Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([C@H:7]([NH:12][C:13]([C:15]2[O:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][NH2:27])[CH:21]=3)=[CH:18][CH:19]=2)=[O:14])[C:8](=[O:11])[NH:9][CH3:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.Cl[C:36]([O:38][CH2:39][CH:40]([CH3:42])[CH3:41])=[O:37]>CN(C=O)C>[CH:1]1([C@H:7]([NH:12][C:13]([C:15]2[O:16][C:17]([C:20]3[CH:21]=[C:22]([CH:23]=[CH:24][CH:25]=3)[CH2:26][NH:27][C:36](=[O:37])[O:38][CH2:39][CH:40]([CH3:42])[CH3:41])=[CH:18][CH:19]=2)=[O:14])[C:8]([NH:9][CH3:10])=[O:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CNC(=O)[C@@H](NC(=O)c1ccc(-c2cccc(CN)c2)o1)C1CCCCC1
Reactant: CC(C)COC(=O)Cl
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: CNC(=O)[C@@H](NC(=O)c1ccc(-c2cccc(CNC(=O)OCC(C)C)c2)o1)C1CCCCC1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 5-(3-aminomethyl-phenyl)-furan-2-carboxylic acid ((S)-cyclohexyl-methylcarbamoyl-methyl)-amide (37 mg, 0.10 mmol) in DMF (2.0 mL) is added 4-methylmorpholine (44 μL, 0.40 mmol) followed by isobutyl chloroformate (21 mg, 0.15 mmol). After stirring at room temperature for 12 hours, the mixture is evaporated in vacuo and the resulting oil purified on reverse phase HPLC to obtain a white solid, 26 mg, 54%, LC/MS ESI m/z (M+H)+=470.4.
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>O1CCCC1.C(OCC)(=O)C>[C:26]1([NH:25][C:2]2[N:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=2[C:4]([OH:6])=[O:5])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=C(O)c1ccc(C(F)(F)F)nc1Cl
Reactant: Nc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=C(O)c1ccc(C(F)(F)F)nc1Nc1ccccc1
Temperature: -78 °C
Reaction time: 2 h
Yield: 98.8 %

Procedure:
A solution of 2-chloro-6-trifluoromethyl-nicotinic acid (5 g, 22.2 mmol) in tetrahydrofuran (20 mL) cooled to −78° C. was treated with lithium bis(trimethylsilyl)amide (1.0 M solution in tetrahydrofuran, 66.5 mL, 66.5 mmol). This solution was stirred at −78° C. for 2 h. At this time, the reaction was treated with a solution of aniline (19.6 g, 19.2 mL, 210 mmol) in tetrahydrofuran (20 mL). The reaction was allowed to gradually warm to 25° C. and was stirred at 25° C. overnight. At this time, the reaction mixture was diluted with ethyl acetate (250 mL), washed with a saturated aqueous sodium bicarbonate solution (2×150 mL), water (1×50 mL), and a saturated aqueous sodium chloride solution (1×50 mL). The organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was triturated in ether to afford 2-phenylamino-6-trifluoromethyl-nicotinic acid (6.19 g, 96.9%) as a light brown solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=2[N:12]2[C:20](Cl)=[N:21][C:22]([C:23]([NH2:25])=[O:24])=[C:11]2[CH2:10][N:9]=1.[CH3:27][O-:28].[Na+].[K+].[Br-]>CO>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]2[N:12]3[C:20]([O:28][CH3:27])=[N:21][C:22]([C:23]([NH2:25])=[O:24])=[C:11]3[CH2:10][N:9]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[C:14]=2[CH:15]=1
Reactant: C[O-]
Reactant: NC(=O)c1nc(Cl)n2c1CN=C(c1ccccc1Cl)c1cc(Cl)ccc1-2
Agent: [Br-]
Agent: [K+]
Agent: [Na+]
Solvent: CO
Product: COc1nc(C(N)=O)c2n1-c1ccc(Cl)cc1C(c1ccccc1Cl)=NC2

Procedure:
A mixture of 0.3 g (0.00074 mole) of 6-(2-chlorophenyl)-1,8-dichloro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxamide, 1.15 g (0.0028 mole) of sodium methoxide and 15 ml of methanol was heated at 120°-125° in a steel bomb for 24 hrs. The solvent was evaporated in vacuo. The residue was dissolved in methylene chloride, washed with water, dried and evaporated at reduced pressure to give a tan, amorphous solid. After chromatography over silica gel using 5% (v/v) of ethanol in methylene chloride the solid was recrystallized from a solution of ethanol and methylene chloride to give off-white crystals with mp 235°-238° (dec.). Uv λ max 216 mμ (ε=41,000) sh 243 (22,600) max 264 (20,000); ir (KBr) 3445, 3330, 3280 cm-1 (NH2) 1675 (CON) nmr (d-DMSO) δ 4.0 ppm (d, 1) and 5.88 (d, 1) (AB-system, J=12 Hz, C4 -H) 4.06 (s, 3, OCH3) 6.9-7.9 (m, 9, aromatic H and NH2).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[CH:21]([CH3:23])[CH3:22])=[C:10]([C:24]([F:27])([F:26])[F:25])[CH:9]=2)[N:5]=[CH:4][N:3]=1.[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH:21]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[S:14][C:11]1[CH:12]=[CH:13][C:8]([C:6]2[N:5]=[CH:4][N:3]=[C:2]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[CH:7]=2)=[CH:9][C:10]=1[C:24]([F:27])([F:26])[F:25])([CH3:23])[CH3:22]
Reactant: CC(C)c1ccccc1Sc1ccc(-c2cc(Cl)ncn2)cc1C(F)(F)F
Reactant: C1COCCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)c1ccccc1Sc1ccc(-c2cc(N3CCOCC3)ncn2)cc1C(F)(F)F
Temperature: 80 °C
Yield: 72 %

Procedure:
To a solution of compound 47 (0.015 g, 0.0367 mmol) in DMF (1.0 mL) was added morpholine followed by potassium carbonate (0.015 g, 0.109 mmol). The reaction mixture was heated at 80° C. for 16 hours. The solid was removed through filtration, and the filtrate was directly purified by preparative HPLC, to give a yellow solid, 43 (0.012 g, 72%). 1H-NMR (CDCl3, 400 MHz) δ 1.19 (d, J=6.8 Hz, 6H), 3.51 (heptet, J=6.8 Hz, 1H), 3.69 (t, J=4.9 Hz, 4H), 3.81 (t, J=4.9 Hz, 4H), 6.80 (s, 1H), 6.90 (d, J=8.5 Hz, 1H), 7.20–7.24 (m, 1H), 7.43 (s, 1H), 7.44 (s, 1H), 7.48 (d, J=7.6 Hz, 1H), 7.87 (d, J=8.2 Hz, 1H), 8.26 (s, 1H), 8.67(s, 1H). MS (APCI) m/z 460 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](=O)[CH3:10])=[CH:4][CH:3]=1.[NH2:12][CH2:13][CH2:14][O:15][CH:16]=[CH2:17]>>[CH:16]([O:15][CH2:14][CH2:13][NH:12][CH:9]([CH3:10])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)=[CH2:17]
Reactant: C=COCCN
Reactant: CC(=O)Cc1ccc(Cl)cc1
Product: C=COCCNC(C)Cc1ccc(Cl)cc1

Procedure:
N-(2-vinyloxyethyl)-α-methyl-β-(4-chlorophenyl) ethyl amine was prepared from 4-chlorophenylacetone and 2-aminoethylvinyl ether according to the method of Example 1 to yield the product (58% yield) as a colorless oil, b.p. 103°-104°/0.4 mm; ND25 1.5199.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13]C(=O)OC(C)(C)C)[CH2:9]1)=[O:7].Cl>CO.O1CCOCC1>[NH2:13][C@H:10]1[CH2:11][CH2:12][N:8]([C:6]([C:2]2[S:1][CH:5]=[CH:4][N:3]=2)=[O:7])[CH2:9]1
Reactant: CC(C)(C)OC(=O)N[C@H]1CCN(C(=O)c2nccs2)C1
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Product: N[C@H]1CCN(C(=O)c2nccs2)C1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of compound 1c (5.5 g, 18.52 mmol) in MeOH (30 mL) was added an HCl solution in dioxane (4M, 50 mL) at room temperature. The mixture was stirred at room temperature for 4 h. The solvent was removed by evaporation. Ether (100 mL) was added to the residue. The resultant white solid was collected by filtration, washed with hexanes, and dried under reduced pressure. The crude compound 1d was used in the next reaction without further purification. MS m/z (M+H+) 198.
Reaction SMILES: C(OC[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])(=O)C(C)=C.[C:19](OCC(C)C)(=O)C(C)=C>>[CH3:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH:9]([CH3:8])[CH3:19]
Reactant: C=C(C)C(=O)OCCCCCCCCCCCC
Reactant: C=C(C)C(=O)OCC(C)C
Product: CCCCCCCCCC(C)C

Procedure:
24 g of helio fast blue HG (C.I. no. 74160), 6 g of a copolymer formed from 75% of lauryl methacrylate and 25% of isobutyl methacrylate with a molecular weight of 150 000, and 210 g of isododecane are mixed for 10 hours using a bead vibrating mill. 100 g of the dispersion obtained are diluted with 100 g of isododecane and reacted with vigorous stirring over a period of 30 minutes at 25° C. with a mixture of 4.5 g of isobutyl cyanoacrylate and 1.5 g of allyl cyanoacrylate. The dispersion was stirred for a further 2 hours at 25° C., then centrifuged and the isolated solid matter was washed with isododecane, centrifuged again and dried. 30 g of coated blue pigment are obtained.
Reaction SMILES: CSC.S([O:9][CH3:10])(OC)(=O)=O.[C:11]1([S:17][C:18]2([C:21]([CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)=O)[CH2:20][CH2:19]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[OH-].[K+]>C(O)(C)(C)C>[Cl:31][C:28]1[CH:29]=[CH:30][C:25]([CH2:24][CH2:23][C:21]2([C:18]3([S:17][C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=4)[CH2:20][CH2:19]3)[CH2:10][O:9]2)=[CH:26][CH:27]=1
Reactant: O=C(CCc1ccc(Cl)cc1)C1(Sc2ccccc2)CC1
Reactant: COS(=O)(=O)OC
Agent: [K+]
Agent: [OH-]
Solvent: CSC
Solvent: CC(C)(C)O
Product: Clc1ccc(CCC2(C3(Sc4ccccc4)CC3)CO2)cc1
Reaction time: 14 h
Yield: 81.4 %

Procedure:
21 ml (0.29 mol) o& dimethyl sulphide and 32.5 g (0.26 mol) of dimethyl sulphate are added to 40 ml of tert.-butanol and allowed to stand at room temperature for 14 hours. A solution of 30 g (0.095 mol) of 4-chlorophenylethyl 1-phenylmercapto-cyclopropyl ketone in 90 ml of tert.-butanol are first added dropwise to the reaction mixture with stirring and 29.2 g of potassium hydroxide powder are then introduced, while the temperature of the reaction mixture is held at 20 to 30° C. The mixture is stirred for a further 3 hours at 30° C., then the dimethyl sulphide is removed under reduced pressure and the reaction mixture is then poured into 70 ml of a 1% strength aqueous hydrogen peroxide solution. The mixture is extracted with ethyl acetate. The organic phase is washed with water and concentrated by removing the solvent under reduced pressure after drying over sodium sulphate. In this manner, 25.6 g (82% of theory) of 2-(4-chlorophenylethyl)-2-(1-phenylmercapto-cyclopropyl)oxirane are obtained in the form of an oily product which is reacted further without additional purification. ##STR68##
Reaction SMILES: [CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[S:4][C:3]=1/[CH:8]=[CH:9]/[C:10](N(C)C)=O.Cl.[N:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([NH:29][C:30]([NH2:32])=[NH:31])=[CH:25][CH:24]=2)=[CH:18][CH:17]=1.[OH-].[Na+]>O(CCO)C>[CH3:7][C:5]1[S:4][C:3]([C:8]2[CH:9]=[CH:10][N:32]=[C:30]([NH:29][C:26]3[CH:25]=[CH:24][C:23]([CH2:22][C:19]4[CH:18]=[CH:17][N:16]=[CH:21][CH:20]=4)=[CH:28][CH:27]=3)[N:31]=2)=[C:2]([CH3:1])[N:6]=1
Reactant: Cc1nc(C)c(/C=C/C(=O)N(C)C)s1
Reactant: N=C(N)Nc1ccc(Cc2ccncc2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: COCCO
Product: Cc1nc(C)c(-c2ccnc(Nc3ccc(Cc4ccncc4)cc3)n2)s1

Procedure:
A mixture of 3-dimethylamino-1-(2,4-dimethyl-thiazol-5-yl)-propenone (1 mmol, 0.21 g) and N-(4-pyridin-4-ylmethyl-phenyl)-guanidine hydrochloride (2 mmol, 0.40 mg) in 2-methoxylethanol was treated with NaOH (40 mg). The reaction mixture was allowed to heat at reflux for 2 d. The solvent was evaporated and the residue was crystallised from EtOAc/MeOH to afford the title compound as an orange solid. 1H-NMR (300 MHz, d6-DMSO) δ3.00 (s, 3H, CH3), 3.02 (s, 3H, CH3), 4.29 (s, 2H, CH2), 7.44 (d, 1H, J=5.5 Hz, pyrimidinyl-H), 7.56 (m, 2H, Ph-H), 7.61 (m, 2H, Ar—H), 8.09 (m, 2H, Ph-H), 8.82 (m, 2H, Ar—H), 8.87 (d, 1H, J=5.5 Hz, pyrimidinyl-H). DE MALDI-TOF MS: {M+H}+=377.52 (C21H19N5S requires 373.48).
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([S:8]([C:11]2[CH:12]=[C:13]([CH:18]=[CH:19][CH:20]=2)[C:14]([NH:16][NH2:17])=[O:15])(=[O:10])=[O:9])[CH2:4][CH2:3]1.[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([OH:31])=[C:26]([C:28](=O)[CH3:29])[CH:27]=1>CO.C(O)(=O)C>[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([OH:31])=[C:26](/[C:28](=[N:17]/[NH:16][C:14](=[O:15])[C:13]2[CH:18]=[CH:19][CH:20]=[C:11]([S:8]([N:5]3[CH2:6][CH2:7][CH:2]([CH3:1])[CH2:3][CH2:4]3)(=[O:10])=[O:9])[CH:12]=2)/[CH3:29])[CH:27]=1
Reactant: CC(=O)c1cc(Cl)ccc1O
Reactant: CC1CCN(S(=O)(=O)c2cccc(C(=O)NN)c2)CC1
Solvent: CC(=O)O
Solvent: CO
Product: C/C(=N\NC(=O)c1cccc(S(=O)(=O)N2CCC(C)CC2)c1)c1cc(Cl)ccc1O
Temperature: 120 °C
Yield: 13.6 %

Procedure:
3-((4-methylpiperidin-1-yl)sulfonyl)benzohydrazide (70 mg, 0.235 mmol) and 1-(5-chloro-2-hydroxyphenyl)ethanone (40.2 mg, 0.235 mmol) was dissolved in Methanol (Volume: 4 ml) in the presence of acetic acid as a catalyst and then the reaction mixture was heated via microwave irradiation to 120° C. for 30 min. Reaction was monitored by TLC. After completion of the reaction, following cooling, the solvent was removed by vacuum and the resulting crude material was purified by flash column chromatography (2% CH3OH/CH2Cl2) afforded the title compound (E)-N′-(1-(5-chloro-2-hydroxyphenyl)ethylidene)-3-((4-methylpiperidin-1-yl)sulfonyl)benzohydrazide (15 mg, 0.032 mmol, 13.60% yield) as a solid. 1H NMR (CDCl3, 400 MHz): δ 8.11 (m, 2H), 7.81 (m, 1H), 7.59 (m, 1H), 7.39 (m, 1H), 7.19 (m, 1H), 6.89 (m, 1H), 3.69 (m, 2H), 2.41 (m, 2H), 2.24 (m, 2H), 1.63 (m, 2H), 1.24 (m, 4H), 0.87 (d, 3H, J=4.4 Hz). Mass [M+H]+: 450.2
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[C:18]([F:19])=[CH:17][CH:16]=[C:15]([F:20])[C:11]=2[C:12]([OH:14])=[O:13])=O)=[CH:4][C:3]=1[N+:21]([O-:23])=[O:22].ClCCl.N1C(F)=NC(F)=NC=1[F:29]>O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([F:29])[C:10]3[C:18]([F:19])=[CH:17][CH:16]=[C:15]([F:20])[C:11]=3[C:12](=[O:14])[O:13]2)=[CH:4][C:3]=1[N+:21]([O-:23])=[O:22]
Reactant: O=C(O)c1c(F)ccc(F)c1C(=O)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: Fc1nc(F)nc(F)n1
Solvent: O
Solvent: ClCCl
Product: O=C1OC(F)(c2ccc(Cl)c([N+](=O)[O-])c2)c2c(F)ccc(F)c21
Temperature: 0 °C
Reaction time: 2 h
Yield: 76.3 %

Procedure:
To a solution of 2-[(4-chloro-3-nitrophenyl)carbonyl]-3,6-difluorobenzoic acid (7.0 g, 22.00 mmol) at 0° C. in anhydrous dichloromethane (40 mL) pyridine (1.70 ml, 22.00 mmol) was added, followed by the addition of cyanuric fluoride (1.90 ml, 24.20 mmol). The reaction mixture was stirred for 120 minutes at 0° C. Water (35 mL) was added to the reaction mixture and it was stirred for 10 min at 0° C. The resulting slurry was filtered through a pad of Celite and washed with dichloromethane. The filtrate was partitioned with water and the organic layer was washed with water. It was dried over anhydrous sodium sulfate. Filtration and concentration gave a crystalline product. It was collected by filtration and dried in vacuo, to give 3-(4-chloro-3-nitrophenyl)-3,4,7-trifluoro-2-benzofuran-1(3H)-one (5.77 g, 82% yield). MS (EI) for C14H5ClF3NO4: 342 (M−).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]1[C:11](=[O:42])[CH:12]([CH:15]([OH:41])[C:16]3[N:17]=[CH:18][N:19]([C:22]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:20]=3[CH3:21])[CH2:13][CH2:14][C:6]1=[C:5]2[CH3:43].N1C=CC=CC=1.[C:50](OC(=O)C)(=[O:52])[CH3:51]>ClCCl>[C:50]([O:41][CH:15]([C:16]1[N:17]=[CH:18][N:19]([C:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:20]=1[CH3:21])[CH:12]1[C:11](=[O:42])[N:7]2[C:8]3[C:4]([C:5]([CH3:43])=[C:6]2[CH2:14][CH2:13]1)=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=3)(=[O:52])[CH3:51]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1c2n(c3ccc(Cl)cc13)C(=O)C(C(O)c1ncn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c1C)CC2
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)OC(c1ncn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c1C)C1CCc2c(C)c3cc(Cl)ccc3n2C1=O

Procedure:
To a solution of 2-chloro-8,9-dihydro-7-[(hydroxy)-(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]-10-methylpyrido[1,2-a]indol-6(7H)-one (1.64 g) in dichloromethane (32 ml) were added pyridine (0.83 ml) and acetic anhydride (0.53 ml). The solution was refluxed for 24 hours. After being cooled, the solution was washed with water twice and brine, dried over sodium sulfate, and evaporated, to give 7-[(acetoxy)(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]-2-chloro-8,9-dihydro-10-methylpyrido[1,2-a]indol-6(7H)-one (1.49 g).
Reaction SMILES: [OH:1][C@@H:2]([C@H:4]1[C:25](=[O:26])[N:6]2[C@@H:7]([C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=3)=[O:13])[C:8](=O)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].[N:27]([CH2:30][CH2:31][S:32][C:33]1[N:34]=[CH:35][N:36]2[CH:40]=[C:39]([Sn](CCCC)(CCCC)CCCC)[S:38][C:37]=12)=[N+:28]=[N-:29]>>[N:27]([CH2:30][CH2:31][S:32][C:33]1[N:34]=[CH:35][N:36]2[CH:40]=[C:39]([C:8]3[C@H:9]([CH3:10])[C@@H:5]4[C@@H:4]([C@H:2]([OH:1])[CH3:3])[C:25](=[O:26])[N:6]4[C:7]=3[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=3)=[O:13])[S:38][C:37]=12)=[N+:28]=[N-:29]
Reactant: C[C@@H](O)[C@H]1C(=O)N2[C@@H](C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)[C@H](C)[C@H]12
Reactant: CCCC[Sn](CCCC)(CCCC)c1cn2cnc(SCCN=[N+]=[N-])c2s1
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(c3cn4cnc(SCCN=[N+]=[N-])c4s3)[C@H](C)[C@H]12
Yield: 70 %

Procedure:
The procedure of Example 1a) was repeated, except that 3.10 g of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 4.62 g of 7-(2-azidoethyl)thio-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole were used as the starting compounds. Thus, 3.41 g of 4-nitrobenzyl (1S,5R,6S)-2-[7-(2-azidoethyl)thioimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate was prepared.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[N:42]1([C@H:47]2[CH2:51][CH2:50][NH:49][CH2:48]2)[CH2:46][CH2:45][CH2:44][CH2:43]1>CN(C=O)C>[NH:3]1[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:1]=[C:2]1[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([C:15]([N:49]2[CH2:50][CH2:51][C@H:47]([N:42]3[CH2:46][CH2:45][CH2:44][CH2:43]3)[CH2:48]2)=[O:17])=[CH:18][CH:19]=1
Reactant: C1CCN([C@H]2CCNC2)C1
Reactant: O=C(O)c1ccc(Cc2nc3ccccc3[nH]2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: O=C(c1ccc(Cc2nc3ccccc3[nH]2)cc1)N1CC[C@H](N2CCCC2)C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 73 %

Procedure:
A solution of methyl 4-((1H-benzo[d]imidazol-2-yl)methyl)benzoate (400 mg, 1.5 mmol) in methanol was treated with aqueous sodium hydroxide (2.5 M, 3.75 mmol), heated at reflux temperature for 3 h and concentrated in vacuo. The resultant residue was dispersed in water and acidified with excess formic acid. The resultant precipitate was removed by filtration, washed with water and dried under vacuum overnight to provide 4-((1H-benzo[d]imidazol-2-yl)methyl)benzoic acid (92%) as a white solid, [M+H] 253.2. A solution of 4-((1H-benzo[d]imidazol-2-yl)methyl)benzoic acid (200 mg, 0.79 mmol) in DMF was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (183 mg, 0.952 mmol) and 1-hydroxybenzotriazole (134 mg, 0.873 mmol), stirred at room temperature for 3 h, treated with a solution of (3′S)-1,3′-bipyrrolidine (166.6 mg, 1.19 mmol) in DMF, stirred at room temperature for 6 h and concenrated in vacuo. This residue was partitioned between aqueous potassium carbonate (1.0 M) and dichloromethane. The organic phase was washed with water, dried over sodium sulfate and concentrated under reduced pressure. Purification of the concentrate by flash column chromatography (silica, dichloromethane:methanol 20:1 to 10:1) afforded the title compound (73%), identified by mass spectral analysis. [M+H] 253.2.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]=[CH:13][C:14]=1[CH3:15])[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH3:2].[Br:16]N1C(=O)CCC1=O.C(OCC)(=O)C>N(C(C)(C)C#N)=NC(C)(C)C#N.CCCCCC>[Br:16][CH2:15][C:14]1[CH:13]=[CH:12][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][C:4]=1[O:3][CH2:1][CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)c1ccc(C)c(OCC)c1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CCOC(=O)c1ccc(CBr)c(OCC)c1
Reaction time: 14 h
Yield: 87 %

Procedure:
To a mixture of ethyl 3-ethoxy-4-methylbenzoate (2.0 g), N-bromosuccinimide (1.9 g) and ethyl acetate (40 mL) was added 2,2′-azobis(2-methylpropionitrile) (15 mg), followed by stirring for 14 hours under heating with reflux. The mixture was left to be cooled, hexane was added thereto, the precipitated solid was separated by filtration, and the obtained filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane:5/95) to obtain ethyl 4-(bromomethyl)-3-ethoxybenzoate (2.4 g).
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]2[N:11]([C:15](I)=[CH:16][N:17]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[CH:24]([P:34]([O:39][CH2:40][CH3:41])(=[O:38])[O:35][CH2:36][CH3:37])([P:26]([O:31][CH2:32][CH3:33])(=[O:30])[O:27][CH2:28][CH3:29])[CH3:25]>C1COCC1>[CH2:36]([O:35][P:34]([CH:24]([P:26]([O:31][CH2:32][CH3:33])([O:27][CH2:28][CH3:29])=[O:30])[CH2:25][C:15]1[N:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:10]2=[N:17][CH:16]=1)(=[O:38])[O:39][CH2:40][CH3:41])[CH3:37]
Reactant: Ic1cnc2c(OCc3ccccc3)cccn12
Reactant: CCOP(=O)(OCC)C(C)P(=O)(OCC)OCC
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCOP(=O)(OCC)C(Cc1cnc2c(OCc3ccccc3)cccn12)P(=O)(OCC)OCC
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 69 %

Procedure:
As shown in FIG. 6, 8-Benzyloxy-3-iodo-imidazo[1,2-α]pyridine 31 (Example 20).(7.0 g, 20 mmol) in anhydrous THF (200 mL) was stirred at −78° C., under argon, then n-BuLi (2.5 M, 16.0 mL, 40 mmol) in hexanes was added slowly, keeping the temperature below −70° C. . The resulting mixture was stirred for 10 min, then tetraethyl ethene-1,1-bisphosphonate 3 (6.0 g, 20.0 mmol) in anhydrous THF (20 mL) was added slowly, keeping the temperature below −70° C. The reaction mixture was stirred for an additional 10 minutes, cooled to room temperature, and then quenched with saturated NH4Cl (100 mL). The mixture was then extracted with CH2Cl2 (200 mL×3) and the organic phase washed with water (200 mL×2). The resultant organic phase was then dried with Na2SO4, concentrated under reduced pressure and purified on silica gel (CombiFlash, EtOAc/MeOH elution) to afford [2-(8-Benzyloxy-imidazo[1,2-α]pyridin-3-yl)-1-(diethoxy-phosphoryl)-ethyl]-phosphonic acid diethyl ester 35 as yellowish brown oil. 7.18 g, 69% yield.
Reaction SMILES: [CH:1]([CH2:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[CH:29]=2)=[O:26])([CH2:13][C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)=[O:15])[C:5]1=[O:36])=O.Cl.[CH3:38][NH:39][CH3:40].C([BH3-])#N.[Na+]>CO>[CH3:35][O:34][C:30]1[CH:29]=[C:28]([NH:27][C:25](=[O:26])[NH:24][C:6]2([CH2:13][C:14]([NH:16][C:17]3[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=3)=[O:15])[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[N:4]([CH2:3][CH2:1][N:39]([CH3:40])[CH3:38])[C:5]2=[O:36])[CH:33]=[CH:32][CH:31]=1
Reactant: CNC
Reactant: COc1cccc(NC(=O)NC2(CC(=O)Nc3ccc(C)cc3)C(=O)N(CC=O)c3ccccc32)c1
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: COc1cccc(NC(=O)NC2(CC(=O)Nc3ccc(C)cc3)C(=O)N(CCN(C)C)c3ccccc32)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 26.2 %

Procedure:
To a solution of 0.386 g of (RS)-1-(formylmethyl)-3-(N′-(3-methoxyphenyl)ureido)-3-((4-methylphenyl) aminocarbonylmethyl)indolin-2-one in 50 ml of methanol was added 0.8 g of dimethylamine hydrochloride at room temperature, and 1.0 g of sodium cyanoborohydride was then added thereto. The mixture was stirred at room temperature for 1 day, followed by concentration. The concentrate was diluted with dichloromethane and washed with an aqueous solution of sodium chloride. The organic layer was dried over anhydrous sodium sulfate and concentrated. The crude product was washed with dichloromethane to afford 0.107 g (26%) of the title compound.