Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[N:3]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:4]2[N:5]([CH2:9][CH2:10][N:11]=2)[C:6](=[O:8])[CH:7]=1.O.[N:17]([O-])=[O:18].[Na+]>CC(O)=O>[NH2:1][C:2]1[N:3]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:4]2[N:5]([CH2:9][CH2:10][N:11]=2)[C:6](=[O:8])[C:7]=1[N:17]=[O:18]
Reactant: CC(C)CN1C(N)=CC(=O)N2CCN=C21
Reactant: O=N[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: CC(C)CN1C2=NCCN2C(=O)C(N=O)=C1N
Reaction time: 0.5 h

Procedure:
To a solution of 5.00 g. (0.024 mole) of the product of Procedure 30 in 15 ml. H2O and 4 ml. HOAc (0°) was added (portionwise) 1.72 g. (0.024 mole) NaNO2. The mixture was stirred at 24° for 30 min., cooled to 0° and filtered to yield 4.44 g. (72%) of a purple solid, mp 203°-205° d.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([CH:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:3][CH2:2]1.[CH3:13][C:14]([O:17][C:18](ON=C(C1C=CC=CC=1)C#N)=[O:19])([CH3:16])[CH3:15].C([O-])([O-])=O.[K+].[K+]>C1COCC1.C(Cl)(Cl)Cl>[N:1]1([C:18]([O:17][C:14]([CH3:16])([CH3:15])[CH3:13])=[O:19])[CH2:6][CH2:5][CH:4]([CH:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:3][CH2:2]1
Reactant: CC(C)(C)OC(=O)ON=C(C#N)c1ccccc1
Reactant: C1CC(C2CCNCC2)CCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(C2CCNCC2)CC1
Yield: 45.4 %

Procedure:
To 4,4′-bipiperidine (5.48 g, 32.6 mmol) in THF (160 mL) and CHCl3 (160 mL) was added BOC-On (4.01 g) in THF (90 mL) dropwise over a 8 h period. The reaction was then concentrated and purified by flash chromatography. The residue was taken up in 1M KHSO4 (250 mL) and washed with diethyl ether (three times). K2CO3 (38.0 g, 275 mmol) was added to the aqueous layer which was subsequently extracted with CHCl3 (3×), dried (MgSO4) and concentrated to provide the title compound of step A (1.98 g, 7.40 mmol, 45%). 1H NMR (400 MHz, CDCl3) δ ppm 1.06-1.18 (m, 5H), 1.42 (s, 9H), 1.58-1.69 (m, 6H), 2.50-2.61 (m, 4H), 3.06 (d, J=12.1 Hz, 2H), 4.08 (br. s., 2H).
Reaction SMILES: [C:1]1([C:11]2[C:23]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH2:16][C:15]=3[C:14]([C:24]#[N:25])=[C:13]([N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)[CH:12]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[H-].[Na+].C1C[O:37]CC1>>[C:1]1([C:11]2[C:23]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[C:16](=[O:37])[C:15]=3[C:14]([C:24]#[N:25])=[C:13]([N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)[CH:12]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: N#Cc1c(N2CCCCC2)cc(-c2cccc3ccccc23)c2c1Cc1ccccc1-2
Reactant: C1CCOC1
Agent: [H-]
Agent: [Na+]
Product: N#Cc1c(N2CCCCC2)cc(-c2cccc3ccccc23)c2c1C(=O)c1ccccc1-2
Temperature: 2.5 °C

Procedure:
A solution of 4-(naphthalen-1-yl)-2-(piperidin-1-yl)-9H-fluorene-1-carbonitrile (400 mg) in THF was added sodium hydride (37 mg) and was stirred at 0-5° C. for less than five minutes. After completion, the reaction solvent was evaporated under vacuum and the crude solid obtained was quenched with ice water and subsequently neutralized by dilute HCL. The precipitate thus obtained was filtered and purified on a silica gel column using ethyl acetate-hexane as eluent. Light red solid; mp 202-204° C.; ESIMS 0.415 (M++1); IR (KBr) 2221 (CN), 1719 cm−1 (CO), HRMS calcd. for C29H22N2O 414.1732. Found 414.1714.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[N:19]=[CH:18][C:17]([CH:20]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH3:21])=[CH:16][CH:15]=1.[B:28](OC(C)C)([O:33]C(C)C)[O:29]C(C)C>O1CCCC1>[F:13][C:14]1[C:15]([B:28]([OH:33])[OH:29])=[CH:16][C:17]([CH:20]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH3:21])=[CH:18][N:19]=1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: CC(c1ccc(F)nc1)N1CCOCC1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CC(c1cnc(F)c(B(O)O)c1)N1CCOCC1
Temperature: -78 °C
Reaction time: 1 h
Yield: 96 %

Procedure:
A stirred solution of diisopropylamine (2.152 mL, 15.35 mmol) in tetrahydrofuran (20 mL) was treated with n-butyllithium 1.6M in Hexanes (9.60 mL, 15.35 mmol) at −40° C. The yellow solution was stirred at the same temperature for 1 h and then cooled to −78° C. A solution of 4-(1-(6-fluoropyridin-3-yl)ethyl)morpholine (2.69 g, 12.79 mmol) in THF (15 mL) was added via cannula over 20 min. The deep-red mixture was stirred at the same temperature for 1.5 h. Then a solution of triisopropyl borate (4.41 mL, 19.19 mmol) in THF (10 mL) was added slowly into the mixture. The resulting mixture was stirred at the same temperature for 30 min and then the cooling bath was removed. After the reaction mixture had warmed to room temperature, the tan mixture was quenched with 1 N NaOH (aq) (15 mL) and stirred. The separated aqueous layer was removed and the flask was rinsed with 1 N NaOH (aq) (2×20 mL) and the organic layer was extracted with 1 N NaOH (2×10 mL). The aqueous layer was collected and carefully acidified with 5N HCl until acidic (pH 5 about 6) and the resulting cloudy mixture was extracted with EtOAc (3×30 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The product remained in the aqueous layer. The aqueous layer was frozen and the water removed by lyophilization. The mixture was diluted with 1:1 MeOH/DCM and placed into a sonicator for 5 min. The mixture was filtered through a fine-fritted funnel and the filtrate was concentrated in vacuo to give 2-fluoro-5-(1-morpholinoethyl)pyridin-3-ylboronic acid (3.120 g, 12.28 mmol, 96% yield) as a yellow solid. 1H NMR (400 MHz, d4-MeOH) δ 8.00 (dd, J=8.22, 2.54 Hz, 1H) 7.88 (d, J=2.35 Hz, 1H) 3.68 (t, J=4.69 Hz, 4H) 3.40-3.54 (m, 1H) 2.56 (d, J=10.76 Hz, 2H) 2.35-2.50 (m, 2H) 1.41 (t, J=6.65 Hz, 3H). m/z (ESI, +ve ion) 255.1 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[Mg]Br.Cl[Si:12]1([CH2:17][Cl:18])[CH2:16][CH2:15][CH2:14][CH2:13]1>C1COCC1>[Cl:18][CH2:17][Si:12]1([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])[CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: ClC[Si]1(Cl)CCCC1
Reactant: Fc1ccc([Mg]Br)c(F)c1
Solvent: C1CCOC1
Product: Fc1ccc([Si]2(CCl)CCCC2)c(F)c1

Procedure:
In the same apparatus and procedures as Example 4-ii) was prepared 15.3 g (0.079 mol) of 2,4-difluorophenylmagnesiumbromide solution in THF, and the followed by coupling with 1-chloro-1-chloromethyl-1-silacyclopentane prepared from the above procedure i) for 1hr at 60° C. In the same method as Example 1 was treated the reaction product to give 3.5 g of 1-chloromethyl -1-(2,4-difluorophenyl)-1-silacyclopentane (56°-7° C. /0.3 mmHg).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[C:9]2[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:27][CH3:28]>O>[CH2:27]([O:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[C:9]2[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[CH:4][CH:3]=1)[CH3:28]
Reactant: CCI
Reactant: CC(C)(C)OC(=O)Nc1cccc2ccc(O)cc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Product: CCOc1ccc2cccc(NC(=O)OC(C)(C)C)c2c1
Temperature: 60 °C
Reaction time: 2 h
Yield: 67.5 %

Procedure:
Next, to a mixture of tert-butyl (7-hydroxy-1-naphthyl)carbamate (64.0 g, 247 mmol) and cesium carbonate (161 g, 493 mmol) in 300 mL anhydrous DM was added iodoethane (42.3 g, 272 mmol) at room temperature. The mixture was stirred at 60° C. for 2 hours. Water was added to the mixture, and the product was extracted with ethylacetate. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. To the obtained residue was added diisopropyl ether and the precipitate was collected and dried to afford tert-butyl (7-ethoxy-1-naphthyl)carbamate (47.9 g, 67.5% yield).
Reaction SMILES: [CH:1]([C:3]1[C:4]([O:14][CH2:15][C:16]2[CH:41]=[CH:40][C:19]([O:20][CH2:21][C:22]3[N:23]=[C:24]([C:28]4[CH:33]=[CH:32][C:31]([CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:30][CH:29]=4)[O:25][C:26]=3[CH3:27])=[C:18]([O:42][CH3:43])[CH:17]=2)=[N:5][N:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:7]=1)=O.[Cl-].[CH2:45]([C:47]1[S:48][CH:49]=[C:50]([CH2:52][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:51]=1)[CH3:46].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH2:45]([C:47]1[S:48][CH:49]=[C:50](/[CH:52]=[CH:1]\[C:3]2[C:4]([O:14][CH2:15][C:16]3[CH:41]=[CH:40][C:19]([O:20][CH2:21][C:22]4[N:23]=[C:24]([C:28]5[CH:29]=[CH:30][C:31]([CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:32][CH:33]=5)[O:25][C:26]=4[CH3:27])=[C:18]([O:42][CH3:43])[CH:17]=3)=[N:5][N:6]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:7]=2)[N:51]=1)[CH3:46]
Reactant: CCc1nc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cs1
Reactant: CCOC(=O)Cc1ccc(-c2nc(COc3ccc(COc4nn(-c5ccccc5)cc4C=O)cc3OC)c(C)o2)cc1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)Cc1ccc(-c2nc(COc3ccc(COc4nn(-c5ccccc5)cc4/C=C\c4csc(CC)n4)cc3OC)c(C)o2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 29.9 %

Procedure:
A mixture of ethyl (4-{4-[(4-{[(4-formyl-1-phenyl-1H-pyrazol-3-yl)oxy]methyl}-2-methoxyphenoxy)methyl]-5-methyl-1,3-oxazol-2-yl}phenyl)acetate (2.00 g), [(2-ethyl-1,3-thiazol-4-yl)methyl]triphenylphosphonium chloride (2.19 g), anhydrous potassium carbonate (713 mg) and N,N-dimethylformamide (30 mL) was stirred at room temperature for 16 hrs. The reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:4 to 1:1, v/v) to give ethyl {4-[4-({4-[({4-[(Z)-2-(2-ethyl-1,3-thiazol-4-yl)ethenyl]-1-phenyl-1H-pyrazol-3-yl}oxy)methyl]-2-methoxyphenoxy}methyl)-5-methyl-1,3-oxazol-2-yl]phenyl}acetate as colorless crystals (0.71 g, yield 31%). The crystals were recrystallized from tetrahydrofuran-hexane. melting point: 136-137° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[NH:7][C:8]1[C:9]([C:13]2[CH:18]=[CH:17][C:16]([C:19]#N)=[CH:15][CH:14]=2)=[N:10][O:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=[O:34].[Na+].[K+]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:21])[NH:7][C:8]1[C:9]([C:13]2[CH:18]=[CH:17][C:16]([CH:19]=[O:34])=[CH:15][CH:14]=2)=[N:10][O:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: O=C([O-])[C@H](O)[C@@H](O)C(=O)[O-]
Reactant: CC(C)(C)OC(=O)Nc1conc1-c1ccc(C#N)cc1
Agent: CC(C)C[AlH]CC(C)C
Agent: [K+]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)Nc1conc1-c1ccc(C=O)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of [3-(4-cyano-phenyl)-isoxazol-4-yl]-carbamic acid tert-butyl ester (1.88, 6.6 mmol) in toluene (50 mL) was cooled to 0° C. under Ar. DIBAL (6.7 mL, 1M in CH2Cl2, 6.7 mmol) was added dropwise to the solution and the reaction mixture was allowed to warm to rt and stirred for 1 h. DIBAL (6.7 mL, 1M in CH2Cl2, 6.7 mmol) was added again and the reaction mixture was stirred an additional 30 min. Saturated, aqueous Rochelle salt was added and the reaction mixture was stirred overnight. The phases were extracted three times with ethyl acetate. The combined organic phases were washed with brine and dried over MgSO4. Filtration followed by removal of volatiles under reduced pressure afforded a waxy solid from which [3-(4-Formyl-phenyl)-isoxazol-4-yl]-carbamic acid tert-butyl ester was isolated as a white solid (1.34 g, 70%) by column chromatography (50% ethyl acetate in hexane).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][N:3]=1.[NH:11]1[CH2:15][CH2:14][CH:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:12]1>>[NH2:8][C:5]1[CH:4]=[N:3][C:2]([N:11]2[CH2:15][CH2:14][CH:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:20])[CH3:22])[CH2:12]2)=[N:7][CH:6]=1
Reactant: CC(C)(C)OC(=O)NC1CCNC1
Reactant: O=[N+]([O-])c1cnc(Cl)nc1
Product: CC(C)(C)OC(=O)NC1CCN(c2ncc(N)cn2)C1
Yield: 65.2 %

Procedure:
Following General procedure H, 2-chloro-5-nitropyrimidine (500 mg, 3.1 mmol) was reacted with tert-butyl pyrrolidin-3-ylcarbamate (632 mg, 3.5 mmol) followed by reduction to afford the desired product (565 mg, 65%) as a purple solid: ESI MS m/z 280 [C13H21N5O2+H]+.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH2:9][CH2:10][N:11]2[S:14]([C:17]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=2[O:24][CH3:25])(=[O:16])=[O:15])=[CH:7][CH:6]=1)=[O:4].[OH-].[K+]>CO.O1CCCC1>[Cl:23][C:21]1[CH:20]=[CH:19][C:18]([O:24][CH3:25])=[C:17]([S:14]([N:11]2[C:12]3[C:8](=[CH:7][CH:6]=[C:5]([C:3]([OH:4])=[O:2])[CH:13]=3)[CH2:9][CH2:10]2)(=[O:15])=[O:16])[CH:22]=1
Reactant: COC(=O)c1ccc2c(c1)N(S(=O)(=O)c1cc(Cl)ccc1OC)CC2
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: COc1ccc(Cl)cc1S(=O)(=O)N1CCc2ccc(C(=O)O)cc21
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A suspension of 1-(5-chloro-2-methoxy-benzenesulfonyl)-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester (2.2 g, 5.8 mmol) in methanol (6 ml) and tetrahydrofuran (6 ml) was treated with 3N KOH (6 ml, 3 equiv.) and stirred at room temperature for 24 hours. The organic solvents were evaporated and the aqueous slurry treated with HCl 3N so as to reach pH 3. The white precipitate was filtered washing with methanol and water and dried under high vacuum to yield 1-(5-chloro-2-methoxy-benzenesulfonyl)-2,3-dihydro-1H-indole-6-carboxylic acid as an off-white solid, 1.9 g (88%). This was used as such in the following reaction.
Reaction SMILES: I[CH:2]([CH3:4])[CH3:3].[CH:5]1([C:8]2[C:15]([CH:16]3[CH2:18][CH2:17]3)=[CH:14][C:11]([CH:12]=[O:13])=[C:10]([OH:19])[C:9]=2[F:20])[CH2:7][CH2:6]1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[CH:5]1([C:8]2[C:15]([CH:16]3[CH2:18][CH2:17]3)=[CH:14][C:11]([CH:12]=[O:13])=[C:10]([O:19][CH:2]([CH3:4])[CH3:3])[C:9]=2[F:20])[CH2:6][CH2:7]1
Reactant: O=Cc1cc(C2CC2)c(C2CC2)c(F)c1O
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)Oc1c(C=O)cc(C2CC2)c(C2CC2)c1F
Reaction time: 2 h
Yield: 97.6 %

Procedure:
2-Iodopropane (862 mg) was added at room temperature to a mixture of 4,5-dicyclopropyl-3-fluoro-2-hydroxybenzaldehyde (744 mg), potassium carbonate (934 mg), and DMF (20 mL), and the mixture was stirred at 60 C for 2 hours in a nitrogen atmosphere. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and saturated saline in this order and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (865 mg).
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:11]([O:18][CH3:19])(=[O:17])[CH2:12][C:13]([O:15][CH3:16])=[O:14].[H-].[Na+].N#N>O>[CH3:16][O:15][C:13](=[O:14])[CH:12]([C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5])[C:11]([O:18][CH3:19])=[O:17]
Reactant: O=C(O)c1ccccc1Br
Reactant: COC(=O)CC(=O)OC
Agent: N#N
Agent: [H-]
Agent: [Na+]
Solvent: O
Product: COC(=O)C(C(=O)OC)c1ccccc1C(=O)O
Temperature: 70 °C
Reaction time: 0.5 h
Yield: 90.9 %

Procedure:
To a rapidly stirred cold suspension (0° C.) of 2-bromobenzoic acid (30.0 g, 149.32 mmol), cuprous bromide (2.14 g, 14.93 mmol) and dimethyl malonate (300 mL) was added NaH (80% in mineral oil, 10.75 g, 358.37 mmol) over a 30 minute period, while a stream of dry N2 was passed over the mixture. After the addition of the NaH had been completed, the mixture was stirred for 10 minutes at room temperature and 30 minutes at 70° C. (external oil bath temperature). At this point, the suspension had turned to a solid mass, which was dissolved in H2O (1000 mL). The aqueous layer was extracted with diethyl ether (3×500 mL) and was acidified with HCl (2N). The mixture was extracted with EtOAc and dried over MgSO4. Evaporation gave an off-white solid which was recrystallized from Et2O/hexane (-20° C.) to give a white solid (34.2 g, 90.9%).
Reaction SMILES: [C:1](Cl)(=O)[C:2]([Cl:4])=[O:3].C(C1[CH:15]=[CH:14][C:13]([S:16]([N:19]=[N+:20]=[N-:21])(=[O:18])=[O:17])=[CH:12][CH:11]=1)(O)=O>CN(C)C=O>[N:19]([S:16]([C:13]1[CH:14]=[CH:15][C:1]([C:2]([Cl:4])=[O:3])=[CH:11][CH:12]=1)(=[O:17])=[O:18])=[N+:20]=[N-:21]
Reactant: [N-]=[N+]=NS(=O)(=O)c1ccc(C(=O)O)cc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Product: [N-]=[N+]=NS(=O)(=O)c1ccc(C(=O)Cl)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Under Argon at 0° C. and while stiffing, 0.7 ml oxalylchloride were added dropwise to a suspension of 908 mg (4 mmol) 4-carboxybenzene sulfonyl azide (Aldrich). The mixture was allowed to warm to room temperature. Then, 10 μl DMF (dimethylformamide) were added. After stirring for 1 h at room temp. a clear solution was formed. The solvent was removed using a rotary evaporator.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[F:12])[N:5]=[CH:4][N:3]=1.[F:13][C:14]1[CH:15]=[C:16]([CH:28]=[CH:29][CH:30]=1)[CH2:17][N:18]1[C:26]2[C:21](=[CH:22][C:23]([NH2:27])=[CH:24][CH:25]=2)[CH:20]=[N:19]1.C(N(C(C)C)CC)(C)C>C(O)(C)C>[F:12][C:10]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:11]=1[C:2]([NH:27][C:23]1[CH:22]=[C:21]3[C:26](=[CH:25][CH:24]=1)[N:18]([CH2:17][C:16]1[CH:28]=[CH:29][CH:30]=[C:14]([F:13])[CH:15]=1)[N:19]=[CH:20]3)=[N:3][CH:4]=[N:5]2
Reactant: Fc1cccc2ncnc(Cl)c12
Reactant: Nc1ccc2c(cnn2Cc2cccc(F)c2)c1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: Fc1cccc(Cn2ncc3cc(Nc4ncnc5cccc(F)c45)ccc32)c1
Temperature: 80 °C
Yield: 82.6 %

Procedure:
A mixture of 4-chloro-5-fluoroquinazoline (1.82 g, 10 mmol), 1-(3-fluorobenzyl)-1H-indazol-5-amine (2.41 g, 10 mmol, obtained as described in WO 98/02438) and diisopropylethylamine (1.74 ml, 10 mmol) in isopropanol (20 ml) was heated at 80° C. for 45 minutes. On cooling to ambient temperature, the product was filtered off and washed with isopropanol and ether. The precipitated solid was dried under high vacuum to give 5-fluoro-N-[1-(3-fluorobenzyl)-1H-indazol-5-yl]quinazolin-4-amine (3.2 g, 83%); NMR Spectrum (CDCl3) 5.61 (s, 2H), 6.88 (d, 1H), 6.98 (m, 2H), 7.25 (m, 2H), 7.37 (d, 1H), 7.53 (dd, 1H), 7.73 (m, 2H), 8.09 (s, 1H), 8.19 (s, 1H), 8.49 (d, 1H), 8.69 (s, 1H); Mass spectrum MH+ 388.
Reaction SMILES: [CH3:1][C:2]1[C:20]([CH3:21])=[C:19]([N+:22]([O-])=O)[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12](=[O:16])[CH2:13][O:14][CH3:15])[CH:6]=1.CO.[H][H]>[Pt].CC(O)=O>[NH2:22][C:19]1[CH:18]=[CH:17][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12](=[O:16])[CH2:13][O:14][CH3:15])[CH:6]=2)=[C:2]([CH3:1])[C:20]=1[CH3:21]
Reactant: COCC(=O)Nc1cc(Oc2ccc([N+](=O)[O-])c(C)c2C)ccn1
Reactant: [H][H]
Agent: [Pt]
Solvent: CO
Solvent: CC(=O)O
Product: COCC(=O)Nc1cc(Oc2ccc(N)c(C)c2C)ccn1

Procedure:
A solution of N-(4-(2,3-dimethyl-4-nitrophenoxy)pyridin-2-yl)-2-methoxyacetamide (90 mg, 0.272 mmol) in a mixture MeOH (30 mL) and AcOH (2.0 mL) was subjected to hydrogenation by passage through a Thales H-cube (1.0 mL min−1, 50° C., 55 mm 10% Pt/C Cat-Cart, full hydrogen mode) and was then evaporated in vacuo to afford the title compound, Intermediate H5, (82 mg, 100%); Rt 1.21 min (Method 2); m/z 302 (M+H)+ (ES+).
Reaction SMILES: [CH3:1][NH:2][CH2:3][C:4]1[CH:9]=[CH:8][N:7]=[CH:6][CH:5]=1.[C:10]1([N:16]=[C:17]=[O:18])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(Cl)(Cl)Cl>[CH3:1][N:2]([CH2:3][C:4]1[CH:9]=[CH:8][N:7]=[CH:6][CH:5]=1)[C:17]([NH:16][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:18]
Reactant: O=C=Nc1ccccc1
Reactant: CNCc1ccncc1
Solvent: ClC(Cl)Cl
Product: CN(Cc1ccncc1)C(=O)Nc1ccccc1
Yield: 81 %

Procedure:
4-(Methylaminomethyl)pyridine (5 g), dry chloroform (500 ml) and phenyl isocyanate (5 g) were stirred together at room temperature for 2 hours. The chloroform was then evaporated in vacuo and the resultant oil was redissolved in the minimum quantity of chloroform and chromatographed on a "Florisil" (Trade Mark) (100 g) column using chloroform containing gradually increasing quantities of methanol (up to 2.5%) as eluting solvent. Appropriate fractions (identified by t.l.c.) were combined and evaporated in vacuo to give 1-methyl-1-(4-pyridylmethyl)-3-phenylurea as an oil (8.0 g).
Reaction SMILES: [C:1]([N:4]1[CH2:8][CH:7]([N:9]=[N+]=[N-])[CH2:6][CH:5]1[CH2:12][OH:13])(=[O:3])[CH3:2].[H][H]>[Pd].CO>[C:1]([N:4]1[CH2:8][C@@H:7]([NH2:9])[CH2:6][C@H:5]1[CH2:12][OH:13])(=[O:3])[CH3:2]
Reactant: CC(=O)N1CC(N=[N+]=[N-])CC1CO
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CC(=O)N1C[C@@H](N)C[C@H]1CO
Yield: 89.6 %

Procedure:
92.4 g of 10% Pd—C was added to a solution of 534 g of N-acetyl-4-azido-2-hydroxymethylpyrrolidine and 2.6 L of methanol, and this was hydrogenated (30 hours) at a normal pressure until the raw material disappeared, while the atmosphere in the container was substituted for hydrogen gas every one hour. After filtration, the solution was concentrated under reduced pressure to obtain 411 g of (2S, 4S)-N-acetyl-4-amino-2-hydroxymethylpyrrolidine, more specifically, (2S,4S)-(−)-1-acetyl-4-amino-2-hydroxymethyl-pyrrolidine as an oil.
Reaction SMILES: C(N(CC)C(C1C=CC=CC=1S([C:14]1[C@H:15]([CH3:45])[C@@H:16]2[C@@H:33]([C@H:34]([O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])[CH3:35])[C:32](=[O:44])[N:17]2[C:18]=1[C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=1)=[O:20])=O)=O)C.[N+:48]([C:51]1[CH:64]=[CH:63][C:54]([CH2:55][O:56][C:57]([NH:59][CH2:60][CH2:61][SH:62])=[O:58])=[CH:53][CH:52]=1)([O-:50])=[O:49]>>[Si:37]([O:36][C@@H:34]([C@H:33]1[C:32](=[O:44])[N:17]2[C:18]([C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=3)=[O:20])=[C:14]([S:62][CH2:61][CH2:60][NH:59][C:57]([O:56][CH2:55][C:54]3[CH:63]=[CH:64][C:51]([N+:48]([O-:50])=[O:49])=[CH:52][CH:53]=3)=[O:58])[C@H:15]([CH3:45])[C@H:16]12)[CH3:35])([C:40]([CH3:41])([CH3:42])[CH3:43])([CH3:39])[CH3:38]
Reactant: O=C(NCCS)OCc1ccc([N+](=O)[O-])cc1
Reactant: CCN(CC)C(=O)c1ccccc1S(=O)C1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)[C@H]([C@@H](C)O[Si](C)(C)C(C)(C)C)[C@H]2[C@H]1C
Product: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(SCCNC(=O)OCc3ccc([N+](=O)[O-])cc3)[C@H](C)[C@H]12
Yield: 83 %

Procedure:
Following a procedure similar to that described in Example 21(b), but using 4-nitrobenzyl (1R, 5S,6S)-2-(2-diethylcarbamoylphenylsulfinyl)-1-methyl-6-[1(R)-t-butyldimethylsilyloxyethyl]-1-carbapen-2-em-3-carboxylate (prepared as described in Example 39) and 2-(4-nitrobenzyloxycarbonyl)aminoethylmercaptan as starting materials, in relative proportions similar to those used in that Example, the title compound was obtained in a yield of 83%.