Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([CH2:4][C@@H:5]1[C@@H:9](O)[CH2:8][N:7]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6]1)=[N+:2]=[N-:3].C(N(S(F)(F)[F:24])CC)C.C(=O)(O)[O-].[Na+]>ClCCl>[N:1]([CH2:4][C@@H:5]1[C@@H:9]([F:24])[CH2:8][N:7]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6]1)=[N+:2]=[N-:3]
Reactant: CCN(CC)S(F)(F)F
Reactant: [N-]=[N+]=NC[C@H]1CN(Cc2ccccc2)C[C@@H]1O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: [N-]=[N+]=NC[C@H]1CN(Cc2ccccc2)C[C@@H]1F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
(3R,4R)-3-Azidomethyl-1-benzyl-4-hydroxypyrrolidine (566 mg) was dissolved in dichloromethane (9 mL). While this solution was chilled in an ice water bath, diethylaminosulfur trifluoride (0.39 mL) was added dropwise and the mixture was stirred at room temperature for 2 hours. While the reaction vessel was chilled in an ice water bath, a saturated aqueous solution of sodium bicarbonate (9 mL) was added and the mixture was diluted with dichloromethane (15 mL). The dichloromethane layer was separated, washed sequentially with a saturated aqueous solution of sodium bicarbonate (10 mL) and water (10 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: hexane: ethyl acetate=4:1). The first half fraction yielded (3R,4R)-3-azidomethyl-1-benzyl-4-fluoropyrrolidine as a pale brown oil (76.7 mg).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]=[CH:9][C:10](=[O:12])[CH3:11].C[O:14][C:15]1C=CC=C[C:16]=1C1CC(=O)CC(=O)C1>>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:16][C:15](=[O:14])[CH2:11][C:10](=[O:12])[CH2:9]1
Reactant: COc1ccccc1C1CC(=O)CC(=O)C1
Reactant: CC(=O)C=Cc1ccccc1F
Product: O=C1CC(=O)CC(c2ccccc2F)C1

Procedure:
The title compound was prepared from 4-(2-fluoro-phenyl)-but-3-en-2-one (7.3 g, 44.5 mmol), stage 1, following the procedure describing the synthesis of 5-(2-methoxy-phenyl)-cyclohexane-1,3-dione (example 1/a stage 2).
Reaction SMILES: [CH2:1]([C:4]1[N:5]=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[O:7][C:8]=1[CH3:9])[CH:2]=[CH2:3].B1C2CCCC1CCC2.[OH-:27].[Na+].OO>O.C1COCC1>[CH3:17][O:16][C:13]1[CH:12]=[CH:11][C:10]([C:6]2[O:7][C:8]([CH3:9])=[C:4]([CH2:1][CH2:2][CH2:3][OH:27])[N:5]=2)=[CH:15][CH:14]=1
Reactant: [OH-]
Reactant: C=CCc1nc(-c2ccc(OC)cc2)oc1C
Agent: B1C2CCCC1CCC2
Agent: OO
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(-c2nc(CCCO)c(C)o2)cc1
Reaction time: 2 h

Procedure:
The above prepared 4-allyl-2-(4-methoxy-phenyl)-5-methyl-oxazole (4.51 g, 19.7 mmol) was dissolved in 60 ml of abs. THF and and treated at 0° with 100 ml of 9-BBN-solution (0.5 M hexane). Hydroboration was allowed to proceed for 2 h at RT. Afterwards, 56 ml of 3N NaOH and 114.5 ml of 30% H2O2 was added simultaneously, whereby the internal temperature rose to 45°. After 1 h, the heterogeneous mixture was diluted with ice and water, extracted twice with AcOEt, washed water, and dried over natrium sulfate. Evaporation of the solvents, followed by flash chromatography (SiO2, hexane/AcOEt=1/3) yielded 4.54 g of the title compound as colorless oil.
Reaction SMILES: C(N(CC)CC)C.Br[CH2:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:14][CH:13]=1)=O.[C:24]([NH:27][N:28]=[CH:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)(=[NH:26])[NH2:25]>C(O)C>[NH2:26][C:24]1[N:27]([N:28]=[CH:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:14][CH:13]=2)[N:25]=1
Reactant: N=C(N)NN=Cc1ccccc1
Reactant: O=C(CBr)c1ccc(-c2ccccc2)cc1
Solvent: CCO
Solvent: CCN(CC)CC
Product: Nc1nc(-c2ccc(-c3ccccc3)cc2)cn1N=Cc1ccccc1
Temperature: 20 °C
Reaction time: 15 h

Procedure:
7 ml (0.0507 mol) of triethylamine and 13.75 g (0.050 mol) of 2-bromo-4'-phenylaceto-phenone (Aldrich, Buchs, Switzerland; tech., Cat. no. 10,108-7) are added to a solution of 8.11 g (0.05 mol) of benzaldehyde guanylhydrazone in 40 ml of ethanol. The reaction mixture is stirred at 20° C. for 15 hours and is filtered, and the crystallizate is taken up in methylene chloride and acidified to pH 1 with 1N hydrochloric acid. After filtration, the filtration product is taken up in methanol, and 2N sodium hydroxide solution is added until a basic reaction is obtained (pH 11). Filtration is carried out and the crystalline product is washed with methanol/water (1:1). The title compound so obtained melts at 254°-255° C. (decomp.), 1H-NMR (DMSO): δ=8.60 (s, 1H); 8.10 (s, 1H); 7.93-7.98 (m, 2H); 7.67-7.83 (m, 6H); 7.32-7.55 (m, 6H); 6.24 (s, 2H).
Reaction SMILES: [C:1]([O:5][N:6]=[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH2:17][CH2:18][CH2:19][CH2:20][OH:21])[CH:15]=2)[O:10][C:9]([C:22]2[N:27]=[CH:26][N:25]3[CH:28]=[CH:29][CH:30]=[C:24]3[CH:23]=2)=[CH:8]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:38][S:39](Cl)(=[O:41])=[O:40].[Cl-].[NH4+]>ClCCl>[C:1]([O:5]/[N:6]=[C:7]1\[CH:8]=[C:9]([C:22]2[N:27]=[CH:26][N:25]3[CH:28]=[CH:29][CH:30]=[C:24]3[CH:23]=2)[O:10][C:11]2[C:16]\1=[CH:15][C:14]([CH2:17][CH2:18][CH2:19][CH2:20][O:21][S:39]([CH3:38])(=[O:41])=[O:40])=[CH:13][CH:12]=2)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)ON=c1cc(-c2cc3cccn3cn2)oc2ccc(CCCCO)cc12
Reactant: CS(=O)(=O)Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)O/N=c1\cc(-c2cc3cccn3cn2)oc2ccc(CCCCOS(C)(=O)=O)cc12
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A ice-cooled solution of 6-(4-Hydroxy-butyl)-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one O-tert-butyl-oxime (115 mg, 0.28 mmol) (example 102B) in dichloromethane (5 ml) was treated with triethylamine (100 μl, 0.7 mmol) and dropwise with methanesulfonyl chloride (26 μl, 0.34 mmol). The mixture was stirred at room temperature for 3 hours and treated with a saturated solution of ammonium chloride, extracted with dichloromethane, washed with brine, dried over sodium sulfate and concentrated to dryness. The crude mesylate was used for the next step without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:15][C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]([OH:14])=O)=[CH:8]2.[NH4+].O[N:28]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:15][C:16]2[CH:17]=[CH:18][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][CH:21]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]([NH2:28])=[O:14])=[CH:8]2
Reactant: COc1cc(Oc2ccc(S(C)(=O)=O)cc2)cc2cc(C(=O)O)[nH]c12
Reactant: On1nnc2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: [NH4+]
Solvent: CN(C)C=O
Product: COc1cc(Oc2ccc(S(C)(=O)=O)cc2)cc2cc(C(N)=O)[nH]c12
Temperature: 0 °C
Yield: 94.2 %

Procedure:
To an ice-cooled and stirred mixture of 7-methoxy-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylic acid (0.78 g) in N,N-dimethylformamide (20 mL) were added 1-hydroxybenzotriazole ammonium salt (0.66 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.83 g). After stirred at room temperature for 7 h, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed successively with aqueous sodium hydrogen carbonate and brine, dried (MgSO4), filtered, and concentrated to give a light yellow amorphous solid, which was crystallized from ethyl acetate-hexane to give the title compound (733 mg, 94%) as pale yellow crystals. MS 361 (MH+).
Reaction SMILES: [CH2:1]([O:3][C:4]1(OC)[CH:12]=[C:11]([O:13][CH2:14][CH3:15])[CH:10]=[C:6]([C:7](O)=O)[CH:5]1[OH:16])[CH3:2].C(N(CC)CC)C.[C:26](Cl)(=O)[O:27]CC>C1COCC1>[CH2:1]([O:3][C:4]1[C:12]([O:27][CH3:26])=[C:11]([O:13][CH2:14][CH3:15])[CH:10]=[C:6]([CH3:7])[C:5]=1[OH:16])[CH3:2]
Reactant: CCOC(=O)Cl
Reactant: CCOC1=CC(OC)(OCC)C(O)C(C(=O)O)=C1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCOc1cc(C)c(O)c(OCC)c1OC

Procedure:
53 g of 3,5-diethoxy-2-hydroxy-3-methoxybenzoic acid prepared in Referential Example 5 and 45.5 g of triethylamine were dissolved in 400 ml of THF, and 48.4 g of ethyl chlorocarbonate in 100 ml of THF was dropwise added thereto with ice cooling while stirring. After the completion of the dropwise addition, the formed crystals were separated by filtration and washed with 100 ml of THF. The mother liquor was combined with the wash liquid, and a 10% aqueous solution of 30.3 g of sodium borohydride was added to the resultant solution and cooled by ice while stirring. After the completion of the dropwise addition, the mixture was stirred at room temperature for one hr, neutralized with dilute hydrochloric acid and extracted with ethyl acetate. The organic phase was washed with water, dried over anhydrous magnesium sulfate and concentrated. The concentrate was purified by silica gel column chromatography (eluent: n-hexane :ethyl acetate=95.5) to prepare 40 g of the product compound as a colorless oleaginous substance.
Reaction SMILES: C(N)(=O)[C:2]1[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=1)[C:4]([NH2:6])=[O:5].[C:13]([NH2:26])(=[O:25])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([NH2:24])=[O:23].[C:27]([NH2:36])(=[O:35])[CH2:28][CH2:29][CH2:30][CH2:31][C:32]([NH2:34])=[O:33]>>[C:4]([NH2:6])(=[O:5])[C:3]1[CH:2]=[CH:10][C:9]([C:22]([NH2:24])=[O:23])=[CH:8][CH:7]=1.[C:13]([NH2:26])(=[O:25])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([NH2:24])=[O:23].[C:27]([NH2:36])(=[O:35])[CH2:28][CH2:29][CH2:30][CH2:31][C:32]([NH2:34])=[O:33]
Reactant: NC(=O)c1ccccc1C(N)=O
Agent: NC(=O)CCCCC(N)=O
Agent: NC(=O)CCCCCCCCC(N)=O
Product: NC(=O)c1ccc(C(N)=O)cc1

Procedure:
A series of films were prepared using these above four bisamides at an equivalent molar replacement, that is, normalizing to the molecular weights of 396.5, 432.6 and 376.5 for the phthalamide, sebacamide and adipamide replacements of 390.5 m.w. hexamethoxymethyl-melamine. Removal of 1.5 g melamine from a nominal ten g solids formulation therefore resulted in replacement by 1.52 g iso- or terephthalamide, 1.66 g sebacamide and 1.43 g adipamide. Removal of drawn films after curing for 20 minutes at 300° F. as described above allowed the following dynamic mechanical analysis of crosslinking as described in Journal of Coatings Technology, 46, no. 808, 29-42 (1992) by L.W. Hill in the article 'Structure/Property Relationships of Thermoset Coatings.
Reaction SMILES: Cl.[NH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([OH:9])[CH2:5][CH2:4]1.[H-].[Na+].F[C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[CH3:23])[C:19](=[O:24])[N:18]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[CH:17]=[CH:16]2>CC(N(C)C)=O>[NH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([O:9][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][C:22]=2[CH3:23])[C:19](=[O:24])[N:18]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=2)[CH:17]=[CH:16]3)[CH2:5][CH2:4]1
Reactant: COc1ccc(Cn2ccc3cc(F)c(C)cc3c2=O)cc1
Reactant: N[C@H]1CC[C@H](O)CC1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: COc1ccc(Cn2ccc3cc(O[C@H]4CC[C@H](N)CC4)c(C)cc3c2=O)cc1
Temperature: 80 °C
Reaction time: 0.25 h

Procedure:
To a solution of 1.48 g (9.75 mmol) of trans-4-aminocyclohexanol hydrochloride in 20 ml of dimethylacetamide were added 1.95 g (48.77 mmol) of sodium hydride (60%) and the mixture was stirred for 15 minutes. Subsequently 2.90 g (9.75 mmol) of 6-fluoro-2-(4-methoxy-benzyl)-7-methyl-2H-isoquinolin-1-one in 30 ml of dimethylacetamide were added and the reaction mixture was heated to 80° C. for 2 days. After cooling, the mixture was poured into 300 ml of ice water and the precipitated crude product was purified by chromatography. First the remaining starting material was eluted with ethyl acetate/heptane (2:1) and finally the desired product was eluted by pure methanol giving 1.98 g 6-(trans-4-amino-cyclohexyloxy)-2-(4-methoxy-benzyl)-7-methyl-2H-isoquinolin-1-one.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[C:7]([C@@H:9]([NH:12][C:13]([C:15]2[C:16]3[CH:23]=[N:22][N:21]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[C:17]=3[CH:18]=[N:19][CH:20]=2)=[O:14])[CH2:10][CH3:11])[CH:6]=[CH:5][N:4]=1)=[O:2].[CH3:31][Li]>C1COCC1.C(OCC)C>[OH:2][CH:1]([C:3]1[CH:8]=[C:7]([C@@H:9]([NH:12][C:13]([C:15]2[C:16]3[CH:23]=[N:22][N:21]([C:24]4[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=4)[C:17]=3[CH:18]=[N:19][CH:20]=2)=[O:14])[CH2:10][CH3:11])[CH:6]=[CH:5][N:4]=1)[CH3:31]
Reactant: [Li]C
Reactant: CC[C@H](NC(=O)c1cncc2c1cnn2-c1ccc(F)cc1)c1ccnc(C=O)c1
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC[C@H](NC(=O)c1cncc2c1cnn2-c1ccc(F)cc1)c1ccnc(C(C)O)c1
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
To a chilled (−78° C.) solution of 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [(S)-1-(2-formyl-pyridin-4-yl)-propyl]-amide (368 mg, 0.91 mmol) in anhydrous THF (8 mL) was added a solution of 1.6 N methyl lithium (2.28 mL, 3.65 mmol) in diethyl ether and the mixture was slowly warmed to room temperature. After 3.5 hours, the reaction mixture was cooled to −78° C., quenched with saturated aqueous ammonium chloride and extracted with EtOAc (4×60 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with a gradient of 0-10% MeOH in DCM to afford 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid {(S)-1-[2-(1-hydroxy-ethyl)-pyridin-4-yl]-propyl}-amide as a light yellow foam.
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:9]1[C@@:13]2([CH3:28])[CH2:14][CH2:15][CH2:16]/[C:17](=[CH:18]\[CH:19]=[C:20]3\[CH2:21][C@@H:22]([OH:27])[CH2:23][CH2:24][C:25]\3=[CH2:26])/[C@@H:12]2[CH2:11][CH2:10]1)[CH2:3][CH2:4][CH2:5][CH:6]([CH3:8])[CH3:7].I(C1C=CC=CC=1C(O)=O)(=O)=O>C1COCC1.CS(C)=O>[CH3:8][CH:6]([CH2:5][CH2:4][CH2:3][C@H:2]([C@@H:9]1[C@:13]2([CH3:28])[C@H:12]([C@H:17]3[C@H:16]([CH2:15][CH2:14]2)[C@:25]2([CH3:26])[C@H:20]([CH2:21][C:22](=[O:27])[CH2:23][CH2:24]2)[CH2:19][CH2:18]3)[CH2:11][CH2:10]1)[CH3:1])[CH3:7]
Reactant: C=C1CC[C@H](O)C/C1=C/C=C1\CCC[C@]2(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@@H]12
Agent: O=C(O)c1ccccc1I(=O)=O
Solvent: C1CCOC1
Solvent: CS(C)=O
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Yield: 89.5 %

Procedure:
A solution of dihydrocholesterol (1.94 g; 5 mmol) in THF (8 ml) was added to a solution of o-iodoxybenzoic acid I (2.10 g, 7.5 mmol) in DMSO (14 ml). After 2 hr precipitation of a white solid was observed. After 5 hr the reaction solution was poured into Na2CO3 (5%, 40 ml) and extracted with diethyl ether/n-hexane (50:50; 3×30 ml). The combined organic layers were washed with water (2×15 ml), dried over sodium sulfate and brought to dryness under vacuum. The residue was crystallised from ethanol to give 1.73 g (89%) of 5α-cholestan-3-one mp 129°-130° C. (lit. 128°-130° C.: Beilsteins Handbuch der organischen Chemie, III E., 7, 1330b).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:4]=1[OH:12].[OH-].[Na+].Br[CH2:16][CH2:17][CH2:18][Cl:19]>C(O)(C)C>[Cl:19][CH2:18][CH2:17][CH2:16][O:12][C:4]1[CH:5]=[C:6]([N+:9]([O-:11])=[O:10])[CH:7]=[CH:8][C:3]=1[O:2][CH3:1]
Reactant: ClCCCBr
Reactant: COc1ccc([N+](=O)[O-])cc1O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Product: COc1ccc([N+](=O)[O-])cc1OCCCCl
Temperature: 75 °C
Reaction time: 8 h
Yield: 81.8 %

Procedure:
2-methoxy-5-nitrophenol (50 g, 0.30 mol) was combined with 250 mL isopropyl alcohol. 1N sodium hydroxide solution, 310 mL (0.31 mol), was added to the mixture at such a rate that the temperature remained below 40° C. After the addition was completed, the mixture was stirred for at least 30 minutes. The reaction was then charged with 1-bromo-3-chloropropane (93.1 g, 0.59 mol) in a single portion. The mixture was heated to 75° C. and monitored periodically by high performance liquid chromatography (HPLC). After 8 hours, heating was discontinued and the reaction mixture was allowed to cool to ambient temperature overnight. The product gradually precipitated from the mixture as a light yellow/tan solid. Water, 200 mL, was added in a single portion and the resulting slurry was stirred for at least 30 minutes. The slurry was filtered and washed with water. The damp crude product was slurried in 650 mL methanol and heated to reflux until the solids had dissolved or mostly dissolved. The solution was allowed to cool gradually with stirring to ambient temperature over 3-5 hours or longer. The mixture was then cooled to 10-15° C. and held for at least 30 minutes. The solids were filtered and washed with cold methanol. The product was then dried in vacuo to give 60.3 g of 2-(3-chloropropoxy)-1-methoxy-4-nitrobenzene.
Reaction SMILES: C[O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10](=[NH:13])[NH:11][OH:12])[CH:5]=1.C(N(C(C)C)CC)(C)C.[F:24][C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27](Cl)=O>C1COCC1>[F:24][C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27]1[O:12][N:11]=[C:10]([C:6]2[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=2)[C:3]([OH:2])=[O:14])[N:13]=1
Reactant: COC(=O)c1cccc(C(=N)NO)c1
Reactant: O=C(Cl)c1ccccc1F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: O=C(O)c1cccc(-c2noc(-c3ccccc3F)n2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.9 %

Procedure:
To a solution of 3-(N-Hydroxycarbamimidoyl)-benzoic acid methyl ester (60 g, 310 mmol) in anhydrous THF (200 mL) was added diisopropylethylamine (75 mL, 434 mmol) at 5° C., and then to the mixture was added 2-fluorobenzoyl chloride (48.1 mL, 403 mmol) over 20 min. The reaction mixture was stirred for 1 h at room temperature. The precipitate was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethylacetate (400 mL) and then washed with water (200 mL×2). The solvent was removed under reduced pressure and the desired product was crystallized in 60% ethylacetate in hexane to yield the desired product (81 g, 83% yield) as a white solid. 1H-NMR (CDCl3) δ 8.18 (1H), 8.03 (2H), 7.48 (2H), 7.18 (2H), 5.61 (2H), 3.82 (31-1).
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:18]=[CH:17][CH:16]=[C:15]([CH3:19])[C:14]=1[S:20](Cl)(=[O:22])=[O:21]>CN(C1C=CN=CC=1)C>[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[C:14]=1[S:20]([NH: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)(=[O:21])=[O:22]
Reactant: Nc1cccc2cccnc12
Reactant: Cc1cccc(Cl)c1S(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Product: Cc1cccc(Cl)c1S(=O)(=O)Nc1cccc2cccnc12
Yield: 47.9 %

Procedure:
In a similar fashion using route 14 general procedure 27, using 8-aminoquinoline (100 mg, 0.69 mmol), 2-chloro-6-methylbenzenesulfonyl chloride (230 mg, 1.04 mmol) and DMAP (cat.) gave the title compound (110 mg, 48%) after purification by column chromatography with DCM as the eluent.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]4[O:21][CH2:20][O:19][C:17]4=[CH:18][C:13]=3[CH2:12][C:11]([CH3:22])=[N:10][N:9]=2)=[CH:4][CH:3]=1.[C:23](OC(=O)C)(=[O:25])[CH3:24]>C(O)C>[C:23]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]4[O:21][CH2:20][O:19][C:17]4=[CH:18][C:13]=3[CH2:12][C:11]([CH3:22])=[N:10][N:9]=2)=[CH:4][CH:3]=1)(=[O:25])[CH3:24]
Reactant: CC1=NN=C(c2ccc(N)cc2)c2cc3c(cc2C1)OCO3
Reactant: CC(=O)OC(C)=O
Solvent: CCO
Product: CC(=O)Nc1ccc(C2=NN=C(C)Cc3cc4c(cc32)OCO4)cc1
Yield: 76.1 %

Procedure:
10 g (34 mmol) of 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine were stirred for 3 hours with 100 ml of acetic anhydride. The crystals formed were filtered, washed with 5×10 ml of anhydrous ethanol and dried, yielding 9.2 g of raw product, m.p. 252°-254° C. (decomp.). This product was treated with 45 ml of hot 99.5% ethanol. After cooling the crystals were filtered, washed with 3×10 ml of ethanol and dried to give 8.68 g (76.1%) of the aimed product, m.p.: 256°-258° C. (decomp.).
Reaction SMILES: [CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](Cl)=[N:4][C:3]1=[O:13].C(N(CCC)CCC)CC.[C:24]1([CH:30]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[N:31]2[CH2:36][CH2:35][N:34]([CH2:37][CH2:38][CH2:39][NH2:40])[CH2:33][CH2:32]2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>O1CCOCC1>[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH:40][CH2:39][CH2:38][CH2:37][N:34]2[CH2:33][CH2:32][N:31]([CH:30]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:36][CH2:35]2)=[N:4][C:3]1=[O:13]
Reactant: NCCCN1CCN(C(c2ccccc2)c2ccccc2)CC1
Reactant: Cn1c(=O)nc(Cl)c2ccccc21
Agent: CCCN(CCC)CCC
Solvent: C1COCCO1
Product: Cn1c(=O)nc(NCCCN2CCN(C(c3ccccc3)c3ccccc3)CC2)c2ccccc21
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 45.4 %

Procedure:
To a suspension of 1-methyl-4-chloro-2(1H)-quinazolinone (4 g), tri(n-propyl)amine (7.2 g) and dioxane (20 ml) was added 3-[4-(diphenylmethyl)piperazin-1-yl]propylamine (3.5 g) and the mixture was stirred for 1.5 hours at ambient temperature. The reaction mixture was concentrated in vacuo and to the residue was added water. After the aqueous layer was made basic with lN potassium hydroxide aqueous solution, the mixture was extracted twice with chloroform. The chloroform layer was washed with 0.2N potassium hydroxide aqueous solution, with water and with saturated sodium chloride aqueous solution respectively, dried over anhydrous magnesium sulfate and then concentrated in vacuo. After the residue was dissolved in toluene, remaining tri(n-propyl)amine was removed by evaporation in vacuo. This procedure was carried out further twice and then the residual oil was purified by subjecting to a column chromatography on silica gel (70 g) using 2% methanol in chloroform for elution to give a crystal, which was recrystallized from a mixture of ethyl acetate and hexane to give 1-methyl-4-[3-{ 4-(diphenylmethyl)piperazin-1-yl}propylamino]-2(1H)-quinazolinone (2.4 g). m.p. 121°-124° C.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH2:9][CH2:8][N:7]([CH:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[C:6]=2[N:19]=1.C([N-]C(C)C)(C)C.[Li+].[CH:28](=[O:30])[CH3:29].C(OCC)(=O)C>O1CCCC1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH:9]([CH:28]([OH:30])[CH3:29])[CH2:8][N:7]([CH:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[C:6]=2[N:19]=1
Reactant: CC=O
Reactant: CN1C(=O)CCN(C2CCCC2)c2nc(Cl)ncc21
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(O)C1CN(C2CCCC2)c2nc(Cl)ncc2N(C)C1=O
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 86.4 %

Procedure:
In a round bottom flask, 2-chloro-9-cyclopentyl-5-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one (0.840 g, 3.0 mmol) was dissolved in dry tetrahydrofuran (12 mL), cooled to −78° C., then added 2.0 M lithium diisopropyl amide in tetrahydrofuran (6.0 mmol) drop wise. After 30 minutes, acetaldehyde (1.056 g, 24.0 mmol) in 6.0 mL tetrahydrofuran was added slowly drop wise to it, continued stirring for 60 minutes. After disappearing the starting material, cooled the reaction flask to −78° C., then quenched with sat. ammonium chloride solution (3 mL). At room temperature, the resultant reaction mixture was taken into ethyl acetate (50 mL), washed with 0.1 N HCl, ammonium chloride solution and finally with water, dried over sodium sulphate and evaporated. Purified the product using column chromatography with hexane:ethyl acetate mixtures to give the product (0.842 g, 86%). [M+H] calculated for C15H21ClN4O2, 325. found 325.