Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17](=[O:29])[NH:18][C:19]3[CH:20]=[N:21][C:22]4[C:27]([CH:28]=3)=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C>FC(F)(F)C(O)=O.O.ClCCl>[N:21]1[C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:28]=[C:19]([NH:18][C:17]([C:13]2[CH:12]=[C:11]3[C:16](=[CH:15][CH:14]=2)[NH:8][CH2:9][CH2:10]3)=[O:29])[CH:20]=1
Reactant: CC(C)(C)OC(=O)N1CCc2cc(C(=O)Nc3cnc4ccccc4c3)ccc21
Solvent: ClCCl
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: O=C(Nc1cnc2ccccc2c1)c1ccc2c(c1)CCN2
Yield: 99.2 %

Procedure:
A solution of 5-(Quinolin-3-ylcarbamoyl)-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (1.4 g, 3.59 mmol) in trifluoroacetic acid (9 mL), water (1 mL) and dichloromethane (20 mL) was stirred at room temperature for 18 hours. The solvents were evaporated in vacuo and the residue was triturated in aqueous sodium bicarbonate. The product was collected by filtration and washed with water, to give an off white solid 1.03 g (99%). MS: m/z 290 (MH+). 1H NMR (DMSO-d6): δ 3.02 (t, 2 H), 3.56 (t, 2 H), 6.27 (br s, 1 H), 6.54 (d, 1 H), 7.56 (t, 1 H), 7.64 (t, 1 H), 7.71-7.76 (m, 2 H), 7.94 (m, 2 H), 8.82 (d, 1 H), 9.14 (d, 1 H) and 10.23 (s, 1 H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([CH:14]([S:16][CH2:17][C:18]([N:20]2[CH2:25][CH2:24]O[CH2:22][CH2:21]2)=[O:19])[CH3:15])=[CH:10][CH:9]=1.[CH2:26]1CCCCC1.C(OCC)(=O)C>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([CH:14]([S:16][CH2:17][C:18]([N:20]2[CH2:25][CH2:24][CH2:26][CH2:22][CH2:21]2)=[O:19])[CH3:15])=[CH:10][CH:9]=1
Reactant: CC(SCC(=O)N1CCOCC1)c1ccc(-c2ccccc2Cl)cc1
Reactant: C1CCCCC1
Solvent: CCOC(C)=O
Product: CC(SCC(=O)N1CCCCC1)c1ccc(-c2ccccc2Cl)cc1

Procedure:
[1-(2'-Chloro-4-biphenylyl)-ethylthio]-acetic acid morpholide, oil, Rf -value: 0.4 on carrier 1 with cyclohexane/ethyl acetate = 1:1.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:12][C@H:13]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][CH:19]([C:22]2[CH:23]=[C:24]([NH:28][C:29](=[O:33])[CH:30]([CH3:32])[CH3:31])[CH:25]=[CH:26][CH:27]=2)[CH2:18][CH2:17]1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:12][C@H:13]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][CH:19]([C:22]3[CH:23]=[C:24]([NH:28][C:29](=[O:33])[CH:30]([CH3:32])[CH3:31])[CH:25]=[CH:26][CH:27]=3)[CH2:18][CH2:17]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: O=S(=O)(Cl)c1ccc(F)cc1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CC[C@H](N)c3ccccc3)CC2)c1
Product: CC(C)C(=O)Nc1cccc(C2CCN(CC[C@H](NS(=O)(=O)c3ccc(F)cc3)c3ccccc3)CC2)c1

Procedure:
Prepared by Procedure Q1 and Scheme AC using 4-fluorobenzenesulfonyl chloride and N-(3-{1-[(3S)-3-amino-3-phenylpropyl]-4-piperidinyl}phenyl)-2-methylpropanamide: ESMS m/e: 538.1 (M+H)+.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][S:5](Cl)(=[O:7])=[O:6].N1C=CC=CC=1.[C:15]([O:19][C:20]([C@H:22]([C@@H:32]([CH2:37][CH:38]([CH3:40])[CH3:39])[C:33]([NH:35][NH2:36])=[O:34])[CH2:23]/[CH:24]=[CH:25]/[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>ClCCl>[C:15]([O:19][C:20]([C@H:22]([C@@H:32]([CH2:37][CH:38]([CH3:40])[CH3:39])[C:33]([NH:35][NH:36][S:5]([CH2:4][CH2:3][CH2:2][Cl:1])(=[O:7])=[O:6])=[O:34])[CH2:23]/[CH:24]=[CH:25]/[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:21])([CH3:18])([CH3:17])[CH3:16]
Reactant: CC(C)C[C@@H](C(=O)NN)[C@H](C/C=C/c1ccccc1)C(=O)OC(C)(C)C
Reactant: O=S(=O)(Cl)CCCCl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)C[C@@H](C(=O)NNS(=O)(=O)CCCCl)[C@H](C/C=C/c1ccccc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 46 %

Procedure:
1.85 g of 3-chloropropylsulphonyl chloride and 0.85 g of pyridine were added to a solution of 3.0 g of (E)-2(R)-[1(S)-(tertbutoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvalerohydrazide in 40 ml of dichloromethane. After stirring at room temperature for 2 hours the solvent was evaporated and the residue was triturated with diethyl ether. The mixture was filtered and the solvent was evaporated to give 1.92 g of (E)-2(R)-[1(S)-(tertbutoxycarbonyl)-4-phenyl-3-butenyl]-2′-(3-chloropropylsulphonyl)-4-methylvalerohydrazide in the form of a pale yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[Cl:12])=[O:5].ClC1C=CC=CC=1C(O)C1C=CC(Cl)=CC=1>>[Cl:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[CH:4]([OH:5])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[Cl:12]
Reactant: O=C(c1ccccc1Cl)c1ccccc1Cl
Agent: OC(c1ccc(Cl)cc1)c1ccccc1Cl
Product: OC(c1ccccc1Cl)c1ccccc1Cl

Procedure:
This material was prepared from 2,2′-dichlorobenzophenone using the procedure described for compound (7) (8.96 g, 89%).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][NH2:12])(=[O:10])=[O:9])=[CH:4][CH:3]=1.CN([CH:16]=[C:17]1[C:22](=[O:23])[CH2:21][CH2:20][CH2:19][C:18]1=[O:24])C>CCO>[O:23]=[C:22]1[CH2:21][CH2:20][CH2:19][C:18](=[O:24])[C:17]1=[CH:16][NH:12][NH:11][S:8]([C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=1)(=[O:10])=[O:9]
Reactant: Cc1ccc(S(=O)(=O)NN)cc1
Reactant: CN(C)C=C1C(=O)CCCC1=O
Solvent: CCO
Product: Cc1ccc(S(=O)(=O)NNC=C2C(=O)CCCC2=O)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 100 %

Procedure:
According to Scheme 3 Step 1: 4-Methylbenzenesulfonohydrazide (44.6 mmol, 8.31 g) was added to a solution of 2-((dimethylamino)methylene)cyclohexane-1,3-dione (44.6 mmol, 7.46 g) in EtOH (50 mL) and the reaction mixture was stirred at room temperature for 5 minutes. After evaporation, 13.8 g (44.6 mmol, 100%) of N′-((2,6-dioxocyclohexylidene)methyl)-4-methylbenzenesulfonohydrazide were obtained as an orange oil.
Reaction SMILES: N1CCCC1.[CH:6](=[CH:13][C:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=O)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH:22]1[CH2:26][CH:25]=[CH:24][CH:23]=1.C(O)(=O)C>CO.C(OCC)C.O>[C:7]1([C:6]2[CH2:13][CH:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:24]3[C:25]=2[CH:26]=[CH:22][CH:23]=3)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: C1=CCC=C1
Reactant: O=C(C=Cc1ccccc1)c1ccccc1
Solvent: C1CCNC1
Solvent: CO
Solvent: CCOCC
Product: C1=CC2=C(c3ccccc3)CC(c3ccccc3)C2=C1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 55.1 %

Procedure:
230 g (324 mmol) of pyrrolidine are added dropwise at 0° C. over a period of 45 minutes to a mixture of 45.0 g (216 mmol) of benzalacetophenone and 42.8 g (648 mmol) of cyclopentadiene in 350 ml of methanol. The red reaction solution is stirred for 40 minutes at room temperature and is subsequently admixed at 0° C. with 21 g (346 mmol) of glacial acetic acid. After addition of 300 ml of water and 500 ml of diethyl ether, the product is extracted. The aqueous phase is extracted twice with 250 ml each time of diethyl ether, the combined ether phases are dried over MgSO4 and the solvent is removed under reduced pressure. The crude product is distilled in an oil pump vacuum, giving 30.5 g (55%) of 4,6-diphenyl-5,6-dihydropentalene.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]#[N:11].[O-:12][CH2:13][CH3:14].[Na+].[Na].C(O)C>C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]([C:13](=[O:12])[CH3:14])[C:10]#[N:11]
Reactant: CC[O-]
Reactant: N#CCc1ccc(Cl)cc1Cl
Agent: [Na+]
Agent: [Na]
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: O
Product: CC(=O)C(C#N)c1ccc(Cl)cc1Cl
Reaction time: 8 h

Procedure:
A solution of 2,4-dichlorophenylacetonitrile (30.00 gms, 161 mmol) (Aldrich) in dry ethyl acetate (36 ml) was added dropwise to an ethanolic solution of sodium ethoxide, prepared in situ from sodium metal (4.90 g, 213 mmol) and dry ethanol (60 ml). This reaction mixture was refluxed for two hours, allowed-to stand overnight at room temperature and the ethanol was evaporated. The yellow solid obtained was dissolved in water and the resulting solution was extracted twice with ether. The aqueous layer was chilled and acidified with hydrochloric acid. The crude product was extracted with ether to give 23.31 g of white solid.
Reaction SMILES: [F:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[C:5]([F:10])[C:3]=1[NH2:4].[ClH:11].[Cl:12][CH2:13][CH2:14][NH:15][CH2:16][CH2:17]Cl.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>O.CO.C(Cl)(Cl)Cl>[ClH:12].[ClH:11].[F:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[C:5]([F:10])[C:3]=1[N:4]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1
Reactant: Nc1c(F)cc(F)cc1F
Reactant: ClCCNCCCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Solvent: O
Product: Fc1cc(F)c(N2CCNCC2)c(F)c1
Yield: 7.1 %

Procedure:
To a solution of 2,4,6-trifluoroaniline (4.4 g) an bis(2-chloroethyl)amine hydrochloride (6.4 g) in water (4.2 ml) was added dropwise a solution of sodium carbonate (3.8 g) in water (8.9 ml) over 40 min under reflux under heating and the mixture was further refluxed under heating for 5.5 hr. To the reaction mixture was added an aqueous solution (8.9 ml) of sodium hydroxide (3.6 g) and the mixture was further refluxed under heating for 2.5 hr. The reaction mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated to give a dark brown oil. The oil was subjected to silica gel column chromatography (developing solvent; chloroform:methanol=9:1) to give the title compound (0.61 g) as a pale-brown solid.
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([CH:10]2[C:15]3[N:16]([CH3:19])[CH:17]=[N:18][C:14]=3[CH2:13][CH2:12][NH:11]2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[CH3:20][O:21][C:22]1[CH:23]=[C:24]([S:28]([NH:31][CH2:32][CH2:33][C:34](O)=[O:35])(=[O:30])=[O:29])[CH:25]=[CH:26][CH:27]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CN1CCOCC1>CN(C=O)C>[C:4]([C:3]1[CH:6]=[CH:7][C:8]([CH:10]2[C:15]3[N:16]([CH3:19])[CH:17]=[N:18][C:14]=3[CH2:13][CH2:12][N:11]2[C:34](=[O:35])[CH2:33][CH2:32][NH:31][S:28]([C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([O:21][CH3:20])[CH:23]=2)(=[O:30])=[O:29])=[CH:9][C:2]=1[F:1])#[N:5]
Reactant: Cn1cnc2c1C(c1ccc(C#N)c(F)c1)NCC2
Reactant: COc1cccc(S(=O)(=O)NCCC(=O)O)c1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: COc1cccc(S(=O)(=O)NCCC(=O)N2CCc3ncn(C)c3C2c2ccc(C#N)c(F)c2)c1
Reaction time: 18 h

Procedure:
2-Fluoro-4-(3-methyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-4-yl)-benzonitrile (Step E) (0.034 g, 0.132 mmol), 3-(3-methoxy-benzenesulfonylamino)-propionic acid (Step G) 0.041 g, 0.16 mmol), HOBT (0.022 g, 0.16 mmol), EDC (0.031 g, 0.16 mmol) and N-methylmorpholine (0.043 mL, 0.40 mmol) were dissolved in DMF (3 mL) and stirred for 18 h. The reaction mixture was concentrated in vacuo, diluted with CH2Cl2 and saturated NaHCO3 solution and separated. The aqueous layer was washed with CH2Cl2 (2×, the organic layers combined, dried (Na2SO4), filtered and concentrated to give the title compound.
Reaction SMILES: [CH3:1][C:2]1[C:3]2[C:8]([CH:9]=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[C:16](Cl)(=[O:20])[C:17](Cl)=[O:18].[Cl-].[Al+3].[Cl-].[Cl-].Cl>C(=S)=S>[CH3:1][C:2]1[C:3]2[C:8](=[CH:7][CH:6]=[CH:5][CH:4]=2)[C:9]2=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[C:11]3[C:16](=[O:20])[C:17]2=[O:18]
Reactant: Cc1c2ccccc2cc2ccccc12
Reactant: O=C(Cl)C(=O)Cl
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Product: Cc1c2ccccc2c2c3c(cccc13)C(=O)C2=O
Reaction time: 2 h

Procedure:
To a cold (−10° C., brine/ice cooling bath) stirred mixture of 5.43 g (28.2 mmol) of 9-methylanthracene and oxalyl chloride (13.50 mL, 159.5 mmol) in CS2 (60 mL) was added aluminium chloride (6.0 g, 45 mmol). The solution changed from a red-orange colour to a very intense dark crimson colour and vigorous effervescence was observed (hydrogen chloride) and an exotherm occurred raising the reaction temperature from −10° C. to −4° C. After a few minutes stirring the exotherm eased off and an intense dark red tar deposited from the solution which lightened to a yellow colour, the reaction mixture was then stirred cold for a period of 2 hours. After 2 hours, additional CS2 (60 mL) and aluminium chloride (4.5 g, 33.7 mmol) were added, and stirring was continued for 2 hours at 0° C. and then overnight at room temperature. HCl (2M, aq, 150 mL) was then added to the reaction mixture [NOTE: Extreme caution, very exothermic reaction ensues that causes vigorous reflux of reaction solvent], the reaction mixture was then stirred vigorously for 2 hours (large egg-shaped magnetic stirrer follower stirred at 1250 rpm) to decompose the dark red tar to an orange precipitate which was then collected by filtration, washed with water (2×150 mL), and then digested well with 300 mL of 5% NaOH(aq) for a period of 1 hour. The insoluble solids were collected by filtration, washed with water (2×50 mL), and dried in vacuo in a vacuum oven (oil immersion pump) to constant mass (22 hours). Yield: 2.411 g (34.7%, pale orange powder).
Reaction SMILES: [CH3:1][C:2]1[N:6]2[C:7]3[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][C:8]=3[N:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:10](=[O:12])[CH2:11][C:5]2=[N:4][N:3]=1.[C:24](OC(=O)C)(=[O:26])[CH3:25]>N1C=CC=CC=1>[CH3:1][C:2]1[N:6]2[C:7]3[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:26])[CH3:25])=[CH:19][C:8]=3[N:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:10](=[O:12])[CH2:11][C:5]2=[N:4][N:3]=1
Reactant: Cc1nnc2n1-c1ccc(N)cc1N(c1ccccc1)C(=O)C2
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)Nc1ccc2c(c1)N(c1ccccc1)C(=O)Cc1nnc(C)n1-2

Procedure:
3.47 g of 1-methyl-8-amino-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one and 1.02 g of acetic anhydride in 50 ml pyridine is stirred for 12 hours then refluxed for 30 minutes. The reaction is evaporated; the residue is taken up in chloroform, washed with dilute aqueous sodium bicarbonate, with water and dried. The solvent is evaporated to give the title compound.
Reaction SMILES: ClN1C(=O)CCC1=O.[CH2:9]([S:11][CH2:12][CH3:13])[CH3:10].[CH2:14]([C@H:21]([NH:46][C:47](=[O:59])[C@@H:48]([N:52]1[CH2:57][CH2:56][CH2:55][NH:54][C:53]1=[O:58])[CH:49]([CH3:51])[CH3:50])[CH2:22][C@H:23]([OH:45])[C@@H:24]([NH:32][C:33](=[O:44])[CH2:34][O:35][C:36]1[C:41]([CH3:42])=[CH:40][CH:39]=[CH:38][C:37]=1[CH3:43])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(CC)CC)C>O1CCCC1>[CH2:14]([C@H:21]([NH:46][C:47](=[O:59])[C@@H:48]([N:52]1[CH2:57][CH2:56][CH2:55][NH:54][C:53]1=[O:58])[CH:49]([CH3:51])[CH3:50])[CH2:22][C@H:23]([O:45][CH:9]([S:11][CH2:12][CH3:13])[CH3:10])[C@@H:24]([NH:32][C:33](=[O:44])[CH2:34][O:35][C:36]1[C:37]([CH3:43])=[CH:38][CH:39]=[CH:40][C:41]=1[CH3:42])[CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: Cc1cccc(C)c1OCC(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@H](Cc1ccccc1)NC(=O)[C@H](C(C)C)N1CCCNC1=O
Reactant: CCSCC
Agent: O=C1CCC(=O)N1Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCSC(C)O[C@@H](C[C@H](Cc1ccccc1)NC(=O)[C@H](C(C)C)N1CCCNC1=O)[C@H](Cc1ccccc1)NC(=O)COc1c(C)cccc1C
Temperature: -10 °C
Reaction time: 1.5 h

Procedure:
A slurry of N-chlorosuccinimide (6.5 g, 48.7 mmol) in tetrahydrofuran (50 mL) was cooled to −10° C., followed by addition of diethyl sulfide (7.0 mL) and then by addition of a solution of Example 3 (5.0 g) in tetrahydrofuran (20 mL). A solution of triethylamine (9.0 mL) in tetrahydrofuran (15 mL) was then added dropwise and the mixture was stirred at −10° C. for 1.5 h. The reaction was quenched with 10% Na2CO3 and extracted twice with ethyl acetate. The combined organic was washed with water and brine and dried over MgSO4, filtered and evaporated to give the crude product (7.5 g).
Reaction SMILES: [CH3:1][C:2]1[CH:26]=[C:25]([CH3:27])[CH:24]=[C:23]([CH3:28])[C:3]=1[C:4]([P:6]([CH2:19][C:20]([OH:22])=[O:21])([C:8](=[O:18])[C:9]1[C:14]([CH3:15])=[CH:13][C:12]([CH3:16])=[CH:11][C:10]=1[CH3:17])=[O:7])=[O:5].C(=O)([O-])O.[Na+:33]>O>[CH3:15][C:14]1[CH:13]=[C:12]([CH3:16])[CH:11]=[C:10]([CH3:17])[C:9]=1[C:8]([P:6]([C:4](=[O:5])[C:3]1[C:23]([CH3:28])=[CH:24][C:25]([CH3:27])=[CH:26][C:2]=1[CH3:1])([CH2:19][C:20]([O-:22])=[O:21])=[O:7])=[O:18].[Na+:33]
Reactant: Cc1cc(C)c(C(=O)P(=O)(CC(=O)O)C(=O)c2c(C)cc(C)cc2C)c(C)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: Cc1cc(C)c(C(=O)P(=O)(CC(=O)[O-])C(=O)c2c(C)cc(C)cc2C)c(C)c1

Procedure:
2-(bis(2,4,6-trimethylbenzoyl)phosphoryl)acetic acid (example 18b) (0.1 g, 0.25 mmol, 1 eq.) is suspended in distilled water (2 ml) and sodium hydrogencarbonate (21.0 mg, 0.25 mmol, 1 eq.) is added. A clear pale yellow solution is obtained. After removing the water in vacuo at room temperature, a pale yellow crystalline powder is isolated (Yield: quantitative). It is evident that the same procedure can be performed to synthesise other alkali salts of 2-(bis(2,4,6-trimethylbenzoyl)phosphoryl)acetic acid from carbonates or hydrogen-carbonates (e.g. with potassium hydrogen carbonate, or lithium carbonate).
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N+:10]([O-])=O)[C:5]=1[CH2:13][N:14]=[N+]=[N-].C(O)C>[Pd].C(O)(=O)C>[NH2:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:4]2[C:5]=1[CH2:13][NH:14][C:3]2=[O:2]
Reactant: COC(=O)c1cccc([N+](=O)[O-])c1CN=[N+]=[N-]
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCO
Product: Nc1cccc2c1CNC2=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 62.9 %

Procedure:
1 g (4.2 mmol) of 2-(azidomethyl)-3-nitrobenzoic acid methyl ester is added to 10 ml of ethanol and 2 ml of glacial acetic acid and mixed with 148.5 mg of Pd/C. After stirring overnight at room temperature under hydrogen atmosphere, the catalyst is suctioned off via a glass-fiber filter, and the filtrate is evaporated to the dry state. The residue is chromatographed on a Flashmaster (mobile solvent). 391.5 mg (62.4%) of the desired compound is isolated.
Reaction SMILES: [Cl-].O[NH3+].CC[O:6]CC.[CH2:9]([O:11][C:12](=[NH:24])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH3:10]>O>[C:12](=[N:24][OH:6])([O:11][CH2:9][CH3:10])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCCCCCCCCC(=N)OCC
Reactant: CCOCC
Agent: [Cl-]
Agent: [NH3+]O
Solvent: O
Product: CCCCCCCCCCCC(=NO)OCC
Temperature: 2 °C
Yield: 77 %

Procedure:
A mixture containing fourteen grams of hydroxylammonium chloride dissolved in 100 ml of water was added to 100 ml of ether in a 250 ml flask. The resulting mixture was cooled to 2° C. and 45.4 g of ethyldodecaneimidate were added to the mixture with stirring. The reaction mixture was stirred for an additional 30 minutes at 2° C. The layers were separated and the aqueous layer was extracted three times with 75 ml of ether. The ether layer and washings were combined and then dried over sodium sulfate and concentrated to yield 37.3 g (77% yield) of ethyl dodecane hydroximate as a white, solid substance. IR and NMR analyses confirmed the structure.
Reaction SMILES: [C:1]([OH:9])(=[O:8])[C:2]([CH2:4][C:5](O)=[O:6])=[CH2:3].[CH2:10]([NH2:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>O>[CH2:10]([N:17]1[C:5](=[O:6])[CH2:4][CH:2]([C:1]([OH:9])=[O:8])[CH2:3]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: NCc1ccccc1
Reactant: C=C(CC(=O)O)C(=O)O
Solvent: O
Product: O=C(O)C1CC(=O)N(Cc2ccccc2)C1
Temperature: 130 °C
Reaction time: 0.5 h

Procedure:
A mixture of itaconic acid (130 g, 1.00 mol) and benzylamine (107 g, 1.00 mol) were heated to 130° C. After 30 minutes, the reaction mixture was cooled and diluted with water (200 mL). The resulting slurry was filtered, washed with cold water, dissolved in aqueous sodium hydroxide, and treated with active carbon. The slurry was filtered to remove the carbon, and the aqueous solution was acidified with hydrochloric acid to precipitate solids. The solids were recrystallized from ethanol to afford 1-benzyl-5-oxopyrrolidine-3-carboxylic acid that was used without additional purification.
Reaction SMILES: [N:1]([CH3:4])=[C:2]=[O:3].[NH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([NH:20][C:21]3[N:25]([CH2:26][C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)[C:24]4[CH:34]=[CH:35][CH:36]=[CH:37][C:23]=4[N:22]=3)[CH2:16][CH2:15]2)=[CH:8][CH:7]=1>O1CCCC1>[F:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][N:25]2[C:24]3[CH:34]=[CH:35][CH:36]=[CH:37][C:23]=3[N:22]=[C:21]2[NH:20][CH:17]2[CH2:16][CH2:15][N:14]([CH2:13][CH2:12][C:9]3[CH:10]=[CH:11][C:6]([NH:5][C:2]([NH:1][CH3:4])=[O:3])=[CH:7][CH:8]=3)[CH2:19][CH2:18]2)=[CH:32][CH:31]=1
Reactant: Nc1ccc(CCN2CCC(Nc3nc4ccccc4n3Cc3ccc(F)cc3)CC2)cc1
Reactant: CN=C=O
Solvent: C1CCOC1
Product: CNC(=O)Nc1ccc(CCN2CCC(Nc3nc4ccccc4n3Cc3ccc(F)cc3)CC2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 39.9 %

Procedure:
A mixture of 0.6 parts of isocyanatomethane, 4.43 parts of N-[1-[2-(4-aminophenyl)ethyl]-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine and 135 parts of tetrahydrofuran was stirred for 3 hours at room temperature. The precipitated product was filtered off and crystallized from acetonitrile, yielding 2 parts (39.9%) of N-[4-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]phenyl]-N'methylurea; mp. +300° C. (compound 57).
Reaction SMILES: [NH2:1][C@@H:2]1[C@@H:7]2[O:8][C@@H:4]([CH2:5][CH2:6]2)[C@@H:3]1[C:9]([O:11][CH3:12])=[O:10].CCN(CC)CC.[O:20](C(OC(C)(C)C)=O)[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=O>C(#N)C>[C:24]([O:23][C:21]([NH:1][C@@H:2]1[C@@H:7]2[O:8][C@@H:4]([CH2:5][CH2:6]2)[C@@H:3]1[C:9]([O:11][CH3:12])=[O:10])=[O:20])([CH3:27])([CH3:26])[CH3:25]
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Reactant: COC(=O)[C@@H]1[C@H](N)[C@H]2CC[C@@H]1O2
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COC(=O)[C@@H]1[C@H](NC(=O)OC(C)(C)C)[C@H]2CC[C@@H]1O2
Temperature: 80 °C
Yield: 92.1 %

Procedure:
A solution of (1S,2R,3S,4R)-methyl 3-amino-7-oxabicyclo[2.2.1]heptane-2-carboxylate (11) (500 mg, 2.4 mmol), Et3N (0.85 ml, 6 mmol) and BOC2O (0.66 ml, 2.88 mmol) in acetonitrile was stirred at rt for 2 h and then heated at 80° C. for 30 min when TLC confirmed completion of reaction. Acetonitrile was removed and the crude product was purified by column chromatography using silica gel (100-200 mesh) to afford the desired compound (600 mg, 92%) as a colourless oil.
Reaction SMILES: [CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13]([NH:15][CH:16]([CH3:21])[CH2:17][C:18](O)=[O:19])=[O:14])=[CH:11][N:10]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:7]3=[N:8][CH:9]=2)[CH2:3][CH2:2]1.C(Cl)CCl.Cl.[CH2:35]([NH2:37])[CH3:36]>C(Cl)Cl.CN(C)C1C=CN=CC=1.O>[CH2:35]([NH:37][C:18]([CH2:17][CH:16]([NH:15][C:13]([C:12]1[C:6]2[C:7](=[N:8][CH:9]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[N:5]=2)[N:10]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:27])[CH3:28])[CH:11]=1)=[O:14])[CH3:21])=[O:19])[CH3:36]
Reactant: CCN
Reactant: CC(CC(=O)O)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(C3CC3)nc12
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCCl
Solvent: O
Solvent: ClCCl
Product: CCNC(=O)CC(C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(C3CC3)nc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.5 %

Procedure:
To a solution of 3-{[2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-butyric acid (0.14 g, 0.33 mmol) in CH2Cl2 (5 mL) was added EDC (0.083 g, 0.43 mmol), 4-(dimethylamino)pyridine (0.053 g, 0.43 mmol), and ethylamine hydrochloride (0.035 g, 0.43 mmol). The reaction mixture was stirred at room temperature overnight then diluted with H2O and extracted with CH2Cl2. The combined organics were washed with brine, dried over Na2SO4 and concentrated. The residue was purified by SiO2 chromatography (2% MeOH/CH2Cl2) to obtain 0.114 g (78%) of 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-ethylcarbamoyl-1-methyl-ethyl)-amide as an oil.