Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl.N([O-])=O.[Na+].S(=O)(=O)(O)N.[N-:27]=[N+:28]=[N-].[Na+]>O.C(Cl)(Cl)Cl.CO>[N:1]([C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:15])[CH3:14])[CH:5]=[C:6]([Cl:8])[CH:7]=1)=[N+:27]=[N-:28]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(C)OC(=O)Nc1cc(N)cc(Cl)c1
Agent: Cl
Agent: NS(=O)(=O)O
Agent: O=N[O-]
Solvent: O
Solvent: ClC(Cl)Cl
Solvent: CO
Product: CC(C)(C)OC(=O)Nc1cc(Cl)cc(N=[N+]=[N-])c1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 57 %

Procedure:
Step A-3. A stirred solution of 3-amino-5-chlorophenylcarbamic acid, 1,1-dimethylethyl ester (A-2, 2.06 g, 8.49 mmol) in 170 mL of a 50:50 mixture of methanol and 0.1N aqueous HCl is cooled to 0° C. An aqueous solution of sodium nitrite (1.2 M, 8.5 mL) is added dropwise. After 10 min, sulfamic acid (0.824 g) is added and then sodium azide (0.662 g) in 2.5 mL of water is added dropwise. The reaction mixture is stirred at 0° C. for 15 min, then poured into chloroform (500 mL). The phases are separated and the aqueous layer is extracted with chloroform (2×100 mL). The combined organic layers are dried (MgSO4), filtered and concentrated. The organic residue is purified by flash chromatography using 10% ethyl acetate in hexane as the eluent to afford 1.30 g of 3-azido-5-chlorophenylcarbamic acid, 1,1-dimethylethyl ester. (A-3). IR (neat) 2140 cm-1 ; 1H NMR (CDCl3) δ7.17 (m, 1 H), 7.00 (m, 1 H), 6.68 (m, 1 H), 6.53 (bs, 1 H), 1.51 (s, 9 H); 13C NMR (CDCl3) δ152.0, 141.9, 140.5, 135.6, 114.6, 113.5, 106.8, 81.3, 28.1; Mass Spec (70eV, EI) m/z 268 (parent), 212, 184, 156, 140, 128, 105, 57 (base), 40; Exact Mass calculated for C11H13ClN4O2 : 268.0727. Found: 268.0733.
Reaction SMILES: [I:1][CH2:2][C:3]1[N:4]=[C:5]([C:14]2[CH:19]=[CH:18][C:17](C)=[CH:16][CH:15]=2)[O:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C1([C:27](=[O:32])C(=NO)C)C=CC=CC=1.C(=O)C1C=CC=C(OC)C=1>>[I:1][CH2:2][C:3]1[N:4]=[C:5]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:32][CH3:27])[CH:15]=2)[O:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CC(=NO)C(=O)c1ccccc1
Reactant: Cc1ccc(-c2nc(CI)c(-c3ccccc3)o2)cc1
Agent: COc1cccc(C=O)c1
Product: COc1cccc(-c2nc(CI)c(-c3ccccc3)o2)c1

Procedure:
Analogously to the building block synthesis of 4-iodomethyl-5-phenyl-2-p-tolyl-oxazole, 1-phenyl-1,2-propanedione-2-oxime and m-anisaldehyde gave 4-iodomethyl-2-(3-methoxyphenyl)-5-phenyloxazole.
Reaction SMILES: [Na+].[Na+].[Na+].P(C1C=C(S([O-])(=O)=O)C=CC=1)(C1C=C(S([O-])(=O)=O)C=CC=1)C1C=C(S([O-])(=O)=O)C=CC=1.[O:35]1[CH:39]=[N:38][N:37]=[C:36]1[C:40]1[CH:45]=[CH:44][C:43](B(O)O)=[CH:42][CH:41]=1.Cl[C:50]1[C:55]([S:56]([N:59]([C:67]2[C:72]([O:73][CH3:74])=[N:71][C:70]([CH3:75])=[CH:69][N:68]=2)[C:60](=[O:66])[O:61][CH2:62][CH:63]([CH3:65])[CH3:64])(=[O:58])=[O:57])=[CH:54][CH:53]=[CH:52][N:51]=1>O.C1(C)C(C)=CC=CC=1.C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:62]([O:61][C:60]([N:59]([C:67]1[C:72]([O:73][CH3:74])=[N:71][C:70]([CH3:75])=[CH:69][N:68]=1)[S:56]([C:55]1[C:50]([C:43]2[CH:44]=[CH:45][C:40]([C:36]3[O:35][CH:39]=[N:38][N:37]=3)=[CH:41][CH:42]=2)=[N:51][CH:52]=[CH:53][CH:54]=1)(=[O:58])=[O:57])=[O:66])[CH:63]([CH3:65])[CH3:64]
Reactant: COc1nc(C)cnc1N(C(=O)OCC(C)C)S(=O)(=O)c1cccnc1Cl
Reactant: OB(O)c1ccc(-c2nnco2)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=S(=O)([O-])c1cccc(P(c2cccc(S(=O)(=O)[O-])c2)c2cccc(S(=O)(=O)[O-])c2)c1
Solvent: CCN(CC)CC
Solvent: O
Solvent: Cc1ccccc1C
Product: COc1nc(C)cnc1N(C(=O)OCC(C)C)S(=O)(=O)c1cccnc1-c1ccc(-c2nnco2)cc1
Temperature: 105 °C
Reaction time: 1 h
Yield: 76.8 %

Procedure:
Palladium acetate (0.4144 g) and 3,3′,3″-phosphinidyne tris(benzenesulphonic acid) trisodium salt 30% w/w aq sol (3.26 g) were dissolved in water (35 ml) over 6 minutes in an ultrasonic bath. The yellow solution was added to a stirred slurry of [4-(1,3,4-oxadiazol-2-yl)phenyl]boronic acid (10 g) and isobutyl [(2-chloropyridin-3-yl)sulfonyl](3-methoxy-5-methylpyrazin-2-yl)carbamate (16.86 g) in xylene (100 ml), industrial methylated spirit (50 ml) and triethylamine (17 ml). The catalyst dissolution flask was then washed in with water (5 ml) and the reaction mixture heated to reflux (80° C.) on an oil bath (105° C.) and stirred at reflux for 24.5 hours. The reaction mixture was cooled to 30° C. and filtered through a Whatman GF/B glass filter paper and the lower aqueous phase separated off. The reaction flask and filter cake was washed with xylene (20 ml). The xylene wash was used to re-extract the aqueous phase. The combined organic phases were stirred and heated to reflux (85° C.) in a clean 500 ml 4-necked flask equipped with overhead stirrer, water condenser, and nitrogen atmosphere. Essochem solvent 30 (hydrocarbons Bp 100-130° C.) (100 ml) was added dropwise over 6 min and the mixture was allowed to self cool to ambient temperature and then further cooled to −5° C. and held for 1 hour. The product was filtered off and washed with Essochem solvent 30 (50 ml). The cake was dried on the filter for 3 hours to give 15.20 g@100% strength, yield 76.8%. 270 MHz 1H-NMR Spectrum: 0.70 (d, 6H), 1.72 (m, 1H), 2.51 (s, 3H), 3.84 (d, 2H), 4.00 (s, 3H), 7.59 (m, 1H); 7.80 (d, 2H), 7.90 (s, 1H), 8.17 (d, 2H), 8.50 (s, 1H), 8.90 (m, 1H) and 9.00 (d, 1H). Mass Spectrum MH+=525.2 (C24H25N6O6S=525.16).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[Cl:12][C:13]1[CH:14]=[C:15]([S:19](Cl)(=[O:21])=[O:20])[CH:16]=[CH:17][CH:18]=1>CN(C1C=CN=CC=1)C>[Cl:12][C:13]1[CH:14]=[C:15]([S:19]([NH:1][C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[N:10]=[CH:9][CH:8]=[CH:7]3)(=[O:21])=[O:20])[CH:16]=[CH:17][CH:18]=1
Reactant: O=S(=O)(Cl)c1cccc(Cl)c1
Reactant: Nc1cccc2cccnc12
Agent: CN(C)c1ccncc1
Product: O=S(=O)(Nc1cccc2cccnc12)c1cccc(Cl)c1
Yield: 60.3 %

Procedure:
In the similar fashion using route 14 general procedure 27, 8-aminoquinoline (200 mg, 1.38 mmol), 3-chlorobenzenesulfonyl chloride (270 mg, 1.3 mmol) and DMAP (cat.) gave the title compound (250 mg, 59%) after purification by column chromatography with DCM as the eluent.
Reaction SMILES: [CH2:1]([S:4]([N:7]1[CH2:12][CH2:11][C:10]([C@@H:19]([NH2:21])[CH3:20])([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:9][CH2:8]1)(=[O:6])=[O:5])[CH2:2][CH3:3].CCN(C(C)C)C(C)C.[Cl:31][C:32]1[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[C:33]=1[C:34](Cl)=[O:35]>CN(C=O)C>[Cl:31][C:32]1[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[C:33]=1[C:34]([NH:21][C@H:19]([C:10]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:9][CH2:8][N:7]([S:4]([CH2:1][CH2:2][CH3:3])(=[O:5])=[O:6])[CH2:12][CH2:11]1)[CH3:20])=[O:35]
Reactant: O=C(Cl)c1c(Cl)cccc1Cl
Reactant: CCCS(=O)(=O)N1CCC(c2ccccn2)([C@H](C)N)CC1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCCS(=O)(=O)N1CCC(c2ccccn2)([C@H](C)NC(=O)c2c(Cl)cccc2Cl)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of {(1S)-1-[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}amine (80 mg, 0.26 mmol) in DMF (0.7 mL) was treated with i-Pr2NEt (0.2 mL, 1.15 mmol) and 2,6-dichloro-benzoyl chloride (0.15 mL, 0.8 mmol) and stirred at room temperature for 30 min. The reaction mixture was purified directly by reverse phase HPLC to afford the desired product.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][CH2:8][CH2:9][CH:10]=O)=[CH:3][CH:2]=1.[CH3:12][C:13]1[CH:14]=[C:15]([C:20]2[NH:21][C:22]3[C:27]([C:28]=2[CH:29]([CH3:32])[CH2:30][NH2:31])=[CH:26][C:25]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:24][CH:23]=3)[CH:16]=[C:17]([CH3:19])[CH:18]=1.S([O-])([O-])(=O)=O.[Mg+2].[BH4-].[Na+]>>[CH3:19][C:17]1[CH:16]=[C:15]([C:20]2[NH:21][C:22]3[C:27]([C:28]=2[CH:29]([CH3:32])[CH2:30][NH:31][CH2:10][CH2:9][CH2:8][CH2:7][C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)=[CH:26][C:25]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:24][CH:23]=3)[CH:14]=[C:13]([CH3:12])[CH:18]=1
Reactant: Cc1cc(C)cc(-c2[nH]c3ccc(S(C)(=O)=O)cc3c2C(C)CN)c1
Reactant: O=CCCCc1ccncc1
Agent: O=S(=O)([O-])[O-]
Agent: [BH4-]
Agent: [Mg+2]
Product: Cc1cc(C)cc(-c2[nH]c3ccc(S(C)(=O)=O)cc3c2C(C)CNCCCCc2ccncc2)c1
Temperature: -5 °C
Reaction time: 0.25 h
Yield: 42.2 %

Procedure:
A mixture of 4-pyridin-4-yl-butyraldehyde (23 mg), 2-[2-(3,5-dimethylphenyl)-5-methanesulfonyl-1H-indol-3-yl]propylamine (50 mg) and magnesium sulfate (76 mg) were diluted with 1.5 mL CDCl3 and stirred at -5° C. After 15 minutes, a solution of sodium borohydride (6.8 mg in 1.5 mL dry methanol) were added and the mixture stirred at low temperature for an additional 20 minutes. At this time the reaction was quenched by the addition of water, extracted with ethyl acetate and the organic portion washed sequentially with water and brine then dried over sodium sulfate. Purification of the concentrate by preparative TLC on silica gel (methylene chloride:methanol, 9:1) gave the title compound (29 mg).
Reaction SMILES: [OH-].[K+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]([CH:22]2[CH2:27][CH2:26][N:25](C(OCC)=O)[CH2:24][CH2:23]2)[C:11](=[O:21])[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=2)=[CH:6][CH:5]=1>CC(O)C>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]([CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[C:11](=[O:21])[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=2)=[CH:6][CH:5]=1
Reactant: CCOC(=O)N1CCC(N(C(=O)Cc2cccc(OC)c2)c2ccc(Cl)cc2)CC1
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)O
Product: COc1cccc(CC(=O)N(c2ccc(Cl)cc2)C2CCNCC2)c1

Procedure:
To a stirred and warm (40° C.) solution of 12 parts of potassium hydroxide in 200 parts of 2-propanol are added at once 21 parts of ethyl 4-{N-(4-chlorophenyl)-N-[(3-methoxyphenyl)acetyl]-amino}-1-piperidinecarboxylate and the whole is stirred and refluxed for 17 hours. The reaction mixture is cooled, filtered and evaporated. The semi-solid residue is acidified with a diluted hydrochloric acid solution, washed with 1,1'-oxybisethane and the aqueous acid phase is alkalized with sodium hydroxide solution. The free base is extracted with trichloromethane. The extract is dried and evaporated. The residue is crystallized from a mixture of 1,1'-oxybisethane and hexane, yielding 7.8 parts of N-(4-chlorophenyl)-3-methoxy-N-(4-piperidinyl)benzeneacetamide; mp. 85.7° C.
Reaction SMILES: [CH2:1]([C:3]1[O:4][C:5]2[CH:12]=[CH:11][C:10]3[CH:13]=[C:14]([CH3:17])[CH:15]=[CH:16][C:9]=3[CH:8]([C:18]3[C:19](=[S:36])[NH:20][C:21](=[O:35])[N:22]([CH2:24][C:25]4[O:26][CH:27]=[C:28]([C:30]([O:32]CC)=[O:31])[N:29]=4)[CH:23]=3)[C:6]=2[N:7]=1)[CH3:2].O.[OH-].[Li+]>CO.O>[CH2:1]([C:3]1[O:4][C:5]2[CH:12]=[CH:11][C:10]3[CH:13]=[C:14]([CH3:17])[CH:15]=[CH:16][C:9]=3[CH:8]([C:18]3[C:19](=[S:36])[NH:20][C:21](=[O:35])[N:22]([CH2:24][C:25]4[O:26][CH:27]=[C:28]([C:30]([OH:32])=[O:31])[N:29]=4)[CH:23]=3)[C:6]=2[N:7]=1)[CH3:2]
Reactant: CCOC(=O)c1coc(Cn2cc(C3c4ccc(C)cc4C=Cc4oc(CC)nc43)c(=S)[nH]c2=O)n1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCc1nc2c(o1)C=Cc1cc(C)ccc1C2c1cn(Cc2nc(C(=O)O)co2)c(=O)[nH]c1=S
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A mixture of the product of step (ii) (0.55 g) and lithium hydroxide monohydrate (0.46 g) in methanol (10 ml) and water (10 ml) was stirred at room temperature for 3 hours. The solution was concentrated under reduced pressure to 10 ml and partitioned between 2M hydrochloric acid and ethyl acetate. The organic phase was dried (MgSO4) and the solvent evaporated under reduced pressure. Purification was by reverse phase chromatography eluting with 50% methanol in 0.1% aqueous ammonium acetate followed by lyophilisation.
Reaction SMILES: [NH3:1].[Cl:2][C:3]1[N:8]=[C:7]([Cl:9])[CH:6]=[C:5](OC(F)(F)F)[N:4]=1>C(OC)(C)(C)C>[NH2:1][C:7]1([Cl:9])[CH:6]=[CH:5][N:4]=[C:3]([Cl:2])[NH:8]1
Reactant: N
Reactant: FC(F)(F)Oc1cc(Cl)nc(Cl)n1
Solvent: COC(C)(C)C
Product: NC1(Cl)C=CN=C(Cl)N1
Reaction time: 1 h
Yield: 32.5 %

Procedure:
4.3 g (0.25 mol) of gaseous ammonia were passed into a mixture of 23.3 g (0.1 mol) of 2,4-dichloro-6-trifluoromethoxypyrimidine in 150 ml of methyl tert-butyl ether in the course of 45 minutes at from -50° to -45° C. while stirring. Stirring was continued for 30 minutes at -50° C., one hour at -30° C. and one hour at 25° C. The precipitate which had separated out was filtered off under suction, washed with water and dried, 5.4 g (33.1% of theory) of 4-amino-2,4-dichloropyrimidine of melting point 270°-272° C. being obtained as a byproduct. The filtrate was washed with water, dried, partially evaporated down under reduced pressure and chromatographed using 5:1 petroleum ether/ether, 3 g (12.8% of theory) of starting material being obtained as a colorless oil in the first fractions and 9 g (42% of theory) of the title compound being obtained as colorless crystals of melting point 55°-56° C. in the subsequent fraction. The conversion was 48.3%.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]([S:11][C:12]1[C:17]([C:18]#[N:19])=[CH:16][C:15]([CH2:20][CH3:21])=[CH:14][N:13]=1)([CH3:10])([CH3:9])[CH3:8].[CH2:22](OCC)C>>[C:7]([S:11][C:12]1[C:17]([CH2:18][NH2:19])=[CH:16][C:15]([CH2:20][CH3:21])=[C:14]([CH3:22])[N:13]=1)([CH3:10])([CH3:9])[CH3:8]
Reactant: CCc1cnc(SC(C)(C)C)c(C#N)c1
Reactant: CCOCC
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: CCc1cc(CN)c(SC(C)(C)C)nc1C
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
To a suspension of lithium aluminum hydride (54 mg, 1.42 mmol) in diethyl ether (10 mL), under a nitrogen atmosphere, was added dropwise a solution of 2-t-butylthio-3-cyano-5-ethylpyridine (222 mg, 0.95 mmol) in diethyl ether (6 mL). After stirring for 3.5 hours at room temperature, the reaction was quenched with saturated aqueous sodium sulfate and the ether layer dried (Na2SO4), filtered and evaporated to give 219 mg (96%) of crude oily product.
Reaction SMILES: FC1C=CC=CC=1C(Cl)=O.[C:11]1([C:21](Cl)=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1.[NH2:24][C:25]1[CH:26]=[C:27]([CH:38]=[CH:39][N:40]=1)[C:28]([NH:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29]>>[C:11]1([C:21]([NH:24][C:25]2[CH:26]=[C:27]([CH:38]=[CH:39][N:40]=2)[C:28]([NH:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1
Reactant: Nc1cc(C(=O)NCc2ccccc2)ccn1
Reactant: O=C(Cl)c1cccc2ccccc12
Agent: O=C(Cl)c1ccccc1F
Product: O=C(NCc1ccccc1)c1ccnc(NC(=O)c2cccc3ccccc23)c1
Yield: 20 %

Procedure:
Following the procedure as describe in Example 6, making variations as required to replace 2-fluorobenzoyl chloride with 1-naphthoyl chloride to react with 2-amino-N-benzylisonicotinamide, 2-(1-naphthamido)-N-benzylisonicotinamide was obtained as a colorless solid in 20% yield: mp 65-67° C. (hexanes/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 9.70 (s, 1H), 8.72 (s, 1H), 8.29-8.22 (m, 1H), 7.95 (d, J=8.3 Hz, 1H), 7.97-7.84 (m, 1H), 7.76 (d, J=5.2 Hz, 1H), 7.69 (d, J=5.2 Hz, 1H), 7.50-7.31 (m, 7H), 7.28-7.24 (m, 2H), 7.08 (t, J=5.8 Hz, 1H), 4.59 (d, J=5.7 Hz, 2H); MS (ES+) m/z 382.5 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([CH3:12])[C:9]2[CH:8]=[C:7]3[O:13][C:14]([CH3:18])([CH3:17])[CH:15]=[CH:16][C:6]3=[CH:5][C:4]=2[N:3]=1.CN1C=CN=C1.Cl[O-].[Na+].S([O-])([O-])(=[O:30])=S.[Na+].[Na+]>C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:11]=[C:10]([CH3:12])[C:9]2[CH:8]=[C:7]3[O:13][C:14]([CH3:18])([CH3:17])[C@H:15]4[O:30][C@H:16]4[C:6]3=[CH:5][C:4]=2[N:3]=1
Reactant: Cc1cc(Cl)nc2cc3c(cc12)OC(C)(C)C=C3
Reactant: O=S([O-])([O-])=S
Agent: Cn1ccnc1
Agent: [Na+]
Agent: [O-]Cl
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1cc(Cl)nc2cc3c(cc12)OC(C)(C)[C@H]1O[C@@H]31
Yield: 94 %

Procedure:
To a solution of 7-chloro-2,2,9-trimethyl-2H-pyrano[2,3-g]quinoline (200 mg, 0.77 mmol) in ethyl acetate (3.0 mL), N-methyl imidazole (0.012 mL, 0.154 mmol) and ent-Ph,Ph salen manganese complex (8.0 mg, 0.0077 mmol) were added at room temperature and sodium hypochlorite aqueous solution (1.0 g, 1.513 mol/kg, 1.54 mmol) was added dropwise in water bath, and the resulting mixture was stirred in water bath for 40 minutes. In water bath, sodium hypochlorite aqueous solution (1.0 g, 1.513 mol/kg, 1.54 mmol) was added dropwise, and the resulting mixture was further stirred in water bath for 30 minutes. Upon the completion of the reaction, sodium thiosulfate aqueous solution was added to the reaction solution, the resulting solution was filtered through celite and extracted. The organic phase was washed with sodium hydrogencarbonate aqueous solution and then with sodium chloride aqueous solution, and then dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was purified by column chromatography (hexane/ethyl acetate=10/1) to obtain (3S*,4S*)-7-chloro-3,4-epoxy-2,2,9-trimethyl-3,4-dihydro-2H-pyrano[2,3-g]quinoline (yield: 94%).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][N:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([OH:13])=O.O.ON1C2C=CC=CC=2N=N1.[CH3:25][O:26][C:27]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[C:28]=1[CH2:29][NH2:30]>CN(C=O)C>[CH3:36][O:35][C:31]1[CH:32]=[CH:33][CH:34]=[C:27]([O:26][CH3:25])[C:28]=1[CH2:29][NH:30][C:11]([C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[N:7][CH:6]=2)[N:1]=1)=[O:13]
Reactant: O=C(O)c1ccc2cnccc2n1
Reactant: COc1cccc(OC)c1CN
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Product: COc1cccc(OC)c1CNC(=O)c1ccc2cnccc2n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 97.6 %

Procedure:
To a stirring mixture of 2-[1,6]naphthyridinecarboxylic acid (50 mg, 0.287 mmol) in anhydrous DMF (1.0 mL) at room temperature was added sequentially 1-hydroxybenzotriazole hydrate (42.7 mg, 0.316 mmol), 2,6-dimethoxybenzylamine (75.0 mg, 0.431 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarboiimide hydrochloride (61.8 mg, 0.316 mmol). The resulting mixture was allowed to stir at room temperature overnight and it was found to be clear. The solvent was removed under vacuum. Flash column chromatography of the residue (50% hexane/ethyl acetate to 100% ethyl acetate) afforded the desired product as a white solid (90.6 mg, 98%): m.p. 169-171° C.
Reaction SMILES: C([Li])CCC.CN(C)CCN(C)C.[CH-:14]1[CH:18]=[CH:17][CH:16]=[CH:15]1.[CH-:19]1[CH:23]=[CH:22][CH:21]=[CH:20]1.[Fe+2:24].F[B:26]([C:36]1[C:41]([CH3:42])=[CH:40][C:39]([CH3:43])=[CH:38][C:37]=1[CH3:44])[C:27]1[C:32]([CH3:33])=[CH:31][C:30]([CH3:34])=[CH:29][C:28]=1[CH3:35]>CCCCCC>[C:28]1([CH3:35])[CH:29]=[C:30]([CH3:34])[CH:31]=[C:32]([CH3:33])[C:27]=1[B:26]([C:36]1[C:37]([CH3:44])=[CH:38][C:39]([CH3:43])=[CH:40][C:41]=1[CH3:42])[C-:14]1[CH:18]=[CH:17][CH:16]=[CH:15]1.[C-:19]1([B:26]([C:36]2[C:37]([CH3:44])=[CH:38][C:39]([CH3:43])=[CH:40][C:41]=2[CH3:42])[C:27]2[C:32]([CH3:33])=[CH:31][C:30]([CH3:34])=[CH:29][C:28]=2[CH3:35])[CH:23]=[CH:22][CH:21]=[CH:20]1.[Fe+2:24]
Reactant: c1cc[cH-]c1
Reactant: Cc1cc(C)c(B(F)c2c(C)cc(C)cc2C)c(C)c1
Agent: [Fe+2]
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: CCCCCC
Product: Cc1cc(C)c(B(c2c(C)cc(C)cc2C)[c-]2cccc2)c(C)c1
Temperature: 25 °C

Procedure:
15.4 ml (24.7 mmol) of a 1.6 M solution of n-butyllithium in n-hexane were added dropwise to a mixture of 2.87 g=3.7 ml (24.7 mmol) of N,N,N′,N′-tetramethylethylenediamine and 4 ml of n-hexane over a period of 5 minutes while stirring at room temperature. The reaction mixture was stirred for another 20 minutes at room temperature and a solution of 1.86 g (10 mmol) of ferrocene in 70 ml of n-hexane was then added dropwise over a period of 25 minutes. The reaction mixture was stirred at room temperature for 6 hours and a solution of 6.62 g (24.7 mmol) of fluorodimesitylborane in n-hexane was then added dropwise over a period of 30 minutes. After stirring at room temperature for 16 hours the n-hexane was removed on a rotary evaporator, the red, semisolid residue was taken up in 400 ml of dichloromethane, the organic phase was admixed with 3 ml of water, stirred vigorously for 30 minutes and subsequently dried over magnesium sulfate. After the desiccant had been filtered off, the organic phase was evaporated to dryness. The red crude product (about 6.8 g, purity according to HPLC: 95–98%) was stirred once with hot n-hexane and subsequently recrystallized from ethanol until a purity of 99.8% as determined by HPLC had been reached. The yield, at a purity of 99.8% as determined by HPLC, was 4.7 g, corresponding to 68.8%.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:14]=[CH:15][C:16]=1[N+:17]([O-])=O)[CH2:7][N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)([O-])=O>C(O)C>[N:8]1([CH2:7][C:6]2[CH:5]=[C:4]([NH2:1])[C:16]([NH2:17])=[CH:15][CH:14]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1
Reactant: O=[N+]([O-])c1ccc(CN2CCOCC2)cc1[N+](=O)[O-]
Solvent: CCO
Product: Nc1ccc(CN2CCOCC2)cc1N
Temperature: 17.5 °C
Reaction time: 48 h
Yield: 75.5 %

Procedure:
4-(3,4-Dinitrobenzyl)morpholine (21 g, 101 mmol) was suspended in ethanol (0.9 L) and the vessel purged with nitrogen. 10% Palladium on charcoal (1.05 g) was suspended in ethanol (25 mL) and added to the substrate. The mixture was cooled in ice then the atmosphere exchanged for hydrogen. The mixture was allowed to warm to 15-20° C. and hydrogenation continued at ambient pressure for 2 days. The vessel was purged with nitrogen then the mixture was filtered through Celite, rinsing with ethanol (0.3 L) in portions. Concentration afforded the title compound (15.8 g, 97%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([N:19]=C=O)[CH:17]=[CH:18][C:13]=2[N:12]([CH3:22])[C:11](=[O:23])[C:10]([CH3:25])([CH3:24])[N:9]=1.ClC1C=CC=CC=1C1C2C=C(NC(NCCO)=O)C=CC=2N(C)C(=O)C(C)(C)N=1>C(OCC)(=O)C.CCCCCC>[NH2:19][C:16]1[CH:17]=[CH:18][C:13]2[N:12]([CH3:22])[C:11](=[O:23])[C:10]([CH3:25])([CH3:24])[N:9]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[C:14]=2[CH:15]=1
Reactant: CN1C(=O)C(C)(C)N=C(c2ccccc2Cl)c2cc(N=C=O)ccc21
Agent: CN1C(=O)C(C)(C)N=C(c2ccccc2Cl)c2cc(NC(=O)NCCO)ccc21
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CN1C(=O)C(C)(C)N=C(c2ccccc2Cl)c2cc(N)ccc21

Procedure:
From 8 g (0.024 ml) of 7-amino-5-(o-chlorophenyl)-1,3-dihydro-1,3,3-trimethyl-2H-1,4-benzodiazepin-2-one there is obtained, in analogy to the details in Example 4, via [5-(o-chlorophenyl)-2,3-dihydro-1,3,3-trimethyl-2-oxo-1H-1,4-benzodiazepin-7-yl]isocyanate, 1-[5-(o-chlorophenyl)-2,3-dihydro-1,3,3-trimethyl-2-oxo-1H-1,4-benzodiazepin-7-yl]-3-(2-hydroxyethyl)urea of melting point 85°-110° (ethyl acetate/n-hexane).
Reaction SMILES: N([O-])=O.[Na+].[Cl:5][C:6]1[C:12]([CH3:13])=[CH:11][CH:10]=[C:9]([Cl:14])[C:7]=1N.Cl.[CH3:16][S:17]SC>O.C(O)(=O)C.[Cu]>[Cl:5][C:6]1[C:7]([S:17][CH3:16])=[C:9]([Cl:14])[CH:10]=[CH:11][C:12]=1[CH3:13]
Reactant: CSSC
Reactant: Cc1ccc(Cl)c(N)c1Cl
Agent: [Cu]
Agent: Cl
Agent: O=N[O-]
Solvent: CC(=O)O
Solvent: O
Product: CSc1c(Cl)ccc(C)c1Cl
Temperature: 0 °C

Procedure:
A solution of sodium nitrite (12.0 g) in water was added to a stirred suspension of 2,6-dichloro-3-methylaniline (30.0 g) in a mixture of glacial acetic acid and concentrated hydrochloric acid. While maintaining the temperature below 10° C. The mixture was stirred at 0° C. for three quarters of an hour then added to a mixture of dimethyl disulphide (20 ml) and copper powder (0.25 g) in glacial acetic acid. The mixture was stirred for 4 hours and extracted with ether. The organic layer was washed with aqueous sodium carbonate (2M), water, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness to give 2,4-dichloro-3-(methylsulphenyl)toluene (27.2 g) as a red liquid NMR (CDCl3) 2.4(s,3H), 2.45(s,3H), 7.15(d,1H), 7.3(d,1H).