Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH3:2][N:3]1[CH2:7][CH2:6][CH2:5][C:4]1=[NH:8].O.[OH-].[Na+].[CH3:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[C:14]=1[N:20]=[C:21]=[O:22]>C1C=CC=CC=1>[CH3:19][C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([CH3:12])[C:14]=1[NH:20][C:21]([N:8]=[C:4]1[CH2:5][CH2:6][CH2:7][N:3]1[CH3:2])=[O:22]
Reactant: Cc1cccc(C)c1N=C=O
Reactant: CN1CCCC1=N
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccccc1
Solvent: O
Product: Cc1cccc(C)c1NC(=O)N=C1CCCN1C

Procedure:
To a stirring solution of 6.73 g. (0.05 mole) of 1-methyl- 2-iminopyrrolidine hydrochloride in about 2 ml. of water is added about 50 ml. of benzene followed by 10 ml. of 50% NaOH. After stirring 1 min. the benzene layer is decanted onto anhydrous potassium carbonate. The extraction is repeated twice. The combined benzene extracts are filtered from a drying agent (dicalite pad) and rinsed well with dry benzene. To the filtrate is added in one portion with stirring 7.36 g. (0.05 mole) of 2,6-dimethylphenylisocyanate. The reaction mixture is stirred overnight. Solvent removal and recrystallization from ethyl acetate-ether gives the product, 1-(2,6 -dimethylphenyl)-3-(1-methyl-2-pyrrolidylidene)urea, as white crystals, m.p. = 119°-120° C.
Reaction SMILES: C[O-].[Na+].[C:4](OC(C)(C)C)(=O)C.C(O[C:15]([C:17]1[CH:18]=[C:19]2[CH:25]=[CH:24][O:23][C:20]2=[CH:21][N:22]=1)=[O:16])C.C(O)(=O)C.Cl>C1(C)C=CC=CC=1>[C:15]([C:17]1[CH:18]=[C:19]2[CH:25]=[CH:24][O:23][C:20]2=[CH:21][N:22]=1)(=[O:16])[CH3:4]
Reactant: CC(=O)OC(C)(C)C
Reactant: CCOC(=O)c1cc2ccoc2cn1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: CC(=O)c1cc2ccoc2cn1
Temperature: 60 °C
Reaction time: 3 h
Yield: 72 %

Procedure:
As 405 mg (7.5 mmol) of sodium methoxide was stirred in 5 mL of toluene, 1.16 g (10.0 mmol) of tert-butyl acetate was added dropwise at room temperature to the solution. Then, 956 mg (5.0 mmol) of 5-ethoxycarbonylfuro[2,3-c]pyridine dissolved in 5 mL of toluene was added dropwise at room temperature to the above solution. After all the solution had been added, the reaction mixture was heated to 60° C., a reaction was carried out for 3 hours. The resulting reaction mixture was then neutralized with 450 mg (7.5 mmol) of acetic acid, the solution was stirred for 30 minutes, 1.5 mL (7.5 mmol) of 5 N hydrochloric acid was then added, and the solution was stirred for 5 hours at 60° C. to carry out a reaction. The solution was then returned to room temperature, the organic layer was separated, the aqueous layer was extracted twice with 5 mL of methylene chloride, and the combined organic layer was dried with anhydrous magnesium sulfate and then concentrated in a rotary evaporator. The resulting solids were recrystallized from a mixed solvent of toluene-hexane, giving 580 mg (72% yield) of 5-acetylfuro[2,3-c]pyridine in a purity of 99% by HPLC.
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[O:7][C:6](=[O:8])[CH:5]([CH3:9])[C:4](=[O:10])[O:3]1.ClC[C:14]1[CH:21]=[CH:20][C:17]([CH:18]=[CH2:19])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+].C1C2NC3C(=CC=CC=3)SC=2C=CC=1>C(OCC)(=O)C.CC(C)=O>[CH3:11][C:2]1([CH3:1])[O:3][C:4](=[O:10])[CH:5]([CH2:9][C:14]2[CH:21]=[CH:20][C:17]([CH:18]=[CH2:19])=[CH:16][CH:15]=2)[C:6](=[O:8])[O:7]1
Reactant: CC1C(=O)OC(C)(C)OC1=O
Reactant: C=Cc1ccc(CCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: c1ccc2c(c1)Nc1ccccc1S2
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: C=Cc1ccc(CC2C(=O)OC(C)(C)OC2=O)cc1
Reaction time: 8 h
Yield: 21.3 %

Procedure:
To a 500 mL 3-necked round bottomed flask equipped with a stir bar, thermowell, and a condenser connected to a nitrogen line was added 10.0 g (0.0632 mole) of 2,2,5-trimethyl-1,3-dioxane-4,6-dione, 10.6 g (0.0632 mol) of p-(chloromethyl)styrene, 35 g (0.2528 mol) of potassium carbonate and 200 mL of acetone. Approximately 1 g of phenothiazine was added as a stabilizer. The mixture was refluxed with stirring overnight at which time it was allowed to cool, diluted with 200 mL of ethyl acetate and filtered through a bed of Celite. The filtrate was washed with water and brine and dried overnight over anhydrous sodium sulfate. The suspension was filtered and the filtrate evaporated on a rotary evaporator to a light brown oil which spontaneously crystallized. The crystals were collected and washed with 35-65 petroleum ether to yield 3.5 g of 2,2-dimethyl-5-(4-vinylbenzyl)-1,3-dioxane-4,6-dione as shown by formula (III).
Reaction SMILES: [F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[C:6]([N:8]([CH:10]([CH2:17][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[NH:20][CH:19]=1)[CH2:11][CH2:12][CH2:13][C:14]([OH:16])=O)[CH3:9])=[O:7].C(N(CC)CC)C.[Cl:43][C:44]1[CH:50]=[C:49]([CH3:51])[CH:48]=[CH:47][C:45]=1[NH2:46]>C(Cl)Cl.C(OCC)(=O)C>[Cl:43][C:44]1[CH:50]=[C:49]([CH3:51])[CH:48]=[CH:47][C:45]=1[NH:46][C:14](=[O:16])[CH2:13][CH2:12][CH2:11][CH:10]([N:8]([C:6](=[O:7])[C:5]1[CH:4]=[C:3]([C:2]([F:35])([F:34])[F:1])[CH:29]=[C:28]([C:30]([F:33])([F:31])[F:32])[CH:27]=1)[CH3:9])[CH2:17][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[NH:20][CH:19]=1
Reactant: Cc1ccc(N)c(Cl)c1
Reactant: CN(C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(CCCC(=O)O)Cc1c[nH]c2ccccc12
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: Cc1ccc(NC(=O)CCCC(Cc2c[nH]c3ccccc23)N(C)C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c(Cl)c1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
160 mg (0.268 mmol) of 5-[N-(3,5-bistrifluoromethyl-benzoyl)-N-methyl-amino]-6-(1H-indol-3-yl)-hexanoic acid are dissolved in 10 ml of methylene chloride, and then 222 ml (1.34 mmol) of triethylamine, 48 ml (0.382 mmol) of 2-chloro-4-methyl-aniline and 271 ml of 50% propylphosphonic acid anhydride solution in ethyl acetate are added. The reaction mixture is stirred at room temperature for 20 hours, then washed twice with aqueous potassium carbonate solution. The aqueous phase is extracted twice with methylene chloride, and the organic phases are combined, dried over magnesium sulfate and concentrated by evaporation. The residue is chromatographed on silica gel with ethyl acetate/petroleum ether (first 1:2, then 3:1). The title compound is obtained in the form of white crystals. MS (EI): 352, 241, 222, 213, 130. TLC: ethyl acetate, Rf =0.59.
Reaction SMILES: [F:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][N:7]2[CH2:12][CH:11]([CH2:13][CH2:14][N:15]([O:17][CH3:18])[CH3:16])[NH:10][CH2:9][C:8]2=[O:19])=[CH:4][CH:3]=1.[CH:22]([N:25]=[C:26]=[O:27])([CH3:24])[CH3:23]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:8](=[O:19])[CH2:9][N:10]([C:26]([NH:25][CH:22]([CH3:24])[CH3:23])=[O:27])[CH:11]([CH2:13][CH2:14][N:15]([O:17][CH3:18])[CH3:16])[CH2:12]2)=[CH:20][CH:21]=1
Reactant: CON(C)CCC1CN(Cc2ccc(F)cc2)C(=O)CN1
Reactant: CC(C)N=C=O
Solvent: ClCCl
Product: CON(C)CCC1CN(Cc2ccc(F)cc2)C(=O)CN1C(=O)NC(C)C
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A solution of 1-(4-fluorobenzyl)-5-{2-[methoxy(methyl)amino]ethyl}piperazine-2-one (784 mg, 2.65 mmol) in anhydrous CH2Cl2 (13 mL) was treated with isopropyl isocyanate (391 μL, 3.98 mmol) and stirred under inert atmosphere at ambient temperature for 18 h. The solvent was removed in vacuo, and the resulting oil was purified by silica gel chromatography (EtOAc to 5% MeOH/EtOAc to 10% MeOH/EtOAc) to afford the title urea as a light orange oil.
Reaction SMILES: [NH2:1][C:2]1[C:27]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([I:35])=[CH:31][C:30]=2[F:36])=[CH:26][C:25]([F:37])=[CH:24][C:3]=1[O:4][C:5]1[CH:6]=[C:7]([CH:21]=[CH:22][CH:23]=1)[CH2:8][NH:9][S:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])(=[O:12])=[O:11].[CH:38]1([S:41](Cl)(=[O:43])=[O:42])[CH2:40][CH2:39]1>N1C=CC=CC=1.C1(C)C=CC=CC=1>[CH:38]1([S:41]([NH:1][C:2]2[C:27]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([I:35])=[CH:31][C:30]=3[F:36])=[CH:26][C:25]([F:37])=[CH:24][C:3]=2[O:4][C:5]2[CH:6]=[C:7]([CH:21]=[CH:22][CH:23]=2)[CH2:8][NH:9][S:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])(=[O:12])=[O:11])(=[O:43])=[O:42])[CH2:40][CH2:39]1
Reactant: CC(C)(C)OC(=O)NS(=O)(=O)NCc1cccc(Oc2cc(F)cc(Nc3ccc(I)cc3F)c2N)c1
Reactant: O=S(=O)(Cl)C1CC1
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)NS(=O)(=O)NCc1cccc(Oc2cc(F)cc(Nc3ccc(I)cc3F)c2NS(=O)(=O)C2CC2)c1
Reaction time: 16 h
Yield: 79.2 %

Procedure:
864 mg of crude tert-butyl [(3-{2-amino-5-fluoro-3-[(2-fluoro-4-iodophenyl)amino]phenoxy}benzyl)sulfamoyl]carbamate (1.37 mmol, 1 eq.) were dissolved in 13 mL pyridine and 250 mg cyclopropyl sulfonyl chloride (1.78 mmol, 1.3 eq.) and stirring was continued at that temperature for 16 h. The reaction mixture was diluted with toluene and concentrated in vacuo. The residue was partitioned between ethyl acetate and water, the aqueous layer was reextracted with ethyl acetate. The combined organic layers were dried, filtered and concentrated in vacuo. The residue was further purified by flash column chromatography (hexan to hexan/ethyl acetate 1:1 gradient) to yield 814 mg of the target compound (70% UV-purity), which was used for the subsequent transformation.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][C:11]([CH3:28])([CH3:27])[CH2:12][C@H:13]1[CH2:17][O:16]C(C)(C)[N:14]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(NC(=O)[C@H](C)C[C@H](O)[C@@H](NC(OC(C)(C)C)=O)CC(C)(C)CC(N1C2C(=CC=CC=2)CC(C(OCC)=O)C1)=O)CCC>CO>[CH2:1]([O:8][CH2:9][CH2:10][C:11]([CH3:28])([CH3:27])[CH2:12][C@H:13]([NH:14][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:17][OH:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(CCOCc1ccccc1)C[C@H]1COC(C)(C)N1C(=O)OC(C)(C)C
Agent: CCCCNC(=O)[C@H](C)C[C@H](O)[C@H](CC(C)(C)CC(=O)N1CC(C(=O)OCC)Cc2ccccc21)NC(=O)OC(C)(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: CC(C)(CCOCc1ccccc1)C[C@@H](CO)NC(=O)OC(C)(C)C

Procedure:
The title compound is prepared starting from 75.2 g of 4(S)-(4-benzyloxy-2,2-dimethylbutyl)-3-tert-butoxycarbonyl-2,2-dimethyl-1,3-oxazolidine and 2.0 g of p-toluenesulfonic acid hydrate in 500 ml of methanol analogously to Example 20a): Rf (A)=0.31; FAB-MS: (M+H)+ =352; anal. calc. for C20H33NO4 : C68.34%, H9.46%, N3.99%; found C68.14%, H9.37%, N3.98%.
Reaction SMILES: F[C:2](F)(F)C(O)=O.[OH:8][C:9]1[C:10]([O:30][CH3:31])=[CH:11][C:12]2[C:21]3[CH:22]=[C:23]4[O:28][CH2:27][O:26][C:24]4=[CH:25][C:20]=3[CH2:19][CH:18]3[C:13]=2[C:14]=1[CH2:15][N:16]([CH3:29])[CH2:17]3.C1(C)C=CC=CC=1.[OH-].C1([N+](C)(C)C)C=CC=CC=1>CN(C)C=O>[CH3:31][O:30][C:10]1[C:9]([O:8][CH3:2])=[C:14]2[CH2:15][N:16]([CH3:29])[CH2:17][CH:18]3[CH2:19][C:20]4[CH:25]=[C:24]5[O:26][CH2:27][O:28][C:23]5=[CH:22][C:21]=4[C:12](=[C:13]23)[CH:11]=1
Reactant: COc1cc2c3c(c1O)CN(C)CC3Cc1cc3c(cc1-2)OCO3
Reactant: O=C(O)C(F)(F)F
Agent: C[N+](C)(C)c1ccccc1
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: COc1cc2c3c(c1OC)CN(C)CC3Cc1cc3c(cc1-2)OCO3

Procedure:
10.65 g. (±)-5,6,6a,7-tetrahydro-3-hydroxy-2-methoxy-9,10-methylenedioxy-5-methyl-4H-dibenz(de,g)isoquinoline trifluoroacetate (see Example 1) are dissolved in 500 ml. of a mixture of toluene and dimethyl formamide (9:1) in a manner analogous to that described in Example 7 and methylated with phenyltrimethyl ammonium hydroxide. When the methylation is finished (monitoring with TLC), the reaction mixture is evaporated in a vacuum. After partitioning the residue between water and methylene chloride, working up the organic phase and crystallising from methanol/chloroform, there is obtained (±)-5,6,6a,7-tetrahydro-2,3-dimethoxy-9,10-methylenedioxy-5-methyl-4H-dibenz(de,g)isoquinoline in the form of cream-coloured crystals; m.p. 169°-172° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH:14]=O)=[CH:12][N:11]=[C:10]([NH:16][C:17](=[O:19])[CH3:18])[CH:9]=2)=[C:4]([F:20])[CH:3]=1.[CH3:21][NH2:22]>ClCCl>[F-:20].[C:17]([NH:16][C:10]1[CH:9]=[C:8]2[C:13](=[CH:12][N:11]=1)[CH:14]=[N+:22]([CH3:21])[C:4]1[CH:3]=[C:2]([Cl:1])[CH:7]=[CH:6][C:5]2=1)(=[O:19])[CH3:18]
Reactant: CN
Reactant: CC(=O)Nc1cc(-c2ccc(Cl)cc2F)c(C=O)cn1
Solvent: ClCCl
Product: CC(=O)Nc1cc2c(cn1)c[n+](C)c1cc(Cl)ccc21
Product: [F-]
Temperature: 25 °C
Reaction time: 12 h
Yield: 93.1 %

Procedure:
To a stirred solution of N-(4-(4-chloro-2-fluorophenyl)-5-formylpyridin-2-yl)acetamide (0.39 g, 1.332 mmol) and 4 Å molecular sieves (50 mg) in dichloromethane (35 mL) at 0° C. was added methyl amine (8M in EtOH, 0.041 g, 0.166 mL, 1.332 mmol) dropwise and the reaction was stirred at rt overnight (12 h). The reaction mixture was diluted with DCM (40 mL) and filtered through a bed of diatomaceous earth (Celite®). The filtrate was concentrated under reduced pressure to afford 2-acetamido-8-chloro-6-methylbenzo[c][2,7]naphthyridin-6-ium fluoride (450 mg, 1.24 mmol, 93% yield) as a yellow solid that was used in the next step without purification. LC/MS (ESI) m/e 286.1 [(M)+, calcd for C15H13ClN3O 286.1]; LC/MS retention time (Method D): tR=0.71 min.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11](/[CH:14]=[CH:15]/[CH:16]=O)=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.[CH:18]([CH:21]1[CH2:26][C:25](=O)[CH2:24][C:23](=[O:28])[CH2:22]1)([CH3:20])[CH3:19].[NH2:29][C:30]1[NH:34][N:33]=[CH:32][CH:31]=1.[CH2:35]1[CH:37]([CH2:38][C:39]([NH2:41])=[O:40])[CH2:36]1>>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11](/[CH:14]=[CH:15]/[CH:16]3[C:24]4[C:23](=[O:28])[CH2:22][CH:21]([CH:18]([CH3:19])[CH3:20])[CH2:26][C:25]=4[NH:29][C:30]4[NH:34][N:33]=[CH:32][C:31]3=4)=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:36]1[CH:37]([CH2:38][C:39]([NH2:41])=[O:40])[CH2:35]1
Reactant: O=C/C=C/c1ccc(-c2cccc(F)c2)cn1
Reactant: Nc1ccn[nH]1
Reactant: CC(C)C1CC(=O)CC(=O)C1
Agent: NC(=O)CC1CC1
Product: CC(C)C1CC(=O)C2=C(C1)Nc1[nH]ncc1C2/C=C/c1ccc(-c2cccc(F)c2)cn1

Procedure:
The title compound is prepared as a mixture of diastereomers according to procedure A from 50 mg of (E)-3-[5-(3-fluorophenyl)pyridin-2-yl]propenal, 34 mg of 5-isopropylcyclohexane-1,3-dione and 40 mg of 5-amino-1H-pyrazole-3-cyclo-propylmethylcarboxamide.
Reaction SMILES: [CH2:1]([C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH2:8])=[CH:5][CH:4]=1)[CH3:2].C[O:12][C:13](=O)[C:14]1[C:19]([I:20])=[CH:18][C:17]([F:21])=[CH:16][C:15]=1[CH2:22]Br.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1>[F:21][C:17]1[CH:16]=[C:15]2[C:14](=[C:19]([I:20])[CH:18]=1)[C:13](=[O:12])[N:8]([CH2:7][C:6]1[CH:9]=[CH:10][C:3]([CH2:1][CH3:2])=[CH:4][CH:5]=1)[CH2:22]2
Reactant: CCc1ccc(CN)cc1
Reactant: COC(=O)c1c(I)cc(F)cc1CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: CCc1ccc(CN2Cc3cc(F)cc(I)c3C2=O)cc1
Temperature: 100 °C
Reaction time: 2 h
Yield: 46.6 %

Procedure:
A mixture of 4-ethyl-benzyl amine (1.3 mmol), 2-bromomethyl-4-fluoro-6-iodo-benzoic acid methyl ester (0.374 g, 1.0 mmol), and K2CO3 (0.277 g, 2 mmol) in toluene (4 mL) was heated with stirring at 100° C. for 2 h. The resulting mixture was filtered and concentrated. Silica gel column chromatography using 30% ethyl acetate in hexane afforded 5-fluoro-7-iodo-2-(4-ethyl-benzyl)-2,3-dihydro-isoindol-1-one (0.184 g, 47%). 1H NMR (300 MHz, CDCl3): δ (ppm) 1.20 (t, 3H), 2.65 (q, 2H), 4.16 (s, 2H), 4.74 (s, 2H), 7.10 (d, 1H), 7.23-7.33 (m, 4H), 7.63 (d, 1H). GC-MS: m/z 395 (M)+.
Reaction SMILES: [N:1]1[N:10]2[C:4]([CH2:5][NH:6][C:7]3[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=3[CH2:9]2)=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:22]1([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:23]([C:28]([NH:30][C:31]2[N:36]=[CH:35][C:34]([C:37](Cl)=[O:38])=[CH:33][CH:32]=2)=[O:29])=[CH:24][CH:25]=[CH:26][CH:27]=1>ClCCl.O>[N:1]1[N:10]2[C:4]([CH2:5][N:6]([C:37]([C:34]3[CH:33]=[CH:32][C:31]([NH:30][C:28]([C:23]4[C:22]([C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=5)=[CH:27][CH:26]=[CH:25][CH:24]=4)=[O:29])=[N:36][CH:35]=3)=[O:38])[C:7]3[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=3[CH2:9]2)=[CH:3][CH:2]=1
Reactant: O=C(Cl)c1ccc(NC(=O)c2ccccc2-c2ccccc2)nc1
Reactant: c1ccc2c(c1)Cn1nccc1CN2
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(Nc1ccc(C(=O)N2Cc3ccnn3Cc3ccccc32)cn1)c1ccccc1-c1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 82.5 %

Procedure:
To a chilled (0° C.) solution of 0.185 g of 5,10-dihydro-4H-pyrazolo[5,1-c][1,4]benzodiazepine and 417 μl of triethylamine in 3.5 ml of dichloromethane is added 0.35 g of 6-(2-biphenylcarbonyl)aminopyridine-3-carbonyl chloride in 1.5 ml of dichloromethane. The mixture is stirred at room temperature under argon for 16 hours, diluted with 40 ml of dichloromethane and 20 ml of water. The organic layer is separated, washed with 20 ml of brine and dried (Na2SO4). The solution is filtered through a thin pad of hydrous magnesium silicate. The filtrate is concentrated to dryness under vacuum to give 0.4 g of solid. The solid is purified on silica gel prep-plates with ethyl acetate-hexane (3:1) as eluent to give 170 mg of a brown glass, m.p. 110°-150° C.
Reaction SMILES: [C:1]([C:4]1[CH:17]=[CH:16][C:15]2[O:14][C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[S:7][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].ClC1C=C(C=CC=1)C(OO)=O.[OH-:29].[Ca+2].[OH-:31]>C(Cl)Cl>[C:1]([C:4]1[CH:17]=[CH:16][C:15]2[O:14][C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[S:7](=[O:31])(=[O:29])[C:6]=2[CH:5]=1)(=[O:3])[CH3:2]
Reactant: [OH-]
Reactant: CC(=O)c1ccc2c(c1)Sc1ccccc1O2
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [Ca+2]
Solvent: ClCCl
Product: CC(=O)c1ccc2c(c1)S(=O)(=O)c1ccccc1O2
Temperature: 25 °C
Reaction time: 3 h
Yield: 75.6 %

Procedure:
To a solution of 2-acetyl phenoxathiin (J.A.C.S. 1936, 58, 717) (484 mg, 2 mmol) in methylene chloride (25 mL) there was added 85% m-chloroperoxy benzoic acid (MCPBA 1.015 g, 5 mmol) and the mixture stirred at room temperature. After 3 hours, more MCPBA was added (250 mg) and stirring was continued for a further hour. Enough methylene chloride was added to dissolve the solids, followed by calcium hydroxide (3 g); after stirring for a further 5 minutes, the mixture was filtered and the filtrate evaporated to a solid residue which was triturated with ether (10 mL) and filtered to afford the sulfone (415 mg) as a white solid, m.p.: 163°-165° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:12]([OH:14])=O)[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.P(C#N)(=O)(OCC)OCC.[NH2:32][CH2:33][CH2:34][N:35]1[C:44]2[C:39](=[C:40]([F:49])[CH:41]=[CH:42][C:43]=2[O:45][CH2:46][CH2:47][CH3:48])[C:38](=[O:50])[C:37]([C:51]2[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][CH:52]=2)=[CH:36]1>O.CN(C=O)C>[F:49][C:40]1[CH:41]=[CH:42][C:43]([O:45][CH2:46][CH2:47][CH3:48])=[C:44]2[C:39]=1[C:38](=[O:50])[C:37]([C:51]1[CH:52]=[CH:53][C:54]([O:57][CH3:58])=[CH:55][CH:56]=1)=[CH:36][N:35]2[CH2:34][CH2:33][NH:32][C:12]([C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10][OH:11])=[O:14]
Reactant: CCCOc1ccc(F)c2c(=O)c(-c3ccc(OC)cc3)cn(CCN)c12
Reactant: CC(C)(C)OC(=O)N[C@@H](CO)C(=O)O
Agent: CCOP(=O)(C#N)OCC
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: CCCOc1ccc(F)c2c(=O)c(-c3ccc(OC)cc3)cn(CCNC(=O)[C@H](CO)NC(=O)OC(C)(C)C)c12
Temperature: 25 °C
Reaction time: 20 h
Yield: 74.8 %

Procedure:
A DMF solution (0.5 ml) of N-(tert-butoxycarbonyl)-L-serine (174 mg, 0.85 mmol), triethylamine (198 mg, 1.96 mmol), diethyl phosphorocyanidate (DEPC, 176 mg, 0.97 mmol) and DMF (0.5 ml) were sequentially added to a DMF solution (1 ml) of 1-(2-aminoethyl)-5-fluoro-3-(4-methoxyphenyl)-8-propoxy-1H-quinolin-4-one (300 mg, 0.81 mmol) while ice-cooling, and stirred at room temperature for 20 hours. Water was added to the reaction mixture and then subjected to extraction using ethyl acetate. The thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution twice. The washed product was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified using silica gel column chromatography (dichloromethane:methanol=40:1→30:1). The purified product was concentrated to dryness under reduced pressure, giving a white amorphous solid of tert-butyl ((S)-1-{2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]ethylcarbamoyl}-2-hydroxyethyl)carbamate (338 mg, yield: 75%).
Reaction SMILES: [C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH2:7].C([O:11][C:12](=O)[C:13](Br)([CH3:15])[CH3:14])C>C(O)C>[CH3:14][C:13]1([CH3:15])[NH:8][CH:1]2[CH:2]([CH2:3][CH2:4][CH2:5][CH2:6]2)[NH:7][C:12]1=[O:11]
Reactant: CCOC(=O)C(C)(C)Br
Reactant: Nc1ccccc1N
Solvent: CCO
Product: CC1(C)NC2CCCCC2NC1=O

Procedure:
5.4 parts of o-phenylene diamine are placed in a flask and ethyl-2-bromoisobutyrate added thereto with ethanol solvent. The reaction mixture is heated and 3,3-dimethyl-3,4-dihydroquinoxalin-2-one is recovered. Upon hydrogenation in the presence of catalyst, 3,3-dimethyl-decahydroquinoxalin-2-one is formed which, when used at 0.5 phr concentration in polypropylene in a manner analogous to that set forth in Example 1A hereinabove, provides stabilization for about 2000 hours (see Table I)
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13]CCCO2)=[CH:4][C:3]=1[N+:14]([O-])=O.[H][H].[Cl:19][CH2:20][C:21](Cl)=[O:22].C(=O)(O)[O-].[Na+]>[Ni].O1CCCC1>[Cl:19][CH2:20][C:21]([NH:14][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:2]=1[OH:1])[CH:8]=[O:13])=[O:22]
Reactant: O=[N+]([O-])c1cc(C2OCCCO2)ccc1O
Reactant: O=C(Cl)CCl
Reactant: [H][H]
Agent: [Ni]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: O=Cc1ccc(O)c(NC(=O)CCl)c1
Reaction time: 1 h
Yield: 52.7 %

Procedure:
2-[4-Hydroxy-3-nitro-phenyl]-1,3-dioxane (5.6 g, 24.9 mmol) is reduced in the presence of Raney nickel in 50 mL of tetrahydrofuran (THF) under a hydrogen atmosphere. When the theoretical amount of hydrogen is taken up, the catalyst is removed by filtration. Chloroacetyl chloride (2.5 g, 22.2 mmol) and sodium bicarbonate (3.6 g, 42.3 mmol) are added to the filtrate at room temperature and the mixture is stirred for 1 hour under argon. The solvent is evaporated and the remaining solid is taken up in 50 mL of methanol. The solution is acidified to a pH of about one with 1.0 N HCl and stirred at room temperature for 1 hour. The precipitate is collected and dried under vacuum to give 2.5 g (65% yield) of 3-(chloroacetylamino)-4-hydroxy-benzaldehyde as a hydrate; mp 190-192° C.
Reaction SMILES: [Br:1][C:2]1[C:3]([Cl:22])=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[CH3:23][N:24]([CH3:30])[CH2:25][CH2:26][CH2:27][NH:28][CH3:29].[CH3:31][CH2:32][N:33]([CH:37]([CH3:39])[CH3:38])[CH:34]([CH3:36])[CH3:35]>CC(O)C>[Br:1][C:2]1[C:3]([N:28]([CH2:27][CH2:26][CH2:25][N:24]([CH3:30])[CH3:23])[CH3:29])=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[CH3:31][CH2:32][N:33]([CH:37]([CH3:39])[CH3:38])[CH:34]([CH3:36])[CH3:35].[ClH:22]
Reactant: O=C(Nc1ccc(OC(F)(F)F)cc1)c1cnc(Cl)c(Br)c1
Reactant: CNCCCN(C)C
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: CN(C)CCCN(C)c1ncc(C(=O)Nc2ccc(OC(F)(F)F)cc2)cc1Br
Product: Cl
Temperature: 25 °C

Procedure:
A mixture of 5-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 12.2, 237 mg, 0.60 mmol), N1,N1,N3-trimethylpropane-1,3-diamine (84 mg, 0.72 mmol), iPrOH (2.4 mL) and DIPEA (0.205 mL, 0.155 g, 1.2 mmol) were subjected to MW irradiation at 140° C. for 120 min. The vial was cooled to RT and the RM was evaporated to dryness under reduced pressure. No further purification was required to afford the title compound in an equimolar mixture with DIPEA hydrochloride. UPLC-MS (Condition 8) tR=2.18 min, m/z=475.1 [M+H]+, m/z=473.1 [M−H]−.