Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][C:3]([N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[C:9](=[O:16])[NH:8][C:7]2[CH:17]=[CH:18][CH:19]=[CH:20][C:6]1=2)=[O:4].[CH3:21][N:22]1[CH2:27][CH2:26][N:25]([CH2:28][C@@H:29]2[CH2:33][CH2:32][CH2:31][NH:30]2)[CH2:24][CH2:23]1.C(OCC)(=O)C.N>ClCCl.CO.C1CCCCC1.C(O)C>[CH3:21][N:22]1[CH2:23][CH2:24][N:25]([CH2:28][C@@H:29]2[CH2:33][CH2:32][CH2:31][N:30]2[CH2:2][C:3]([N:5]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[C:9](=[O:16])[NH:8][C:7]3[CH:17]=[CH:18][CH:19]=[CH:20][C:6]2=3)=[O:4])[CH2:26][CH2:27]1
Reactant: O=C1Nc2ccccc2N(C(=O)CCl)c2ccccc21
Reactant: CN1CCN(C[C@@H]2CCCN2)CC1
Agent: N
Solvent: CO
Solvent: C1CCCCC1
Solvent: ClCCl
Product: CN1CCN(C[C@@H]2CCCN2CC(=O)N2c3ccccc3NC(=O)c3ccccc32)CC1

Procedure:
The title compound is prepared analogously to Example 31 from 5-(chloroacetyl)-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one and (S)-(+)-2-[(4-methyl-1-piperazinyl)methyl]pyrrolidine to give colorless crystals, mp. 168°-170° C. (ethyl acetate). [α]D20 =-18.9° C. (ethanol). RF 0.33 (Merck ready-made TLC plates, silica gel 60 F-254; eluant: dichloromethane/methanol/cyclohexane/conc. ammonia [120:24:30:2]). A second isomer (RF 0.30) can be detected in the mother liquors by thin layer chromatography.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]=[C:10]([NH2:12])[NH:9][N:8]=1.[C:13]([N:16]1[C:24]2[C:19](=[CH:20][C:21]([C:25](=O)[CH2:26][C:27](OCC)=[O:28])=[CH:22][CH:23]=2)[CH:18]=[N:17]1)(=[O:15])[CH3:14].CC1C=CC(S(O)(=O)=O)=CC=1>C1(OC2C=CC=CC=2)C=CC=CC=1.CCCCCC>[C:13]([N:16]1[C:24]2[C:19](=[CH:20][C:21]([C:25]3[NH:12][C:10]4[N:9]([N:8]=[C:7]([C:2]5[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=5)[N:11]=4)[C:27](=[O:28])[CH:26]=3)=[CH:22][CH:23]=2)[CH:18]=[N:17]1)(=[O:15])[CH3:14]
Reactant: CCOC(=O)CC(=O)c1ccc2c(cnn2C(C)=O)c1
Reactant: Nc1nc(-c2ccccn2)n[nH]1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCCCCC
Solvent: c1ccc(Oc2ccccc2)cc1
Product: CC(=O)n1ncc2cc(-c3cc(=O)n4nc(-c5ccccn5)nc4[nH]3)ccc21
Temperature: 170 °C
Reaction time: 1 h

Procedure:
To a solution of 3-(pyridin-2-yl)-1H-1,2,4-triazol-5-amine (150 mg, 0.93 mmol) in diphenyl ether (3 mL) was added ethyl 3-(1-acetyl-1H-indazol-5-yl)-3-oxopropanoate (510 mg, 1.86 mmol) and TsOH (8 mg, 0.05 mmol), and the mixture was stirred for 1 h at 170° C. The resulting solution was diluted with n-hexane (8 ml), and the product was collected by filtration and washed with methanol (2 ml) to afford 5-(1-acetyl-1H-indazol-5-yl)-2-(pyridin-2-yl)-4H,7H-[1,2,4]triazolo[1,5-α]pyrimidin-7-one as a brown crude solid (120 mg, crude).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:6]=2[N:7]=1.[NH2:22][C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[C:26]([NH2:28])=[O:27].C(N(CC)CC)C>O1CCOCC1>[Cl:1][C:2]1[N:3]=[C:4]([NH:22][C:23]2[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=2)[C:26]([NH2:28])=[O:27])[C:5]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:6]=2[N:7]=1
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c(Cl)nc(Cl)nc32)cc1
Reactant: NC(=O)c1cccc(N)c1
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: Cc1ccc(S(=O)(=O)n2ccc3c(Nc4cccc(C(N)=O)c4)nc(Cl)nc32)cc1
Yield: 33.2 %

Procedure:
A solution of 2,4-dichloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine (200 mg, 0.580 mmol), 3-aminobenzamide (83 mg, 0.61 mmol) and triethylamine (0.200 mL, 1.44 mmol) in dioxane (5 mL) was stirred at 110° C. for 20 h. It was concentrated in vacuo. After the residue was acidified with HOAc (1 mL), it was purified by HPLC to give 3-(2-chloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)benzamide (85 mg).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.C(Cl)Cl.N1C=CC=CC=1.Cl[C:20]([O:22][CH:23]([CH3:25])[CH3:24])=[O:21]>C1(C)C=CC=CC=1.CC(OC)(C)C.O>[C:20](=[O:21])([O:22][CH:23]([CH3:25])[CH3:24])[O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1
Reactant: CC(C)OC(=O)Cl
Reactant: O=Cc1ccc(O)cc1
Solvent: ClCCl
Solvent: O
Solvent: Cc1ccccc1
Product: CC(C)OC(=O)Oc1ccc(C=O)cc1
Yield: 100 %

Procedure:
To a 250 mL dry round bottom flask were added 4-hydroxybenzaldehyde (4.88 g, 40.0 mmol), anhydrous CH2Cl2 (40 mL) and pyridine (4.2 mL, 52.0 mmol). The mixture was stirred in an ice-water bath, then a solution of isopropyl chloroformate in toluene (1.0 M, 48.0 mL) was added. After stirring at 0° C. for 2 hours, water (100 mL) and MTBE (300 mL) were added to the reaction mixture. The aqueous layer was separated, and the MTBE layer was washed, respectively, with cold water (80 mL), cold 5% NaOH aqueous solution (80 mL), cold water (80 mL), cold 0.5 N HCl aqueous solution (80 mL) and cold water (80 mL). The organic layer was dried over Na2SO4, and the solvent was evaporated to give 4-formylphenyl isopropyl carbonate (8.50 g) as pale yellow oil. Yield: 100%. 1H NMR (CDCl3, 300 MHz): δ=9.71 (s, 1H), 7.64 (d, J=8.4 Hz, 2H), 7.10 (d, J=8.7 Hz, 2H), 4.73 (seventet, J=6.0 Hz, 1H), 1.12 (d, J=6.3 Hz, 6H).
Reaction SMILES: Br[CH2:2][C:3]1[CH:10]=[C:9]([C:11]2([O:29][C@H:28]([CH2:30][O:31]C(=O)C)[C@@H:23]([O:24]C(=O)C)[C@H:18]([O:19]C(=O)C)[C@H:13]2[O:14]C(=O)C)[OH:12])[CH:8]=[CH:7][C:4]=1[C:5]#[N:6].[F:35][C:36]([F:48])([F:47])[O:37][C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1.C(=O)([O-])[O-].[K+].[K+].CC(C)=O>[Cl-].[Na+].O.[Pd](Cl)Cl.O>[OH:12][C@:11]1([C:9]2[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[C:3]([CH2:2][C:41]3[CH:40]=[CH:39][C:38]([O:37][C:36]([F:35])([F:47])[F:48])=[CH:43][CH:42]=3)[CH:10]=2)[O:29][C@H:28]([CH2:30][OH:31])[C@@H:23]([OH:24])[C@H:18]([OH:19])[C@H:13]1[OH:14]
Reactant: OB(O)c1ccc(OC(F)(F)F)cc1
Reactant: CC(=O)OC[C@H]1OC(O)(c2ccc(C#N)c(CBr)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: Cl[Pd]Cl
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: O
Solvent: CC(C)=O
Product: N#Cc1ccc([C@@]2(O)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)cc1Cc1ccc(OC(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
An Ar filled flask is charged with 2-bromomethyl-4-(2,3,4,6-tetra-O-acetyl-D-glucopyranos-1-yl)-benzonitrile (0.25 g), 4-trifluoromethoxy-phenylboronic acid (0.20 g), potassium carbonate (0.26) and a 3:1 mixture of degassed acetone and water (4 mL). The mixture is stirred at room temperature for 5 min, before it is cooled in an ice-bath. Then palladium dichloride (5 mg) is added and the reaction mixture is stirred for 16 h at ambient temperature. The mixture is then diluted with brine and extracted with ethyl acetate. The combined extracts are dried over sodium sulfate and the solvent is removed under reduced pressure. The residue is dissolved in methanol (9 mL) and treated with 4 M aqueous potassium hydroxide solution (1 mL). The resulting solution is stirred at ambient temperature for 1 h and then neutralized with 1 M hydrochloric acid. The methanol is evaporated, and the residue is diluted with brine and extracted with ethyl acetate. The organic extracts collected are dried over sodium sulfate, and the solvent is removed. The residue is chromatographed on silica gel (dichloromethane/methanol 1:0->8:1).
Reaction SMILES: O.C([O:4][C:5](=O)[CH:6]([O:8][C:9]1[C:18]([N+:19]([O-])=O)=[CH:17][C:16]2[CH2:15][CH2:14][CH2:13][CH2:12][C:11]=2[CH:10]=1)[CH3:7])C>C(O)(=O)C.[Fe]>[CH3:7][CH:6]1[O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:18]=2[NH:19][C:5]1=[O:4])[CH2:15][CH2:14][CH2:13][CH2:12]3
Reactant: CCOC(=O)C(C)Oc1cc2c(cc1[N+](=O)[O-])CCCC2
Agent: [Fe]
Solvent: CC(=O)O
Solvent: O
Product: CC1Oc2cc3c(cc2NC1=O)CCCC3
Yield: 81 %

Procedure:
In a mixture of 10 ml of glacial acetic acid with 1.25 ml of water, 2-(5,6,7,8-tetrahydro-3-nitro-2-naphthoxy)-propionic acid ethyl ester is dissolved and mixed in portions with 960 mg of iron powder. It is heated, cooled and poured onto water. The crystals are suctioned off and washed with water, dissolved again with ethyl acetate and washed with soda solution, the organic phase is washed with brine, dried with magnesium sulfate and concentrated by evaporation. 740 mg, yield 81%, results.
Reaction SMILES: [C:1]([Cl:6])(=O)[C:2](Cl)=O.CN(C)C=O.[C:12]1([N:18]2[C:25]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=CC(=O)[NH:21][C:19]2=[O:20])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>ClCCl>[Cl:6][C:1]1[CH:2]=[C:25]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:19](=[O:20])[N:21]=1
Reactant: O=c1cc(-c2ccccc2)n(-c2ccccc2)c(=O)[nH]1
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=c1nc(Cl)cc(-c2ccccc2)n1-c1ccccc1
Yield: 34.9 %

Procedure:
Oxalyl chloride (3.1 g, 24.4 mmol) was added to a mixture of N,N-dimethylformamide (1.8 g, 24.6 mmol) in dichloromethane (30 ml) at −5° C. to 0° C. under stirring. After the completion of addition the reaction temperature was allowed to reach 20° C. to 25° C. 1,6-Diphenyluracil (4.0 g, 15.2 mmol) was added in portions to the resulted suspension for 2.5 hrs. The reaction mixture was heated to reflux for 4 hours under stirring and continued stirring for 12 hours at room temperature. The reaction mass was poured onto sodium hydroxide solution (150 ml, 0.25 N) and collected the dichloromethane layer. The dichloromethane layer was washed with hydrochloric acid (200 ml, 0.025N), water and saturated sodium chloride solution successively. The organic extract was dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the title compound (1.5 g, 35%, HPLC purity 99.8%), mp: 141-143° C.
Reaction SMILES: Cl[C:2]1[C:11]([C:12]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=[O:13])=[C:10]([CH3:23])[C:9]2[C:4](=[CH:5][C:6]([C:24]([F:27])([F:26])[F:25])=[CH:7][CH:8]=2)[N:3]=1.Cl.[CH2:29]([NH2:31])[CH3:30].CCN(C(C)C)C(C)C.[OH-].[Na+]>CCOC(C)=O.CC#N>[CH2:29]([NH:31][C:2]1[C:11]([C:12]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=[O:13])=[C:10]([CH3:23])[C:9]2[C:4](=[CH:5][C:6]([C:24]([F:27])([F:26])[F:25])=[CH:7][CH:8]=2)[N:3]=1)[CH3:30]
Reactant: CCN
Reactant: Cc1c(C(=O)NCc2cccc(F)c2)c(Cl)nc2cc(C(F)(F)F)ccc12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CCNc1nc2cc(C(F)(F)F)ccc2c(C)c1C(=O)NCc1cccc(F)c1
Temperature: 180 °C
Yield: 83.3 %

Procedure:
A mixture of 238 mg (0.6 mmol) 2-chloro-N-(3-fluorobenzyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid amide, 146 mg (1.8 mmol) ethylamine hydrochloride, 469 μl (2.7 mmol) DIPEA and MeCN (1,6 ml) was heated in a sealed vessel with microwave radiation to 180° C. for 2 h. After cooling to RT, dilution was carried out with EtOAc (30 ml) and a 2M aq. NaOH sol. (5 ml). The organic phase was then separated, washed with water and brine, dried over MgSO4 and concentrated in a vacuum. After column chromatographic separation (silica gel, EtOAc/hexane 3:7) of the residue, 188 mg (0.5 mmol, 77%) 2-ethylamino-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid amide (example 1) was obtained. MS: m/z 406.1 [M+H]+.
Reaction SMILES: Cl.[CH:2]1([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH:16][C:17]2[CH:25]=[CH:24][C:20]([C:21](Cl)=[O:22])=[CH:19][CH:18]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.O1CCOCC1.[NH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35].CN(C1C=CC=CN=1)C>C(N(CC)CC)C.C(Cl)Cl>[CH:2]1([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH:16][C:17]2[CH:25]=[CH:24][C:20]([C:21](=[O:22])[NH:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])=[CH:19][CH:18]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: O=C(Cl)c1ccc(NCCCCCCCCC2CCCCC2)cc1
Reactant: CCOC(=O)CN
Agent: CN(C)c1ccccn1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: CCOC(=O)CNC(=O)c1ccc(NCCCCCCCCC2CCCCC2)cc1
Temperature: 25 °C

Procedure:
A solution of 18.0 g. of 4-(8-cyclohexyloctylamino)benzoyl chloride hydrochloride in 100 ml. of dioxane is added to freshly prepared ethyl glycinate in 300 ml. of CH2Cl2 containing 1 g. of dimethylaminopyridine and 10 ml. of triethylamine. After 16 hours at room temperature the reaction mixture was refluxed for 2 hours, cooled and filtered. The mother liquor is extracted with water and 10% hydrochloric acid. The solution is dried over magnesium sulfate and concentrated in vacuo to an amber liquid. A 6 g. sample is pre-absorbed on 30 g. of silica III and placed on 250 ml. of alumina and eluted with ether giving 4.2 g. of solid. Thin-layer chromatography (hexane:ethylacetate, 3:1) indicates three components so this material (3 g.) is chromatographed on silica giving a solid which is recrystallized from acetonitrile to yield the product.
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:9]2[NH:8][C:7]3[CH2:12][C@@H:13]([NH:15][C:16](=[O:21])[O:17][CH:18]([CH3:20])[CH3:19])[CH2:14][C:6]=3[C:5]=2[CH:4]=1)#[N:2].[Cl:22][C:23]1[CH:28]=[CH:27][N:26]=[C:25]([CH2:29]Cl)[C:24]=1[O:31][CH3:32].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O>[CH:18]([O:17][C:16](=[O:21])[NH:15][C@@H:13]1[CH2:12][C:7]2[N:8]([CH2:29][C:25]3[C:24]([O:31][CH3:32])=[C:23]([Cl:22])[CH:28]=[CH:27][N:26]=3)[C:9]3[CH:10]=[CH:11][C:3]([C:1]#[N:2])=[CH:4][C:5]=3[C:6]=2[CH2:14]1)([CH3:19])[CH3:20]
Reactant: CC(C)OC(=O)N[C@@H]1Cc2[nH]c3ccc(C#N)cc3c2C1
Reactant: COc1c(Cl)ccnc1CCl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1c(Cl)ccnc1Cn1c2c(c3cc(C#N)ccc31)C[C@H](NC(=O)OC(C)C)C2
Temperature: 25 °C
Reaction time: 8 h
Yield: 92.1 %

Procedure:
To a solution of (S)-isopropyl 7-cyano-1,2,3,4-tetrahydrocyclopenta[b]indol-2-ylcarbamate (680 mg, 2.40 mmol) and 4-chloro-2-(chloromethyl)-3-methoxypyridine (553 mg, 2.88 mmol) in dimethylformamide (5 mL) is added cesium carbonate (1.17 g, 3.60 mmol) and the mixture stirred at room temperature overnight. The reaction mixture is diluted with water and the beige solid is filtered. It is rinsed with water and then dried in a vacuum oven at 50° C. for 48 h to obtain a gray solid (970 mg, 92%). LC-ES/MS m/z 439.0 [M+H]+.
Reaction SMILES: [F:1][C@:2]12[C@@H:22]([OH:23])[CH2:21][C@@:20]3([CH3:24])[C@@H:12]([CH2:13][CH:14]=[C:15]3[C:16](=[O:19])[CH2:17]I)[C@@H:11]1[CH2:10][CH2:9][C:8]1[C@:3]2([CH3:26])[CH:4]=[CH:5][C:6](=[O:25])[CH:7]=1.S(=O)(O)[O-].[Na+].O>O1CCOCC1>[F:1][C@:2]12[C@@H:22]([OH:23])[CH2:21][C@@:20]3([CH3:24])[C@@H:12]([CH2:13][CH:14]=[C:15]3[C:16](=[O:19])[CH3:17])[C@@H:11]1[CH2:10][CH2:9][C:8]1[C@:3]2([CH3:26])[CH:4]=[CH:5][C:6](=[O:25])[CH:7]=1
Reactant: C[C@]12C=CC(=O)C=C1CC[C@H]1[C@@H]3CC=C(C(=O)CI)[C@@]3(C)C[C@H](O)[C@@]12F
Agent: O=S([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: CC(=O)C1=CC[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]12C
Reaction time: 0.5 h
Yield: 59.2 %

Procedure:
A solution of 1.8 g of 9-fluoro-21-iodo-11β-hydroxypregna-1,4,16-triene-3,20-dione in 135 ml of dioxane is stirred with 90 ml of 5% sodium bisulfite at 105°C under nitrogen for 1.5 hours. The solution is cooled, poured into water, stirred for 30 minutes and filtered. The solid is washed with water and dried in a vacuum oven at 60°C over phosphorous pentoxide to give 780 mg of material. Crystallization from chloroform-methanol gives 420 mg of the title compound, melting point 327°-328°C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[C:5]1[CH:26]=[CH:25][C:24]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])=[CH:23][C:6]=1[CH:7]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH:21]=O)[CH:14]=1)[O:8]2.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:38][CH2:39][O:40][C:41]([CH3:43])=[O:42]>C1(C)C=CC=CC=1.[Cl-].[Na+].O>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[C:5]1[CH:26]=[CH:25][C:24]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])=[CH:23][C:6]=1[CH:7]([C:13]1[CH:14]=[C:15]([CH:16]=[CH:17][CH:18]=1)[O:19][CH2:20]/[CH:21]=[CH:43]/[C:41]([O:40][CH2:39][CH3:38])=[O:42])[O:8]2
Reactant: COc1cccc2c1-c1ccc(NS(C)(=O)=O)cc1C(c1cccc(OCC=O)c1)O2
Reactant: CCOC(C)=O
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [Cs+]
Solvent: Cc1ccccc1
Solvent: O
Product: CCOC(=O)/C=C/COc1cccc(C2Oc3cccc(OC)c3-c3ccc(NS(C)(=O)=O)cc32)c1

Procedure:
A solution of Example 94A (0.040 g, 0.089 mmol), triethylphosphono-acetate (0.030 g., 0.130 mmol) and cesium carbonate (0.109 g, 0.336 mmol) in toluene (1 mL) was stirred at 80° C. for 16 hours and then diluted with EtOAc (10 mL) and brine (25 mL). The layers were separated and the organic layer was dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by HPLC using aqueous 0.1% TFA and CH3CN to provide the titled compound (1H NMR (300 MHz, DMSO-d6) δ 9.85 (s, 1H), 8.33 (d, J=9.1 Hz, 1H), 7.26-7.22 (m, 2H), 7.13 (t, J=8 Hz, 1H), 6.92-6.80 (m, 4H), 6.73 (d, J=8 Hz, 1H), 6.65 (d, J=9 Hz, 1H), 6.19 (s, 1H), 6.08-6.02 (m, 2H), 4.75-4.73 (m, 2H), 4.13 (q, J=7 Hz, 2H), 3.88 (s, 3H), 3.00 (s, 3H), 1.22 (t, J=7 Hz, 3H); MS (ESI, −Q1MS) m/e 508 (M−H).
Reaction SMILES: C([O:3][C:4]([CH:6]1[CH2:9][CH2:8][N:7]1[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:5])C.COC(C)(C)C>O>[CH2:10]([N:7]1[CH2:8][CH2:9][CH:6]1[C:4]([OH:5])=[O:3])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CCOC(=O)C1CCN1Cc1ccccc1
Solvent: O
Solvent: COC(C)(C)C
Product: O=C(O)C1CCN1Cc1ccccc1
Temperature: 40 °C
Reaction time: 7 h

Procedure:
10.0 g of N-Benzylazetidine-2-carboxylic acid ethyl ester, 29.6 g of t-butyl methyl ether and 26.7 g of water are mixed at 20 to 25° C. and then 0.333 g of Enzyme (Chirazyme L-2) was added thereto and the resulting solution was heated to 40° C. and stirred for 7 hours. Settled solution was separated into an aqueous phase and an organic phase. The aqueous phase was washed twice with t-butyl methyl ether to yield an aqueous solution of optically active N-benzylazetidine-2-carboxylic acid and a combined organic phase of N-benzylazetidine-2-carboxylic acid ethyl ester. Results of the same analysis as in the Example 1 is shown in Table 8.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([OH:7])[CH2:2]1.C(N(CC)CC)C.[CH3:15][S:16](Cl)(=[O:18])=[O:17]>C1COCC1.C(Cl)Cl.C(OCC)(=O)C>[CH3:15][S:16]([N:1]1[CH2:6][CH2:5][CH2:4][CH:3]([OH:7])[CH2:2]1)(=[O:18])=[O:17]
Reactant: OC1CCCNC1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: ClCCl
Product: CS(=O)(=O)N1CCCC(O)C1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
Piperidin-3-ol (5.0 g, 49.4 mmol) was dissolved in 1/1 THF/methylene chloride (100 mL). Triethylamine (17 mL, 123 mmol) was added, and the solution was cooled to 0° C. Methanesulfonyl chloride (4.0 mL, 52 mmol) was added dropwise. The mixture was warmed to r.t. and stirred overnight. The reaction was diluted with ethyl acetate (800 mL), washed with 1 N HCl (100 mL), water (75 mL), saturated aqueous sodium bicarbonate (75 mL) and brine (75 mL), and then dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure and purified via silica gel chromatography (ethyl acetate) to afford the title compound as a clear oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[S:14][C:15]([C:19]([O:21]CC)=O)=[C:16]([CH3:18])[N:17]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].O.[NH2:25][NH2:26]>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[S:14][C:15]([C:19]([NH:25][NH2:26])=[O:21])=[C:16]([CH3:18])[N:17]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10]
Reactant: NN
Reactant: CCOC(=O)c1sc(-c2cc(OC)c(OC)c(OC)c2)nc1C
Solvent: O
Solvent: CCO
Product: COc1cc(-c2nc(C)c(C(=O)NN)s2)cc(OC)c1OC
Yield: 59 %

Procedure:
Ethyl 2-(3,4,5-trimethoxyphenyl)-4-methylthiazole-5-carboxylate prepared in Example 4 (6.2 g corresponding to its 0.02 mol), 6.1 g (0.1 mol) of hydrazine hydrate of purity of 82% and 150 ml of ethanol were heated for 6 hours at a temperature of 90° C. The crystals, which separated out after cooling the reaction mixture, were recrystallized from 95% aqueous ethanolic solution to obtain the object consisting of faintly yellow scale-like crystals, amounting to 3.8 g and melting at 179.5° to 181° C. at a yield of 59%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([OH:16])=O)=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18].[NH2:21][CH2:22][CH:23]([OH:31])[CH2:24][N:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>>[Cl:20][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Cl:1])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([NH:21][CH2:22][CH:23]([OH:31])[CH2:24][N:25]2[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]2)=[O:16])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18]
Reactant: NCC(O)CN1CCCCC1
Reactant: O=C(O)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1
Product: O=C(NCC(O)CN1CCCCC1)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1

Procedure:
Prepared according to the procedure described for example 70 from 5-((3,5-dichloropyridin-4-yl)thio)-4-nitrothiophene-2-carboxylic acid (500 mg, 1.4 mmol) and 1-amino-3-(piperidin-1-yl)propan-2-ol (270 mg, 1.7 mmol) from the above. The title compound was obtained as a solid (125.0 mg, 18% yield). 1H NMR (400 MHz, d6-DMSO) δ: 9.10 (1H, m), 9.00 (2H, m), 8.47 (1H, s), 5.82 (1H, m), 4.03 (1H, m), 3.23 (2H, m), 3.14 (1H, m), 2.92 (2H, m), 2.85 (1H, m), 1.80 (2H, m), 1.67 (2H, m), 1.35 (1H, m). MS m/z: 491.15, 493.16 [M+H]+.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]#[N:16])=[CH:10][CH:9]=2)=[O:5])[CH3:2]>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([CH2:15][NH2:16])=[CH:10][CH:9]=2)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cc2cc(C#N)ccc2[nH]1
Solvent: ClCCl
Product: CCOC(=O)c1cc2cc(CN)ccc2[nH]1

Procedure:
A solution of 5-Cyano-1H-indole-2carboxylic acid ethyl ester (1.8 grams, 8.4 mmole) and Bu4N+BH3− in methylene chloride (80 ml) was refluxed for 4 hours. The mixture was concentrated to a brown oil which was dissolved in 10% hydrochloric acid (50 ml) and refluxed for 1 hour. The mixture was extracted with ethyl acetate (discarded) and the pH was neutralized. The aqueous was extracted with ethyl acetate. The combined extracts were dried over Na2SO4, filtered, and concentrated to give a solid. (0.920 g). MW 218.258; MS (m/e) 218 (M+).
Reaction SMILES: Cl.[C:2]([CH2:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:13][CH2:12]2)[CH:6]=1)#[N:3].[CH3:27][OH:28]>>[NH:3]=[C:2]([O:28][CH3:27])[CH2:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([N:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:15][CH2:16]2)[CH:6]=1
Reactant: CO
Reactant: N#CCc1ccnc(N2CCN(C(=O)OCc3ccccc3)CC2)c1
Agent: Cl
Product: COC(=N)Cc1ccnc(N2CCN(C(=O)OCc3ccccc3)CC2)c1

Procedure:
Hydrochloric acid gas was bubbled into a stirred solution of benzyl 4-(4-(cyanomethyl)pyridin-2-yl)piperazine-1-carboxylate (500 mg, 1.5 mmol) in dry MeOH (10 mL) for 5 h at 0° C., and then concentrated at 10° C. to give the crude product, which was used directly for the next step. MS (ES+) C20H24N4O3 requires: 368, found: 369 [M+H]+.
Reaction SMILES: [C:1]1([NH:7][C:8](=[O:35])[NH:9][C:10]2[CH:34]=[CH:33][C:13]([C:14]([N:16]3[CH2:21][CH2:20][N:19]([CH2:22][C:23]4[CH:24]=[C:25]([CH:30]=[CH:31][CH:32]=4)[C:26]([O:28]C)=[O:27])[CH2:18][CH2:17]3)=[O:15])=[CH:12][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O1CCOCC1.O.[OH-].[Li+]>O>[C:1]1([NH:7][C:8](=[O:35])[NH:9][C:10]2[CH:11]=[CH:12][C:13]([C:14]([N:16]3[CH2:21][CH2:20][N:19]([CH2:22][C:23]4[CH:24]=[C:25]([CH:30]=[CH:31][CH:32]=4)[C:26]([OH:28])=[O:27])[CH2:18][CH2:17]3)=[O:15])=[CH:33][CH:34]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)c1cccc(CN2CCN(C(=O)c3ccc(NC(=O)Nc4ccccc4)cc3)CC2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: O=C(Nc1ccccc1)Nc1ccc(C(=O)N2CCN(Cc3cccc(C(=O)O)c3)CC2)cc1
Temperature: 25 °C
Reaction time: 60 h
Yield: 102.5 %

Procedure:
Methyl 3-((4-(4-(3-phenylureido)benzoyl)piperazin-1-yl)methyl)benzoate (0.47 g, 1 mmol) was suspended in a mixture of water (5 mL)/1,4-dioxane (15 mL) and treated with lithium hydroxide mono-hydrate (0.168 g, 4 mmol). The mixture was stirred at room temperature for 60 hours and was filtered over fluted paper. The filtrate was concentrated under vacuum and then acidified with 1M hydrochloric acid. The mixture was extracted with ethyl acetate (×4) and the combined organic layers were dried on magnesium sulfate, filtered and concentrated under vacuum to give the title compound (0.47 g).