Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC(C)([O-])C.[K+].[CH3:7][O:8][C:9]1[CH:10]=[C:11]([OH:19])[CH:12]=[C:13]([O:17][CH3:18])[C:14]=1[O:15][CH3:16].[CH3:20][C:21]1[N:22]=[C:23]([CH3:44])[N:24]2[C:29]=1[C:28](N1C=NC=N1)=[N:27][C:26]([C:35]1[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=1)=[N:25]2>O1CCCC1>[CH3:20][C:21]1[N:22]=[C:23]([CH3:44])[N:24]2[C:29]=1[C:28]([O:19][C:11]1[CH:12]=[C:13]([O:17][CH3:18])[C:14]([O:15][CH3:16])=[C:9]([O:8][CH3:7])[CH:10]=1)=[N:27][C:26]([C:35]1[CH:36]=[CH:37][C:38]([N+:41]([O-:43])=[O:42])=[CH:39][CH:40]=1)=[N:25]2
Reactant: COc1cc(O)cc(OC)c1OC
Reactant: Cc1nc(C)n2nc(-c3ccc([N+](=O)[O-])cc3)nc(-n3cncn3)c12
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: COc1cc(Oc2nc(-c3ccc([N+](=O)[O-])cc3)nn3c(C)nc(C)c23)cc(OC)c1OC
Temperature: 70 °C

Procedure:
A solution of 40 mg (0.33 mmol) of potassium tert-butoxide and 60 mg (0.33 mmol) of 3,4,5-trimethoxyphenol in 50 ml of tetrahydrofuran is stirred for 30 min. 70 mg (0.22 mmol) of 5,7-dimethyl-2-(4-nitrophenyl)-4-(1H-1,2,4-triazol-1-yl)imidazo-[5,1-f][1,2,4]triazine from example 11A are added thereto and the mixture is heated for 3 h at 70° C. After cooling, the solvent is removed and the residue is purified by chromatography (eluent gradient: dichloromethane/methanol 200:1-100:1).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]Cl)=[C:6]([C:12]([Cl:15])([Cl:14])[Cl:13])[CH:5]=1)([O-:3])=[O:2].[CH3:16][CH:17]([SH:19])[CH3:18]>>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10][S:19][CH:17]([CH3:18])[CH3:16])=[C:6]([C:12]([Cl:15])([Cl:14])[Cl:13])[CH:5]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(SCl)c(C(Cl)(Cl)Cl)c1
Reactant: CC(C)S
Product: CC(C)SSc1ccc([N+](=O)[O-])cc1C(Cl)(Cl)Cl
Yield: 92.3 %

Procedure:
As in Example 1, 61 g of 4-nitro-2-trichloromethylbenzenesulfenyl chloride is reacted with 15 g of 2 -propylmercaptan. There is obtained 63 g (91% of theory) of (4-nitro-2-trichloromethylphenyl)-isopropyl disulfide.
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:37]2([CH3:38])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:36]2[CH2:35][CH2:34][C@@:33]2([CH3:39])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([S:23]C(OC2C=CC=CC=2)=O)[CH3:22])[CH2:12][C@@H:11]([OH:40])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Br[CH2:42][C:43]#[C:44][C:45]([CH3:48])([OH:47])[CH3:46].O1CCCC1.[OH-].[K+]>CO>[Si:1]([O:8][C@@H:9]1[C@@:37]2([CH3:38])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:36]2[CH2:35][CH2:34][C@@:33]2([CH3:39])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([S:23][CH2:42][C:43]#[C:44][C:45]([OH:47])([CH3:48])[CH3:46])[CH3:22])[CH2:12][C@@H:11]([OH:40])[CH2:10]1)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]
Reactant: C[C@H](SC(=O)Oc1ccccc1)C1=CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Reactant: CC(C)(O)C#CCBr
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: C[C@H](SCC#CC(C)(C)O)C1=CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Yield: 73.2 %

Procedure:
Under the same conditions as in Example 3, 1α-(tert-butyldimethylsilyloxy)-3β-hydroxy-20(S)-phenoxycarbonylthiopregna-5,7,16-triene (59.4 mg, 0.102 mmol), 5-bromo-2-methyl-3-pentyn-2-ol (90.5 mg, 0.511 mmol), tetrahydrofuran (1 ml) and 1M KOH solution in methanol (1 ml) were reacted and worked up, and then the residue was purified by preparative thin layer chromatography (0.5 mm×2, dichloromethane:ethyl acetate=5:1, developed twice) to give the title compound as a colorless oil (41.6 mg, 73%).
Reaction SMILES: [O:1]=[C:2]1[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2([C:17]([N:19]3[CH2:23][CH2:22][C@@:21]4([C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=5[C:25](=[O:32])[O:24]4)[CH2:20]3)=[O:18])[CH2:16][CH2:15]2)=[CH:10][CH:9]=1.C(#N)C.C(N(CC)CC)C.[CH3:43][S:44](Cl)(=[O:46])=[O:45]>>[CH3:43][S:44]([N:6]1[CH2:5][CH2:4][N:3]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3([C:17]([N:19]4[CH2:23][CH2:22][C@@:21]5([C:27]6[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=6[C:25](=[O:32])[O:24]5)[CH2:20]4)=[O:18])[CH2:16][CH2:15]3)=[CH:10][CH:9]=2)[C:2](=[O:1])[CH2:7]1)(=[O:46])=[O:45]
Reactant: CS(=O)(=O)Cl
Reactant: O=C1O[C@]2(CCN(C(=O)C3(c4ccc(N5CCNCC5=O)cc4)CC3)C2)c2ccccc21
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CS(=O)(=O)N1CCN(c2ccc(C3(C(=O)N4CC[C@@]5(C4)OC(=O)c4ccccc45)CC3)cc2)C(=O)C1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of (1R)-1′-({1-[4-(2-oxopiperazin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one (36 mg, 0.000083 mol) in acetonitrile (0.5 mL, 0.01 mol) were added triethylamine (29 μL, 0.00021 mol) and methanesulfonyl chloride. After stirring at rt for 3 hours, the crude product was isolated and purified by prep-HPLC. LC/MS: 510.2 (M+H+).
Reaction SMILES: [N+:1]([C:4]1[N:5]=[CH:6][NH:7][CH:8]=1)([O-:3])=[O:2].[CH3:9][O:10][C:11](=[O:15])[CH:12]=[CH:13][CH3:14]>>[CH3:9][O:10][C:11](=[O:15])[CH2:12][CH:13]([N:7]1[CH:8]=[C:4]([N+:1]([O-:3])=[O:2])[N:5]=[CH:6]1)[CH3:14]
Reactant: CC=CC(=O)OC
Reactant: O=[N+]([O-])c1c[nH]cn1
Product: COC(=O)CC(C)n1cnc([N+](=O)[O-])c1

Procedure:
4-nitroimidazole was reacted with methyl-3-methylacrylate to provide the title compound: 1H NMR (400 MHz, CDCl3) 1.62 (d, 3H, J=7.0 Hz), 2.81 (d, 2H, J=7.0 Hz), 3.66 (s, 3H), 4.78 (m, 1H), 7.53 (d, 1H, J=1.6 Hz), 7.82 (d, 1H, J=1.6 Hz); MS m/z 214.1 (M+1).
Reaction SMILES: [F:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])=[C:4](I)[CH:3]=1.[CH2:18]([S:20][CH2:21][C:22]([CH3:26])([OH:25])[C:23]#[CH:24])[CH3:19]>>[CH2:18]([S:20][CH2:21][C:22]([C:23]1[N:12]([S:13]([CH3:16])(=[O:15])=[O:14])[C:5]2[C:4]([CH:24]=1)=[CH:3][C:2]([F:1])=[C:7]([C:8]([F:11])([F:10])[F:9])[CH:6]=2)([OH:25])[CH3:26])[CH3:19]
Reactant: CS(=O)(=O)Nc1cc(C(F)(F)F)c(F)cc1I
Reactant: C#CC(C)(O)CSCC
Product: CCSCC(C)(O)c1cc2cc(F)c(C(F)(F)F)cc2n1S(C)(=O)=O

Procedure:
This compound was prepared using the general Sonagashira procedure as described in the General Procedures Example C. The starting material was N-(4-fluoro-2-iodo-5-trifluoromethyl-phenyl)-methanesulfonamide (0.77 g, 2.0 mmol) and 1-ethylsulfanyl-2-methyl-but-3-yn-2-ol (0.29 g, 2.0 mmol), reacted to yield the title compound as a golden oil.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:15][CH2:16][CH3:17])=[C:9]([O:12][CH2:13][CH3:14])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:18]#[N:19].[NH2:20][C:21]1[CH:29]=[C:28]2[C:24]([CH:25]=[CH:26][NH:27]2)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCO>[CH2:13]([O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:15][CH2:16][CH3:17])[N:5]=[CH:4][C:3]([C:18]#[N:19])=[C:2]2[NH:20][C:21]1[CH:29]=[C:28]2[C:24]([CH:25]=[CH:26][NH:27]2)=[CH:23][CH:22]=1)[CH3:14]
Reactant: CCOc1cc2ncc(C#N)c(Cl)c2cc1OCC
Reactant: Nc1ccc2cc[nH]c2c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCO
Product: CCOc1cc2ncc(C#N)c(Nc3ccc4cc[nH]c4c3)c2cc1OCC
Temperature: 100 °C
Yield: 54.9 %

Procedure:
A solution of 964 mg (3.50 mM) of 4-chloro-6,7-diethoxy-quinoline-3-carbonitrile and 830 mg (6.29 mM) of 6-Aminoindole in 5 ml of 2-methoxyethanol was refluxed for 3 hours. To the warm solution was added 1 ml of 1M sodium carbonate and the sample was heated for 5 minutes at 100° C., then poured into 300 ml of ice water. The solid was collected, washed with water followed by ether and dried under vacuum at 80° C. to yield 712 mg of 6,7-Diethoxy-4-(1H-indol-6-ylamino)-quinoline-3-carbonitrile as a yellow solid: mass spectrum (electrospray, m/e): M+H 373.0, mp=128-130° C.
Reaction SMILES: [OH-].[Na+].[CH2:3]([O:10][C:11]1[C:26]([C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)=[CH:25][CH:24]=[CH:23][C:12]=1[C:13]([O:15]CC1C=CC=CC=1)=[O:14])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>O1CCOCC1.CO>[CH2:3]([O:10][C:11]1[C:26]([C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)=[CH:25][CH:24]=[CH:23][C:12]=1[C:13]([OH:15])=[O:14])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: O=C(OCc1ccccc1)c1cccc(-c2cccnc2)c1OCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1COCCO1
Product: O=C(O)c1cccc(-c2cccnc2)c1OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 66.6 %

Procedure:
A 2 mol/L aqueous solution of sodium hydroxide (1.3 mL) was added to a solution mixture of the obtained benzyl 2-(benzyloxy)-3-(pyridin-3-yl)benzoate (0.35 g) in dioxane (3.5 mL) and methanol (3.5 mL), followed by stirring at room temperature for 1 hour. A 2 mol/L aqueous solution of sodium hydroxide (1.3 mL) was added to the reaction mixture, followed by stirring at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and water was added to the residue. After adjusting the pH to 4.5 with 6 mol/L hydrochloric acid, ethyl acetate was added thereto. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. Diisopropyl ether was added to the obtained residue, and the solid substance was collected by filtration to obtain 0.18 g of 2-(benzyloxy)-3-(pyridin-3-yl)benzoic acid as a white solid.
Reaction SMILES: [CH3:1][CH:2]([OH:7])[CH2:3][CH2:4][CH2:5][Br:6].ClC(Cl)(Cl)C(=N)O[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C1CCCCC1.FC(F)(F)S(O)(=O)=O>ClCCl>[Br:6][CH2:5][CH2:4][CH2:3][CH:2]([CH3:1])[O:7][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: N=C(OCc1ccccc1)C(Cl)(Cl)Cl
Reactant: CC(O)CCCBr
Agent: O=S(=O)(O)C(F)(F)F
Solvent: ClCCl
Solvent: C1CCCCC1
Product: CC(CCCBr)OCc1ccccc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 52 %

Procedure:
To a solution of 1-methyl-4-bromo-1-butanol (9.0 g, 0.05384 mol) and benzyl 2,2,2-trichloroacetimidate (16.3 g,) in a mixture of anhydrous cyclohexane (100 ml) and anhydrous dichloromethane (50 ml) cooled to 0° C., trifluoromethanesulfonic acid (1.0 ml) was added, and the mixture was stirred overnight at room temperature under argon. The mixture was filtered, washed with a saturated solution of NaHCO3 (250 ml) and deionized water (250 ml), and dried with anhydrous Na2SO4. The solvents were removed by distillation under reduced pressure. The crude product (9.2 g) was subjected to vacuum distillation, giving 7.2 g of colorless viscous liquid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:13]([C:14]([O-])=[O:15])=[C:12]([CH3:17])[NH:11][C:10]([CH3:18])=[C:9]2[C:19]([O:21][CH2:22][CH2:23][C:24]#[N:25])=[O:20])[CH:5]=[CH:6][CH:7]=1.[NH2:26][CH2:27][C:28]([NH:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:29].Cl.CN(C)CCCN=C=NCC.C(OCC)(=O)C>CN(C)C1C=CN=CC=1.ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:13]([C:14](=[O:15])[NH:26][CH2:27][C:28](=[O:29])[NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[C:12]([CH3:17])[NH:11][C:10]([CH3:18])=[C:9]2[C:19]([O:21][CH2:22][CH2:23][C:24]#[N:25])=[O:20])[CH:5]=[CH:6][CH:7]=1
Reactant: NCC(=O)Nc1ccccc1
Reactant: CC1=C(C(=O)[O-])C(c2cccc(Cl)c2)C(C(=O)OCCC#N)=C(C)N1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC1=C(C(=O)NCC(=O)Nc2ccccc2)C(c2cccc(Cl)c2)C(C(=O)OCCC#N)=C(C)N1

Procedure:
179 mg (0.49 mmol) of mono(2-cyanoethyl) 4-(3-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, 245mg (1.63 mmol) of 2-amino-N-phenylacetamide, 129 mg (0.67 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 11 mg (0.09 mmol) of 4-dimethylaminopyridine were stirred in 10 ml of dichloromethane at room temperature overnight. Ethyl acetate was added to the reaction mixture, and the product was washed with 1 N hydrochloric acid and then with a saturated aqueous sodium hydrogencarbonate solution. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by the silica gel chromatography (chloroform/methanol=100/1) to obtain the title compound.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[C:22]3[S:21][C:20]([NH:23][C:24]([C:26]4[CH:31]=[CH:30][N:29]=[C:28](Cl)[CH:27]=4)=[O:25])=[N:19][C:18]=3[C:17]([O:33][CH3:34])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:35](=[O:38])([O-])[O-].[Cs+].[Cs+]>N1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[C:22]3[S:21][C:20]([NH:23][C:24]([C:26]4[CH:31]=[CH:30][N:29]=[C:28]([N:8]5[CH2:6][CH2:35][O:38][CH2:10][CH2:9]5)[CH:27]=4)=[O:25])=[N:19][C:18]=3[C:17]([O:33][CH3:34])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: O=C([O-])[O-]
Reactant: COc1ccc(C2=CCN(C(=O)OC(C)(C)C)CC2)c2sc(NC(=O)c3ccnc(Cl)c3)nc12
Agent: [Cs+]
Solvent: C1COCCN1
Product: COc1ccc(C2=CCN(C(=O)OC(C)(C)C)CC2)c2sc(NC(=O)c3ccnc(N4CCOCC4)c3)nc12
Yield: 90.6 %

Procedure:
0.30 g (0.60 mMol) 4-{2-[(2-chloro-pyridine-4-carbonyl)-amino]-4-methoxy-benzothiazol-7-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester were heated to 130° C. for 24 h in 1 ml morpholine and 0.39 g (1.2 mMol) cesium carbonate. The morpholin has been removed in vacuo. The residue has been triturated in ethyl acetate and subsequently subjected to column chromatography (ethyl acetate) to yield 0.15 g (45%) 4-{4-methoxy-2-[(2-morpholin-4-yl-pyridine-4-carbonyl)-amino]-benzothiazol-7-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as a yellow foam. ES-MS m/e (%): 552 ([M+H]−, 100).
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]([NH:10]N)[CH:7]=[CH:8][CH:9]=1.[C:12]([S:16][CH2:17][C:18](=O)[CH2:19][C:20]([CH3:26])([CH3:25])[C:21]([O:23][CH3:24])=[O:22])([CH3:15])([CH3:14])[CH3:13]>C(O)(C)(C)C>[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:7]([C:17]([S:16][C:12]([CH3:15])([CH3:14])[CH3:13])=[C:18]([CH2:19][C:20]([CH3:25])([CH3:26])[C:21]([O:23][CH3:24])=[O:22])[NH:10]2)=[CH:8][CH:9]=1
Reactant: COC(=O)C(C)(C)CC(=O)CSC(C)(C)C
Reactant: COc1cccc(NN)c1
Agent: Cl
Solvent: CC(C)(C)O
Product: COC(=O)C(C)(C)Cc1[nH]c2cc(OC)ccc2c1SC(C)(C)C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of 4.2 g of 3-methoxyphenylhydrazine hydrochloride and 4.9 g of methyl 5-(t-butylthio)-2,2-dimethyl-4-oxopentanoate in 100 mL of t-butanol was refluxed for 18 hours. The mixture was cooled to R.T., and evaporated to dryness. The residue was suspended in ether (150 ml) and stirred for 30 min. The salts were filtered and the filtrate evaporated to dryness to give a residue which was chromatographed on flash silica gel using as eluant ethyl acetate:toluene (1:99) to isolate the title compound as the most polar product; m.p. 133° C.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].O1C2C=CC([C:16]3(C(OCC)=O)[CH:25]=[C:24]4[C:19]([CH:20]=[CH:21][C:22]5[O:28][CH2:27][O:26][C:23]=54)=[N:18][CH:17]3[C:29]([O:31][CH2:32]C)=[O:30])=CC=2OC1.[OH2:39]>C1COCC1>[O:39]1[C:22]2[CH:21]=[CH:20][C:19]([C:25]3[C:24]4[C:19](=[CH:20][CH:21]=[C:22]5[O:28][CH2:27][O:26][C:23]5=4)[N:18]=[C:17]4[C:29](=[O:30])[O:31][CH2:32][C:16]=34)=[CH:24][C:23]=2[O:26][CH2:27]1
Reactant: O
Reactant: CCOC(=O)C1N=c2ccc3c(c2=CC1(C(=O)OCC)c1ccc2c(c1)OCO2)OCO3
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C1OCc2c1nc1ccc3c(c1c2-c1ccc2c(c1)OCO2)OCO3
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a suspension of and lithium aluminum Hydride (LAH) (2.0 g) in THF (50 ml) was gradually added diethyl 8-(1,3-benzodioxol-5-yl)-1,3-dioxolo[4,5-f]quinoline-7,8-dicarboxylate (2.4 g) which was synthesized by the ordinally method described in E. A. Fehnel, Journal of organic Chemistry, vol.31, 2899-2092, 1966 or W. Ried, et al., Chemische Berichte, vol.85,204-216, at 0° C. The mixture was stirred for 1 hour at room temperature. To the reaction mixture was added water to stop the reaction, then the insoluble solid was filtered off with Celite. The filtrate was extracted with ethyl acetate and the extract was washed with water and dried with magnesium sulfate. The solvent was removed by distillation and the obtained residue was dissolved in ethanol (100 ml), and 10% Pd--C (2.5 g) was added thereto. The mixture was stirred overnight at room temperature. The catalyst was filtered off, and the solvent was removed by distillation. The obtained residue was dissolved in chloroform (300 ml) and manganese dioxide (20 g) was added thereto, then the mixture was stirred for 3 hours at room temperature. The manganese dioxide was filtered off with Celite and the filtrate was concentrated under reduced pressure. The obtained crude crystals were washed with diisopropyl ether and the entitled compound (0.9 g) was obtained. For elemental analysis, some of the entitle compound was recrystallized from THF.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[Cl:17])[CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH:8]([CH2:12][NH2:13])[CH2:7]1.[NH2:18][C:19]([C:21]1[CH:26]=[CH:25][C:24]([CH2:27][C:28](O)=[O:29])=[CH:23][CH:22]=1)=[O:20]>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[Cl:17])[CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH:8]([CH2:12][NH:13][C:28](=[O:29])[CH2:27][C:24]2[CH:25]=[CH:26][C:21]([C:19]([NH2:18])=[O:20])=[CH:22][CH:23]=2)[CH2:7]1
Reactant: NC(=O)c1ccc(CC(=O)O)cc1
Reactant: NCC1CN(Cc2ccc(Cl)c(Cl)c2)CCO1
Product: NC(=O)c1ccc(CC(=O)NCC2CN(Cc3ccc(Cl)c(Cl)c3)CCO2)cc1
Yield: 11.5 %

Procedure:
Example 10 was prepared in an analogous manner to Example 1 using a mixture of Intermediate 1 (0.055 g) and [4-(aminocarbonyl)phenyl]acetic acid (0.036 g) to give the title compound (0.01 g).
Reaction SMILES: [Si]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][CH2:18][CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]2)=[CH:12][CH:11]=1)(C(C)(C)C)(C)C.CC(C)=[O:34].OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[C:25]([N:22]1[CH2:23][CH2:24][CH:19]([CH2:18][CH2:17][CH2:16][C:13]2[CH:14]=[CH:15][C:10]([C:9]([OH:34])=[O:8])=[CH:11][CH:12]=2)[CH2:20][CH2:21]1)([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26]
Reactant: CC(C)(C)OC(=O)N1CCC(CCCc2ccc(CO[Si](C)(C)C(C)(C)C)cc2)CC1
Reactant: CC(C)=O
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Product: CC(C)(C)OC(=O)N1CCC(CCCc2ccc(C(=O)O)cc2)CC1
Reaction time: 0.25 h

Procedure:
To a vigorously stirred solution of 20-4 (230 mg, 0.51 mmol) in acetone (5 mL) at 0° C. was added Jones Reagent dropwise until the color changed from green to orange. The excess Jones Reagent was quenched with isopropanol (1 mL) followed by stirring for 15 min. The reaction mixture was diluted with EtOAc and then washed with H2O and brine, dried (MgSO4) and concentrated to give 20-5 as a yellowish oil.
Reaction SMILES: [OH:1][C:2]1[C:7]2=[N:8][C:9]([CH3:13])=[CH:10][C:11](=[O:12])[N:6]2[CH:5]=[CH:4][CH:3]=1.C[O-].[Na+].[Br:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20]Br>C(O)C>[Br:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20][O:1][C:2]1[C:7]2=[N:8][C:9]([CH3:13])=[CH:10][C:11](=[O:12])[N:6]2[CH:5]=[CH:4][CH:3]=1
Reactant: Cc1cc(=O)n2cccc(O)c2n1
Reactant: BrCc1ccccc1Br
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: Cc1cc(=O)n2cccc(OCc3ccccc3Br)c2n1

Procedure:
To 35.2 g of 9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one suspended in 100 ml of absolute ethanol is added a solution of 11.0 g of sodium methoxide in 165 ml of absolute ethanol. To this is then added 50.0 g o-bromobenzyl bromide dissolved in 25 ml of absolute ethanol. The mixture is then heated under reflux for about 6 hours and worked up to give 9-[(o-bromobenzyl)oxy]-2-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one, m.p. 144°-146°, after recrystallization from ethyl acetate.
Reaction SMILES: [NH2:1][C:2](=[N:36][N+:37]([O-:39])=[O:38])[NH:3][CH2:4][CH2:5][CH2:6][C@H:7]([C:24]([NH:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][NH2:35])=[CH:30][CH:29]=1)=[O:25])[NH:8][C:9](=[O:23])[CH:10]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[N+]([NH:43][C:44]([NH:46][C:47](N)=[O:48])=[O:45])([O-])=O.C(N(C(C)C)CC)(C)C>CO>[NH2:43][C:44]([NH:46][C:47]([NH:35][CH2:34][C:31]1[CH:30]=[CH:29][C:28]([CH2:27][NH:26][C:24](=[O:25])[C@@H:7]([CH2:6][CH2:5][CH2:4][NH:3][C:2]([NH2:1])=[N:36][N+:37]([O-:39])=[O:38])[NH:8][C:9](=[O:23])[CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[CH:33][CH:32]=1)=[O:48])=[O:45]
Reactant: NCc1ccc(CNC(=O)[C@@H](CCCNC(N)=N[N+](=O)[O-])NC(=O)C(c2ccccc2)c2ccccc2)cc1
Reactant: NC(=O)NC(=O)N[N+](=O)[O-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CO
Product: NC(=O)NC(=O)NCc1ccc(CNC(=O)[C@@H](CCCNC(N)=N[N+](=O)[O-])NC(=O)C(c2ccccc2)c2ccccc2)cc1
Reaction time: 14 h

Procedure:
A mixture of 0.53 g (0.997 mMol) of (R)-N5 -[amino(nitroimino)-methyl]-N-[[4-(aminomethyl)phenyl]methyl]-N2 -(diphenylacetyl)-ornithinamide, 0.16 g (1.08 mMol) of nitrobiuret, 50 ml of methanol and 0.2 ml of diisopropylethylamine was refluxed for 5 hours with stirring. The same amount of nitrobiuret and diisopropylethylamine was added again and the mixture was refluxed for a further 3 hours. The crystals obtained after leaving the mixture to stand for 14 hours at ambient temperature were suction filtered, washed thoroughly with methanol and diethylether and dried in vacuo. 0.51 g (83% of theory) of colourless crystals were obtained, Mp. 214-218° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([OH:24])[CH:14]=[C:15]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:7]1=2)[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:33]1[CH:38]=[N:37][CH:36]=[CH:35][N:34]=1>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:24][C:33]3[CH:38]=[N:37][CH:36]=[CH:35][N:34]=3)[CH:14]=[C:15]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:7]1=2)[CH3:2]
Reactant: CCOC(=O)CC1OB(O)c2cc(O)cc(OCc3ccccc3)c21
Reactant: Clc1cnccn1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCOC(=O)CC1OB(O)c2cc(Oc3cnccn3)cc(OCc3ccccc3)c21
Temperature: 80 °C
Yield: 46.9 %

Procedure:
A suspension of (4-benzyloxy-1,6-dihydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester (710 mg, 2.08 mmol) and Cs2CO3 (1.36 g, 4.16 mmol) in DMF (10 mL) was treated with 2-chloropyrazine (357 mg, 3.11 mmol) at room temperature and the reaction was heated to 80° C. for 3 h. The reaction mixture was concentrated to dryness. The residue was diluted with water and adjusted pH to 3 by 1N HCl. The aqueous phase was extracted with ethyl acetate. The organic phase was separated, dried (Na2SO4), and concentrated. The residue was purified by preparative HPLC to afford the title compound (410 mg, 50%). MS calcd for (C22H21BN2O6+H)+: 421.2. MS found: (M+H)+=421.2.
Reaction SMILES: [ClH:1].C(OC([N:12]([CH2:16][CH:17]1[C:26]2[C:21](=[CH:22][C:23]([OH:28])=[C:24]([OH:27])[CH:25]=2)[CH2:20][CH2:19][NH:18]1)[CH:13]([CH3:15])[CH3:14])=O)C1C=CC=CC=1.Cl>C(O)(=O)C>[ClH:1].[ClH:1].[CH:13]([NH:12][CH2:16][CH:17]1[C:26]2[C:21](=[CH:22][C:23]([OH:28])=[C:24]([OH:27])[CH:25]=2)[CH2:20][CH2:19][NH:18]1)([CH3:15])[CH3:14]
Reactant: CC(C)N(CC1NCCc2cc(O)c(O)cc21)C(=O)OCc1ccccc1
Agent: Cl
Solvent: CC(=O)O
Product: CC(C)NCC1NCCc2cc(O)c(O)cc21
Yield: 86.5 %

Procedure:
A mixture of 1-(N-benzyloxycarbonyl-N-isopropylaminomethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3.5 g), conc. hydrochloric acid (20 ml) and acetic acid (20 ml) was refluxed for 1 hour. The reaction mixture was concentrated to dryness under reduced pressure and the residue was crystallized with a mixture of acetone and water. The crystals were recrystallized from a mixture of methanol and ether to give 1-(N-isopropylaminomethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline dihydrochloride (1.15 g), mp 268° to 270° C. (dec).