as a colorless semi-solid after work-up and mass-guided preparative HPLC purification. 1H NMR (CD3OD, 400 MHz): δ=8.01 (d, 2H), 7.61 (t, 1H), 7.44 (t, 2H), 7.01 (q, 1H), 4.12 (m, 2H), 3.01 (2s, 3H), 1.62-1.58 (dd, 3H). MS (ESI) m/z 304.05 (M+Na)+; 280.11 (M−H)−.
Reaction SMILES: [OH:1][C:2]1[C:6](=[O:7])[O:5][CH:4]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.S(=O)(=O)(O)O.O.Cl[CH2:26]Cl>CO>[OH:1][C:2]1[C:6](=[O:7])[O:5][CH:4]([CH2:8][CH2:9][C:10]([O:12][CH3:26])=[O:11])[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=C(O)CCC1OC(=O)C(O)=C1c1ccccc1
Reactant: ClCCl
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CO
Product: COC(=O)CCC1OC(=O)C(O)=C1c1ccccc1
Reaction time: 3 h

Procedure:
To a solution of 3-(4-hydroxy-5-oxo-3-phenyl2,5-dihydro-2-furyl)propionic acid (3.85 g) in dry methanol (60 ml) was added conc. sulfuric acid (3.8 ml) in one portion at 5° C. After stirring for 3 hours at ° C., the mixture was poured into a mixture of water (100 ml) and dichloromethane (50 ml). The aqueous layer was extracted with dichloromethane (50 ml) once again. The combined organic layers were washed with water three times, dried, and evaporated to dryness. To the residue was added diethyl ether and the solid was collected by filtration to yield methyl 3-(4-hydroxy-5-oxo-3-phenyl-2,5-dihydro-2-furyl)propionate (3.49 g).
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1([CH3:16])[C:8]([CH3:10])([CH3:9])[O:7][B:6]([C:11]2[CH:12]=[N:13][NH:14][CH:15]=2)[O:5]1.FC(F)(F)S(O[CH2:23][CH:24]([F:34])[CH2:25][O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])(=O)=O>CN(C=O)C.C(OCC)C>[Si:27]([O:26][CH2:25][CH:24]([F:34])[CH2:23][N:14]1[CH:15]=[C:11]([B:6]2[O:7][C:8]([CH3:9])([CH3:10])[C:4]([CH3:16])([CH3:3])[O:5]2)[CH:12]=[N:13]1)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: CC(C)(C)[Si](C)(C)OCC(F)COS(=O)(=O)C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CC1(C)OB(c2cnn(CC(F)CO[Si](C)(C)C(C)(C)C)c2)OC1(C)C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
NaH (0.247 g, 6.17 mmol) was suspended in 10 mL of DMF. 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.958 g, 4.94 mmol) was added in 5 mL of DMF dropwise via syringe and the mixture was stirred at room temperature for 30 minutes. Then 3-{[tert-butyl(dimethyl)silyl]oxy}-2-fluoropropyl trifluoromethanesulfonate (1.40 g, 4.11 mmol) was added in 5 mL of DMF dropwise via syringe. After 20 minutes, the reaction mixture was diluted in diethyl ether, washed with water (3×50 mL) and brine then dried over magnesium sulfate, filtered and concentrated to afford 1-(3-{[tert-butyl(dimethyl)silyl]oxy}-2-fluoropropyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.
Reaction SMILES: CI.[C:3]1([S:13]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([O:25][CH2:26][CH2:27][O:28][S:29]([C:32]4[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=4)(=[O:31])=[O:30])[CH:23]=3)[NH:18][N:17]=2)(=[O:15])=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1.[C:39](=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[CH3:39][N:18]1[C:19]2[C:24](=[CH:23][C:22]([O:25][CH2:26][CH2:27][O:28][S:29]([C:32]3[CH:33]=[CH:34][C:35]([CH3:38])=[CH:36][CH:37]=3)(=[O:30])=[O:31])=[CH:21][CH:20]=2)[C:16]([S:13]([C:3]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH:6]=[CH:5][CH:4]=2)(=[O:14])=[O:15])=[N:17]1
Reactant: O=C([O-])[O-]
Reactant: Cc1ccc(S(=O)(=O)OCCOc2ccc3[nH]nc(S(=O)(=O)c4cccc5ccccc45)c3c2)cc1
Agent: [Cs+]
Solvent: CI
Solvent: CC(C)=O
Product: Cc1ccc(S(=O)(=O)OCCOc2ccc3c(c2)c(S(=O)(=O)c2cccc4ccccc24)nn3C)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Methyliodide (0.06 mL, 0.96 mmol) was added to a chilled mixture of toluene -4-sulfonic acid 2-[3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl ester (0.401 g, 0.767 mmol) and cesium carbonate (0.29 g, 0.89 mmol) in acetone (10 mL). The reaction mixture was stirred at ambient temperature under nitrogen for 3 hours. It was then partitioned in ethyl acetate and water. The organic phase was washed with brine, dried with anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography with 25-40% ethyl acetate in hexane, 100% chloroform and 1% methanol in chloroform. Drying at 65° C. in vacuo for yielded toluene-4-sulfonic acid 2-[1-methyl-3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl ester as a buff foam (0.224 g, 54.4%). 1HNMR (400 MHz, DMSO-d6): δ8.27 (d, 1H, J=8.54 Hz), 8.55 (dd, 1H, J=7.42 Hz and 1.16 Hz), 8.30 (d, 1H, J=8.35 Hz), 8.05-8.07 (m, 1H), 7.72-7.76 (m, 3H), 7.60-7.70 (m, 3H), 7.31 (d, 2H, J=8.01 Hz), 7.18 (d, 1H, J=2.20 Hz), 7.00-7.03 (m, 1H), 4.35-4.37 (m, 2H), 4.22-4.24 (m, 2H), 4.07 (s, 3H), 2.28 ppm (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([CH3:12])[C:9]=1[O:10][CH3:11])[CH2:5]Cl.[CH2:13]([NH:16][C:17]1[C:18]([N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[N:19][CH:20]=[CH:21][CH:22]=1)[CH2:14][CH3:15]>>[CH3:11][O:10][C:9]1[C:2]([CH3:1])=[CH:3][C:4]([CH2:5][N:26]2[CH2:27][CH2:28][N:23]([C:18]3[C:17]([NH:16][CH2:13][CH2:14][CH3:15])=[CH:22][CH:21]=[CH:20][N:19]=3)[CH2:24][CH2:25]2)=[CH:7][C:8]=1[CH3:12]
Reactant: CCCNc1cccnc1N1CCNCC1
Reactant: COc1c(C)cc(CCl)cc1C
Product: CCCNc1cccnc1N1CCN(Cc2cc(C)c(OC)c(C)c2)CC1

Procedure:
Following the general procedure of EXAMPLE 1 and making non-critical variations but starting with 3,5-dimethyl-4-methoxybenzyl chloride (I, PREPARATION 4, 0.41 g) and 1-[3-(propylamino)-2-pyridinyl]piperazine (II, PREPARATION 7, 0.42 g), the title compound is obtained.
Reaction SMILES: Cl.Cl[CH2:3][C:4]1[C:5]([NH2:11])=[N:6][C:7]([CH3:10])=[N:8][CH:9]=1.C(N(CC)CC)C.[CH3:19][O:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[CH2:27][NH:26][CH2:25][CH2:24]2>CN(C)C=O>[CH3:19][O:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[CH2:27][N:26]([CH2:3][C:4]1[C:5]([NH2:11])=[N:6][C:7]([CH3:10])=[N:8][CH:9]=1)[CH2:25][CH2:24]2
Reactant: COc1ccc2c(c1)CCNC2
Reactant: Cc1ncc(CCl)c(N)n1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1ccc2c(c1)CCN(Cc1cnc(C)nc1N)C2
Temperature: 25 °C
Reaction time: 3 h
Yield: 22.2 %

Procedure:
A suspension of 0.80 g (0.00412 mol) of 5-chloromethyl-2-methyl-pyrimidin-4-ylamine hydrochloride in 17 ml of dimethylformamide was treated with 1.7 ml (0.0124 mol) of triethylamine and 0.87 g (0.0053 mol) of 6-methoxy-1,2,3,4-tetrahydro-isoquinoline and the mixture was stirred at room temperature under argon for 3 hours. The mixture was completely freed from the solvents and the residue was triturated in 20 ml of water. The resulting crystals were filtered off under suction, chromatographed over silica gel with dichloromethane/methanol 9:1 as the eluent and recrystallized from ethyl acetate/n-hexane. 0.26 g (22%) of 5-(6-methoxy-3,4-dihydro-1H-isoquinolin-2-ylmethyl)-2-methyl-pyrimidin-4-ylamine was obtained as white crystals; m.p. 142°-143°.
Reaction SMILES: [H-].COCCO[Al+]OCCOC.[Na+].[H-].[N:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[C:17]([C:25]#[C:26][CH2:27][OH:28])[CH:16]=1>C1COCC1>[N:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[C:17](/[CH:25]=[CH:26]/[CH2:27][OH:28])[CH:16]=1
Reactant: OCC#Cc1cnc2ccccc2c1
Agent: COCCO[Al+]OCCOC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: OC/C=C/c1cnc2ccccc2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a dry, jacketed 250-mL three-necked round-bottom flask was charged sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al, 70% wt. solution in toluene, 11.0 g, 38.1 mmol, 1.39 eq) and anhydrous THF (20 mL). To this precooled (0-2° C.) and magnetically stirred solution was added a THF (50 mL) solution of the 3-(3-quinolyl)-2-propyn-1-ol (5.0 g, 27.32 mmol) via pressure equalizing dropping funnel. The temperature was not allowed to rise above 15° C. After the addition was complete (20 minutes) the mixture was allowed to warm up to room temperature and stirred for one hour. The solution was then cooled to 0° C. and quenched by the addition of aqueous 10% sulfuric acid (20 mL) such that the internal temperature did not rise above 15° C. The biphasic reaction mixture was then washed with ethyl acetate (3×100 mL). The pH of the aqueous acidic product solution was then adjusted to pH 9-10 with aq. conc. NH4OH and back extracted into ethyl acetate (2×125 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give exclusively 3-(3-quinolyl) trans-2-propen-1-ol as a solid: 4.1 g, 81%.
Reaction SMILES: [NH:1]([C:8]1[CH:16]=[C:15]([C:17](O)=[O:18])[C:14]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:13][C:9]=1[C:10](O)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C)C=CC(NC2C=C(C(O)=O)C(NC3C=CC(C)=CC=3)=CC=2C(O)=O)=CC=1>>[CH:24]1[CH:25]=[C:26]2[C:17]([C:15]3[C:14]([NH:20][C:21]2=[CH:22][CH:23]=1)=[CH:13][C:9]1[C:10]([C:7]2[C:2]([NH:1][C:8]=1[CH:16]=3)=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:11])=[O:18]
Reactant: O=C(O)c1cc(Nc2ccccc2)c(C(=O)O)cc1Nc1ccccc1
Agent: Cc1ccc(Nc2cc(C(=O)O)c(Nc3ccc(C)cc3)cc2C(=O)O)cc1
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 125 °C

Procedure:
A stirred vessel is charged with 450 parts of polyphosphoric acid containing 83.0% P2O5. Then 37.5 parts of 2,5-dianilinoterephthalic acid and 112.5 parts of 2,5-di-(4-toluidino)terephthalic acid are introduced at 125° C. with stirring and the mixture is heated at 125° C. for 1 hour during which ring closure takes place to form the quinacridone. The reaction mixture is then metered over the course of 5 minutes into a second stirred vessel containing 1731.8 parts of 40% strength phosphoric acid and is hydrolyzed at 25° C. with stirring. During hydrolysis, the temperature rises to 110° C. Following the hydrolysis, the phosphoric acid strength is 55%. The mixture is cooled to 90° C., 823.4 parts of water at 25° C. are added and stirred at 90° C. for 1 hour. Thereafter, the mixed-crystal pigment is filtered off with suction, washed to neutrality with water and dried at 80° C.
Reaction SMILES: [CH2:1]([S:3](Cl)(=[O:5])=[O:4])[CH3:2].[C:7]([O:11][C:12]([N:14]([C:22]1[C:27]([C:28]#[C:29][Si:30]([CH3:33])([CH3:32])[CH3:31])=[N:26][C:25]([N:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)=[CH:24][N:23]=1)[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:13])([CH3:10])([CH3:9])[CH3:8].CCN(C(C)C)C(C)C>CN(C=O)C>[C:7]([O:11][C:12]([N:14]([C:22]1[C:27]([C:28]#[C:29][Si:30]([CH3:31])([CH3:33])[CH3:32])=[N:26][C:25]([N:34]2[CH2:35][CH2:36][N:37]([S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])[CH2:38][CH2:39]2)=[CH:24][N:23]=1)[C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:13])([CH3:8])([CH3:9])[CH3:10]
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1ncc(N2CCNCC2)nc1C#C[Si](C)(C)C
Reactant: CCS(=O)(=O)Cl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCS(=O)(=O)N1CCN(c2cnc(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)c(C#C[Si](C)(C)C)n2)CC1
Reaction time: 0.08 h
Yield: 109.3 %

Procedure:
Ethanesulfonyl chloride (147.0 mg, 108.3 μL, 1.143 mmol) was added slowly to a stirred solution of tert-butyl N-tert-butoxycarbonyl-5-(piperazin-1-yl)-3-((trimethylsilyl)ethynyl)pyrazin-2-ylcarbamate (494 mg, 1.039 mmol) and DIPEA (161.2 mg, 217.3 μL, 1.247 mmol) in DMF (5 mL) at ambient temperature. The reaction was allowed to stir for 5 minutes and then partitioned between EtOAc/water. The aqueous layer was extracted with EtOAc (3×) and the combined organics washed with brine, dried (MgSO4), filtered and concentrated to give the product as a terracotta oil (645 mg, quantitative yield). MS (ES+) 590.05
Reaction SMILES: [CH2:1]([OH:3])[CH3:2].[Br:4][C:5]1[N:14]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:8]2[CH:9]=[N:10][NH:11][C:12](=[O:13])[C:7]=2[C:6]=1[CH2:23]Br.C(O)C.[O-]CC.[Na+]>O>[Br:4][C:5]1[N:14]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:8]2[CH:9]=[N:10][NH:11][C:12](=[O:13])[C:7]=2[C:6]=1[CH2:23][O:3][CH2:1][CH3:2]
Reactant: C[Si](C)(C)CCOCn1c(Br)c(CBr)c2c(=O)[nH]ncc21
Reactant: CCO
Agent: CC[O-]
Agent: [Na+]
Solvent: O
Product: CCOCc1c(Br)n(COCC[Si](C)(C)C)c2cn[nH]c(=O)c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 56 %

Procedure:
To 23 ml of ethanol solution containing 1.06 g (2.42 mmol) of 2-bromo-3-bromomethyl-1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Reference example 24-(f) was added 3.33 g (9.78 mmol) of 20% sodium ethoxide ethanol solution, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer after separation was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was applied to silica gel column chromatography (Eluent; hexane:ethyl acetate=2:1→1:1 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 549 mg of the title compound as a white solid. (Yield: 56%)
Reaction SMILES: [N+:1]([CH:4]=[C:5](SC)[NH:6][CH2:7][CH2:8][S:9][CH2:10][C:11]1[NH:15][CH:14]=[N:13][C:12]=1[CH3:16])([O-:3])=[O:2].[CH2:19]([NH2:21])[CH3:20]>>[N+:1]([CH:4]=[C:5]([NH:21][CH2:19][CH3:20])[NH:6][CH2:7][CH2:8][S:9][CH2:10][C:11]1[NH:15][CH:14]=[N:13][C:12]=1[CH3:16])([O-:3])=[O:2]
Reactant: CCN
Reactant: CSC(=C[N+](=O)[O-])NCCSCc1[nH]cnc1C
Product: CCNC(=C[N+](=O)[O-])NCCSCc1[nH]cnc1C

Procedure:
Reaction of 1-nitro-2-methylthio-2-[2-((4-methyl-5-immidazolyl)-methylthio)ethylamino]ethylene with ethylamine according to the process of Example 2(ii) yielded the title compound, m.p. 171°-172°.