Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[CH:13][C:9]([C:10](O)=[O:11])=[CH:8][C:7]=1[O:15][CH3:16].S(Cl)([Cl:19])=O>ClCCl>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([Cl:19])=[O:11])=[CH:8][C:7]=1[O:15][CH3:16]
Reactant: O=S(Cl)Cl
Reactant: COc1cc(C(=O)O)ccc1OCCCCl
Solvent: ClCCl
Product: COc1cc(C(=O)Cl)ccc1OCCCCl
Yield: 60.8 %

Procedure:
To a mixture of 4-(3-chloropropoxy)-3-methoxybenzoic acid (2.4 g, 10 mmol) in dichloromethane (5 ml) was added thionyl chloride (0.9 ml, 12 mmol) dissolved in dichloromethane (5 ml). The reaction was stirred and refluxed for 1 hour, and then the dichloromethane was removed in vacuo to leave a dark oil. The oil was triturated with hexane and the solid that formed while scratching with a glass rod was collected to afford 1.6 g of 4-(3-chloropropoxy)-3-methoxybenzoyl chloride, m.p.=60°-63° C.
Reaction SMILES: Br[C:2]1[C:3]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14]C)=[O:13])=[CH:7][CH:6]=2.[S:22]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23]1>>[C:16]1([C:3]2[C:2]([C:24]3[CH:25]=[CH:26][S:22][CH:23]=3)=[N:11][C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:12]([OH:14])=[O:13])[CH:9]=3)[N:4]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: OB(O)c1ccsc1
Reactant: COC(=O)c1ccc2nc(-c3ccccc3)c(Br)nc2c1
Product: O=C(O)c1ccc2nc(-c3ccccc3)c(-c3ccsc3)nc2c1
Yield: 41.5 %

Procedure:
The product was obtained via a Suzuki coupling reaction using the method previously shown in Example 20, Step 3, using methyl 3-bromo-2-phenylquinoxaline-6-carboxylate (100 mg, 0.29 mmol, 1.00 equiv) and thiophen-3-ylboronic acid (55.7 mg, 0.44 mmol, 1.50 equiv) as reactants. Purification via silica gel column (dichloromethane/methanol (10:1)) afforded 40 mg (39%) of 2-phenyl-3-(thiophen-3-yl)quinoxaline-6-carboxylic acid as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].[OH:10][CH2:11][CH:12]([CH2:14]O)[OH:13].S(=O)(=O)(O)O.O>C1C=CC=CC=1>[OH:13][CH:12]1[CH2:11][O:10][CH:5]([C:4]2[CH:7]=[CH:8][CH:9]=[C:2]([F:1])[CH:3]=2)[O:6][CH2:14]1
Reactant: O=Cc1cccc(F)c1
Reactant: OCC(O)CO
Agent: O=S(=O)(O)O
Solvent: c1ccccc1
Solvent: O
Product: OC1COC(c2cccc(F)c2)OC1
Yield: 73.2 %

Procedure:
A mixture of 3-fluorobenzaldehyde (24.8 g, 0.2 mole), glycerol (18.4 g, 0.2 mole) and 40% sulfuric acid (2.0 ml) in benzene (200 ml) was heated with stirring under a Dean-Stark apparatus until water ceased to collect (approximately 2.5 hours). The mixture was cooled, neutralized with potassium carbonate and, after adding 200 ml of ether, washed with water (3 × 100 ml). The washed solution was dried over magnesium sulfate and concentrated under reduced pressure to give 29.0 g of colorless oil which was distilled under 0.025 mm using a short path distillation apparatus to give 18.9 g, nD24 1.5160, of 5-hydroxy-2-(3-fluorophenyl)-1,3-dioxane which distilled at a bath temperature of 86°-105° C.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH:8]2[CH2:10][CH2:9]2)=[CH:6][C:5]([NH:11][CH2:12][C:13]([O:15]CC)=[O:14])=[C:4]([OH:18])[CH:3]=1.O1CCCC1.O[Li].O.Cl>O>[Cl:1][C:2]1[C:7]([CH:8]2[CH2:10][CH2:9]2)=[CH:6][C:5]([NH:11][CH2:12][C:13]([OH:15])=[O:14])=[C:4]([OH:18])[CH:3]=1
Reactant: CCOC(=O)CNc1cc(C2CC2)c(Cl)cc1O
Agent: Cl
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)CNc1cc(C2CC2)c(Cl)cc1O
Temperature: 60 °C
Reaction time: 2 h
Yield: 46.5 %

Procedure:
To a solution of ethyl 2-(4-chloro-5-cyclopropyl-2-hydroxyphenylamino)acetate (290 mg, 0.89 mmol) in of 4:1 mixture of tetrahydrofuran and water (30 mL) at RT, LiOH.H2O (226 mg, 5.34 mmol) was added and the resulting mixture was stirred for 2 h at 60° C. The mixture was acidified with aqueous HCl (1N) to adjust the pH to 3-5 and then extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford the product (100 mg, 47% yield). 1H NMR (400 MHz, DMSO-d6) δ: 9.64 (s, 1H), 6.66 (s, 1H), 5.96 (s, 1H), 3.81 (s, 2H), 1.89-1.96 (m, 1H), 0.84-0.87 (m, 2H), 0.54-0.56 (m, 2H).
Reaction SMILES: [C:1]([N:8]1[C@@H:13]([CH3:14])[CH2:12][CH2:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].I([O-])(=O)(=O)=[O:16].[Na+]>C(OCC)(=O)C.O.O.[Ru](=O)=O>[C:1]([N:8]1[C@@H:13]([CH3:14])[CH2:12][CH2:11][CH2:10][C:9]1=[O:16])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: C[C@H]1CCCCN1C(=O)OC(C)(C)C
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: O=[Ru]=O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: C[C@H]1CCCC(=O)N1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 24 h
Yield: 58.6 %

Procedure:
Ruthenium(IV) oxide hydrate (0.8 g, 0.006 mol) then a solution of N-BOC-6(S)-methyl-piperidine (4.00 g, 0.020 mol) in ethyl acetate (240 ml) were added to a solution of sodium periodate (21.36 g, 0.100 mole) in water (200 ml) and strongly stirred for 24 hours at room temperature under argon atmosphere. After separation the aqueous phase was extracted with ethyl acetate (3×100 ml). The combined organic phases were dried with magnesium sulfate and then treated with activated carbon, giving a colorless solution that was evaporated on a rotavapor at 30° C. The residue (3.98 g) was purified by silicagel (125 g) column chromatography with cyclohexane-ethyl acetate (1-1, v/v), furnishing a product (2.50 g, 59% yield) which according to its 1H-NMR spectrum was pure enough for the next reaction step.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.CN(C)CCO[C:15]1[CH:20]=[C:19]([B:21]([OH:23])[OH:22])[CH:18]=[CH:17][N:16]=1>>[N:4]1([CH2:3][CH2:2][O:1][C:15]2[CH:20]=[C:19]([B:21]([OH:23])[OH:22])[CH:18]=[CH:17][N:16]=2)[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1
Reactant: OCCN1CCOCC1
Reactant: CN(C)CCOc1cc(B(O)O)ccn1
Product: OB(O)c1ccnc(OCCN2CCOCC2)c1

Procedure:
[2-(2-Morpholin-4-yl-ethoxy)-4-pyridinyl]-boronic acid is prepared from N-(2-hydroxyethyl)-morpholine according to the procedure described for the preparation of [2-(2-dimethylamino-ethoxy)-4-pyridinyl]-boronic acid. MS (m/z): 253 (M+1).
Reaction SMILES: Cl[CH:2]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)[C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:4]=1.[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([NH:33][CH2:34][CH2:35][C:36]([O:38]CC)=[O:37])=[O:32])=[CH:27][CH:26]=1>>[CH:18]1([CH:2]([NH:24][C:25]2[CH:26]=[CH:27][C:28]([C:31]([NH:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37])=[O:32])=[CH:29][CH:30]=2)[C:3]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:4]=2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: CCOC(=O)CCNC(=O)c1ccc(N)cc1
Reactant: ClC(c1nn(-c2ccccc2)c2ccccc12)C1CCCCC1
Product: O=C(O)CCNC(=O)c1ccc(NC(c2nn(-c3ccccc3)c3ccccc23)C2CCCCC2)cc1

Procedure:
Using 3-[chloro(cyclohexyl)methyl]-1-phenyl-1H-indazole (370 mg) synthesized above and ethyl 3-{[(4-aminophenyl)carbonyl]amino}propanoate (269 mg) synthesized in Example 1(2) and in the same manner as in Example A7(3), the title object compound (79.1 mg, 14%) was obtained as a pale-yellow solid.
Reaction SMILES: [CH2:1]([NH:8][C@@H:9]([C:12]([OH:14])=[O:13])[CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:22][C:23](Cl)=[O:24].[OH-].[Na+]>O.CCCCCCC.O1CCCC1>[CH2:1]([N:8]1[C:23](=[O:24])[CH2:22][O:11][CH2:10][C@@H:9]1[C:12]([OH:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)[C@@H](CO)NCc1ccccc1
Reactant: O=C(Cl)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCCCCCC
Product: O=C(O)[C@H]1COCC(=O)N1Cc1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 91.1 %

Procedure:
A 300 gallon hastelloy reactor was charged with N-benzyl-D-serine (50.0 kg) followed by the addition of tetrahydrofuran (THF, 271.2 kg). This solution was then cooled to 0° C. and a potassium carbonate (53.1 kg) solution in water (152.5 L) was added in one portion while maintain the temperature between −5° C. and 5° C. The temperature was adjusted back to 0° C. and then chloroacetyl chloride (40.2 kg) was added portion wise over 1 h while keeping the temperature below 4° C. The mixture was stirred for 30 min between 0-4° C. and another portion of chloroacetyl chloride (4.4 kg) was added in one portion. Stirring was continued for and additional 30 min at 0-4° C. A 50% aqueous sodium hydroxide (82.0 kg) solution was added over 50 min while keeping the reaction temperature below 10° C. A final pH endpoint of 13-13.5 should be obtained. After the addition is complete, the solution was cooled to 3-5° C. and stirred at this temperature for 4 h. After determining the reaction was complete (HPLC), it was warmed to 20-22° C. and heptane (75.0 kg) was added and vigorously stirred. The basic aqueous layer was collected, the heptane was removed, and the aqueous layer was placed back into the reactor. The basic aqueous solution was washed once again with heptane (107.8 kg) and placed back into the reactor where it was cooled to 3° C. and then adjusted down to <pH 2.0 by portion wise addition of 12N HCl (193.8 kg) over 1-1.5 h, while keeping the temperature <6° C. After the acid addition was complete, the white solid suspension was cooled to 3-5° C., stirred for an additional 2 h, and then filtered. The cake was then rinsed with cold (3-5° C.) water (50.0 L), pulled dry, and then placed under vacuum at 55-60° C. until the LOD is <0.6% giving the title compound (54.9 kg, 91.2% yield) as a white solid. 1H NMR (DMSO-d6) δ 7.37-7.24 (m, 5H), 5.25 (d, J=15.4 Hz, 1H), 4.17 (m, 2H), 4.12 (m 1H), 3.94 (dd, J=5.6, 3.2 Hz, 1H), 3.92 (dd, J=16.8, 3.2 Hz, 1H), 3.82 (d, J=15.4 Hz, 1H).
Reaction SMILES: [CH3:1][C:2]([CH3:12])=[CH:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[C:7]#[N:8]>CO.[Pd]>[CH2:3]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[C:7]#[N:8])[CH:2]([CH3:12])[CH3:1]
Reactant: CC(C)=Cc1cccc(C#N)c1
Agent: [Pd]
Solvent: CO
Product: CC(C)Cc1cccc(C#N)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 94 %

Procedure:
To a solution of 3-(2-methyl-1-propenyl)benzonitrile (5.80 g) in methanol (50 ml) was added 10% palladium on activated carbon (1 g), and the mixture was stirred under hydrogen atmosphere (3 atm) at 25° C. for 1 hour. The catalyst was filtered off and the filtrate was evaporated to give 3-isobutylbenzonitrile (5.52 g) as a pale yellow oil.
Reaction SMILES: [C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:20]=[CH:21][CH:22]=1)[C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[C:14]([OH:19])[CH:13]=1)=[O:10])([CH3:5])[CH3:4])#[N:2].F[C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>>[C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:20]=[CH:21][CH:22]=1)[C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[C:14]([O:19][C:24]2[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=2)[CH:13]=1)=[O:10])([CH3:4])[CH3:5])#[N:2]
Reactant: Cc1ccc(NC(=O)c2cccc(C(C)(C)C#N)c2)cc1O
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: Cc1ccc(NC(=O)c2cccc(C(C)(C)C#N)c2)cc1Oc1ccc([N+](=O)[O-])cc1

Procedure:
Using 3-(1-cyano-1-methylethyl)-N-(3-hydroxy-4-methylphenyl)benzamide (1.47 g, 5.0 mmol), 1-fluoro-4-nitrobenzene (0.77 g, 5.5 mmol) and potassium carbonate (0.69 g, 5.0 mmol), and in the same manner as in Example A25(iii), the title compound (2.08 g, quantitatively) was obtained as a yellow oil.
Reaction SMILES: [CH:1]1([N:7]2[CH2:13][C:12]([F:15])([F:14])[C:11](=[O:16])[N:10]([CH3:17])[C:9]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([OH:29])=O)=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:8]2=3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:58]1([N:63]2[CH2:68][CH2:67][N:66]([NH2:69])[CH2:65][CH2:64]2)[CH2:62][CH2:61][CH2:60][CH2:59]1>>[CH:1]1([N:7]2[CH2:13][C:12]([F:14])([F:15])[C:11](=[O:16])[N:10]([CH3:17])[C:9]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([NH:69][N:66]5[CH2:65][CH2:64][N:63]([CH:58]6[CH2:62][CH2:61][CH2:60][CH2:59]6)[CH2:68][CH2:67]5)=[O:29])=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:8]2=3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: COc1cc(C(=O)O)ccc1Nc1ncc2c(n1)N(C1CCCCC1)CC(F)(F)C(=O)N2C
Reactant: NN1CCN(C2CCCC2)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Product: COc1cc(C(=O)NN2CCN(C3CCCC3)CC2)ccc1Nc1ncc2c(n1)N(C1CCCCC1)CC(F)(F)C(=O)N2C

Procedure:
The title compound was synthesized from 4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 1-N-cyclopentyl piperazine-4-amine. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.11-1.92 (m, 18H) 2.93 (br. s., 4H) 3.31 (s, 3H) 3.93 (s, 3H) 4.06 (t, J=13.39 Hz, 2H) 4.44 (m, 1H) 7.41 (d, J=8.0 Hz, 1H) 7.43 (s, 1H) 7.90 (s, 1H) 8.21 (s, 1H) 8.27 (d, J=8.34 Hz, 1H) 9.37 (s, 1H). Melting point: 98-99° C. [M+H] calculated for C31H42F2N8O3, 613. found 613.
Reaction SMILES: [H-].[Na+].[CH:3]1([C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[C:14]([F:21])[CH:13]=2)=[O:10])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.[CH3:22]I>CN(C=O)C>[CH:3]1([C:9]([N:11]([C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[C:14]([F:21])[CH:13]=2)[CH3:22])=[O:10])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]1
Reactant: CI
Reactant: O=C(Nc1ccc([N+](=O)[O-])c(F)c1)C1CCCCC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN(C(=O)C1CCCCC1)c1ccc([N+](=O)[O-])c(F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 82.1 %

Procedure:
60% Sodium hydride powder (1.1 mmol, 0.045 g) was added in portions to a cooled solution of cyclohexyl-N-(3-fluoro-4-nitrophenyl)carboxamide (1 mmol, 0.266 g) and methyl iodide (1.2 mmol, 0.16 g) in DMF (5 mL). The reaction mixture was stirred overnight at room temperature. The solvent was removed under reduced pressure and the residue was dissolved in CH2Cl2 (50 mL) and washed with 10% NaHCO3, brine, H2O, dried over Na2SO4 and the solvent evaporated to afford 0.23 g of the title compound as a yellow oily residue (Yield: 82%).
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:12])=[C:4]([C:9](=[O:11])[CH3:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[Br:19][CH2:20][CH2:21]Br>CN(C)C=O.O>[Br:1][C:2]1[C:3]([O:12][CH2:21][CH2:20][Br:19])=[C:4]([C:9](=[O:11])[CH3:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CC(=O)c1cc(Cl)cc(Br)c1O
Reactant: BrCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(=O)c1cc(Cl)cc(Br)c1OCCBr
Temperature: 50 °C
Reaction time: 8 h
Yield: 123.4 %

Procedure:
A suspension of 3′-bromo-5′-chloro-2′-hydroxyacetophenone (2.4 g, 10 mmol), potassium carbonate (2.8 g, 20 mmol) and 1,2-dibromoethane (3.5 mL, 41 mmol) in anhydrous N,N-dimethylformamide (30 mL) was stirred at 50° C. overnight. After cooling, the reaction mixture was diluted with water (100 mL), and the whole was extracted with ethyl acetate (100 mL). The organic layer was washed with saturated aqueous ammonium chloride solution (50 mL, twice) and brine (50 mL) and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give the title reference compound (4.4 g) as orange oil (Quantitative).
Reaction SMILES: [CH2:1]([C:3]1[NH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:6]=2)[CH3:2].[C:16](Cl)(=[O:19])[CH2:17][CH3:18]>>[CH2:1]([C:3]1[NH:4][C:5]2[C:10]([C:11]=1[C:16](=[O:19])[CH2:17][CH3:18])=[CH:9][CH:8]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:6]=2)[CH3:2]
Reactant: CCc1cc2ccc(C(=O)OC)cc2[nH]1
Reactant: CCC(=O)Cl
Product: CCC(=O)c1c(CC)[nH]c2cc(C(=O)OC)ccc12

Procedure:
Methyl 2-ethyl-3-propionylindole-6-carboxylate (435 mg) was prepared from methyl 2-ethylindole-6-carboxylate (660 mg) and propionyl chloride (0.62 ml) in a similar manner to that of Preparation 1 (5).
Reaction SMILES: [C:1]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])(=[O:7])[CH2:2][CH2:3][C:4]([O-:6])=O.[ClH:13].Cl.[NH2:15][CH2:16][C:17]1[O:21][C:20]([C:22]([O:24][C:25]2[CH:34]=[CH:33][C:32]3[C:27](=[CH:28][CH:29]=[C:30]([C:35](=[NH:37])[NH2:36])[CH:31]=3)[CH:26]=2)=[O:23])=[CH:19][CH:18]=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[ClH:13].[C:9]([O:8][C:1]([CH2:2][CH2:3][C:4]([NH:15][CH2:16][C:17]1[O:21][C:20]([C:22]([O:24][C:25]2[CH:34]=[CH:33][C:32]3[C:27](=[CH:28][CH:29]=[C:30]([C:35](=[NH:36])[NH2:37])[CH:31]=3)[CH:26]=2)=[O:23])=[CH:19][CH:18]=1)=[O:6])=[O:7])([CH3:12])([CH3:11])[CH3:10]
Reactant: CC(C)(C)OC(=O)CCC(=O)[O-]
Reactant: N=C(N)c1ccc2cc(OC(=O)c3ccc(CN)o3)ccc2c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)CCC(=O)NCc1ccc(C(=O)Oc2ccc3cc(C(=N)N)ccc3c2)o1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 68 %

Procedure:
To 11.4 g of mono-t-butyl succinate, 23.5 g of 6-amidino-2-naphthyl 5-aminomethylfuran-2-carboxylate dihydrochloride and 0.66 g of DMAP was added 115 ml of pyridine, and the mixture was stirred with ice-cooling. After 10 minutes, 25.6 g of DCC was added and the mixture was stirred for 3 hours while cooling with ice and for 16 hours at room temperature. The precipitated crystals were filtered off, and the filtrate was added in small portions into 2 l of ether and stirred at room temperature for 3 l hours. After removing the supernatant by decantation, 1 l of acetone was added to the residue and stirred for 1 hour. The precipitate was collected by filtration, then dissolved in 60 ml of methanol and 3 g of active carbon was added to the solution. The mixture was stirred for 30 minutes while cooling with ice, then the insolubles were filtered off and the filtrate was added into 1.5 l of acetone. The mixture was stirred for 5 hours while cooling with ice, and the precipitated crystals were collected by filtration to obtain 21 g of the intended product.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]([CH3:15])[CH2:10][C:11](=[O:14])[NH:12][N:13]=2)=[CH:4][CH:3]=1.[C:16]1(=O)[CH2:20][CH2:19][C:18](=[O:21])[CH2:17]1>C(O)C.C(O)(=O)C>[O:21]=[C:18]1[CH2:19][CH2:20][C:16]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[CH:9]([CH3:15])[CH2:10][C:11](=[O:14])[NH:12][N:13]=3)=[CH:4][CH:3]=2)=[CH:17]1
Reactant: O=C1CCC(=O)C1
Reactant: CC1CC(=O)NN=C1c1ccc(N)cc1
Solvent: CCO
Solvent: CC(=O)O
Product: CC1CC(=O)NN=C1c1ccc(NC2=CC(=O)CC2)cc1
Yield: 33.8 %

Procedure:
0.51 g of 4,5-dihydro-6-(4-aminophenyl)-5-methyl-3(2H)-pyridazinone and 0.25 g of cyclopentane-1,3-dione were suspended in a mixture of 5 ml of ethanol and 5 ml of acetic acid and the resulting suspension was refluxed for 7 hours. After cooled, deposited crude crystal was collected by filtrating and recrystallized from DMF-heptane-CHCl3 to give 0.24 g of the title compound. m.p. >300° C. NMR (solvent DMSO-d6 -CDCl3) δ 1.20 (d, 3H), 2.32-3.32 (m, 7H), 5.60 (S, 1H), 7.56 (dd, 4H), 9.82 (S, 1H), 10.80 (S, 1H).
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:23]=[CH:22][C:21]3[C:17](=[C:18]([CH3:25])[N:19]([CH3:24])[N:20]=3)[CH:16]=2)[C:11](=[O:26])[CH:10]=1)C1C=CC=CC=1>C(O)C.[C].[Pd]>[CH3:24][N:19]1[C:18]([CH3:25])=[C:17]2[C:21]([CH:22]=[CH:23][C:15]([N:12]3[CH:13]=[CH:14][C:9]([OH:8])=[CH:10][C:11]3=[O:26])=[CH:16]2)=[N:20]1
Reactant: Cc1c2cc(-n3ccc(OCc4ccccc4)cc3=O)ccc2nn1C
Agent: [Pd]
Solvent: CCO
Product: Cc1c2cc(-n3ccc(O)cc3=O)ccc2nn1C
Temperature: 25 °C
Reaction time: 3 h
Yield: 78.2 %

Procedure:
To a solution of 4-(benzyloxy)-1-(2,3-dimethyl-2H-indazol-5-yl)pyridin-2(1H)-one (1.8 g) in ethanol (40 ml) was added 10% palladium carbon (0.56 g), and the mixture was stirred under a hydrogen atmosphere at room temperature for 3 hr. The insoluble material was filtered off, and the obtained filtrate was concentrated under reduced pressure to give the title compound (1.04 g).
Reaction SMILES: [CH2:1]1[O:14][C:13]2[CH:12]=[CH:11][C:5]([CH:6]=[CH:7][N+:8]([O-:10])=[O:9])=[CH:4][C:3]=2[O:2]1.[CH3:15][N:16]([CH3:20])[C:17](=[S:19])[S-:18].C[NH2+]C>C(=S)=S>[CH3:15][N:16]([CH3:20])[C:17](=[S:18])[S:19][CH:6]([CH2:7][N+:8]([O-:10])=[O:9])[C:5]1[CH:11]=[CH:12][C:13]2[O:14][CH2:1][O:2][C:3]=2[CH:4]=1
Reactant: CN(C)C(=S)[S-]
Reactant: O=[N+]([O-])C=Cc1ccc2c(c1)OCO2
Agent: C[NH2+]C
Solvent: S=C=S
Product: CN(C)C(=S)SC(C[N+](=O)[O-])c1ccc2c(c1)OCO2

Procedure:
As in Example 17, reaction of 3,4-(methylenedioxy)-β-nitrostyrene with dimethylammonium dimethyldithiocarbamate in the presence of carbon disulfide gave 3,4-(methylenedioxy)-α-(nitromethyl)benzyl dimethyldithiocarbamate melting at 122° C.- 124° C. when recrystallized without heating from acetone-ethanol solution.
Reaction SMILES: FC(F)(F)C(O)=O.C(OC([N:15]([C:20]1[CH:32]=[CH:31][C:23]([CH:24]=[CH:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:22][CH:21]=1)[CH2:16][CH2:17][O:18][CH3:19])=O)(C)(C)C>>[CH3:19][O:18][CH2:17][CH2:16][NH:15][C:20]1[CH:32]=[CH:31][C:23]([CH:24]=[CH:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:22][CH:21]=1
Reactant: CCOC(=O)C=Cc1ccc(N(CCOC)C(=O)OC(C)(C)C)cc1
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)C=Cc1ccc(NCCOC)cc1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 70.7 %

Procedure:
Trifluoroacetic acid (3 ml) was added to ethyl 4-[N-tert-butoxycarbonyl-N-(2-methoxyethyl)amino]cinnamate (932 mg) in ice water bath and stirred for 15 minutes at same temperature. The solvent was evaporated under reduced pressure. The residue was partitioned between ethyl acetate and aqueous sodium bicarbonate solution. The organic layer was washed with water and brine, dried over magnesium sulfate and evaporated in vacua. The residue was chromatographed on silica gel eluting to a mixture of n-hexane and ethyl acetate (3:1) and recrystallized from a mixture of n-hexane and ethyl acetate to give ethyl 4-(2-methoxyethylamino)cinnamate (470 mg) as crystals.
Reaction SMILES: [NH2:1][CH:2]1[CH2:6][N:5]([CH3:7])[N:4]([CH3:8])[CH2:3]1.[CH3:9][O:10][C:11]1[CH:12]=[C:13]([CH:17]=[C:18]([O:22][CH3:23])[C:19]=1[O:20][CH3:21])[C:14](Cl)=[O:15]>>[CH3:23][O:22][C:18]1[CH:17]=[C:13]([CH:12]=[C:11]([O:10][CH3:9])[C:19]=1[O:20][CH3:21])[C:14]([NH:1][CH:2]1[CH2:6][N:5]([CH3:7])[N:4]([CH3:8])[CH2:3]1)=[O:15]
Reactant: COc1cc(C(=O)Cl)cc(OC)c1OC
Reactant: CN1CC(N)CN1C
Product: COc1cc(C(=O)NC2CN(C)N(C)C2)cc(OC)c1OC

Procedure:
The title compound was prepared as described in Example 3 of U.S. Pat. No. 4,207,327 from 4-amino-1,2-dimethylpyrazolidine and 3,4,5-trimethoxybenzoyl chloride, m.p. 163°-166° C.
Reaction SMILES: [Cl:1]Cl.[NH2:3][C:4]1[CH:5]=[CH:6][C:7]2[N:13]([CH3:14])[C:12](=[O:15])[C:11]([CH3:17])([CH3:16])[N:10]=[C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])[C:8]=2[CH:25]=1>Cl>[NH2:3][C:4]1[CH:5]=[CH:6][C:7]2[N:13]([CH3:14])[C:12](=[O:15])[C:11]([CH3:17])([CH3:16])[N:10]=[C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])[C:8]=2[C:25]=1[Cl:1]
Reactant: ClCl
Reactant: CN1C(=O)C(C)(C)N=C(c2ccccc2F)c2cc(N)ccc21
Agent: Cl
Product: CN1C(=O)C(C)(C)N=C(c2ccccc2F)c2c1ccc(N)c2Cl

Procedure:
Chlorine gas is conducted slowly at between -5° and 0° through a solution of 6 g (0.019 mol) of 7-amino-5-(o-fluorophenyl)-1,3-dihydro-1,3,3-trimethyl-2H-1,4-benzodiazepin-2-one in 70 ml of concentrated hydrochloric acid until the starting material has almost completely been consumed. The reaction mixture is poured into a mixture of ice and soda solution, whereupon it is extracted with methylene chloride and the extract is dried and evaporated. The residue is chromatographed on 300 g of silica gel with methylene chloride/ethyl acetate (10:1) as the elution agent. From ether-petroleum ether there is obtained 7-amino-6-chloro-5-(o-fluorophenyl)-1,3-dihydro-1,3,3-trimethyl-2H-1,4-benzodiazepin-2-one of melting point 192°-193°.