Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:7][CH2:8][N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17](Cl)[C:12]=2[CH:11]=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[CH2:19]([O:21][CH:22]([N:24]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[N:25]1)[CH3:23])[CH3:20].C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:7][CH2:8][N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([C:27]3[CH:26]=[N:25][N:24]([CH:22]([O:21][CH2:19][CH3:20])[CH3:23])[CH:28]=3)[C:12]=2[CH:11]=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]
Reactant: CC(C)(C)C(=O)OCn1ccc2c(Cl)ncnc21
Reactant: CCOC(C)n1cc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Product: CCOC(C)n1cc(-c2ncnc3c2ccn3COC(=O)C(C)(C)C)cn1
Temperature: 82 °C

Procedure:
To the quenched reaction mixture, which contains crude POM-protected chlorodeazapurine (3f) made as described above was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (14, 200 g, 0.75 mol, 1.10 equiv) and potassium carbonate (K2CO3, 189 g, 1.37 mol, 2.0 equiv) at room temperature. The resulting mixture was degassed by passing a stream of nitrogen through the solution for 15 minutes before being treated with tetrakis(triphenylphosphine)-palladium(0) (7.9 g, 0.68 mmol, 0.01 equiv) and the resulting reaction mixture was heated at reflux (about 82° C.) for 10 hours. When the reaction was deemed complete by TLC (1:1 hexanes/ethyl acetate) and LCMS, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (2 L) and water (1 L). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (500 mL). The combined organic layers were washed with water (2×1 L) and brine (1 L) before being concentrated under reduced pressure to afford crude {4-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate (18) as a pale-yellow oil, which was directly used in the subsequent de-protection reaction without further purification.
Reaction SMILES: [OH:1][N:2]=[C:3]([C:9]#[N:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5].O.Cl[C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14].C(=O)([O-])O.[Na+]>CC(C)=O>[CH2:16]([O:15][C:13]([O:1][N:2]=[C:3]([C:9]#[N:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[O:14])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CCOC(=O)C(C#N)=NO
Reactant: O=C(Cl)OCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: CCOC(=O)C(C#N)=NOC(=O)OCc1ccccc1
Reaction time: 3 h
Yield: 80.1 %

Procedure:
A mixture of ethyl 2-hydroxyimino-2-cyanoacetate (8.5 g). water (30 ml) and acetone (4 ml) is stirred at 0°C, and benzyl chloroformate (9.4 g) is added thereto. The resulting mixture is, after adjusted to pH 7 to 8 with the addition of an aqueous solution of sodium hydrogencarbonate, stirred for 3 hours and then filtered. The residue is washed with water and dried to give ethyl 2-benzyloxycarbonyloxyimino-2-cyanoacetate (12.2 g) as crystals. M.P. 101° to 102.5°C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C:9]1=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.Cl.[NH2:23][C@H:24]([C:29]([NH2:31])=[O:30])[CH2:25][CH2:26][S:27][CH3:28].O>CCO.C(Cl)Cl>[CH3:28][S:27][CH2:26][CH2:25][C@@H:24]1[NH:23][C:11]2([CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[NH:31][C:29]1=[O:30]
Reactant: CC(C)(C)OC(=O)N1CCCCC1=O
Reactant: CSCC[C@H](N)C(N)=O
Agent: Cl
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: CSCC[C@@H]1NC2(CCN(C(=O)OC(C)(C)C)CC2)NC1=O

Procedure:
N-tert-Butyloxycarbonylpiperidone (5.9 g, 29.8 mmol) and triethylamine (3.02 g, 29.8 mmol) were added to a solution of (S)-methioninamide hydrochloride (5.5 g, 29.8 mmol) in dry EtOH (66 ml) and the mixture was heated for 2.5 h under reflux. After addition of water (50 ml) and CH2Cl2 (200 ml), the organic phase was separated off and the aqueous phase was extracted with CH2Cl2 (3×20 ml). The combined organic phases were dried over Na2SO4. After filtration, the solvent was distilled off. tert-Butyl 3-(S)-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4,5]decane-8-carboxylate was obtained in a yield of 8.0 g (82%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])O[CH:7]=[CH:6]2.[CH3:14][N:15]1[CH2:21][CH2:20][CH2:19][N:18]([C:22]2[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=2)[CH2:17][CH2:16]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:28]([C:25]1[CH:24]=[CH:23][C:22]([N:18]3[CH2:19][CH2:20][CH2:21][N:15]([CH3:14])[CH2:16][CH2:17]3)=[CH:27][CH:26]=1)[CH2:7][CH2:6]2
Reactant: CN1CCCN(c2ccc(N)cc2)CC1
Reactant: COc1ccc2c(=O)occc2c1
Product: COc1ccc2c(c1)CCN(c1ccc(N3CCCN(C)CC3)cc1)C2=O

Procedure:
6-Methoxy-isochromen-1-one and 4-(4-methyl-[1,4]diazepan-1-yl)-phenylamine were reacted according to Method AC. In this way the product was obtained with molecular weight 365.48 (C22H27N3O2); MS (ESI): 366 (M+H+).
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][N:28]=1)[C:6]([NH:8][C:9]1[S:10][C:11]2[C:17]([CH:18]3[CH2:23][O:22][CH2:21][CH2:20][O:19]3)=[CH:16][CH:15]=[C:14]([O:24][CH3:25])[C:12]=2[N:13]=1)=[O:7].[CH3:29][CH2:30][O-:31].[Na+]>C(O)C>[O:19]1[CH2:20][CH2:21][O:22][CH2:23][CH:18]1[C:17]1[C:11]2[S:10][C:9]([NH:8][C:6](=[O:7])[C:5]3[CH:26]=[CH:27][N:28]=[C:3]([CH2:2][O:31][CH2:30][CH3:29])[CH:4]=3)=[N:13][C:12]=2[C:14]([O:24][CH3:25])=[CH:15][CH:16]=1
Reactant: CC[O-]
Reactant: COc1ccc(C2COCCO2)c2sc(NC(=O)c3ccnc(CCl)c3)nc12
Agent: [Na+]
Solvent: CCO
Product: CCOCc1cc(C(=O)Nc2nc3c(OC)ccc(C4COCCO4)c3s2)ccn1
Yield: 67.9 %

Procedure:
To a solution of 50 mg (0.12 mmol) (+)-2-chloromethyl-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-isonicotinamide in 2 ml ethanol was added 1.32 ml (3.57 mmol) sodium ethylate solution (2.71 M solution in ethanol) and the mixture ultrasonicated at room temperature for 2 h. The reaction mixture was then poured onto water and extracted three times with dichloromethane. The organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (1/1 acetone/heptane) followed by trituration in ether afforded 35 mg (68%) (+)-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-2-ethoxymethyl-isonicotinamide as an off-white solid. [α]D20=+60.7° (c=0.94, CHCl3), ES-MS m/e (%): 430 (M+H+, 100).
Reaction SMILES: Cl.[Br:2][C:3]1[CH:12]=[C:11]([N+:13]([O-:15])=[O:14])[C:10]([NH2:16])=[C:9]2[C:4]=1[CH2:5][CH2:6][NH:7][CH2:8]2.[F:17][C:18]([F:28])([F:27])[C:19]1[CH:24]=[CH:23][C:22]([CH:25]=O)=[CH:21][CH:20]=1.C([BH3-])#N.[Na+]>CO.O>[Br:2][C:3]1[CH:12]=[C:11]([N+:13]([O-:15])=[O:14])[C:10]([NH2:16])=[C:9]2[C:4]=1[CH2:5][CH2:6][N:7]([CH2:25][C:22]1[CH:21]=[CH:20][C:19]([C:18]([F:17])([F:27])[F:28])=[CH:24][CH:23]=1)[CH2:8]2
Reactant: Nc1c([N+](=O)[O-])cc(Br)c2c1CNCC2
Reactant: O=Cc1ccc(C(F)(F)F)cc1
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Solvent: CO
Product: Nc1c([N+](=O)[O-])cc(Br)c2c1CN(Cc1ccc(C(F)(F)F)cc1)CC2
Reaction time: 2.5 h
Yield: 50.9 %

Procedure:
A solution of the product from Example 5 (1 g, 3.24 mmol) and α,α,α-trifluro-p-tolualdehyde (1.22 g, 7 mmol) in 2:1 MeOH/H2O (50 mL) was treated with sodium cyanoborohydride (0.56 g, 9 mmol) portionwise under nitrogen and stirred for 2.5 hours. The precipitate was filtered, washed with hexane and dried to give the title compound (0.71 g, 51% yield) as a yellow solid, mp=119-120° C.
Reaction SMILES: N[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:5]=[C:4]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[N:3]=1.Cl.[O:27]1CCOCC1.N([O-])=O.[Na+]>O>[CH2:11]([O:10][C:8]([C:7]1[C:2](=[O:27])[NH:3][C:4]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[CH:5][C:6]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[O:9])[CH3:12]
Reactant: C1COCCO1
Reactant: CCOC(=O)c1cc(-c2ccc(OC)cc2)nc(N)c1C(=O)OCC
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: CCOC(=O)c1cc(-c2ccc(OC)cc2)[nH]c(=O)c1C(=O)OCC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 100 mg of 2-amino-3,4-diethoxycarbonyl-6-(4-methoxyphenyl)pyridine were added 2 ml of 1N hydrochloric acid and 5 ml of dioxane, and thereto was added dropwise a solution of 26 mg (1.3 eq.) of sodium nitrite dissolved in 0.5 ml of water under ice-cooling. The mixture was stirred at room temperature overnight. The solvent was distilled off. The residue was neutralized with sodium hydrogencarbonate, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried. The solvent was distilled off. The resulting crude crystals were recrystallized from ethanol.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][CH:3]=1.[CH:9]#[C:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(OP([O-])OCC)C>[Pd](Cl)Cl.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:9]([C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][CH:3]=1)#[C:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: C#CCCCCCCCC
Reactant: Brc1ccc(I)cc1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: CCOP([O-])OCC
Product: CCCCCCCCC#Cc1ccc(Br)cc1
Temperature: 55 °C
Yield: 98 %

Procedure:
A synthesis protocol was designed to test the modular approach to synthesis of the conductive compositions of the present invention (FIG. 3). The model conductive composition 5b was prepared using 1-iodo-4-bromobenzene as a precursor to the body structure, 1-decyne as the tail group moiety, and diethylphosphite as the head group moiety. To a 500 mL schlenk flask with egg-shaped stirbar under argon, palladium dichloride (1.0 mmol, 0.177 g), copper(I) iodide (2.36 mmol, 0.450 g), and triphenylphosphine (2.0 mmol, 0.525 g) were added in a glovebox under argon. On a schlenk line, 1-iodo-4-bromo-benzene (50 mmol, 14.15 g, compound 1) was added, the vessel was stoppered, and the flask was placed under vacuum and backfilled with argon (3×). The flask was fitted with a septum under positive argon pressure and degassed diisopropyl amine (100 mL) was added via cannula under positive argon pressure with stirring. Next, degassed 1-decyne (50 mmol, 6.91 g, compound 2) was added via syringe under argon. Finally, dry, degassed tetrahydrofuran was added via cannula transfer under argon, the vessel sealed with a glass stopper and allowed to stir at ambient for 16 h followed by heating to 55° C. for one hour. After cooling to ambient temperature, the solvent was removed by roto-evaporation, the residue dissolved in diethyl ether (200 mL) and washed with ammonium chloride (sat. aqueous, 3×100 mL). The organic layer was separated and dried over magnesium sulfate, filtered and the solvent removed by roto-evaporation. The resulting oil was dissolved in hexanes and plugged through silica gel. Removal of the solvent resulted in a yellow oil of 4-decynyl-bromo-benzene 3 (14.34 g, 98% yield).
Reaction SMILES: [CH2:1]([C@@H:8]([CH2:12][CH2:13][C@H:14]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:15]([O:17][CH3:18])=[O:16])[C:9]([OH:11])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[NH2:33][C@H:34]1[CH2:40][CH2:39][CH2:38][CH2:37][N:36]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:35]1=[O:47].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:19]([C@@H:14]([CH2:13][CH2:12][C@H:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:9](=[O:11])[NH:33][C@@H:34]1[CH2:40][CH2:39][CH2:38][CH2:37][N:36]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:35]1=[O:47])[C:15]([O:17][CH3:18])=[O:16])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: COC(=O)[C@H](CC[C@H](Cc1ccccc1)C(=O)O)Cc1ccccc1
Reactant: N[C@H]1CCCCN(c2ccccc2)C1=O
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)[C@H](CC[C@H](Cc1ccccc1)C(=O)N[C@@H]1CCCCN(c2ccccc2)C1=O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 70.9 %

Procedure:
To a round bottom flask was added (2R,5R)-2,5-dibenzyl-6-methoxy-6-oxohexanoic acid (278 mg, 0.817 mmol), (S)-3-amino-1-phenylazepan-2-one trifluoroacetic acid salt (260 mg, 0.817 mmol), HOBT (163 mg, 1.062 mmol), EDC (204 mg, 1.062 mmol), Hunig's base (317 mg, 2.45 mmol) and DMF (5 mL). The reaction was stirred at rt for 2 days. The reaction mixture was partitioned between EtOAc and water. The organic phase was isolated, washed with aqueous 0.5 N HCl, saturated aqueous NaHCO3 and saturated aqueous NaCl. The organic phase was then dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 30-60% EtOAc/Hex to give (2R,5R)-methyl 2,5-dibenzyl-6-oxo-6-((R)-2-oxo-1-phenylazepan-3-ylamino)hexanoate (305 mg, 0.579 mmol, 70.9% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.38 (t, J=7.7 Hz, 2H), 7.32-7.20 (m, 5H), 7.20-7.06 (m, 8H), 6.75 (d, J=6.2 Hz, 1H), 4.70 (dd, J=10.0, 6.3 Hz, 1H), 3.90 (dd, J=15.3, 11.4 Hz, 1H), 3.67-3.47 (m, 4H), 2.95-2.82 (m, 2H), 2.77-2.57 (m, 3H), 2.43-2.30 (m, 1H), 2.02-1.78 (m, 3H), 1.77-1.39 (m, 5H), 1.35-1.20 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:27])([F:26])[F:25])[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH:20]([OH:22])[CH3:21])=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:26])([F:25])[F:27])[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20](=[O:22])[CH3:21])=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: Cc1cc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)ccc1C(C)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(=O)c1ccc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1C
Temperature: 25 °C
Reaction time: 1 h
Yield: 75 %

Procedure:
To a solution of 1-{4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-phenyl}-ethanol (i.e. the product of example S.2, Step 1, 160 mg, 0.38 mmol) in CH2Cl2 (10 mL) was added Dess-Martin-Periodinane (243 mg, 0.57 mmol, 1.5 equiv.) in small portions. The mixture was stirred at room temperature over night, then saturated aqueous NaHCO3-solution was added and the mixture was left at room temperature for 1 h. The layers were separated and the organic layer was washed with water, dried over Na2SO4 and evaporated in vacuum to give the title compound (120 mg, 75%), which was used in the next reaction without further purification.
Reaction SMILES: [C:1]([CH2:4][N:5]([C:10]1[CH:15]=[CH:14][C:13]([NH:16]/[C:17](=[C:24]2\[C:25](=[O:36])[NH:26][C:27]3[C:32]\2=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=3)/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:12][CH:11]=1)[S:6]([CH3:9])(=[O:8])=[O:7])([OH:3])=O.[Cl-].[CH3:38][NH2+:39][CH3:40].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)C(C)C)C>CN(C=O)C>[CH3:38][N:39]([CH3:40])[C:1]([CH2:4][N:5]([C:10]1[CH:15]=[CH:14][C:13]([NH:16]/[C:17](=[C:24]2\[C:25](=[O:36])[NH:26][C:27]3[C:32]\2=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=3)/[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:12][CH:11]=1)[S:6]([CH3:9])(=[O:8])=[O:7])=[O:3]
Reactant: C[NH2+]C
Reactant: CS(=O)(=O)N(CC(=O)O)c1ccc(N/C(=C2\C(=O)Nc3ccc([N+](=O)[O-])cc32)c2ccccc2)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CN(C)C(=O)CN(c1ccc(N/C(=C2\C(=O)Nc3ccc([N+](=O)[O-])cc32)c2ccccc2)cc1)S(C)(=O)=O

Procedure:
Prepared analogously to Example 18 from (Z)-3-{1-[4-(N-carboxymethyl-N-methylsulphonyl-amino)-phenylamino]-1-phenyl-methylidene}-5-nitro-2-indolinone, dimethylammonium chloride, HOBt, TBTU and N-ethyl-N,N-diisopropylamine in DMF.
Reaction SMILES: [NH2:1][C:2]1[CH2:3][C:4]([C:14]([N:16]([CH2:20][CH2:21][CH3:22])[CH2:17][CH2:18][CH3:19])=[O:15])=[CH:5][C:6]2[CH:12]=[CH:11][C:10](Br)=[CH:9][C:7]=2[N:8]=1.[C:23]([C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1)#[N:24]>>[NH2:1][C:2]1[CH2:3][C:4]([C:14]([N:16]([CH2:20][CH2:21][CH3:22])[CH2:17][CH2:18][CH3:19])=[O:15])=[CH:5][C:6]2[CH:12]=[CH:11][C:10]([C:29]3[CH:28]=[CH:27][CH:26]=[C:25]([C:23]#[N:24])[CH:30]=3)=[CH:9][C:7]=2[N:8]=1
Reactant: CCCN(CCC)C(=O)C1=Cc2ccc(Br)cc2N=C(N)C1
Reactant: N#Cc1cccc(B(O)O)c1
Product: CCCN(CCC)C(=O)C1=Cc2ccc(-c3cccc(C#N)c3)cc2N=C(N)C1

Procedure:
The title compound was prepared by the procedure as described in Example 124 (Step F) using (1E,4E)-2-amino-8-bromo-N,N-dipropyl-3H-benzo[b]azepine-4-carboxamide and 3-cyanophenylboronic acid. MS APCI (+) m/z 387 (M+1) detected; 1H-NMR (400 MHz, CDCl3) d 7.91 (m, 1H), 7.87-7.89 (m, 1H), 7.63-7.65 (m, 1H), 7.55 (t, 1H), 7.51 (br s, 1H), 7.40 (d, 1H), 7.30 (dd, 1H), 6.85 (s, 1H), 3.46 (br s, 4H), 2.90 (s, 2H), 1.62-1.72 (m, 4H), 0.94 (t, 6H).
Reaction SMILES: [O-:1][CH2:2][CH3:3].[Na+].[Br:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([NH:16][CH3:17])[N:10]=[C:9]2Cl>>[Br:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([NH:16][CH3:17])[N:10]=[C:9]2[O:1][CH2:2][CH3:3]
Reactant: CC[O-]
Reactant: CNc1nc(Cl)c2cc(Br)ccc2n1
Agent: [Na+]
Product: CCOc1nc(NC)nc2ccc(Br)cc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 29.8 %

Procedure:
To a solution of sodium ethoxide (8.11 g, 119.3 mmol) in absolute alcohol (150 mL) was added powder (6-bromo-4-chloro-quinazolin-2-yl)-methyl-amine (13 g, 47.7 mmol) in one portion and the mixture was stirred for 3 hours at room temperature under N2 atmosphere. The excess of alcohol was removed in vacuo and the residue was purified by column to afford (6-bromo-4-ethoxy-quinazolin-2-yl)-methyl-amine (4 g, 14.2 mmol, 29.8%) as a light yellow solid. 1H NMR (DMSO-d6): δ 7.90-7.89 (d, 1H), 7.70-7.67 (dd, 1H), 7.33-7.31 (m, 1H), 7.21-7.20 (dd, 1H), 4.45-4.44 (q, 2H), 2.83-2.82 (d, 3H), 1.40-1.37 (t, 3H).
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]=1[N:13]=[CH:12][N:11]=[C:10]2[NH:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([NH:23][C:24]([C:26]2[CH:27]=[N:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=2)=[O:25])[CH:18]=1)=O.C1COCC1.CC(O)C.[OH-].[NH4+:44]>O>[CH3:33][O:32][C:29]1[N:28]=[CH:27][C:26]([C:24]([NH:23][C:19]2[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=2)[CH2:16][NH:15][C:10]2[C:9]3[C:14](=[C:5]([C:3]([NH2:44])=[O:2])[CH:6]=[CH:7][CH:8]=3)[N:13]=[CH:12][N:11]=2)=[O:25])=[CH:31][CH:30]=1
Reactant: COC(=O)c1cccc2c(NCc3cccc(NC(=O)c4ccc(OC)nc4)c3)ncnc12
Reactant: [NH4+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(C(=O)Nc2cccc(CNc3ncnc4c(C(N)=O)cccc34)c2)cn1
Reaction time: 8 h

Procedure:
To a 40-mL vial with magnetic stirbar at 25° C. was added 4-{3-[(6-Methoxy-pyridine-3-carbonyl)-amino]-benzylamino}-quinazoline-8-carboxylic acid methyl ester (0.18 g, 0.4 mmol, 1 eq.) and THF (2 mL) and 2-propanol (2 mL). An approx. equal volume (i.e.; 2 mL) of concentrated aqueous ammonium hydroxide solution (28-30% soln.) was then added and stirring continued overnight. Water (15 mL) was added to the reaction mixture and a precipitate immediately began to form. The precipitate was collected and purified further via preparative HPLC afforded the desired compound as a white solid (13.9 mg) LCMS (ESI) 429.2 (M+H).
Reaction SMILES: [OH:1][NH:2][CH2:3][CH2:4][CH2:5][P:6](=[O:9])([OH:8])[OH:7].[C:10](OC(=O)C)(=[O:12])C.C(O)=O.[OH-].[Mg+2].[OH-]>O>[CH:10]([N:2]([CH2:3][CH2:4][CH2:5][P:6](=[O:8])([OH:7])[OH:9])[OH:1])=[O:12]
Reactant: O=P(O)(O)CCCNO
Reactant: CC(=O)OC(C)=O
Agent: [Mg+2]
Agent: [OH-]
Solvent: O=CO
Solvent: O
Product: O=CN(O)CCCP(=O)(O)O
Yield: 65.8 %

Procedure:
An oily 3-(N-formyl-N-hydroxyamino)propylphosphonic acid (12.05 g.), which was prepared by the reaction of 3-(N-hydroxyamino)propylphosphonic acid (15.5 g.), acetic anhydride (12.3 g.) and formic acid (9.8 ml.) conducted in substantially the same manner as that of Example (31), was dissolved in water (80 ml.) and treated with magnesium hydroxide (5.83 g.) for 15 minutes under ice-cooling with stirring.
Reaction SMILES: Br[C:2]([CH3:12])([CH3:11])[C:3]([NH:5][C:6]([N:8]([CH3:10])[CH3:9])=[O:7])=[O:4].[Na+].[C:14]([O:17][CH2:18][C:19]1[CH2:20][S:21][C@@H:22]2[C@H:29]([NH:30][C:31](=[O:40])/[C:32](/[C:35]3[O:36][CH:37]=[CH:38][CH:39]=3)=[N:33]\[OH:34])[C:28](=[O:41])[N:23]2[C:24]=1[C:25]([O-:27])=[O:26])(=[O:16])[CH3:15].CCO.C([O-])(=O)C>CS(C)=O>[C:14]([O:17][CH2:18][C:19]1[CH2:20][S:21][C@@H:22]2[C@H:29]([NH:30][C:31](=[O:40])/[C:32](=[N:33]\[O:34][C:2]([C:3]([NH:5][C:6]([N:8]([CH3:10])[CH3:9])=[O:7])=[O:4])([CH3:12])[CH3:11])/[C:35]3[O:36][CH:37]=[CH:38][CH:39]=3)[C:28](=[O:41])[N:23]2[C:24]=1[C:25]([OH:27])=[O:26])(=[O:16])[CH3:15]
Reactant: CN(C)C(=O)NC(=O)C(C)(C)Br
Reactant: CC(=O)OCC1=C(C(=O)[O-])N2C(=O)[C@@H](NC(=O)/C(=N\O)c3ccco3)[C@H]2SC1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCO
Product: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)/C(=N\OC(C)(C)C(=O)NC(=O)N(C)C)c3ccco3)[C@H]2SC1
Yield: 59 %

Procedure:
This compound was prepared from 1-(2-bromo-2-methylpropionyl)-3,3-dimethylurea and (6R,7R)-3-acetoxymethyl-7-[Z-2-(fur-2-yl)-2-hydroxyiminoacetamido]-ceph-3-em-4-carboxylic acid sodium salt by the method described in Example 1. λmax (EtOH) 275 nm (ε 16,500), νmax (Nujol) 3260 (NH), 3700-2100 (bonded OH), 1788 (β-lactam), 1735 (acetate), 1720 (--CO2H), 1670, 1540 cm-1 (--CONH), τ (DMSO d6) 7.09 (N(Me)2), 0.97 (--CONHCO--), 8.5 (C(Me)2), 2.06, 3.28, 3.16 (furyl), 0.18 (CONH), 4.01 (7 H), 4.71 (6 H), 6.25, 6.46 (2--CH2 --), 4.97, 5.29 (3--CH2 --), 7.98 (CH3CO). Yield: 59%.
Reaction SMILES: [H-].COCCO[Al+]OCCOC.[Na+].[H-].CC1C=CC(S([N:25]2[CH2:29][CH2:28][CH2:27][C@H:26]2[CH2:30][N:31]2[C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=3[CH2:35][S:34][C:33]3[CH:42]=[CH:43][CH:44]=[CH:45][C:32]2=3)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[NH:25]1[CH2:29][CH2:28][CH2:27][C@H:26]1[CH2:30][N:31]1[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[CH2:35][S:34][C:33]2[CH:42]=[CH:43][CH:44]=[CH:45][C:32]1=2
Reactant: Cc1ccc(S(=O)(=O)N2CCC[C@H]2CN2c3ccccc3CSc3ccccc32)cc1
Agent: COCCO[Al+]OCCOC
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: c1ccc2c(c1)CSc1ccccc1N2C[C@@H]1CCCN1
Temperature: 25 °C
Yield: 55.1 %

Procedure:
Sodium bis(2-methoxyethoxy)aluminium hydride ("Red-Al"-registered Trade Mark) (20.8 ml of a 3.4M solution in toluene) was added to a solution of (S)-5,11-dihydro-5-(1-[4-methylphenylsulphonyl]-2-pyrrolidinylmethyl)dibenzo[b,e][1,4]thiazepine (see Preparations 15 and 16) (8.0 g) in toluene (50 ml) and the mixture heated under reflux for 27 hours, allowed to cool to room temperature, quenched by the addition of 2.5M aqueous sodium hydroxide solution, diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulphate and evaporated under reduced pressure. The residue was purified by chromatography on silica gel, performing a gradient elution initially using dichloromethane as eluant and changing to dichloromethane/saturated methanolic ammonia (90:10). Appropriate fractions were combined and evaporated under reduced pressure to give the title compound as a colourless oil, (2.9 g, 55%), [α]589 -4.9° (c=1.065 in ethanol).