Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:14])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[NH2:6].Cl[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[CH3:2][O:3][C:4](=[O:14])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[NH:6][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17]
Reactant: O=C(Cl)OCc1ccccc1
Reactant: COC(=O)[C@@H](N)Cc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COC(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1
Reaction time: 3 h
Yield: 95.8 %

Procedure:
20.0 g (92.73 mmol) of (L)-phenylalanine methyl ester hydrochloride was suspended in 93 ml of toluene, and 15.82 g (92.73 mmols) of benzyl chloroformate was added thereto. 130 ml of an aqueous solution of 1M sodium carbonate was dropwise added thereto, while keeping it at 7° C. or lower, and stirred for 3 hours. After this was subjected to phase separation, the resulting organic layer was washed with 60 ml of 0.1N hydrochloric acid and 60 ml of a saturated aqueous solution of sodium hydrogen carbonate, and then dried with anhydrous sodium sulfate. This was filtered and concentrated to obtain 28.75 g (96.8 wt. %, 88.81 mmol) of the above-entitled compound. The yield was 95.8%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]([OH:13])=O)[NH:8][C:5]2=[CH:6][N:7]=1.[O:14]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[O:17][CH2:16][CH:15]1[CH2:24][NH2:25]>>[O:14]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[O:17][CH2:16][CH:15]1[CH2:24][NH:25][C:11]([C:9]1[NH:8][C:5]2=[CH:6][N:7]=[C:2]([Cl:1])[CH:3]=[C:4]2[CH:10]=1)=[O:13]
Reactant: O=C(O)c1cc2cc(Cl)ncc2[nH]1
Reactant: NCC1COc2ccccc2O1
Product: O=C(NCC1COc2ccccc2O1)c1cc2cc(Cl)ncc2[nH]1

Procedure:
The title compound was prepared as outlined in EXAMPLE 1 from 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (Preparation 18) and 2,3-dihydrobenzo[1,4]dioxin-2-ylmethylamine. The product was purified by mass directed purification to give the title compound as a yellow solid. δH (CD3OD): 3.69–3.73 (2H, m), 3.97–4.03 (1H, m), 4.32–4.42 (2H, m), 6.77–6.88 (4H, m), 7.10 (1H, s), 7.67 (1H, s), 8.58 (1H, s); m/z (ES+)=344 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:17]4[S:21][C:20](SCC)=[N:19][C:18]4=[O:25])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:28]([F:31])([F:30])[F:29])[CH:3]=1.[CH3:32][N:33]1[CH2:38][CH2:37][NH:36][C@H:35]([CH3:39])[CH2:34]1>>[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:17]4[S:21][C:20]([N:36]5[CH2:37][CH2:38][N:33]([CH3:32])[CH2:34][C@H:35]5[CH3:39])=[N:19][C:18]4=[O:25])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:28]([F:31])([F:30])[F:29])[CH:3]=1
Reactant: C[C@@H]1CN(C)CCN1
Reactant: CCSC1=NC(=O)C(=Cc2ccc3c(cnn3Cc3ccc(Cl)cc3C(F)(F)F)c2)S1
Product: C[C@@H]1CN(C)CCN1C1=NC(=O)C(=Cc2ccc3c(cnn3Cc3ccc(Cl)cc3C(F)(F)F)c2)S1

Procedure:
5-({1-[4-Chloro-2-(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-2-(2(R),4-dimethylpiperazin-1-yl)-1,3-thiazol-4(5H)-one was prepared from 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazol-4-one and 1,3-(R)-Dimethyl-piperazine following general procedure C.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].I[CH2:14][CH3:15].Cl>C1COCC1.O>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[CH2:14][CH3:15])=[CH:4][CH:3]=1
Reactant: Brc1ccc2cc[nH]c2c1
Reactant: CCI
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCn1ccc2ccc(Br)cc21
Temperature: 25 °C
Reaction time: 0.58 h
Yield: 70.4 %

Procedure:
A solution of 6-bromoindole (1.01 g, 5.15 mmol) in THF (10 mL) was cooled in an ice bath. Sodium hydride (0.459 g of 60% dispersion in oil, 11.5 mmol) was added. After stirring for 35 minutes at room temperature under nitrogen, the reaction mixture was again cooled in an ice bath, and iodoethane (0.90 mL, 11 mmol) was added. The mixture was stirred for 2 hours at room temperature, poured into excess water, acidified with 2N hydrochloric acid and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was purified by flash chromatography using hexane as an eluant to yield 6-bromo-1-ethyl-1H-indole (0.812 g, 71%) as a yellow oil. 1HNMR (300 MHz, DMSO-d6): δ 7.75 (s, 1H), 7.5 (d, 1H, J=7.8 Hz), 7.45 (d, 1H, J=3.9 Hz), 7.15 (dd, 1H, J=7.8 Hz and 1.6 Hz), 6.45 (s, 1H), 4.2 (q, 2H, J=7.1 Hz), and 1.35 ppm (t, 3H, J=7.0 Hz).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4](=O)[C:5]2[NH:6][CH:7]=[N:8][C:9]=2[N:10]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:13]>N1C=CC=CC=1>[CH3:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([SH:13])[N:3]=1
Reactant: Cc1nc2nc[nH]c2c(=O)[nH]1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: c1ccncc1
Product: Cc1nc(S)c2[nH]cnc2n1
Yield: 53.9 %

Procedure:
To 2-Methylhypoxanthine (1.3 g, 8.6 mmol) and P2S5 (5 g) was added pyridine (50 mL). The mixture was refluxed for 4 h. The pyridine was distilled away and NaOH (50 mL) was added to the residue. A brown precipitate was filtered away. The precipitate was dried in a vacuum oven at 80° C. for 24 h to give the desired product (.77 g, 46.3%) as a light brown solid. mp>300° C. DCI/MC (M+1)=167. (300 MHz) 1H-nmr (DMSO-d6) δ: 8.3 (s, 1H), 2.45 (s, 3H).
Reaction SMILES: [C:1]1(=[O:22])[N:5]([CH:6]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:7](O)=[O:8])[C:4](=[O:17])[C:3]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:2]12.C(N1C=CN=C1)([N:25]1C=CN=C1)=O.[OH-].[NH4+]>O1CCCC1.O>[C:1]1(=[O:22])[N:5]([CH:6]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:7]([NH2:25])=[O:8])[C:4](=[O:17])[C:3]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:2]12
Reactant: O=C(O)C(Cc1ccccc1)N1C(=O)c2ccccc2C1=O
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: [NH4+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: NC(=O)C(Cc1ccccc1)N1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 83.6 %

Procedure:
To a stirred solution of 2-phthalimido-3-phenylpropionic acid (2.95 g, 10.0 mmol) in tetrahydrofuran (25 mL) are added carbonyldiimidazole (1.62 g, 10.0 mmol) and a few crystals of 4-N,N-dimethylaminopyridine, followed by 15 mL of tetrahydrofuran. The reaction mixture is stirred at room temperature for 45 minutes and 1 mL of concentrated ammonium hydroxide then is added. After 10 minutes, the reaction mixture is diluted with 50 mL water and the resulting slurry is partially concentrated to remove the tetrahydrofuran and filtered. The solid is washed with water and dried in vacuo (60° C., <1 mm) to afford 2.46 g (84%) of 2-phthalimido-3-phenylpropionamide as a white powder: mp 224°-226° C.; 1H NMR (DMSO-d6, 250 MHz) δ7.79 (s, 4H, Ar), 7.71 (br s, 1H, CONH2), 7.32 (br s, 1H, CONH2), 7.20-7.02 (m, 5H, Ar), 5.06-4.98 (m, 1H), 3.56-325 (m 2H); 13C NMR (DMSO-d6, 250 MHz)d: 169.6, 168.0, 137,1, 134.3, 131.2, 129.5, 128.1, 126.3, 122.9, 54.2, 33.7. Anal. Calculated for C17H14N2O3. Theoretical: C, 69.38; H,4.79; N, 9.52. Found: C, 69.37; H, 4.73; N, 9.43.
Reaction SMILES: [CH3:1][C:2]1([CH3:22])[C@@H:4]([C:5]#[C:6][C:7]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])=[O:8])[C@H:3]1[C:15]([O:17]C(C)(C)C)=[O:16].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:22][C:2]1([CH3:1])[C@@H:4]([C:5]#[C:6][C:7]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])=[O:8])[C@H:3]1[C:15]([OH:17])=[O:16]
Reactant: CCCCCOC(=O)C#C[C@H]1[C@@H](C(=O)OC(C)(C)C)C1(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CCCCCOC(=O)C#C[C@H]1[C@@H](C(=O)O)C1(C)C
Yield: 112 %

Procedure:
A mixture of 5.24 g of the product of Step A, 50 ml of toluene and 250 mg of p-toluene sulfonic acid was refluxed until gas evolution ceased and was then evaporated to dryness under reduced pressure to obtain 4.8 g of crude (1R,cis) 2,2-dimethyl-3-(pentyloxycarbonyl-ethynyl)-cyclopropane-carboxylic acid which was used as is for the next step.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]4[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=4)[CH:17]=3)=[C:11]([CH3:28])[N:10]=2)=[CH:7][N:6]=[C:5](SC)[N:4]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.[CH3:42][NH2:43]>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]4[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=4)[CH:17]=3)=[C:11]([CH3:28])[N:10]=2)=[CH:7][N:6]=[C:5]([NH:43][CH3:42])[N:4]=1
Reactant: COc1nc(SC)ncc1-c1ccc(Oc2ccnc(-c3cnn(C)c3)c2)c(C)n1
Reactant: CN
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CNc1ncc(-c2ccc(Oc3ccnc(-c4cnn(C)c4)c3)c(C)n2)c(OC)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 69.4 %

Procedure:
A solution of Example C2 (0.15 g, 0.357 mmol) in DCM (5 mL) was treated portion-wise with mCPBA (0.11 g, 0.43 mmol), stirred at RT overnight, treated with methylamine (2.0M in THF, 3.6 mL, 7.2 mmol) and stirred at RT for 4 h. The mixture was treated with satd. NaHCO3, extracted with DCM (3×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to obtain 4-methoxy-N-methyl-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-amine (100 mg, 70%). MS (ESI) m/z: 404.2 (M+H+).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[C:10]([O:18][CH2:19][C@@H:20]3[O:24][C:23](=[O:25])[NH:22][CH2:21]3)[CH:9]=2)=[CH:4][C:3]=1[O:26][CH3:27].I[CH:29]([CH3:31])[CH3:30].C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>CN(C=O)C>[CH:29]([O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[C:10]([O:18][CH2:19][C@@H:20]3[O:24][C:23](=[O:25])[NH:22][CH2:21]3)[CH:9]=2)=[CH:4][C:3]=1[O:26][CH3:27])([CH3:31])[CH3:30]
Reactant: COc1cc(-c2cc(OC[C@H]3CNC(=O)O3)c3cccnc3c2)ccc1O
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1cc(-c2cc(OC[C@H]3CNC(=O)O3)c3cccnc3c2)ccc1OC(C)C
Temperature: 50 °C
Reaction time: 16 h
Yield: 85 %

Procedure:
A mixture of 59 mg (R)-5-[7-(4-hydroxy-3-methoxy-phenyl)-quinolin-5-yloxymethyl]-oxazolidin-2-one (Example 13), 19.3 μl 2-iodopropane and 44 mg potassium carbonate in DMF (10 ml) was stirred at 50° C. for 16 hours. The mixture was poured into EtOAc and washed with water then brine and dried over Na2SO4. Purification by FCC over SiO2, eluting with EtOAc-MeOH from 100:0 to 95:5 yielded 56 mg (85%) of (R)-5-[7-(4-Isopropoxy-3-methoxy-phenyl)-quinolin-5-yloxymethyl]-oxazolidin-2-one (Example 16) as an oily residue.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:11][CH:10]=1.C(N(CC)CC)C.[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][CH:30]=1>ClCCl.CCOCC>[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([S:35]([NH:1][CH:2]2[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]2[CH2:8][C:9]2[CH:10]=[CH:11][C:12]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:13][CH:14]=2)(=[O:37])=[O:36])=[CH:31][CH:30]=1
Reactant: CCOC(=O)Cc1ccc(CC2CCCCC2N)cc1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CCOCC
Product: CCOC(=O)Cc1ccc(CC2CCCCC2NS(=O)(=O)c2ccc(Cl)cc2)cc1

Procedure:
Obtained by operating as in example 1c from 6.1 g (22 mmoles) of ethyl 4-[(2-aminocyclohexyl)methyl]benzeneacetate, 2.7 g (26.5 mmoles) of triethylamine in 150 ml of dichloromethane and 4.6 g (22 mmoles) of 4-chlorobenzenesulfonyl chloride in 50 ml of ether. The colorless oil obtained (yield=quantitative) is used without any other purification.
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:8]([NH:10][CH:11]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH:12]([OH:28])[C:13]([N:15]1[CH2:26][CH:25]([Cl:27])[CH2:24][C@H:16]1[C:17]([NH:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:14])=[O:9])[CH2:4][C:5](=[O:7])[NH2:6].[N+:36]([C:39]1[CH:40]=[C:41]2[C:46](=[CH:47][CH:48]=1)[N:45]=[C:44]([C:49](O)=[O:50])[CH:43]=[N:42]2)([O-:38])=[O:37]>>[N+:36]([C:39]1[CH:40]=[C:41]2[C:46](=[CH:47][CH:48]=1)[N:45]=[C:44]([C:49]([NH:2][C@H:3]([C:8]([NH:10][C@@H:11]([CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C@H:12]([OH:28])[C:13]([N:15]1[CH2:26][C@@H:25]([Cl:27])[CH2:24][C@H:16]1[C:17]([NH:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:14])=[O:9])[CH2:4][C:5](=[O:7])[NH2:6])=[O:50])[CH:43]=[N:42]2)([O-:38])=[O:37]
Reactant: O=C(O)c1cnc2cc([N+](=O)[O-])ccc2n1
Reactant: CC(C)(C)NC(=O)[C@@H]1CC(Cl)CN1C(=O)C(O)C(Cc1ccccc1)NC(=O)[C@@H](N)CC(N)=O
Agent: Cl
Product: CC(C)(C)NC(=O)[C@@H]1C[C@H](Cl)CN1C(=O)[C@@H](O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)c1cnc2cc([N+](=O)[O-])ccc2n1
Yield: 29.6 %

Procedure:
Following a procedure similar to that described in Example 14, but using 490 mg (0.92 mmol) of 1-[3-(L-asparaginyl)amino-2-hydroxy-4-phenylbutyryl]-4-chloro-N-t-butyl-L-prolinamide hydrochloride and 220 mg (1.01 mmol) of 6-nitroquinoxaline-2-carboxylic acid (prepared as described in Preparation 22), 190 mg of the title compound were obtained as a pale yellow powder, melting at 153°-156° C.
Reaction SMILES: C(NC1SC=C(C(=NOC)C(N[CH:13]2[C:45](=[O:46])[N:15]3[C:16]([C:29]([O:31]C(C4C=CC=CC=4)C4C=CC=CC=4)=[O:30])=[C:17](S/C=C\C4C=NC=CC=4)[CH2:18][S:19][C@H:14]23)=O)N=1)=O.[F:50][C:51]([F:62])([F:61])[S:52]([O:55]CCN=[N+]=[N-])(=[O:54])=[O:53]>CN(C)C=O>[F:50][C:51]([F:62])([F:61])[S:52]([OH:55])(=[O:54])=[O:53].[S:19]1[C@@H:14]2[CH2:13][C:45](=[O:46])[N:15]2[C:16]([C:29]([OH:31])=[O:30])=[CH:17][CH2:18]1
Reactant: CON=C(C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(S/C=C\c3cccnc3)CS[C@H]12)c1csc(NC=O)n1
Reactant: [N-]=[N+]=NCCOS(=O)(=O)C(F)(F)F
Solvent: CN(C)C=O
Product: O=C(O)C1=CCS[C@@H]2CC(=O)N12
Product: O=S(=O)(O)C(F)(F)F
Temperature: 40 °C
Reaction time: 3 h
Yield: 144.6 %

Procedure:
To a solution of benzhydryl 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylate (syn isomer) (2 g) in N,N-dimethylformamide (10 ml) was added 2-azidoethyl trifluoromethanesulfonate (2.4 g) at ambient temperature, and the mixture was stirred at 40° C. for 3 hours and then at ambient temperature through the night. The mixture was evaporated in vacuo to give a residue. The residue was subjected to column chromatography on silica gel and eluted with a mixture of ethyl acetate and tetrahydrofuran (1:1). The fractions containing the object compound were combined and evaporated in vacuo to give benzhydryl 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-(Z)-2-{1-(2-azidoethyl)-3-pyridinio}vinylthio]-3-cephem-4-carboxylate trifluoromethanesulfonate (syn isomer) (1.36 g).
Reaction SMILES: [SH:1][CH:2]1[N:5]([C:6](=[C:11](O)[CH3:12])[C:7]([O:9][CH3:10])=[O:8])[C:4](=[O:14])[CH:3]1[N:15]1[C:19](=[O:20])[C:18]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:17]2[C:16]1=[O:25].Cl[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28].C(N([CH2:42][CH3:43])CC)C>O1CCCC1>[CH2:30]([O:29][C:27]([S:1][CH:2]1[N:5]([C:6](=[C:11]([C:7]([O:9][CH2:10][C:43]2[CH:42]=[CH:23][CH:24]=[CH:17][CH:16]=2)=[O:8])[CH3:12])[C:7]([O:9][CH3:10])=[O:8])[C:4](=[O:14])[CH:3]1[N:15]1[C:19](=[O:20])[C:18]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:17]2[C:16]1=[O:25])=[O:28])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: CCN(CC)CC
Reactant: COC(=O)C(=C(C)O)N1C(=O)C(N2C(=O)c3ccccc3C2=O)C1S
Reactant: O=C(Cl)OCc1ccccc1
Solvent: C1CCOC1
Product: COC(=O)C(=C(C)C(=O)OCc1ccccc1)N1C(=O)C(N2C(=O)c3ccccc3C2=O)C1SC(=O)OCc1ccccc1
Temperature: -65 °C
Reaction time: 1 h
Yield: 188.7 %

Procedure:
To a solution of methyl α-[4-mercapto-3-phthalimido-2-oxoazetidin-1-yl]-α-(1-hydroxyethylidene)acetate (100 mg) in tetrahydrofuran (3 ml) is added benzyl chloroformate (100 mg), and the mixture is cooled to -65° C. To the solution is added triethylamine (60 mg) and stirred for 1 hour. After warming to room temperature, the mixture is evaporated. Purification of the residue by chromatography over silica gel gives methyl α-[4-benzyloxycarbonylthio-3-phthalimido-2-oxoazetidin-1-yl]-α-(1-benzyloxycarbonylethylidene)acetate (160 mg). Yield: 94%. The product contains no isomer at position α. IR: νmaxCHCl3 1790, 1780, 1730 cm-1. NMR: δCDCl3 8.00-7.50 m4H, 7.40s5H, 7.30s5H, 6.27d(5 Hz)1H, 5.90d(5 Hz)1H, 5.27s2H, 5.17s2H, 3.70s3H, 2.47s3H.
Reaction SMILES: C([S:9][CH2:10][CH2:11][C:12]([N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH:15]1[C:23]([OH:25])=[O:24])=[O:13])(=O)C1C=CC=CC=1.[NH3:26]>O.C(OCC)(=O)C>[O:13]=[C:12]([N:26]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH:15]1[C:23]([OH:25])=[O:24])[CH2:11][CH2:10][S:9][S:9][CH2:10][CH2:11][C:12]([N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH:15]1[C:23]([OH:25])=[O:24])=[O:13]
Reactant: N
Reactant: O=C(SCCC(=O)N1c2ccccc2CC1C(=O)O)c1ccccc1
Solvent: CCOC(C)=O
Solvent: O
Product: O=C(O)C1Cc2ccccc2N1C(=O)CCSSCCC(=O)N1c2ccccc2CC1C(=O)O
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
A mixture of 1-[3-(benzoylthio)-1-oxopropyl]-2,3-dihydro-1H-indole-2-carboxylic acid (3.0 g.) and methanolic ammonia (5.5 N solution, 45 ml.) was stirred at room temperature for 2.5 hours, then evaporated under reduced pressure on a rotary evaporator to give a resinous material. The residue was dissolved in water, and the aqueous solution was washed with ethyl acetate three times. The aqueous phase was acidified to pH ca. 2 by dropwise addition of dilute hydrochloric acid, whereby an oil separated. The oil was extracted with ethyl acetate (two times). The combined extract was washed with water, then with saline, and dried over anhydrous sodium sulfate. The ethyl acetate was evaporated on a rotary evaporator under reduced pressure to give an oily residue which was placed under high vacuum to give a solid material. The crude product was dissolved in a small amount of warm ethyl acetate with warming on a steam bath (there was some insoluble solid material which was removed by filtration). The ethyl acetate solution was kept under mild nitrogen stream until a precipitate started to separate. The mixture was chilled in ice, then kept in a refrigerator. The precipitate was collected on a filter and washed with acetonitrile to give 1,1'-dithiobis[3-oxo-1,3-propanediyl]bis[2,3-dihydro-1H-indole-2-carboxylic acid], m.p. 213°-216°.
Reaction SMILES: C[Al](C)C.[CH2:5]([NH2:9])[CH2:6][CH2:7][CH3:8].C([O:12][C:13]([C:15]([CH:38]([CH3:40])[CH3:39])=[CH:16][CH:17]1[O:21][C:20]([CH3:23])([CH3:22])[N:19]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:18]1[CH2:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)=O)C.Cl>CCCCCC.C(Cl)(Cl)Cl.ClCCCl>[CH2:5]([NH:9][C:13]([C:15]([CH:38]([CH3:40])[CH3:39])=[CH:16][CH:17]1[O:21][C:20]([CH3:23])([CH3:22])[N:19]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH:18]1[CH2:31][CH:32]1[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]1)=[O:12])[CH2:6][CH2:7][CH3:8]
Reactant: CCCCN
Reactant: CCOC(=O)C(=CC1OC(C)(C)N(C(=O)OC(C)(C)C)C1CC1CCCCC1)C(C)C
Agent: C[Al](C)C
Agent: Cl
Solvent: ClCCCl
Solvent: CCCCCC
Solvent: ClC(Cl)Cl
Product: CCCCNC(=O)C(=CC1OC(C)(C)N(C(=O)OC(C)(C)C)C1CC1CCCCC1)C(C)C
Temperature: 70 °C
Reaction time: 1 h
Yield: 87.8 %

Procedure:
The procedure of Poss, M. A. and Reid, J. A. (Tet. Lett. 1992, 33 (11), 1411-14) was used. A 2.0M solution of trimethylaluminum (1.25 mL, 2.5 mmol) in hexane was added to a 1,2-dichloroethane (1.25 mL) solution containing butylamine (0.25 mL, 2.5 mmol) at r.t. and stirred for one h. A 1,2-dichloroethane (1.25 mL) solution containing 5-[2-[(ethoxy)carbonyl]-3-methyl-1-butenyl]-4-(cyclohexylmethyl)-2,2-dimethyl-3-oxazolidinecarboxylic acid, 1,1-dimethylethyl ester (424 mg, 1.0 mmol) was added to the reactants prepared above and heated at 70° C. for 16 h. The reaction was cooled to 0° C., diluted with CHCl3, and treated with 1N HCl. The organic phase was separated and the aqueous phase extracted with CHCl3 (2×). The combined organic extracts were dried (Na2SO4), filtered through MgSO4 and concentrated in vacuo. Silica gel chromatography (5:1 hexane:Et2O) of the concentrate afforded the title compound (408 mg, 88%). MS (ESI) m/e 463 (M-H)-.
Reaction SMILES: CC1C=C([N+]([O-])=O)C(C)=CC=1C(=O)C=C(N(C)C)C.NN.[CH3:22][C:23]1[CH:28]=[C:27]([N+:29]([O-])=O)[C:26]([CH3:32])=[CH:25][C:24]=1[C:33]1[NH:37][N:36]=[C:35]([CH3:38])[CH:34]=1>C(O)C.CO.[Pd]>[CH3:32][C:26]1[CH:25]=[C:24]([C:33]2[NH:37][N:36]=[C:35]([CH3:38])[CH:34]=2)[C:23]([CH3:22])=[CH:28][C:27]=1[NH2:29]
Reactant: Cc1cc(-c2cc(C)c([N+](=O)[O-])cc2C)[nH]n1
Agent: [Pd]
Agent: CC(=CC(=O)c1cc(C)c([N+](=O)[O-])cc1C)N(C)C
Agent: NN
Solvent: CO
Solvent: CCO
Product: Cc1cc(-c2cc(C)c(N)cc2C)[nH]n1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
A mixture of 1-(2,5-dimethyl-4-nitrophenyl)-3-(dimethylamino)but-2-en-1-one (100 mg, 0.38 mmol) and hydrazine (60 uL, 1.9 mmol) in ethanol (3 mL) was heated in a microwave at 100° C. for 15 min. The obtained 5-(2,5-dimethyl-4-nitrophenyl)-3-methylpyrazol was dissolved in methanol (10 mL). To the solution was added Pd/C (10%). The reaction mixture was degassed and purged with H2 for several times and stirred under 1 atm. hydrogen gas overnight. The mixture was filtered and concentrated to afford 2,5-Dimethyl-4-(3-methyl-1H-pyrazol-5-yl)aniline. ESMS m/z 202 (M+H+).
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@H:15]2[CH2:16][NH:17][C@@H:10]1[C@H:11]([O:14]2)[O:12][CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].Cl[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25]>CCOCC>[CH2:1]([O:8][C@H:9]1[C@H:15]2[CH2:16][N:17]([C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])[C@@H:10]1[C@H:11]([O:14]2)[O:12][CH3:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CO[C@H]1O[C@@H]2CN[C@H]1[C@H]2OCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Product: CO[C@H]1O[C@@H]2CN(C(=O)OCc3ccccc3)[C@H]1[C@H]2OCc1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 76.1 %

Procedure:
Methyl 3-O-benzyl-2,5-dideoxy-2,5-imino-α-D-lyxofuranoside (13α) (870 mg, 3.70 mmol) was stirred with a 3:2 mixture of ether and saturated aqueous sodium bicarbonate (60 ml). Benzyl chloroformate (1.57 ml, 11.1 mmol) was added to the mixture which was stirred at room temperature for 12 hours. The ether layer was separated and the aqueous phase further extracted with ether (4×25 ml). The combined extracts were dried, filtered and the solvent removed. Purification by flash chromatography (ether-hexane 1:10-1:3) afforded methyl 3-O-benzyl-N-benzyloxycarbonyl-2,5-dideoxy-2,5-imino-α-D-lyxofuranoside (1.04 g, 76%) as a white crystalline solid, m.p. 74°-75° C., Rf 0.2 (ether-hexane 1:3); [α]20D +12.0° (c, 0.98 in chloroform); νmax (chloroform) 2940, 1695 (C=O), 1420, 1260, 1230, 1090 and 750 cm-1 ; 1H NMR δ 3.38, 3.41 (3H, 2× s, CH3); 3.3-3.7 (2H, m, 5,5'-H); 4.05-4.90 (5H, m, H-3, H-2, H-4, CH2Ph); 5.12-5.20 (3H, m, H-1, CH2 -Z); 7.2-7.4 (10H, m, 2×H-Ph). 13C NMR δ 50.71 (t, C-5); 55.15, 55.33 (2×q, Me); 59.63, 60.17 (2×d, C-2); 66.95, 67.08 (2×t, CH2 -Z); 72.28 (t, CH2Ph); 75.09, 75.49, 77.93, 78.48 (4×d, C-3, C-4); 105.67, 105.90 (d, C-1); 127.83, 127.92, 128.15, 128.64 (4×d, HC-Ph); 136.68, 137.46 (2×s, C-Ph); 155.68, 155.81 (2×s, C=O). m/z: 91 (100%), 108 (25%), 158 (20%), 370 (M+H+, 10%). (Found C, 67.98; H, 6.39; N, 3.60. C21H23NO5 requires C, 68.28; H, 6.28; N, 3.79). Methyl 3-O-benzyl-2,5-dideoxy-2,5-imino-β-D-lyxofuranoside (13β) (829 mg, 3.53 mmol) was treated likewise giving methyl 3-O-benzyl-N-benzyloxycarbonyl-2,5-dideoxy-2,5-imino-β-D-lyxofuranoside (1.18 g, 90%) as a clear oil, Rf 0.35 (ether-hexane 1:3); [α]20D -75.2° (c, 0.83 in chloroform); νmax (film) 2930, 1705 (C=O), 1425, 1275, 1255, 1105 and 750 cm-1 ; 1H NMR δ 3.36, 3.42 (3H, 2×s, CH3); 3.50 (1H, 2×d 5-H); 3.67 (1H, 2×d, H-5'); 4.02-4.06 (1H, m, H-3); 4.29 (1H, bs, H-2); 4.49, 4.54 (1H, bs and dd, H-4); 4.52-4.65 (2H, m, CH2Ph); 5.0-5.2 (2H, 2×dd, CH2Ph); 5.21 (1H, s, H-1); 7.28-7.38 (10H, m, H-Ph). 13C NMR δ 50.02 (t, C-5); 55.70, 55.89 (2×q, Me); 60.17, 59.52 (2×d, C-2); 66.79 (t, CH2 -Z); 72.00, 72.10 (t, CH2Ph); 77.56, 78.08, 78.52, 79.18 (4×d, C-3, C-4); 104.71, 105.11 (2×d, C-1); 128.79, 127.96, 128.33, 128.61, 128.78 (5×d, HC-Ph); 137.09, 137.22 (2×s, C-Ph); 156.20, 156.45 (2×s, C=O). m/z: 91 (100%), 370 (M+H+, 60%), 202 (30%). (Found C, 68.08; H, 6.39; N, 3.40. C21H 23 NO5 requires C, 68.28; H, 6.28; N, 3.79).