Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH3:13])=[N:10][C:9]=2[C:14]([N:16]2[CH2:20][CH:19]3[CH2:21][CH2:22][CH2:23][CH:18]3[CH:17]2[CH2:24][N:25]2C(=O)C3C(=CC=CC=3)C2=O)=[O:15])=[CH:4][CH:3]=1.O.NN>CO>[NH2:25][CH2:24][CH:17]1[CH:18]2[CH2:23][CH2:22][CH2:21][CH:19]2[CH2:20][N:16]1[C:14]([C:9]1[N:10]=[C:11]([CH3:13])[S:12][C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)=[O:15]
Reactant: Cc1nc(C(=O)N2CC3CCCC3C2CN2C(=O)c3ccccc3C2=O)c(-c2ccc(F)cc2)s1
Agent: NN
Solvent: CO
Solvent: O
Product: Cc1nc(C(=O)N2CC3CCCC3C2CN)c(-c2ccc(F)cc2)s1

Procedure:
2-((-2-(5-(4-Fluorophenyl)-2-methylthiazole-4-carbonyl)octahydrocyclopenta[c]pyrrol-1-yl)methyl)isoindoline-1,3-dione (1 eq) and hydrazine monohydrate (4 eq) in MeOH was stirred at 70° C. for 3 h and then concentrated in vacuo to a yellow oil. The reaction mixture was diluted with EtOAc and washed with water, brine, dried (MgSO4), and concentrated. The crude residue was purified by chromatography on silica gel (20% MeOH in EtOAc) to firstly remove the impurities and then (2:8:1 MeOH/EtOAc/TEA) to elute the title compound which was concentrated to yield a yellow oil. MS (ESI) 360.3 (M+H).
Reaction SMILES: ClC1C=CC=C([C:8](OO)=[O:9])C=1.[CH3:12][C:13]1[NH:14][C:15](=[O:25])[CH2:16][S:17][C:18]=1[C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1>CO>[CH3:8][O:9][CH:16]1[C:15](=[O:25])[NH:14][C:13]([CH3:12])=[C:18]([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)[S:17]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC1=C(c2ccncc2)SCC(=O)N1
Solvent: CO
Product: COC1SC(c2ccncc2)=C(C)NC1=O
Temperature: 25 °C
Reaction time: 72 h
Yield: 52.4 %

Procedure:
m-Chloroperbenzoic acid (12 g) was added gradually to a stirred suspension of 5-methyl-6-(4-pyridinyl)-2H-1,4-thiazin-3(4H)-one (10 g) in methanol (400 ml) under ice/water-cooling. The reaction mixture was further stirred at ambient temperature for 3 days. The solvent was removed under reduced pressure and the residue was extracted with ethyl acetate, was washed with saturated sodium bicarbonate aqueous solution and successively with water and was dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue was dissolved in chloroform (about 50 ml) and was chromatographed on activated alumina (200 g, about 300 mesh, manufactured by Wako Pure Chemical Industries, Ltd.) cloumn, using chloroform as an eluant. The solvent was removed under reduced pressure and the residue was crystallized from ether to give the titled compound (6 g, yield 51.7%) as pale yellow powder.
Reaction SMILES: BrC1C=C[CH:17]=[CH:16][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[N:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[CH:7]=[CH:6]1.[C:20]([O-])(=O)[CH3:21].[NH4+].[N+:25](C)([O-:27])=[O:26]>>[CH3:15][O:14][C:10]1[CH:11]=[CH:12][C:13]2[N:5]3[C:6]([CH2:17][CH2:16][CH2:3][CH2:4]3)=[C:7]([CH:21]=[CH:20][N+:25]([O-:27])=[O:26])[C:8]=2[N:9]=1
Reactant: CC(=O)[O-]
Reactant: C[N+](=O)[O-]
Reactant: COc1ccc2c(ccn2Cc2ccccc2Br)n1
Agent: [NH4+]
Product: COc1ccc2c(n1)c(C=C[N+](=O)[O-])c1n2CCCC1

Procedure:
550 mg (2.39 mmol) of the compound obtained in Step C dissolved in 25 ml of nitromethane are heated at 120° C., for 3 hours in the presence of 460 mg (5.97 mmol) of ammonium acetate. After returning to room temperature and evaporation to dryness, the reaction mixture is diluted in dichloromethane and washed with water. The organic phase is dried over magnesium sulphate, filtered and evaporated. After washing with a pentane/diethyl ether mixture, the title compound is obtained in the form of a brown solid.
Reaction SMILES: F[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:11][C:12]3[C:20](I)=[CH:19][C:15]4[CH2:16][CH2:17][O:18][C:14]=4[CH:13]=3)[NH:8]2)=[C:4]([NH2:22])[N:3]=1.C(O)(C(F)(F)F)=O.C1C(=O)[N:34](I)C(=O)C1>C(#N)C>[O:18]1[C:14]2[CH:13]=[C:12]([CH2:11][C:7]3[NH:8][C:9]4[C:5]([N:6]=3)=[C:4]([NH2:22])[N:3]=[C:2]([NH2:34])[N:10]=4)[CH:20]=[CH:19][C:15]=2[CH2:16][CH2:17]1
Reactant: Nc1nc(F)nc2[nH]c(Cc3cc4c(cc3I)CCO4)nc12
Reactant: O=C1CCC(=O)N1I
Solvent: O=C(O)C(F)(F)F
Solvent: CC#N
Product: Nc1nc(N)c2nc(Cc3ccc4c(c3)OCC4)[nH]c2n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
2-fluoro-8-((5-iodo-2,3-dihydrobenzofuran-6-yl)methyl)-9H-purin-6-amine (S16-9). To a suspension of S16-8 (0.45 g, 1.6 mmol) in 50 mL acetonitrile was added 1 mL of TFA. To the resulting solution was added NIS (1.06 g, 4.7 mmol) and the reaction mixture was stirred at rt for 3 h. It was then evaporated to dryness and purified by flash chromatography to give S16-9 (0.408 g, 63%) as a yellow solid. 1H NMR (500 MHz, MeOH-d4) δ 7.67 (s, 1H), 6.76 (s, 1H), 4.59 (m, 2H), 4.28 (s, 2H), 3.21 (m, 2H); MS: m/z 412 (M+H)+.
Reaction SMILES: [CH3:1][S:2][CH:3]1[N:6]([CH2:7][CH2:8][CH2:9][C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:11])[C:5](=[O:18])[CH2:4]1.C1C=C(Cl)C=C(C(OO)=[O:27])C=1>>[CH3:1][S:2]([CH:3]1[N:6]([CH2:7][CH2:8][CH2:9][C:10]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:11])[C:5](=[O:18])[CH2:4]1)=[O:27]
Reactant: CSC1CC(=O)N1CCCC(=O)c1ccccc1
Reactant: O=C(OO)c1cccc(Cl)c1
Product: CS(=O)C1CC(=O)N1CCCC(=O)c1ccccc1
Yield: 89 %

Procedure:
Treatment of 4-methylthio-1-(4-phenyl-4-oxobutyl)azetidin-2-one (0.29 g, 1.09 mmol)with mCPBA as described in Example 2 gave the title compound as a yellow oil (0.27 g, 89%),
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:16])[N:4]([CH2:13][CH2:14][CH3:15])[C:5](=[O:12])[N:6]([CH2:9][CH2:10][CH3:11])[C:7]=1[NH2:8].[CH2:17]([O:24][C:25]1[C:35]([O:36][CH3:37])=[CH:34][C:28](/[CH:29]=[CH:30]/[C:31](O)=O)=[CH:27][C:26]=1[O:38][CH3:39])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[CH2:17]([O:24][C:25]1[C:35]([O:36][CH3:37])=[CH:34][C:28](/[CH:29]=[CH:30]/[C:31]2[NH:1][C:2]3[C:3](=[O:16])[N:4]([CH2:13][CH2:14][CH3:15])[C:5](=[O:12])[N:6]([CH2:9][CH2:10][CH3:11])[C:7]=3[N:8]=2)=[CH:27][C:26]=1[O:38][CH3:39])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: COc1cc(/C=C/C(=O)O)cc(OC)c1OCc1ccccc1
Reactant: CCCn1c(N)c(N)c(=O)n(CCC)c1=O
Product: CCCn1c(=O)c2[nH]c(/C=C/c3cc(OC)c(OCc4ccccc4)c(OC)c3)nc2n(CCC)c1=O
Yield: 74.4 %

Procedure:
Substantially the same procedure as in Reference Example 1 was repeated using 3.30 g (14.5 mmol) of 5,6-diamino-1,3-dipropyluracil and 5.0 g (15.9 mmol) of Compound G. Then, the resultant crude crystals were recrystallized from ethanol/2-propanol to give 5.44 g (yield 74%) of Compound 26 as a white powder.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([N+:11]([O-:13])=[O:12])[C:5]=1[CH3:14].[Br:16]N1C(=O)CCC1=O.C1(=O)NC(=O)CC1>C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([N+:11]([O-:13])=[O:12])[C:5]=1[CH2:14][Br:16]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)c1cc(F)cc([N+](=O)[O-])c1C
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Agent: O=C1CCC(=O)N1
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1cc(F)cc([N+](=O)[O-])c1CBr
Yield: 76.1 %

Procedure:
2.37 g (11.12 mmol) of 5-fluoro-2-methyl-3-nitrobenzoic acid methyl ester is added into 35 ml of carbon tetrachloride, and mixed with 2.24 g (12.24 mmol) of N-bromosuccinimide and 5.4 mg of benzoyl peroxide. After four days of refluxing, and after cooling, the succinimide is suctioned off (glass-fiber filter), and then the filtrate is spun in to the dry state. Chromatography on a Flashmaster yields 2.47 g (75.9%) of the desired compound.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[H-].[Na+].Cl[C:14]1[C:19]([Cl:20])=[CH:18][C:17]([C:21]([F:24])([F:23])[F:22])=[CH:16][N:15]=1.CO>CN(C)C=O>[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C:14]1[C:19]([Cl:20])=[CH:18][C:17]([C:21]([F:24])([F:22])[F:23])=[CH:16][N:15]=1
Reactant: FC(F)(F)c1cnc(Cl)c(Cl)c1
Reactant: Nc1cccc2[nH]ccc12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CO
Product: Nc1cccc2c1ccn2-c1ncc(C(F)(F)F)cc1Cl
Temperature: 25 °C
Reaction time: 18 h
Yield: 47.4 %

Procedure:
4-Aminoindole (5.8 g, 44 mmol) and sodium hydride (80% dispersion in mineral oil, 1.3 g, 44 mmol) were stirred together in N,N-dimethylformamide (60 ml), with ice-bath cooling for 5 minutes, and then 2,3-dichloro-5-trifluoromethylpyridine (5,8 g, 44 mmol) was added slowly. The mixture was stirred at room temperature for 18 hours, and then a small quantity of methanol was added. The mixture was partitioned between diethyl ether and water. The ethereal solution was dried over magnesium sulfate, filtered and the filtrate evaporated in vacuo to give 4-amino-1-(3'-chloro-5'-trifluoromethylpyridin-2-yl)indole (6.5 g) as a dark solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[C:7]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)=[CH:6][CH2:5][CH2:4][CH2:3]1.[CH:18]1[CH:19]=[CH:20][N:21]2[CH2:27][C:26]3[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=3[NH:24][CH2:23][C:22]=12>>[CH:18]1[CH:19]=[CH:20][N:21]2[CH2:27][C:26]3[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=3[N:24]([C:12]([C:11]3[CH:10]=[CH:9][C:8]([C:7]4[C:2]([CH3:1])([CH3:17])[CH2:3][CH2:4][CH2:5][CH:6]=4)=[CH:16][CH:15]=3)=[O:14])[CH2:23][C:22]=12
Reactant: c1ccc2c(c1)Cn1cccc1CN2
Reactant: CC1(C)CCCC=C1c1ccc(C(=O)O)cc1
Product: CC1(C)CCCC=C1c1ccc(C(=O)N2Cc3cccn3Cc3ccccc32)cc1
Yield: 85.5 %

Procedure:
4-(6,6-Dimethyl-cyclohex-1-en-1-yl)-benzoic acid of Step B (0.235 g, 1.02 mmol) and 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.205 g, 1.11 mmol) were reacted in the manner of Example 15, Step D. Purification by flash column chromatography on silica gel, eluting with 20% ethyl acetate in hexane, followed by recrystallization from petroleum ether afforded the title compound (0.346 g) as white crystals, m.p. 118° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]([CH3:9])[C:6]([N+:10]([O-:12])=[O:11])=[CH:5][CH:4]=1.CO[CH:15](OC)[N:16](C)[CH3:17].[CH3:21]N(C)C=O>>[CH3:15][N:16]([CH3:17])[C:9]([C:7]1[C:6]([N+:10]([O-:12])=[O:11])=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[N:8]=1)=[CH2:21]
Reactant: CN(C)C=O
Reactant: COC(OC)N(C)C
Reactant: COc1ccc([N+](=O)[O-])c(C)n1
Product: C=C(c1nc(OC)ccc1[N+](=O)[O-])N(C)C
Temperature: 100 °C
Yield: 100 %

Procedure:
A mixture of 2.0 gm (11.9 mMol) 6-methoxy-3-nitro-2-picoline and 16 mL (119 mMol) dimethylformamide dimethylacetal in 20 mL dimethylformamide was heated at 100° C. for 7 hours. The reaction mixture was concentrated under reduced pressure. The residue was treated with toluene and concentrated under reduced pressure. The residual solid was dried at 50° C. under reduced pressure for 1 hour to provide 2.70 gm (100%) of the desired compound as a red solid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:26])[NH:7][CH2:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[Cl:22])=[CH:13][N:12]2[CH:23]=[CH:24][N:25]=[C:11]2[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([Br:34])C(=O)C1>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6](=[O:26])[NH:7][CH2:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[Cl:22])=[CH:13][N:12]2[C:23]([Br:34])=[CH:24][N:25]=[C:11]2[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NCc1cc2nccn2cc1-c1ccc(Cl)cc1Cl
Reactant: O=C1CCC(=O)N1Br
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)NCc1cc2ncc(Br)n2cc1-c1ccc(Cl)cc1Cl
Temperature: 0 °C
Reaction time: 1 h
Yield: 73.6 %

Procedure:
A solution of [6-(2,4-dichloro-phenyl)-imidazo[1,2-a]pyridin-7-ylmethyl]-carbamic acid tert-butyl ester (543 mg, 1.38 mmol) in DMF (5 mL) was cooled to 0° C., treated with NBS (222 mg, 1.25 mmol), and stirred at 0° C. for 1 h. The reaction mixture was diluted in AcOEt and washed with water and brine. The organic layer was dried over Na2SO4, filtered and evaporated. The residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, [hexane/DCM 1:1]/TBME 95:5→6:4) to yield the title compound (435 mg, 0.92 mmol, 67%) as a beige foam. MS: 472 [M+1]+; HPLC: AtRet=1.93; TLC: RF 0.50 (hexane/DCM/TBME 1:1:2).
Reaction SMILES: [C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].[OH:8][C@@:9]1([CH3:31])[C@@:26]2([CH3:27])[C@@H:13]([CH2:14][CH2:15][C@@H:16]3[C@@H:25]2[CH2:24][CH2:23][C@@:21]2([CH3:22])[C@H:17]3[C@@H](O)C[C:20]2=[O:28])[CH2:12][C:11](=[O:30])[CH2:10]1>N1C=CC=CC=1.C(OCC)(=O)C>[C:5]([O:4][C@@H:1]1[C@H:17]2[C@H:16]3[C@H:25]([CH2:24][CH2:23][C@:21]2([CH3:22])[C:20](=[O:28])[CH2:2]1)[C@:26]1([CH3:27])[C@H:13]([CH2:12][C:11](=[O:30])[CH2:10][C@:9]1([OH:8])[CH3:31])[CH2:14][CH2:15]3)(=[O:7])[CH3:6]
Reactant: C[C@]12[C@@H](CC[C@H]3[C@@H]4[C@@H](O)CC(=O)[C@@]4(C)CC[C@@H]31)CC(=O)C[C@@]2(C)O
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CC(=O)O[C@H]1CC(=O)[C@@]2(C)CC[C@H]3[C@@H](CC[C@H]4CC(=O)C[C@@](C)(O)[C@@]43C)[C@H]12
Temperature: 0 °C

Procedure:
20 ml of acetic anhydride is instilled at room temperature in 10.0 g of 1β,15α-dihydroxy-1α-methyl-5α-androstane-3,17-dione in 40 ml of pyridine. The reaction mixture is stirred into ice/water after 2.5 hours. The precipitated product is suctioned off, dissolved in ethyl acetate and washed neutral with water. The crude product is chromatographed on silica gel with a hexane-ethyl acetate gradient. 8.6 g of 15α-acetoxy-1β-hydroxy-1α-methyl-5α-androstane-3,17-dione is obtained. Melting point 170.0° C.
Reaction SMILES: [CH3:1]C(C)([O-])C.[K+].[Si:7]([O:14][CH2:15][CH2:16][C:17]([C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=1)=O)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1C=CC=CC=1>[Si:7]([O:14][CH2:15][CH2:16][C:17]([C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=1)=[CH2:1])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]
Reactant: CC(C)(C)[Si](C)(C)OCCC(=O)c1ccc(Cl)c(Cl)c1
Reactant: CC(C)(C)[O-]
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: c1ccccc1
Solvent: O
Product: C=C(CCO[Si](C)(C)C(C)(C)C)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 9 h
Yield: 59.1 %

Procedure:
215 g (0.60 mole) of methyltriphenylphosphonium bromide and 54 g (0.48 mole) of potassium t-butoxide were added to 2 liters of dried benzene, and the mixture was stirred for 9 hours at room temperature. At the end of this time, 40 g (0.12 mole) of 3-(3,4-dichlorophenyl)-3-oxo-1-propanol t-butyldimethylsilyl ether [prepared as described in step (b) above] were dissolved in 800 ml of benzene and the resulting solution was slowly added dropwise to the mixture over a period of 2.5 hours. 1 liter of water was then added to the reaction mixture, and the mixture was stirred for 30 minutes, whilst ice-cooling. The organic layer was separated, and then washed with water and with a saturated aqueous solution of sodium chloride, after which it was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography, using hexane as the eluent, to give 23.5 g of the title compound. The physicochemical properties of this product were the same as those of the product produced as described in Example 1(b).
Reaction SMILES: [N:1]([O-])=O.[Na+].[NH2:5][C:6]1[CH:7]=[CH:8][C:9]2[N:15]([CH3:16])[C:14](=[O:17])[CH2:13][N:12]=[C:11]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])[C:10]=2[CH:25]=1.[H+].[B-:27]([F:31])([F:30])([F:29])[F:28]>O>[F:28][B-:27]([F:31])([F:30])[F:29].[F:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:11]1[C:10]2[CH:25]=[C:6]([N+:5]#[N:1])[CH:7]=[CH:8][C:9]=2[N:15]([CH3:16])[C:14](=[O:17])[CH2:13][N:12]=1
Reactant: O=N[O-]
Reactant: CN1C(=O)CN=C(c2ccccc2F)c2cc(N)ccc21
Agent: F[B-](F)(F)F
Agent: [H+]
Agent: [Na+]
Solvent: O
Product: CN1C(=O)CN=C(c2ccccc2F)c2cc([N+]#N)ccc21
Reaction time: 22 h

Procedure:
A solution of 2.9 g (42 mmol) of sodium nitrite in 7 ml of water is added while stirring to a solution, cooled in ice, of 11 g (38.8 mmol) of 7-amino-5-(o-fluorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one in 50 ml of water and 100 ml of 50 percent aqueous hydrofluoboric acid so that the sodium nitrite solution enters below the surface of the mixture (addition time ca 15 minutes). The mixture is stirred at 5° for a further 30 minutes and then left to stand at -24° for 22 hours. The precipitated crystals are filtered off, washed with isopropanol and ether and dried at 14 Torr and room temperature. There is obtained 5-(o-fluorophenyl)-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepine-7-diazonium tetrafluoroborate (1:2) of melting point 120°-125°.
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:15]=[C:14]([O:16][CH2:17][C:18]([C:20]2[CH:29]=[CH:28][C:27]3[C:26]([CH3:31])([CH3:30])[CH2:25][CH2:24][C:23]([CH3:33])([CH3:32])[C:22]=3[CH:21]=2)=[O:19])[CH:13]=[CH:12][C:5]=1[C:6]([O:8][CH2:9][CH:10]=[CH2:11])=[O:7].[CH3:34][O:35][CH2:36][CH2:37][O:38][CH2:39]Cl.O>CN(C=O)C>[CH3:34][O:35][CH2:36][CH2:37][O:38][CH2:39][O:3][C:4]1[CH:15]=[C:14]([O:16][CH2:17][C:18]([C:20]2[CH:29]=[CH:28][C:27]3[C:26]([CH3:31])([CH3:30])[CH2:25][CH2:24][C:23]([CH3:33])([CH3:32])[C:22]=3[CH:21]=2)=[O:19])[CH:13]=[CH:12][C:5]=1[C:6]([O:8][CH2:9][C:10]1[CH:6]=[CH:5][CH:4]=[CH:15][CH:11]=1)=[O:7]
Reactant: C=CCOC(=O)c1ccc(OCC(=O)c2ccc3c(c2)C(C)(C)CCC3(C)C)cc1O
Reactant: COCCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COCCOCOc1cc(OCC(=O)c2ccc3c(c2)C(C)(C)CCC3(C)C)ccc1C(=O)OCc1ccccc1

Procedure:
1.65 g (55 mmol) of sodium hydride (80% in oil) and 50 ml of DMF are introduced into a flask. A solution of 23.6 g (50 mmol) of allyl 2-hydroxy-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthoyl methoxy)benzoate in 200 ml of DMF is added dropwise and the mixture is stirred until evolution of gas has ceased. 6.3 ml (55 mmol) of 2-methoxy ethoxymethyl chloride are then added dropwise and the reaction mixture is stirred for 2 hours. It is poured into water and extracted with ethyl ether, and the organic phase is separated, dried over magnesium sulphate and evaporated. The residue obtained is purified by chromatography on a silica column, eluted with a mixture of dichloromethane/ethyl ether (98:2). After evaporation of the solvents, 19.2 g (69%) of the expected ester are collected in the form of a slightly yellow oil.
Reaction SMILES: [NH2:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:8]3[CH:13]=[C:14]([S:18](Cl)(=[O:20])=[O:19])[C:15]([Br:17])=[CH:16][C:7]=3[CH2:6][CH2:5][C:4]=2[N:3]=1.[CH2:22]([O:24][C:25](=[O:44])[C@H:26]([CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])[NH:27][C:28](=[O:36])[C:29]1[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=1)[CH3:23]>C(Cl)Cl>[NH2:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:8]3[CH:13]=[C:14]([S:18]([NH:35][C:32]4[CH:31]=[CH:30][C:29]([C:28]([NH:27][C@H:26]([C:25]([O:24][CH2:22][CH3:23])=[O:44])[CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[O:36])=[CH:34][CH:33]=4)(=[O:20])=[O:19])[C:15]([Br:17])=[CH:16][C:7]=3[CH2:6][CH2:5][C:4]=2[N:3]=1
Reactant: Nc1nc2c(c(=O)[nH]1)-c1cc(S(=O)(=O)Cl)c(Br)cc1CC2
Reactant: CCOC(=O)CC[C@H](NC(=O)c1ccc(N)cc1)C(=O)OCC
Solvent: ClCCl
Product: CCOC(=O)CC[C@H](NC(=O)c1ccc(NS(=O)(=O)c2cc3c(cc2Br)CCc2nc(N)[nH]c(=O)c2-3)cc1)C(=O)OCC
Temperature: 25 °C
Yield: 26.1 %

Procedure:
3-Amino-8-bromo-5,6-dihydrobenzo[f]quinazolin-1(2H)-one-9-sulfonyl chloride (2.00 g, 4.50 mmole) and N-(4-aminobenzoyl)-L-glutamic acid diethyl ester (7.26 g,22.5 mole) (Aldrich) were placed together in a test tube and melted at 175° C. The mixture was heated for 1 hour, 20 minutes, the cooled residue suspended in methylene chloride and filtered to remove undissolved solid. The filtrate was evaporated to dryness and the residue subjected to chromatography on a Waters Prep 500 instrument (silica column, elution with methanol/methylene chloride(1:24)). The combined fractions containing product were evaporated and the residue dried under high vacuum. The solid was suspended in boiling ethanol (900 ml), the suspension cooled to room temperature and filtered to give diethyl N-(4-(((3-amino-8-bromo-1,2,5,6-tetrahydro-1-oxobenzo[f]quinazolin-9-yl)sulfonyl)amino)benzoyl)-L-glutamate (0.794 g,26%). Mp>250° C. 1H NMR (DMSO-d6, 200 MHz) δ: 1.12 (t, J=7 Hz, 3H, ester-CH3), 1.14 (t, J=7 Hz, 3H, ester-CH3), 1.89-2.09 (m, 2H, glu-CH2), 2.37 (t, J=7 Hz, 2H, glu-CH2), 2.48-2.59 (m, 2H, Ar CH2), 2.77-2.85 (m, 2H, Ar CH2), 3.99 (q, J=7 Hz,2H,ester CH2), 4.05 (q, J=7 Hz, 2H, ester CH2), 4.29-4.40 (m, 1H, glu-CH), 6.84 (br s, 2H, NH2), 7.14 (d, J=9 Hz, 2H, Ar), 7.54 (s, 1H, Ar), 7.69 (d, J=9 Hz, 2H, Ar), 8.48 (d, J=8 Hz, 1H, NH), 9.37 (s, 1H, Ar), 10.87 (br s, 1H, NH), 11.04 (br 5, 1H, NH). Anal. Calculated for C28H30BrN5O8S: 1/4 H2O C,49.38; H,4.51; Br,11.73; N,10.20; S,4.71. Found: C,49.33; H,4.40; Br,11.79; N,10.20; S,4.74.
Reaction SMILES: [CH2:1]([N:4]([CH2:10][CH:11]=O)[C:5](=[O:9])[O:6][CH2:7][CH3:8])[CH:2]=[CH2:3].[CH3:13][NH:14][C@H:15](C(O)=O)[CH3:16]>C1(C)C=CC=CC=1>[CH3:13][N:14]1[CH:15]([CH3:16])[CH2:3][CH:2]2[CH:11]1[CH2:10][N:4]([C:5]([O:6][CH2:7][CH3:8])=[O:9])[CH2:1]2
Reactant: CN[C@@H](C)C(=O)O
Reactant: C=CCN(CC=O)C(=O)OCC
Solvent: Cc1ccccc1
Product: CCOC(=O)N1CC2CC(C)N(C)C2C1

Procedure:
17.2 g (0.1 mol) of ethyl N-allyl-N-(2-oxoethyl) -carbamate are heated under reflux overnight with 10.5 g (0.1 mol) of N-methylalanine in 300 ml of toluene. The mixture is concentrated and the residue is distilled.
Reaction SMILES: [BH4-].[Na+].[F:3][C:4]1[C:16]([F:17])=[C:15]([F:18])[CH:14]=[CH:13][C:5]=1[NH:6][C@@H:7]([CH3:12])[C:8](OC)=[O:9].CO.O>COCCOC>[F:3][C:4]1[C:16]([F:17])=[C:15]([F:18])[CH:14]=[CH:13][C:5]=1[NH:6][C@@H:7]([CH3:12])[CH2:8][OH:9]
Reactant: COC(=O)[C@H](C)Nc1ccc(F)c(F)c1F
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Solvent: COCCOC
Product: C[C@@H](CO)Nc1ccc(F)c(F)c1F
Reaction time: 1 h

Procedure:
At room temperature, sodium borohydride (35.7 mg) was suspended in 1,2-dimethoxyethane (0.2 ml). Then a solution (0.8 ml) of methyl (2S)-2-(2,3,4-trifluoroanilino)propionate (200 mg, 99.8% ee) in DME was added to the solution. After adding methanol (137.4 mg), the liquid reaction mixture was stirred for 1 hour. Then water was added to the liquid reaction mixture followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of ammonium chloride and dried over anhydrous magnesium sulfate. After evaporating the solvent, the obtained residue was subjected to silica gel column chromatography to thereby give 176 mg (99.8% ee) of the title compound as an oily substance. The 1H-NMR and IR spectral data of this product was identical with those of the compound obtained in Example 51.
Reaction SMILES: O[N:2]1[CH2:9][CH2:8][CH2:7][C@H:3]1[C:4]([OH:6])=[O:5].C[Si:11](O)(O)[OH:12]>>[SiH3:11][OH:12].[NH:2]1[CH2:9][C@H:8]([OH:12])[CH2:7][C@H:3]1[C:4]([OH:6])=[O:5]
Reactant: C[Si](O)(O)O
Reactant: O=C(O)[C@@H]1CCCN1O
Product: O=C(O)[C@@H]1C[C@@H](O)CN1
Product: O[SiH3]

Procedure:
According to the process steps of the preceding examples, an aqueous solution of 10 g/l of complex ##STR12## was prepared starting from 5.8 g of 1-hydroxyproline and 4.2 g of methylsilanetriol. The solution contained 1.25 g Si/liter.