Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl-].[Cl:2][C:3]1[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([Cl:31])[C:4]=1[CH2:5][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH2:32]([O:34][C:35](=[O:46])[CH:36]=[C:37]([CH3:45])[CH:38]=[CH:39][CH:40]=[C:41]([CH:43]=O)[CH3:42])[CH3:33].C1OC1CC>>[CH2:32]([O:34][C:35](=[O:46])[CH:36]=[C:37]([CH3:45])[CH:38]=[CH:39][CH:40]=[C:41]([CH3:43])[CH:42]=[CH:5][C:4]1[C:25]([Cl:31])=[CH:26][C:27]([O:29][CH3:30])=[CH:28][C:3]=1[Cl:2])[CH3:33]
Reactant: COc1cc(Cl)c(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)c(Cl)c1
Reactant: CCOC(=O)C=C(C)C=CC=C(C)C=O
Agent: CCC1CO1
Agent: [Cl-]
Product: CCOC(=O)C=C(C)C=CC=C(C)C=Cc1c(Cl)cc(OC)cc1Cl
Reaction time: 2 h

Procedure:
39 g. of 2,6-dichloro-4-methoxy-benzyl-triphenylphosphonium chloride and 16 g. of 7-formyl-3-methyl-octa-2,4,6-trien-1-oic acid ethyl ester are heated at 82°-85° C. under reflux conditions while stirring for 2 hours after the addition of 40 g. of 1,2-butylene oxide. The mixture is then thoroughly extracted with hexane. The hexane extract is washed several times with methanol/water (60:40 parts by volume), dried over sodium sulphate and evaporated under reduced pressure. The residue is purified by absorption on silica gel using hexane for the elution. The 9-(2,6-dichloro-4-methoxyphenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid ethyl ester obtained from the eluate melts at 117°-118° C. after recrystallization from hexane.
Reaction SMILES: [OH:1][C@H:2]1[CH2:6][CH2:5][C@H:4]([NH2:7])[CH2:3]1.[CH2:8]([O:15][C:16](N1C(=O)CCC1=O)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(#N)C>[OH:1][C@H:2]1[CH2:6][CH2:5][C@H:4]([NH:7][C:16](=[O:17])[O:15][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:3]1
Reactant: N[C@H]1CC[C@H](O)C1
Reactant: O=C1CCC(=O)N1C(=O)OCc1ccccc1
Solvent: CC#N
Product: O=C(N[C@H]1CC[C@H](O)C1)OCc1ccccc1
Yield: 981.6 %

Procedure:
A solution of crude trans-3-hydroxycyclopentanamine (0.42 g, 4.2 mmol) and N-(benzyloxycarbonyl)succinimide (1.05 g, 0.42 mmol) in acetonitrile (40 ml) was stirred at ambient temperature under nitrogen for 18 hours. The mixture was concentrated under reduced pressure. The residue was taken up in ethyl acetate (150 ml), washed with water (3×75 ml), and brine (50 ml), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure to give benzyl (trans-3-hydroxycyclopentyl)carbamate (0.97 g, 98%), as a white solid.
Reaction SMILES: [N+](C1C=C(C=CC=1)C(Cl)=O)([O-])=O.[N+](C1C=CC(C(Br)=O)=CC=1)([O-])=O.[N+](C1C=C(C=CC=1)C(Br)=O)([O-])=O.C[C:38]1[CH:46]=[C:45]([N+:47]([O-:49])=[O:48])[CH:44]=[CH:43][C:39]=1[C:40]([Cl:42])=[O:41].CC1C=C(C=CC=1[N+]([O-])=O)C(Cl)=O.[N+](C1C=CC=CC=1C(Cl)=O)([O-])=O.[N+](C1C=CC=CC=1C(Br)=O)([O-])=O>>[N+:47]([C:45]1[CH:44]=[CH:43][C:39]([C:40]([Cl:42])=[O:41])=[CH:38][CH:46]=1)([O-:49])=[O:48]
Reactant: Cc1cc([N+](=O)[O-])ccc1C(=O)Cl
Agent: Cc1cc(C(=O)Cl)ccc1[N+](=O)[O-]
Agent: O=C(Br)c1ccc([N+](=O)[O-])cc1
Agent: O=C(Br)c1cccc([N+](=O)[O-])c1
Product: O=C(Cl)c1ccc([N+](=O)[O-])cc1

Procedure:
3-nitrobenzoyl chloride; 4-nitrobenzoyl bromide; 3-nitrobenzoyl bromide; 2-methyl-4-nitrobenzoyl chloride; 3-methyl-4-nitrobenzoyl chloride; 2-nitrobenzoyl chloride; and 2-nitrobenzoyl bromide.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([NH2:8])[C:5]([NH2:9])=[C:4]([CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH:3]=1.[BrH:17].[N:18]#[C:19][Br:20]>C(O)C.C(Cl)Cl.C(OCC)C>[BrH:20].[BrH:17].[Cl:1][C:2]1[CH:3]=[C:4]([CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:5]2[NH:9][C:19]([NH2:18])=[N:8][C:6]=2[CH:7]=1
Reactant: N#CBr
Reactant: Nc1cc(Cl)cc(CN2CCOCC2)c1N
Agent: Br
Solvent: ClCCl
Solvent: CCO
Solvent: CCOCC
Product: Nc1nc2cc(Cl)cc(CN3CCOCC3)c2[nH]1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 5-chloro-3-(morpholin-4-ylmethyl)benzene-1,2-diamine (458 mg, 1.9 mmol) in ethanol (5 mL) is added a 48% aqueous HBr solution (0.21 mL, 1.9 mmol) followed by a 3M solution of cyanogen bromide (0.95 mL, 2.8 mmol) in CH2Cl2. The reaction is stirred at room temperature for 4 h and is diluted with diethyl ether. The resulting solid is isolated by filtration to afford the title compound as the dihydrobromide salt (595 mg, 73%).
Reaction SMILES: C([O:4][C:5]1[CH:6]=[CH:7][C:8]([O:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])=[N:9][CH:10]=1)(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO>[OH:4][C:5]1[CH:6]=[CH:7][C:8]([O:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])=[N:9][CH:10]=1
Reactant: COC(=O)COc1ccc(OC(C)=O)cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: COC(=O)COc1ccc(O)cn1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 87.8 %

Procedure:
A mixture of 1.4 g of 5-acetoxy-2-(methoxycarbonyl)methoxypyridine, 0.47 g of potassium carbonate and 10 ml of methanol was stirred for 4.5 hours at room temperature. The solvent was distilled off under reduced pressure, and to the resulted residue was added water, then neutralized with hydrochloric acid. The mixture was extracted with ethyl acetate, and organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography to obtain 1.0 g of 5-hydroxy-2-(methoxycarbonyl)methoxypyridine.
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][N:12]1[CH2:22][CH2:21][C:20]2[C:23]3[CH:13]1[CH2:14][C:15](=[O:28])[C:16]=3[C:17]([O:26][CH3:27])=[C:18]([O:24][CH3:25])[CH:19]=2)(C)(C)C.[ClH:30]>C(Cl)Cl.C(O)C.CCOCC>[ClH:30].[ClH:30].[NH2:7][CH2:8][CH2:9][CH2:10][CH2:11][N:12]1[CH2:22][CH2:21][C:20]2[C:23]3[CH:13]1[CH2:14][C:15](=[O:28])[C:16]=3[C:17]([O:26][CH3:27])=[C:18]([O:24][CH3:25])[CH:19]=2
Reactant: COc1cc2c3c(c1OC)C(=O)CC3N(CCCCNC(=O)OC(C)(C)C)CC2
Agent: Cl
Solvent: CCO
Solvent: ClCCl
Solvent: CCOCC
Product: COc1cc2c3c(c1OC)C(=O)CC3N(CCCCN)CC2
Yield: 80 %

Procedure:
[4-(7,8-Dimethoxy-1-oxo-2,2a,4,5-tetrahydro-1H-3-aza-acenaphthylen-3-yl)-butyl]-carbamic acid tert-butyl ester (498 mg, 1.22 mmol) is dissolved in a mixture of CH2Cl2 (10 ml) and ethanol (2 ml) and a solution of 2 N HCl in Et2O is added (6 ml, 12 mmol). A brown precipitate appears, which is collected by filtration (367 mg, 80% yield).
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[CH2:8]O)[CH3:3].[ClH:13].[NH2:14][CH2:15][CH2:16][SH:17]>Cl>[ClH:13].[ClH:13].[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[CH2:8][S:17][CH2:16][CH2:15][NH2:14])[CH3:3]
Reactant: NCCS
Reactant: CN(C)Cc1cccc(CO)c1
Agent: Cl
Product: CN(C)Cc1cccc(CSCCN)c1

Procedure:
Equimolar quantities of 3-(dimethylaminomethyl)benzyl alcohol and cysteamine hydrochloride were heated under reflux for 5 hours in 12N aqueous hydrochloric acid and the mixture was evaporated to give 2-[3-(dimethylaminomethyl)benzylthio]ethylamine dihydrochloride.
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][CH2:9][CH2:10][N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]2[CH:28]=[CH:27][N:26]=[C:25](Cl)[N:24]=2)[CH:18]=1)[S:12]([CH3:15])(=[O:14])=[O:13])(C)(C)C.[NH2:31][CH2:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[OH:40]>>[NH2:7][CH2:8][CH2:9][CH2:10][N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:31][CH2:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[OH:40])[N:24]=2)[CH:18]=1)[S:12]([CH3:15])(=[O:13])=[O:14]
Reactant: CC(C)(C)OC(=O)NCCCN(Cc1cccc(-c2ccnc(Cl)n2)c1)S(C)(=O)=O
Reactant: NCCc1ccccc1O
Product: CS(=O)(=O)N(CCCN)Cc1cccc(-c2ccnc(NCCc3ccccc3O)n2)c1

Procedure:
Intermediate 4 was coupled with 2-(2-amino-ethyl)-phenol following procedure F and the resulting product deprotected following procedure G. LC-MS showed the product had the expected M+H+ of 456. 1H NMR (Varian 300 MHz, CD3OD, shifts relative to the solvent peak at 3.30 ppm) δ 8.3 (m, 3H) 7.8 (d, 1H) 7.6 (m, 1H) 7.5 (d, 1H) 7.1 (d, 1H) 7.0 (m, 1H) 6.7 (d, 2H) 4.5 (s, 2H) 3.9 (m, 2H) 3.4 (m, 2H) 3.0 (m, 5H) 2.8 (m, 2H) 1.8 (m, 2H).
Reaction SMILES: [C:1](=[O:13])([O:7][CH:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)[O:2][CH:3](Cl)[CH2:4][CH3:5].[I-:14].[Na+].CCOCC.O>C(#N)C>[C:1](=[O:13])([O:7][CH:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)[O:2][CH:3]([I:14])[CH2:4][CH3:5]
Reactant: CCC(Cl)OC(=O)OC1CCCC1
Reactant: [I-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Solvent: CCOCC
Product: CCC(I)OC(=O)OC1CCCC1

Procedure:
A solution of 3.11 g of 1-chloropropyl cyclopentyl carbonate and 6 g of sodium iodide in 40 ml of acetonitrile is stirred at 60° C. for 60 minutes and then concentrated under reduced pressure. The residue obtained is distributed with 100 ml of ether and 100 ml of water. The ether layer is separated, washed serially with 50 ml of 5% sodium thiosulfate and 100 ml of saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. The solvent is distilled off under reduced pressure to give the title compound as oily material.
Reaction SMILES: [BH4-].[Na+].[Br:3][C:4]1[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8]([CH:16]=[N:17][CH3:18])=[CH:9]2.Cl>C(O)C>[Br:3][C:4]1[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8]([CH2:16][NH:17][CH3:18])=[CH:9]2
Reactant: CN=Cc1ccc2c(Br)c(OC)ccc2c1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CNCc1ccc2c(Br)c(OC)ccc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.8 %

Procedure:
Sodium borohydride (131 mg, 3.47 mmol) was added under nitrogen to a warm solution of (5-bromo-6-methoxy-naphthalen-2-ylmethylene)-methyl-amine (950 mg, 4.41 mmol), prepared in the previous step, in 30 mL of absolute ethanol. After the addition the reaction was stirred at room temperature for 19 h (overnight). 1 N HCl was added dropwise until the reaction was pH˜1 (litmus paper). The solvent was removed under reduced pressure and the residue partitioned between methylene chloride and water. The aqueous layer was made basic by the addition of 1 N NaOH. The organic layer was separated and the aqueous layer was extracted three times with methylene chloride. The combined extracts were dried (MgSO4) and the solvent removed under reduced pressure to give (5-bromo-6-methoxy-naphthalen-2-ylmethyl)-methyl-amine (900 mg, 94%) as an off-white solid, mp 41-45° C.
Reaction SMILES: F[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[C:5]#[N:6].Cl.[CH2:14]([O:16][C:17](=[O:21])[CH2:18][CH2:19][NH2:20])[CH3:15].CCN(C(C)C)C(C)C>CC(N(C)C)=O.C(OCC)(=O)C>[CH2:14]([O:16][C:17](=[O:21])[CH2:18][CH2:19][NH:20][C:2]1[CH:3]=[C:4]([C:5]#[N:6])[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH3:15]
Reactant: N#Cc1ccc([N+](=O)[O-])c(F)c1
Reactant: CCOC(=O)CCN
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CC(=O)N(C)C
Product: CCOC(=O)CCNc1cc(C#N)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 16 h
Yield: 96.9 %

Procedure:
To a solution of 3-Fluoro-4-nitrobenzonitrile (1.0 g, 6.0 mmol) in DMA (5 mL) were added Beta-Alanine ethyl ester HCl (1.4 g, 9.03 mmol) and DIPEA (1.6 mL, 9.03 mmol). The reaction mixture was stirred at room temperature for 16 h (the reaction was completed; the reaction mixture turned to orange from yellow in color). The reaction mixture was then diluted with ethyl acetate and washed with water (×4). The organic phase was then dried over Na2SO4 and concentrated to afford 1.53 g (96%) of the desired product as yellow solid.
Reaction SMILES: [Br:1][C:2]1[N:6]2[N:7]=[C:8](Cl)[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[CH3:12][O:13][C:14]1[CH:23]=[CH:22][CH:21]=[CH:20][C:15]=1[O:16][CH2:17][CH2:18][NH2:19].CO>C(Cl)Cl>[Br:1][C:2]1[N:6]2[N:7]=[C:8]([NH:19][CH2:18][CH2:17][O:16][C:15]3[CH:20]=[CH:21][CH:22]=[CH:23][C:14]=3[O:13][CH3:12])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1
Reactant: Clc1ccc2ncc(Br)n2n1
Reactant: COc1ccccc1OCCN
Solvent: ClCCl
Solvent: CO
Product: COc1ccccc1OCCNc1ccc2ncc(Br)n2n1
Temperature: 160 °C
Yield: 44.1 %

Procedure:
A mixture of 3-bromo-6-chloro-imidazo[1,2-b]pyridazine (232 mg, 1 mmol) and 2-(2-methoxy-phenoxy)-ethylamine (2 g, 12 mmol) was heated in a microwave at 160° C. for 30 min. The reaction mixture was subjected to ISCO (40 g column, DCM 3 min. then 0-10% MeOH in DCM over 30 min.) to gave the product (160 mg). LRMS (ESI) m/z 363 and 365.1 [(M+H)]+, calc'd for C15H15BrN4O2: 363.22.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[CH3:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][C:14]=1[C:22]([F:25])([F:24])[F:23]>>[CH3:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:5]=[N:4][CH:3]=2)=[CH:15][C:14]=1[C:22]([F:23])([F:24])[F:25]
Reactant: Cc1ccc(B(O)O)cc1C(F)(F)F
Reactant: COC(=O)c1cncc(Br)c1
Product: COC(=O)c1cncc(-c2ccc(C)c(C(F)(F)F)c2)c1

Procedure:
2.2 g (10.3 mmol) of methyl 5-bromonicotinate and 2.5 g (12.4 mmol) of [4-methyl-3-(trifluoromethyl)phenyl]boronic acid were reacted according to the General Method 1A. Yield: 2.6 g (86% of theory)
Reaction SMILES: C[O:2][C:3]1[C:11]2[CH:10]=[C:9]([C:12]3[N:16]=[C:15]([CH3:17])[O:14][N:13]=3)[O:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.B(Br)(Br)Br>>[OH:2][C:3]1[C:11]2[CH:10]=[C:9]([C:12]3[N:16]=[C:15]([CH3:17])[O:14][N:13]=3)[O:8][C:7]=2[CH:6]=[CH:5][CH:4]=1
Reactant: COc1cccc2oc(-c3noc(C)n3)cc12
Agent: BrB(Br)Br
Product: Cc1nc(-c2cc3c(O)cccc3o2)no1
Yield: 72.6 %

Procedure:
By the reactions in the same manner as in Starting Material Synthesis Example 5 using 3-(4-methoxybenzo(b)furan-2-yl)-5-methyl-1,2,4-oxadiazole (1.1 g) and boron tribromide (4.2 ml), the title compound (0.75 g) was obtained as yellow crystals.
Reaction SMILES: [CH2:1]([CH:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:27])[CH2:15][CH2:16][CH2:17][S:18]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:20])=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O-]S(C(F)(F)F)(=O)=O.C([B+]CCCC)CCC.C(N(CC)CC)C.[C:52]1([CH2:58][CH2:59][CH2:60][CH2:61][CH:62]=[O:63])[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>C(Cl)Cl>[CH2:1]([CH:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:27])[CH:15]([CH2:16][CH2:17][S:18]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH:62]([OH:63])[CH2:61][CH2:60][CH2:59][CH2:58][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(CCCS(=O)(=O)c1ccccc1)N1C(=O)OCC1Cc1ccccc1
Reactant: O=CCCCCc1ccccc1
Agent: CCCC[B+]CCCC
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C1OCC(Cc2ccccc2)N1C(=O)C(CCS(=O)(=O)c1ccccc1)C(O)CCCCc1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 141 %

Procedure:
A solution containing (-)-4-benzyl-3-(4-phenylsulfonylbutanoyl)oxazolidin-2-one (2 g, 5.16 mmol) in anhydrous CH2Cl2 (20 mL) is cooled to 0° C. Di-n-butylboron triflate (1 M in CH2Cl2, 6 mL, 6.03 mmol) is added by syringe over 15 minutes followed by the addition of triethylamine (0.68 g, 6.76 mmol). The clear yellow solution is then cooled to -78° C. Freshly distilled 5-phenylpentanal (0.92 g, 5.72 mmol) in anhydrous CH2Cl2 (2 mL) is added dropwise to the reaction mixture. After 30 min, the reaction mixture is warmed to 0° C. and maintained at this temperature for 1 hour. The reaction mixture is quenched by the slow addition of 3:1 MeOH/pH 7 phosphate buffer (30 mL) followed by 2:1 MeOH/30% H2O2 (30 mL) being careful to keep the temperature below 5° C. After the addition is complete, the reaction is maintained an additional hour at 0° C. then concentrated to half-volume in vacuo. The mixture is then diluted with diethyl ether (100 mL) and water (100 mL) and the layers are separated. The organic phase is washed with 5% NaHCO3 (3×50 mL), aqueous NaHSO3 (3×50 mL), water (50 mL), brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated. The crude product is combined with the crude material obtained from four additional reactions performed on identical scale and purified by silica gel chromatography (CH2Cl2 /diethyl ether, 19:1→9:1) to provide 4 g (35%) of (-)-4-benzyl-3-[3-hydroxy-7-phenyl-2-(2-phenylsulfonylethyl)-heptanoyl]-oxazolidin-2-one as a colorless, viscous oil which is homogeneous by TLC analysis [CH2Cl2 /diethyl ether, 19:1, Rf (oxazolidinone)=0.45, Rf (aldol product)=0.40]. [α]23D -20° (c 7.5, CHCl3); 1H NMR (300 MHz, CDCl3) δ 1.42-1.58 (m, 6H), 2.06 (m, 1H), 2.20 (m, 1H), 2.24 (d, J=4 Hz, 1H), 2.58 (t, J=7.5 Hz, 2H), 2.69 (dd, J=13.3, 9.9 Hz, 1H), 3.24 (m, 3H), 3.86 (m, 1H), 3.98 (quint. J=4.2 Hz, 1H), 4.16 (m, 2H), 4.65 (m, 1H), 7.18-7.52 (m, 10H), 7.59 (m, 2H), 7.68 (m, 1H), 7.90 (m, 2H) ppm. Mass spectrum (FAB) m/z 550 (M+H)+.
Reaction SMILES: P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].[NH2:9][C@H:10]([C:13]([OH:15])=[O:14])[CH2:11][SH:12].[CH2:16](O)[CH3:17].C(Cl)(Cl)Cl.C1C=CC=CC=1>C(O)C.Cl.O.[O-][99Tc](=O)(=O)=O.[Na+]>[NH2:9][C@H:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:11][SH:12].[NH2:9][C@H:10]([C:13]([OH:15])=[O:14])[CH2:11][SH:12]
Reactant: CCO
Agent: O=[99Tc](=O)(=O)[O-]
Agent: Cl
Agent: N[C@@H](CS)C(=O)O
Solvent: O
Solvent: c1ccccc1
Solvent: ClC(Cl)Cl
Product: CCOC(=O)[C@@H](N)CS
Temperature: 80 °C
Reaction time: 0.5 h

Procedure:
In a mixture of 0.6 ml of ethanol and 0.1 ml (1 mol/l) of an aqueous HCl solution were dissolved 5 mg of SDH and 1.5 mg of PNP, followed by adding thereto a physiologically acceptable 99mTcO4− solution (0.5 ml, 50 MBq). The resulting mixture was heated at 80° C. for 20 minutes and then cooled to room temperature, after which 1 ml of sodium phosphate buffer (0.05 mol/l) was added thereto to adjust the pH to about 7.8. Subsequently, a solution of 3.0 mg of Cys in 0.50 ml of water was added, and the resulting mixture was allowed to stand at room temperature for 30 minutes. The complex finally obtained was analyzed by HTLC and HPLC. FIG. 6 shows a radiochromatogram of the complex which was obtained by development on a silica gel plate with an ethanol/chloroform/benzene (0.85/2/1.5) mixture. The radiochemical purity of the final complex was higher than 90%. The complex contained a Tc≡N group in which a PNP bidentate ligand was coordinated with the metal ion at trans conformation and a dianion Cys was coordinated with the remaining two positions through the sulfur atom which had lost a proton and the nitrogen atom of the amino group which had lost a proton. As a result of the same experiment as above except using an ester derivative (CysOEt), it was found that the carboxyl group of Cys did not participate in the coordination with the metal. CysOEt is formed by the replacement of the OH group of the carboxyl group of Cys by an ethoxy group, and the radiochemical purity of a final complex obtained from the ligand (CysOEt) was higher than 93% (FIG. 7). Solutions of the complexes, respectively, are all stable.
Reaction SMILES: [N+:1]([C:4]([N+:21]([O-:23])=[O:22])([CH3:20])[CH2:5][N:6]([CH2:11][C:12]([N+:17]([O-:19])=[O:18])([N+:14]([O-:16])=[O:15])[CH3:13])[CH2:7][C:8]([OH:10])=[O:9])([O-:3])=[O:2].S(=O)(=O)(O)O.[CH3:29]O>>[CH3:29][CH:7]([C:8]([OH:10])=[O:9])[N:6]([CH2:11][C:12]([N+:14]([O-:16])=[O:15])([N+:17]([O-:19])=[O:18])[CH3:13])[CH2:5][C:4]([N+:21]([O-:23])=[O:22])([N+:1]([O-:3])=[O:2])[CH3:20]
Reactant: CC(CN(CC(=O)O)CC(C)([N+](=O)[O-])[N+](=O)[O-])([N+](=O)[O-])[N+](=O)[O-]
Reactant: CO
Agent: O=S(=O)(O)O
Product: CC(C(=O)O)N(CC(C)([N+](=O)[O-])[N+](=O)[O-])CC(C)([N+](=O)[O-])[N+](=O)[O-]

Procedure:
A mixture of 20 g. (0.059 mole) of bis-(2,2-dinitropropyl)-glycine, 100 ml. of methanol and 10.0 ml. of concentrated sulfuric acid was refluxed for 90 minutes. The solution was diluted with 250 ml. of methylene chloride and washed with water, 5% sodium carbonate solution and water. The solvent was evaporated to yield 14.0 g. (67.3%) of white solid. Recrystallization from methanol-ether gave crystals, m.p. 94°-95°.
Reaction SMILES: NC1C=CNN=1.O/[CH:8]=[C:9]1\[C:10](=[O:18])[NH:11][C:12]2[C:17]\1=[CH:16][CH:15]=[CH:14][CH:13]=2.[CH3:19][N:20]([CH3:38])[CH2:21][CH2:22][CH2:23][O:24][C:25]1[CH:37]=[CH:36][C:28]([CH2:29][C:30]2[CH:31]=[C:32]([NH2:35])[NH:33][N:34]=2)=[CH:27][CH:26]=1>O1CCCC1>[CH3:38][N:20]([CH3:19])[CH2:21][CH2:22][CH2:23][O:24][C:25]1[CH:37]=[CH:36][C:28]([CH2:29][C:30]2[CH:31]=[C:32]([NH:35][CH:8]=[C:9]3[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[NH:11][C:10]3=[O:18])[NH:33][N:34]=2)=[CH:27][CH:26]=1
Reactant: O=C1Nc2ccccc2/C1=C/O
Reactant: CN(C)CCCOc1ccc(Cc2cc(N)[nH]n2)cc1
Agent: Nc1cc[nH]n1
Solvent: C1CCOC1
Product: CN(C)CCCOc1ccc(Cc2cc(NC=C3C(=O)Nc4ccccc43)[nH]n2)cc1

Procedure:
The named compound is prepared by substituting 5-[4-(3-dimethylamino-propoxy)-benzyl]-2H-pyrazol-3-ylamine for 3-aminopyrazole in the reaction of Example 1. Specifically, E & Z-3-[(hydroxy)-methylene]-1,3-dihydro-indol-2-one (0.0351 gins.) is reacted with 0.0881 gms. of 5-[4-(3-dimethylamino-propoxy)-benzyl)-2H-pyrazol-3-ylamine by refluxing in tetrahydrofuran (2.0 mL). Recrystallization from a mixture of ethyl acetate and hexanes affords the named compound.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][C:9](=[O:13])[NH:10]2)=[CH:5][CH:4]=1.[Cl:14][C:15]1[C:20]([Cl:21])=[CH:19][CH:18]=[CH:17][C:16]=1[N:22]1[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][CH2:30][C:31](O)=[O:32])[CH2:24][CH2:23]1>>[Cl:14][C:15]1[C:20]([Cl:21])=[CH:19][CH:18]=[CH:17][C:16]=1[N:22]1[CH2:23][CH2:24][N:25]([CH2:28][CH2:29][CH2:30][C:31]([O:1][CH2:2][C:3]2[CH:12]=[C:11]3[C:6]([CH2:7][CH2:8][C:9](=[O:13])[NH:10]3)=[CH:5][CH:4]=2)=[O:32])[CH2:26][CH2:27]1
Reactant: O=C(O)CCCN1CCN(c2cccc(Cl)c2Cl)CC1
Reactant: O=C1CCc2ccc(CO)cc2N1
Product: O=C1CCc2ccc(COC(=O)CCCN3CCN(c4cccc(Cl)c4Cl)CC3)cc2N1

Procedure:
(2-Oxo-1,2,3,4-tetrahydroquinolin-7-yl)methyl 4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butanoate (38d) (Scheme 7) was prepared from the carbinol 37 and the carboxylic acid 18d according to the protocol described for the compound 38a (Example 55). White solid, 0.2 g (50%). 1H NMR (400 MHz, CDCl3): δ 1.85 (quintet, J=7.2 Hz, 2H); 2.39-2.42 (m, 4H); 2.59-2.63 (m, 6H); 2.94 (t, J=8.4 Hz, 2H); 3.01 (broad s, 4H); 5.04 (s, 2H); 6.83 (d, J=1.6 Hz, 1H); 6.90-6.93 (m, 1H); 6.96 (dd, J=1.2, 7.6 Hz, 1H); 6.97-7.13 (m, 3H); 9.29 (s, 1H). MS (ESI): m/z=476.10 (M+H+).
Reaction SMILES: [CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([O:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C:12]([N:16]4[CH:20]=[C:19]([C:21]5[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH:22]=5)[CH:18]=[N:17]4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:41])=[O:5])[CH2:3][CH2:2]1>[Pd].CO>[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([O:34][C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[C:12]([N:16]4[CH:20]=[C:19]([CH:21]5[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH2:26]5)[CH:18]=[N:17]4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:41])=[O:5])[CH2:3][CH2:2]1
Reactant: C[C@H]1CCc2c(ccc(-n3cc(C4=CCN(C(=O)OC(C)(C)C)CC4)cn3)c2Oc2ccccc2)N1C(=O)C1CC1
Agent: [Pd]
Solvent: CO
Product: C[C@H]1CCc2c(ccc(-n3cc(C4CCN(C(=O)OC(C)(C)C)CC4)cn3)c2Oc2ccccc2)N1C(=O)C1CC1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 95.8 %

Procedure:
A mixture of (5)-tert-butyl 4-(1-(1-(cyclopropanecarbonyl)-2-methyl-5-phenoxy-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-4-yl)-5,6-dihydropyridine-1(2H)-carboxylate (0.050 g, 0.09 mmol) and palladium on charcoal (10% wt %, 0.040 g) in methanol (15 mL) stirred under an atmosphere of hydrogen for 20 min at room temperature. The reaction mixture was filtered and concentrated under vacuum to afford (S)-tert-butyl 4-(1-(1-(cyclopropanecarbonyl)-2-methyl-5-phenoxy-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-4-yl)piperidine-1-carboxylate (0.048 g, 99%) as a white solid. MS (ESI, pos. ion) m/z 557 [M+H]+.