Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH3:12])[C:3]=1[C:4](O)=[O:5].[CH3:13][NH:14][CH3:15]>>[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH3:12])[C:3]=1[C:4]([N:14]([CH3:15])[CH3:13])=[O:5]
Reactant: CNC
Reactant: COc1cccc(N)c1C(=O)O
Product: COc1cccc(N)c1C(=O)N(C)C

Procedure:
The product was obtained starting from 2-amino-6-methoxybenzoic acid (100 mg, 0.6 mmol) and dimethylamine (2M in THF, 420 μl, 0.84 mmol) according to the method described in example 64, step 6 after extraction with ethyl acetate and purification by silica gel chromatography using an amine phase and a heptane/ethyl acetate gradient as colorless oil (26 mg, 22%).
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12]([OH:14])=O)=[C:7]2[N:6]=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[CH:4]=1.[CH3:27][S:28]([C:31]1[CH:32]=[C:33]([NH2:37])[CH:34]=[CH:35][CH:36]=1)(=[O:30])=[O:29].Cl>>[CH3:27][S:28]([C:31]1[CH:32]=[C:33]([NH:37][C:12]([C:11]2[CH:10]=[N:9][N:8]3[C:3]([C:2]([F:25])([F:26])[F:1])=[CH:4][C:5]([C:15]4[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=4)=[N:6][C:7]=23)=[O:14])[CH:34]=[CH:35][CH:36]=1)(=[O:29])=[O:30]
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Reactant: CS(=O)(=O)c1cccc(N)c1
Agent: Cl
Product: CS(=O)(=O)c1cccc(NC(=O)c2cnn3c(C(F)(F)F)cc(-c4ccc(C(F)(F)F)cc4)nc23)c1

Procedure:
The title compound was prepared from 7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.2) and 3-methanesulfonyl-phenylamine [commercially available as hydrochloride] according to general procedure II. Yellow solid. MS (ISP) 529.3 [(M+H)+]; mp 259° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:13]=1[C:14]([O:16]CC)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC(N(C(OC(C)(C)C)=O)C1SC=C(CC(C)C)C=1C(OCC)=O)=O)(C)(C)C.[OH-].[K+].C(O)(=O)C>CO.O>[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:13]=1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCOC(=O)c1c(CC(C)C)csc1NC(=O)OC(C)(C)C
Agent: CCOC(=O)c1c(CC(C)C)csc1N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: CC(=O)O
Product: CC(C)Cc1csc(NC(=O)OC(C)(C)C)c1C(=O)O

Procedure:
A solution of crude ethyl 2-t-butoxycarbonylamino-4-isobutylthiophene-3-carboxylate and ethyl 2-bis(t-butoxycarbonyl)amino-4-isobutylthiophene-3-carboxylate in methanol (1200 ml) was stirred and a solution of potassium hydroxide (44.8 g, 800 mmol) in water (450 ml) was added. The mixture was heated at 80° C. for 6h and left at room temperature over night. The reaction mixture was diluted with water and the pH adjusted to pH 4-5 with glacial acetic acid under cooling on ice. The product was extracted with ether and after drying with Na2SO4 the ether phase was concentrated in vacuo. The residue was suspended in petroleum ether and 2-t-butoxycarbonylamino-4-isobutylthiophene-3-carboxylic acid (75.2 g) was isolated by filtration. M.p. 154°-155° C. 1H-NMR (CDCl3, δ): 0.95 (d, 6H), 1.55 (s, 9H), 1.9 (m, 1H), 2.7 (d, 2H), 6.35 (s, 1H), 9.3 (br.s, 1H), 10.2 (s, 1H).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][C@H:10]([C@@H:14]([NH:16][O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[CH3:15])[C:11]([OH:13])=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:24](OC=O)(=[O:26])C>N1C=CC=CC=1>[C:1]1([CH2:7][CH2:8][CH2:9][C@H:10]([C@@H:14]([N:16]([CH:24]=[O:26])[O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[CH3:15])[C:11]([OH:13])=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(=O)OC=O
Reactant: C[C@H](NOC1CCCCO1)[C@@H](CCCc1ccccc1)C(=O)O
Solvent: c1ccncc1
Product: C[C@@H]([C@@H](CCCc1ccccc1)C(=O)O)N(C=O)OC1CCCCO1
Temperature: 25 °C
Reaction time: 6 h
Yield: 81 %

Procedure:
To a solution of (2R,3S)-2-(3-phenyl-1-propyl)-3-(2-tetrahydropyranyloxyamino)butanoic acid (21.4 g, 66.7 mmol) in pyridine (100 mL) at 0° C. is added formic acetic anhydride (30 mL). The resulting solution is allowed to warm to 25° C., stirred for 6 h, and then concentrated to dryness under reduced pressure. The resulting gum is dissolved in ethyl acetate (300 mL) and washed sequentially with 1 M hydrochloric acid (200 mL) and saturated aqueous sodium chloride solution. The organic layer is dried over anhydrous magnesium sulfate and concentrated under reduced pressure to provide (2R,3S)-2-(3-Phenyl-1-propyl)-3-(formyl-2-tetrahydropyranyloxyamino)butanoic acid as an oil (18.9 g, 81% yield).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][NH:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[K+].[K+].I[CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>CN(C=O)C.O>[N:23]1([CH2:22][CH2:21][N:11]2[C:12]3[C:7](=[CH:6][CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:13]=3)[CH2:8][CH2:9][CH2:10]2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1
Reactant: ICCN1CCOCC1
Reactant: O=[N+]([O-])c1ccc2c(c1)NCCC2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc2c(c1)N(CCN1CCOCC1)CCC2
Temperature: 70 °C
Yield: 7.2 %

Procedure:
To a solution of 7-nitro-1,2,3,4-tetrahydroquinoline (D1) (246 mg, 1.38 mmol) in DMF (2.7 ml) was added potassium carbonate (574 mg, 4.15 mmol) followed by a solution of 4-(2-iodoethyl)morpholine (500 mg, 2.07 mmol) in DMF (2 ml) and the reaction heated to 70° C. After cooling to ambient temperature the reaction mixture was diluted with water and extracted with EtOAc which was washed with water, dried over MgSO4 and concentrated in vacuo to give the crude product which was purified by silica SPE chromatography. Elution with 80% EtOAc/petroleum ether gave the title compound as an orange gum (29 mg). 1H NMR (250 MHz, CDCl3) δ (ppm): 7.39 (m, 2H), 7.00 (d, 1H), 3.73 (m, 4H), 3.47 (m, 2H), 3.38 (m, 2H), 2.79 (t, 2H), 2.49-2.59 (m, 6H), 1.96 (m, 2H).
Reaction SMILES: C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C([S:43][CH:44]([CH:68]([O:71][CH3:72])[O:69][CH3:70])[CH2:45][NH:46][C:47]([C:49]1[NH:50][C:51]2[C:56]([CH:57]=1)=[CH:55][CH:54]=[CH:53][C:52]=2[NH:58][S:59]([C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][N:63]=1)(=[O:61])=[O:60])=O)C1C=CC=CC=1.C1(SC)C=CC=CC=1.C(=O)([O-])O.[Na+]>ClCCl>[CH3:70][O:69][CH:68]([O:71][CH3:72])[CH:44]1[S:43][C:47]([C:49]2[NH:50][C:51]3[C:56]([CH:57]=2)=[CH:55][CH:54]=[CH:53][C:52]=3[NH:58][S:59]([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][N:63]=2)(=[O:61])=[O:60])=[N:46][CH2:45]1
Reactant: COC(OC)C(CNC(=O)c1cc2cccc(NS(=O)(=O)c3ccccn3)c2[nH]1)SCc1ccccc1
Agent: O=C([O-])O
Agent: O=P(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: CSc1ccccc1
Product: COC(OC)C1CN=C(c2cc3cccc(NS(=O)(=O)c4ccccn4)c3[nH]2)S1
Reaction time: 0.17 h
Yield: 40.6 %

Procedure:
To a solution of triphenylphosphine oxide (849 mg) in dichloromethane (10 mL) was added trifluoromethanesulfonic anhydride (515 μL) under ice-cooling, and the mixture was stirred for 10 min. A solution of N-[2-(benzylthio)-3,3-dimethoxypropyl]-7-[(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxamide (1.5 g) and thioanisole (690 mg) in dichloromethane (10 mL) was added dropwise to the reaction mixture under ice-cooling, and the mixture was stirred for 10 min. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to silica gel column chromatography to give white crystals from a fraction eluted with ethyl acetate:hexane=50:50. The white crystals were purified by preparative HPLC to give the title compound (487 mg, yield 40%) as white crystals. melting point 153° C.
Reaction SMILES: [CH:1]([C:4]1[CH:22]=[CH:21][C:7]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16](OCC)=[O:17])[CH2:11][CH2:10]2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[NH2:23][NH2:24]>C(O)C>[CH:1]([C:4]1[CH:22]=[CH:21][C:7]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]([NH:23][NH2:24])=[O:17])[CH2:11][CH2:10]2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2]
Reactant: NN
Reactant: CCOC(=O)CN1CCN(Cc2ccc(C(C)C)cc2)CC1
Solvent: CCO
Product: CC(C)c1ccc(CN2CCN(CC(=O)NN)CC2)cc1

Procedure:
Synthesized according to General Procedure C: 6{19} (7.15 g, 23.5 mmol, 1 equiv.), anhydrous hydrazine (2.2 mL, 70.4 mmol, 3 equiv.), ethanol (47.4 mL). Purification by silica gel column chromatography (4:1 EtOAc:MeOH) afforded 1{19} (6.19 g, 91%) as a white solid. 1H-NMR (500 MHz, CDCl3): δ 8.17 (br s, 1H), 7.19 (d, 2H, J=8.0 Hz), 7.15 (d, 2H, J=8.0 Hz), 3.81 (br s, 2H), 3.46 (s, 2H), 3.05 (s, 2H), 2.87 (sept, 1H, J=7.0 Hz), 2.51 (br s, 4H), 2.44 (br s, 4H), 1.22 (d, 6H, J=7.0 Hz). 13C-NMR (125 MHz, CDCl3): δ 170.4, 147.6, 134.9, 129.0, 126.1, 62.5, 60.5, 53.5, 52.8, 33.6, 23.9.
Reaction SMILES: [OH:1][CH:2]1[CH:7]([NH:8][CH2:9][CH2:10][CH2:11][CH:12]2[N:16]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][C@H:28]4[C@H:33]([O:34]C(=O)C)[C@@H:32]([O:38]C(=O)C)[C@H:31]([O:42]C(=O)C)[C@@H:30]([C:46]([O:48]C)=[O:47])[O:29]4)=[C:23]([NH:50][C:51](=[O:72])[CH2:52][CH2:53][NH:54]C(OCC4C5C=CC=CC=5C5C4=CC=CC=5)=O)[CH:22]=3)=[O:18])[CH2:15][CH2:14][O:13]2)[CH2:6][CH:5]([O:73][CH:74]2[C:91]3[C:78](=[C:79]([OH:97])[C:80]4[C:81](=[O:96])[C:82]5[C:87]([C:88](=[O:93])[C:89]=4[C:90]=3[OH:92])=[C:86]([O:94][CH3:95])[CH:85]=[CH:84][CH:83]=5)[CH2:77][C@@:76]([OH:102])([C:98](=[O:101])[CH2:99][OH:100])[CH2:75]2)[O:4][CH:3]1[CH3:103].C(O)(=O)C.N1CCCCC1>CO.O.CN(C=O)C>[NH2:54][CH2:53][CH2:52][C:51]([NH:50][C:23]1[CH:22]=[C:21]([CH2:20][O:19][C:17]([N:16]2[CH2:15][CH2:14][O:13][CH:12]2[CH2:11][CH2:10][CH2:9][NH:8][CH:7]2[CH2:6][CH:5]([O:73][CH:74]3[C:91]4[C:78](=[C:79]([OH:97])[C:80]5[C:81](=[O:96])[C:82]6[C:87]([C:88](=[O:93])[C:89]=5[C:90]=4[OH:92])=[C:86]([O:94][CH3:95])[CH:85]=[CH:84][CH:83]=6)[CH2:77][C@@:76]([OH:102])([C:98](=[O:101])[CH2:99][OH:100])[CH2:75]3)[O:4][CH:3]([CH3:103])[CH:2]2[OH:1])=[O:18])[CH:26]=[CH:25][C:24]=1[O:27][C@@H:28]1[O:29][C@H:30]([C:46]([OH:48])=[O:47])[C@@H:31]([OH:42])[C@H:32]([OH:38])[C@H:33]1[OH:34])=[O:72]
Reactant: COC(=O)[C@H]1O[C@@H](Oc2ccc(COC(=O)N3CCOC3CCCNC3CC(OC4C[C@](O)(C(=O)CO)Cc5c(O)c6c(c(O)c54)C(=O)c4c(OC)cccc4C6=O)OC(C)C3O)cc2NC(=O)CCNC(=O)OCC2c3ccccc3-c3ccccc32)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Solvent: CC(=O)O
Solvent: O
Solvent: C1CCNCC1
Product: COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)CC3OC1CC(NCCCC2OCCN2C(=O)OCc2ccc(O[C@@H]3O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]3O)c(NC(=O)CCN)c2)C(O)C(C)O1
Reaction time: 0.58 h
Yield: 27.2 %

Procedure:
To a 0° C. mixture of the doxorubicin oxazolidine 16 (30 mg, 0.021 mmol) in methanol (4 mL) was added a solution of LiOH monohydrate (8.8 mg, 0.21 mmol) in water (2 mL). The mixture was stirred for 35 min and was neutralized with acetic acid (8 uL, 0.21 mmol) to a pH of approximately 7. The mixture was concentrated under reduced pressure to give a residue which was dissolved in DMF (4 mL) and treated with piperidine (1 mL). The reaction mixture was stirred for 5 min, before being concentrated under reduced pressure. The residue was purified via preparative HPLC to yield 6.1 mg (27%) of product: LC-MS m/z (ES+), 1069.13 (M+H)+, 5.64 min.
Reaction SMILES: [C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:10]1(=O)[CH2:15][CH2:14][CH2:13][CH:12]=[CH:11]1.O>O1CCOCC1.C/C(/O)=C/C(C)=O.C1CC=CCCC=C1.[Rh]>[C:1]1([CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C1C=CCCC1
Reactant: OB(O)c1ccccc1
Agent: [Rh]
Agent: C1=C\CC/C=C\CC/1
Agent: CC(=O)/C=C(/C)O
Solvent: C1=CCCC=CCC1
Solvent: C1COCCO1
Solvent: O
Product: c1ccc(C2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a 25-mL three-neck flask were added Rh(acac)(cod) (6.8 mg, 21.8 μmol) and PhB(OH)2 (445 mg, 3.65 mmol), and the atmosphere in the system was substituted with argon. The mixture was added with 3.6 mL of a solution of each ligand (21.8 μmol) in anhydrous dioxane and 2-cyclohexenone (0.073 mL, 0.73 mmol). The mixture was stirred at room temperature for 15 minutes, and added with water (0.18 mL). The reaction mixture was stirred at 100° C. for 3 hours, then added with 9 mL of water, and extracted twice with 9 mL of diethyl ether. The organic layers were combined, washed with 9 mL of saturated sodium chloride solution, and concentrated in an evaporator. The residue was treated by silica gel column chromatography (toluene:ethyl acetate=2:1) to obtain 3-phenylcyclohexane as colorless oil. The resulting optically active 3-phenylcyclohexanone in an amount of 2 mg was dissolved in 1 mL of a mixture of n-heptane and 2-propanol (99:2). This solution was analyzed by HPLC under the following conditions.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:13]([CH3:14])=[CH:12][C:11]([OH:15])=[C:10]([CH:16]=[N:17]O)[C:9]1=[O:19]>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:13]([CH3:14])=[CH:12][C:11]([OH:15])=[C:10]([C:16]#[N:17])[C:9]1=[O:19]
Reactant: Cc1cc(O)c(C=NO)c(=O)n1-c1ccccc1Cl
Solvent: CC(=O)O
Product: Cc1cc(O)c(C#N)c(=O)n1-c1ccccc1Cl
Temperature: 120 °C
Reaction time: 2 h
Yield: 79.9 %

Procedure:
A mixture of 1-(2-chlorophenyl)-4-hydroxy-3-((hydroxyimino)methyl)-6-methylpyridin-2(1H)-one obtained in Step C (3.88 g) and acetic acid (46.4 mL) was stirred at 120° C. for 2 hr, cooled to room temperature, and poured into ice water. The resulting solid was collected by filtration, washed with water, and dried under reduced pressure to give the title compound (2.90 g).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:34])[C:9]([CH2:21][CH2:22][CH2:23][CH2:24][B:25]1[O:29][C:28]([CH3:31])([CH3:30])[C:27]([CH3:33])([CH3:32])[O:26]1)([CH2:17][CH2:18][CH:19]=C)[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:35]=[O+][O-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[C:1]([O:5][C:6]([N:8]([CH3:34])[C:9]([CH2:17][CH2:18][CH:19]=[O:35])([CH2:21][CH2:22][CH2:23][CH2:24][B:25]1[O:26][C:27]([CH3:32])([CH3:33])[C:28]([CH3:30])([CH3:31])[O:29]1)[C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: C=CCCC(CCCCB1OC(C)(C)C(C)(C)O1)(C(=O)OC(C)(C)C)N(C)C(=O)OC(C)(C)C
Reactant: O=[O+][O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CN(C(=O)OC(C)(C)C)C(CCC=O)(CCCCB1OC(C)(C)C(C)(C)O1)C(=O)OC(C)(C)C
Reaction time: 4 h
Yield: 70 %

Procedure:
A solution of tert-butyl 2-(tert-butoxycarbonyl(methyl)amino)-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)hex-5-enoate (1.10 g, 2.29 mmol) in dichloromethane (30 mL) was cooled to −78° C. and treated with ozone until a pale blue-gray color appeared. After TLC indicated the absence of starting material, the ozone inlet tube was replaced with nitrogen and nitrogen was bubbled through the solution for 20 min to remove any excess ozone. Triphenylphosphine (1.50 g, 5.72 mmol, 2.5 equiv) was added in one portion, the cooling bath was removed and the mixture was stirred for 4 h. The solution was concentrated and purified by MPLC (0-40% ethyl acetate in heptane) gave tert-butyl 2-(tert-butoxycarbonyl(methyl)amino)-2-(3-oxopropyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate as a colorless oil (780 mg, 70%). Rf 0.40 (30% ethyl acetate in heptane). ESI MS found for C25H46BNO7 m/z [484.3 (M+1)].
Reaction SMILES: Br[CH2:2][CH:3]1[O:17][C:6]2=[C:7]3[C:12](=[C:13]([CH3:15])[CH:14]=[C:5]2[CH2:4]1)[NH:11][C:10](=[O:16])[CH:9]=[CH:8]3.[CH3:18][N:19]([CH2:21][CH2:22][SH:23])[CH3:20].[OH-].[Na+]>CN(C)C=O.Cl.O>[CH3:18][N:19]([CH3:20])[CH2:21][CH2:22][S:23][CH2:2][CH:3]1[O:17][C:6]2=[C:7]3[C:12](=[C:13]([CH3:15])[CH:14]=[C:5]2[CH2:4]1)[NH:11][C:10](=[O:16])[CH:9]=[CH:8]3
Reactant: CN(C)CCS
Reactant: Cc1cc2c(c3ccc(=O)[nH]c13)OC(CBr)C2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cc2c(c3ccc(=O)[nH]c13)OC(CSCCN(C)C)C2
Temperature: 25 °C
Reaction time: 1 h
Yield: 13.5 %

Procedure:
To a suspension of 2-bromomethyl-5-methyl-2,3,6,7-tetrahydrofuro-[2,3-f]quinoline-7-one (1. 765 g) in dimethylformamide (60 ml), hydrochloric acid salt of 2 (dimethylamino)ethylmercaptan (4.25 g) and caustic soda (2.40 g) in water (20 ml) were added and stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure. The residue was combined with water, and extracted with chloroform. The extract was washed with NaCl solution twice and dried and condensed. The residue was crystallized from chloroform--n-hexane to obtain 1.741 g of the title compound as white powder (mp.: 163°-165° C.).
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9](Cl)[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:19][CH2:20][CH2:21][CH2:22][O-:23].[Na+]>C(O)CCC>[NH2:1][C:2]1[N:10]=[C:9]([O:23][CH2:22][CH2:21][CH2:20][CH3:19])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Nc1nc(Cl)nc2c1ncn2Cc1ccccc1
Reactant: CCCC[O-]
Agent: [Na+]
Solvent: CCCCO
Product: CCCCOc1nc(N)c2ncn(Cc3ccccc3)c2n1
Reaction time: 2 h
Yield: 57.2 %

Procedure:
6-Amino-9-benzyl-2-chloropurine (200 mg, 0.77 mmol) and sodium butylate (370 mg, 3.85 mmol) were dissolved in 1-butanol (20 ml) and then the solution was refluxed on heating under stirring for 2 hours. The reaction mixture was evaporated in vacuo to dryness. To the residue was added water and the mixture was extracted with chloroform. The organic layer was dried on sodium sulfate and evaporated in vacuo to dryness. The residue was purified with silica gel chromatography (2% methanol/chloroform) to of give the subject compound (131 mg, yield 54%).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][NH:11][C:12]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=3[Cl:25])[C:15]([NH:26][C:27](=O)[CH3:28])=[CH:14][N:13]=2)[CH:5]=[CH:4][C:3]=1[N+:30]([O-:32])=[O:31].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:42])=CC=1>COCCOC>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][NH:11][C:12]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=3[Cl:25])[C:15]([NH:26][C:27](=[S:42])[CH3:28])=[CH:14][N:13]=2)[CH:5]=[CH:4][C:3]=1[N+:30]([O-:32])=[O:31]
Reactant: CC(=O)Nc1cnc(NCCNc2ccc([N+](=O)[O-])c(N)n2)nc1-c1ccc(Cl)cc1Cl
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: COCCOC
Product: CC(=S)Nc1cnc(NCCNc2ccc([N+](=O)[O-])c(N)n2)nc1-c1ccc(Cl)cc1Cl

Procedure:
1 mmol of N-[2-({2-[(6-amino-5-nitro(2-pyridyl))amino]ethyl}amino)-4-(2,4-dichlorophenyl)pyrimidin-5-yl]acetamide and 2 mmol of Lawesson's reagent were stirred in 2 ml of DME at 80° C. The reaction mixture was concentrated in vacuo and diluted with water and ethyl acetate. The solution was extracted three times with ethyl acetate, dried over sodium sulfate, and purified by column chromatography eluting with 5-10% methanol/methylene chloride.
Reaction SMILES: [NH2:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][C:8]([O:10]CC)=[O:9].[CH3:17][CH:18]([CH3:37])[CH2:19][CH2:20][CH2:21][N:22]1[C:30]2[C:25](=[CH:26][C:27](/[C:31](/[CH3:36])=[CH:32]/[C:33](O)=[O:34])=[CH:28][CH:29]=2)[CH:24]=[CH:23]1>>[CH3:17][CH:18]([CH3:37])[CH2:19][CH2:20][CH2:21][N:22]1[C:30]2[C:25](=[CH:26][C:27](/[C:31](/[CH3:36])=[CH:32]/[C:33]([NH:1][C:2]3[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=3[O:4][CH2:5][CH2:6][CH2:7][C:8]([OH:10])=[O:9])=[O:34])=[CH:28][CH:29]=2)[CH:24]=[CH:23]1
Reactant: C/C(=C\C(=O)O)c1ccc2c(ccn2CCCC(C)C)c1
Reactant: CCOC(=O)CCCOc1ccccc1N
Product: C/C(=C\C(=O)Nc1ccccc1OCCCC(=O)O)c1ccc2c(ccn2CCCC(C)C)c1

Procedure:
0.41 g of compound 11 was obtained in a similar manner to those described in the Examples 1 and 2 using 2.33 g of ethyl 4-(2-aminophenoxy)butyrate and 1.49 g of 3-[1-(4-methylpentyl)indol-5-yl]isocrotonic acid obtained according to the procedures described in the Reference Examples 1-4.
Reaction SMILES: [CH2:1]([C:3]1[C:4](=[O:10])[NH:5][C:6](=[O:9])[NH:7][CH:8]=1)[CH3:2].[CH2:11]([O:13][CH2:14]Cl)[CH3:12].C(=O)([O-])O.[Na+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.C(Cl)Cl>[CH2:11]([O:13][CH2:14][N:7]1[CH:8]=[C:3]([CH2:1][CH3:2])[C:4](=[O:10])[NH:5][C:6]1=[O:9])[CH3:12]
Reactant: CCOCCl
Reactant: CCc1c[nH]c(=O)[nH]c1=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: C[Si](C)(C)C(C(N)=O)[Si](C)(C)C
Agent: O=C([O-])O
Solvent: ClCCl
Product: CCOCn1cc(CC)c(=O)[nH]c1=O
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 80.7 %

Procedure:
To 100 ml of methylene chloride, 5.1 g (40 mmol) of 5-ethyluracil and 22 ml (0.88 mmol) of bistrimethylsilylacetamide were added under a nitrogen atmosphere and stirred for 40 minutes at room temperature. To this mixture, 4.1 ml (88 mmole) of chloromethyl ethyl ether and 0.15 g (0.4 mmol) of tetrabutylammonium iodide were added and heated under reflux for 15 hours. Then, the reaction mixture was poured carefully into 50 ml of saturated aqueous solution of sodium hydrogencarbonate and filtered through Celite. The organic layer was washed with water, dried on magnesium sulfate and concentrated under reduced pressure. The residue was crystallized from ethyl acetate to obtain 6.4 g of 1-ethoxymethyl-5-ethyluracil (Yield: 81%).
Reaction SMILES: [BH4-].[Na+].C([O:5][C:6]([C:8]1[CH:13]=[CH:12][N:11]=[C:10]([C:14]2[CH:19]=[C:18]([C:20](OCC)=[O:21])[CH:17]=[C:16]([C:25]3[CH:30]=[C:29]([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])[CH:28]=[CH:27][N:26]=3)[N:15]=2)[CH:9]=1)=O)C.[Cl-].[NH4+].[BH4-]>C(O)C>[OH:5][CH2:6][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([C:14]2[CH:19]=[C:18]([CH2:20][OH:21])[CH:17]=[C:16]([C:25]3[CH:30]=[C:29]([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])[CH:28]=[CH:27][N:26]=3)[N:15]=2)[CH:9]=1
Reactant: CCCCCCCCCCCCCCCCCCCc1ccnc(-c2cc(C(=O)OCC)cc(-c3cc(C(=O)OCC)ccn3)n2)c1
Agent: [BH4-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Product: CCCCCCCCCCCCCCCCCCCc1ccnc(-c2cc(CO)cc(-c3cc(CO)ccn3)n2)c1
Temperature: 25 °C
Yield: 79 %

Procedure:
8.2 g of sodium borohydride was added to a suspension of 4,4′-diethoxycarbonyl-4″-nonadecyl-2,2′:6′,2″-terpyridine (6.4 g, 10.0 mmol) in 200 mL of absolute ethanol. The mixture was refluxed for 3 h and cooled to room temperature, and then 200 mL of an ammonium chloride saturated water solution was added to decompose the excess borohydride. The ethanol was removed under vacuum and the precipitated solid was dissolved in a minimal amount of water. The resulting solution was extracted with ethyl acetate (5×200 mL) and dried over sodium sulfate, and the solvent was removed under vacuum. The desired solid was obtained in 79% yield and was used without further purification. Anal. C36H53N3O2: Calcd: C, 77.24; H, 9.54; N, 7.51. Found: C, 77.10; H, 9.47; N, 7.49. MS (ESIMS): m/z: 559.4.
Reaction SMILES: [Br:1][C:2]1[C:3]([F:12])=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1[OH:10])[CH:5]=[O:6].[C:13](=O)([O-])[O-].[K+].[K+].COS(OC)(=O)=O.C(OC(=O)C)C>CN(C=O)C>[Br:1][C:2]1[C:3]([F:12])=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1[O:10][CH3:13])[CH:5]=[O:6]
Reactant: O=C([O-])[O-]
Reactant: O=Cc1cc(F)c(O)c(Br)c1F
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: COS(=O)(=O)OC
Solvent: CN(C)C=O
Product: COc1c(F)cc(C=O)c(F)c1Br
Temperature: 25 °C
Reaction time: 8 h
Yield: 53666 %

Procedure:
To a solution of 3-bromo-2,5-difluoro-4-hydroxybenzaldehyde (48.4 g, 0.193 mmol) in DMF (200 mL) was added potassium carbonate (40.0 g) and dimethylsulfate (27.4 mL). The reaction mixture was stirred at room temperature overnight. The reaction was diluted wit ethylacetate and washed successively with water and brine, dried over magnesium sulfate, filtered and evaporated. The residue was triturated with hexane to afford 26 g of 3-bromo-2,5-difluoro-4-methoxy benzaldehyde. The mother liquor was evaporated and chromatographed on silica gel (0–10% ethyl acetate in hexane) to give 10.86 g of more product. (38% overall yield from 2,5-dinitrophenol).