Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([CH2:4][CH2:5][NH:6][C:7](=[O:21])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]CCC)=[N+:2]=[N-:3].C1C2C(=CC=CC=2)C=CC=1C(Cl)=O.N(CCN)=[N+]=[N-].C(N(CC)CC)C>ClCCl>[N:1]([CH2:4][CH2:5][NH:6][C:7]([C:8]1[CH:9]=[CH:10][C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:17]=1)=[O:21])=[N+:2]=[N-:3]
Reactant: CCCCCCCCCCCCCC(=O)NCCN=[N+]=[N-]
Agent: O=C(Cl)c1ccc2ccccc2c1
Agent: [N-]=[N+]=NCCN
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: [N-]=[N+]=NCCNC(=O)c1ccc2ccccc2c1
Yield: 77 %

Procedure:
As in the synthesis of N-(2-azidoethyl)tetradecanamide, 2-naphthoyl chloride (0.237 g, 1.24 mmol) was reacted with 2-azidoethanamine (0.107 g, 1.24 mmol) and triethylamine (0.252 g, 2.49 mmol) in dichloromethane (5 mL) to give N-(2-azidoethyl)-2-naphthamide (0.234 g, 77%). 1H NMR (300 MHz, CDCl3) δ 8.69 (s, 1H), δ 7.84 (m, 4H), δ 7.50 (m, 2H), 6.97 (t, 1H), δ 3.68 (q, 2H), 3.56 (t, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 168.3, 135.1, 132.8, 131.5, 129.2, 128.8, 128.0, 127.9, 127.1, 123.8, 51.2, 39.8 ppm; HRMS (ESI) calcd for C13H12N4O (M+) 240.1011. found 240.1007.
Reaction SMILES: [CH3:1][CH:2]([CH2:7][CH2:8][CH3:9])[CH:3]([OH:6])[C:4]#[CH:5].N1C=CN=C1.[Si:15](Cl)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16].[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O>[C:18]([Si:15]([CH3:17])([CH3:16])[O:6][CH:3]([CH:2]([CH3:1])[CH2:7][CH2:8][CH3:9])[C:4]#[CH:5])([CH3:21])([CH3:20])[CH3:19]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: C#CC(O)C(C)CCC
Agent: [Cl-]
Agent: [NH4+]
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C#CC(O[Si](C)(C)C(C)(C)C)C(C)CCC
Temperature: 25 °C
Reaction time: 18 h
Yield: 96.7 %

Procedure:
To a solution of 4-methyl-hept-1-yn-3-ol (2.53 g, 0.02 mol) in dry DMF (25 mL) were added imidazole (1.63 g, 0.024 mol) and tert-butyldimethylsilyl chloride (3.62 g, 0.024 mol). The resulting solution was stirred at RT for 18 h and then treated with saturated NH4Cl (15 mL) and EtOAc (120 mL). The organic layer was washed with saturated NH4Cl (20 mL), water (4×20 mL), brine (2×20 mL), dried over sodium sulfate, and concentrated in vacuo to afford a crude product (4.65 g, 97%), as a yellow oil, which was used in the next step without further purification. Rf 0.9 (EtOAc/hexanes 1/9); 1H NMR (CDCl3) δ 0.08 (s, 3H), 0.12 (s, 3H), 0.96-0.85 (m, 15H), 1.57-1.10 (m, 4H), 1.69-1.61 (m, 1H), 2.33 (t, J=2.20 Hz, 1H), 4.22-4.18 (m, 1H).
Reaction SMILES: [CH3:1][CH2:2][C:3](=O)[CH2:4][C:5](=O)[CH2:6][CH3:7].[NH2:10][C:11]1[NH:15][N:14]=[C:13]([CH2:16][CH2:17][CH2:18][N:19]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:20][CH2:21][OH:22])[N:12]=1.[OH-].[Na+].[C:32](O)(=[O:34])[CH3:33]>>[C:32]([O:22][CH2:21][CH2:20][N:19]([CH2:18][CH2:17][CH2:16][C:13]1[N:12]=[C:11]2[N:10]=[C:5]([CH2:6][CH3:7])[CH:4]=[C:3]([CH2:2][CH3:1])[N:15]2[N:14]=1)[C:23]1[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=1)(=[O:34])[CH3:33]
Reactant: Nc1nc(CCCN(CCO)c2ccc(F)cc2)n[nH]1
Reactant: CCC(=O)CC(=O)CC
Reactant: CC(=O)O
Agent: [Na+]
Agent: [OH-]
Product: CCc1cc(CC)n2nc(CCCN(CCOC(C)=O)c3ccc(F)cc3)nc2n1
Temperature: 135 °C

Procedure:
A mixture of 3,5-heptanedione (18.8 mg, 0.147 mmol), 2-{[3-(5-amino-1H-1,2,4-triazol-3-yl)propyl](4-fluorophenyl)amino}ethan-1-ol (50 mg, 0.179 mmol), and glacial acetic acid (1 mL) was added to a 50 mL RBF with a magnetic stirring bar. The flask was fitted with a condenser, and warmed in an oil bath to a gentle reflux at 135° C. for 18 h. Progress of the reaction was monitored by analytical HPLC with UV detection (Rt=5.5 min). The mixture was added to stirring ice/water (15 mL), and the pH was adjusted to basic with 1 N sodium hydroxide. The aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography using a gradient elution of 65-100% ethyl acetate in hexanes. The material was concentrated under reduced pressure and the title compound was obtained (20 mg, 37%). EM (calc.): 413.2; MS (ESI) m/e: 414.2 (M+H)+. 1H NMR (DMSO-d6, 400 MHz) δ ppm: 7.11 (s, 1H), 6.97 (m, 2H), 6.75 (m, 2H), 4.12 (t, 2H), 3.54 (t, 2H), 3.40 (t, 2H), 3.10 (q, 2H), 2.88 (m, 4H), 1.99 (m, 2H), 1.95 (s, 3H), 1.35 (t, 3H), 1.28 (t, 3H).
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:11][CH2:12][CH:13]2[CH2:15][CH2:14]2)=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.[NH2:16][CH:17]([CH:21]1[CH2:23][CH2:22]1)[CH2:18][CH2:19][OH:20]>>[CH:21]1([CH:17]([NH:16][C:8]([C:5]2[CH:4]=[C:3]([O:11][CH2:12][CH:13]3[CH2:15][CH2:14]3)[C:2]([Cl:1])=[CH:7][N:6]=2)=[O:10])[CH2:18][CH2:19][OH:20])[CH2:23][CH2:22]1
Reactant: O=C(O)c1cc(OCC2CC2)c(Cl)cn1
Reactant: NC(CCO)C1CC1
Product: O=C(NC(CCO)C1CC1)c1cc(OCC2CC2)c(Cl)cn1

Procedure:
The title compound was synthesized in analogy to Example 12d, using 5-chloro-4-cyclopropylmethoxy-pyridine-2-carboxylic acid and γ-amino-cyclopropanepropanol (CAN 683220-79-3) as starting materials and isolated (27 mg, 83%) as colorless oil; LC-MS (UV peak area, m/z) 97.6%, 325.1313 (MH+).
Reaction SMILES: [CH3:1][C:2]1[C:6]([CH:7]=[O:8])=[CH:5][NH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].F[C:16]1[C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:19]=[CH:18][N:17]=1.CN(C)C=O>O>[CH:7]([C:6]1[C:2]([CH3:1])=[N:3][N:4]([C:16]2[C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:19]=[CH:18][N:17]=2)[CH:5]=1)=[O:8]
Reactant: Cc1n[nH]cc1C=O
Reactant: COC(=O)c1cccnc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1cccnc1-n1cc(C=O)c(C)n1
Temperature: 60 °C
Reaction time: 16 h
Yield: 63.3 %

Procedure:
A mixture of 3-methyl-1H-pyrazole-4-carbaldehyde (300 mg, 2.72 mmol), potassium carbonate (565 mg, 4.08 mmol), methyl 2-fluoropyridine-3-carboxylate (507 mg, 3.27 mmol) and dimethylformamide (2 mL) is stirred at 60° C. for 16 h. Water is added and the compound is extracted in ethyl acetate. The organic layer is washed with brine, dried over sodium sulfate and solvent is evaporated. The crude mixture is purified by normal phase Isco chromatography using hexane:ethyl acetate, 2:1 as eluent to yield 422 mg of the title compound. MS (m/z): 246 (M+1).
Reaction SMILES: C[O:2][C:3]([C:5]1[CH2:14][C:13](=[O:15])[C:12]2[C:7](=[C:8](Cl)[C:9]([CH3:17])=[C:10](Cl)[CH:11]=2)[N:6]=1)=[O:4].O[Li].O>CO.O.[Pd]>[C:3]([C:5]1[CH2:14][C:13](=[O:15])[C:12]2[C:7](=[CH:8][C:9]([CH3:17])=[CH:10][CH:11]=2)[N:6]=1)([OH:4])=[O:2]
Reactant: COC(=O)C1=Nc2c(cc(Cl)c(C)c2Cl)C(=O)C1
Agent: [Pd]
Agent: [Li]O
Solvent: O
Solvent: CO
Product: Cc1ccc2c(c1)N=C(C(=O)O)CC2=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 98.8 %

Procedure:
2-(Methoxycarbonyl)-4-oxo-6,8-dichloro-7-methylquinoline (28.5 g, 99.6 mmol) was suspended in methanol (1 L) and a solution of LiOH.H2O (20.5 g, 0.5 mol) in water (200 mL) was added to the solution. The resulting reaction mixture was stirred at ambient temperature for 0.5 hours. Pd/C (5.8 g) was added to the reaction mixture and the resulting reaction mixture was shaken under 50 Psi hydrogen overnight. The reaction mixture was filtered, concentrated under reduced pressure to remove methanol, diluted with water (300 mL) and the pH was adjusted to between pH 3 and pH 4 by 2N HCl. The precipitate was collected by filtration, washed with water and dried to afford a white solid, 2-carboxy-4-oxo-7-methylquinoline (20 g, 90%); NMR (DMSO-d6) 2.40 (s, 3), 6.60 (s, 1), 7.20 (d, 1), 7.68 (s, 1), 7.96 (d, 1) ppm.
Reaction SMILES: [CH:1]1([NH:7][C:8]2[C:13]([C:14]3[CH2:18][C:17]4([CH2:23][CH2:22][CH:21]([OH:24])[CH2:20][CH2:19]4)[O:16][N:15]=3)=[CH:12][N:11]=[C:10]3[N:25]([CH2:29][CH3:30])[N:26]=[C:27]([CH3:28])[C:9]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[C:38]1([CH3:48])[CH:43]=[CH:42][C:41]([S:44](Cl)(=[O:46])=[O:45])=[CH:40][CH:39]=1.O>ClCCl>[CH3:48][C:38]1[CH:43]=[CH:42][C:41]([S:44]([O:24][CH:21]2[CH2:22][CH2:23][C:17]3([O:16][N:15]=[C:14]([C:13]4[C:8]([NH:7][CH:1]5[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]5)=[C:9]5[C:27]([CH3:28])=[N:26][N:25]([CH2:29][CH3:30])[C:10]5=[N:11][CH:12]=4)[CH2:18]3)[CH2:19][CH2:20]2)(=[O:46])=[O:45])=[CH:40][CH:39]=1
Reactant: CCn1nc(C)c2c(NC3CCCCC3)c(C3=NOC4(CCC(O)CC4)C3)cnc21
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: CCn1nc(C)c2c(NC3CCCCC3)c(C3=NOC4(CCC(OS(=O)(=O)c5ccc(C)cc5)CC4)C3)cnc21
Reaction time: 5 h

Procedure:
3-[4-(Cyclohexylamino)-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl]-1-oxa-2-azaspiro[4.5]dec-2-en-8-ol (0.0025 mole) (example 26) is dissolved in dichloromethane. Triethyl amine (0.0050 mol) is added at 0° and p-toluene sulphonyl chloride (0.0050 mole) is added. The reaction mixture is stirred for about 5 hrs. Water is added and extraction is done with dichloromethane. The organic layer is washed with brine, dried and concentrated under reduced pressure to give crude product, which is purified by column chromatography.
Reaction SMILES: [SH:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[CH3:11][CH2:12]O.[OH-].[K+].[CH3:16]COC(C)=O>>[CH3:16][C:12]1[N:6]2[C:2](=[N:3][C:4]3[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=32)[S:1][CH:11]=1
Reactant: CCO
Reactant: CCOC(C)=O
Reactant: Sc1nc2ccccc2[nH]1
Agent: [K+]
Agent: [OH-]
Product: Cc1csc2nc3ccccc3n12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-Mercaptobenzoimidazole (15.0 g) was added to EtOH (100 ml) solution of KOH (6.60 g), and the mixture was heated under reflux for 1 hour. After cooling to room temperature, this was mixed with 2-chloroacetone (7.96 ml) and stirred overnight. The reaction solution was mixed with EtOAc and stirred, the insoluble matter was removed by filtration and then the solvent was evaporated under a reduced pressure. The thus obtained oily material was dissolved in concentrated sulfuric acid (100 ml) and stirred at room temperature for 6 hours. The reaction solution was poured into ice water and then neutralized with 28% NH3 aqueous solution, and the resulting precipitate was collected by filtration. This was recrystallized from MeOH to obtain the title compound (9.60 g) as light brown crystals. (J. O. C., 29 (4), 865-9 (1964))
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]([Br:11])[C:8]([F:12])=[CH:7][C:3]=1[C:4](O)=[O:5].[NH2:13][C:14](N)=[O:15]>O>[Br:11][C:9]1[CH:10]=[C:2]2[C:3]([C:4](=[O:5])[NH:13][C:14](=[O:15])[NH:1]2)=[CH:7][C:8]=1[F:12]
Reactant: NC(N)=O
Reactant: Nc1cc(Br)c(F)cc1C(=O)O
Solvent: O
Product: O=c1[nH]c(=O)c2cc(F)c(Br)cc2[nH]1
Temperature: 200 °C
Reaction time: 2 h
Yield: 51.6 %

Procedure:
To a 100 mL round bottom flask, 2-amino-4-bromo-5-fluoro-benzoic acid (0.7 g, 2.99 mmol) and urea (1.07 g, 17.94 mmol) were added. The reaction mixture was stirred at 200° C. for 2 hours. The reaction mixture was allowed to cool to 100° C. and water was added. The aqueous reaction mixture was refluxed for 5-10 minutes and cooled to room temperature to provide the precipitate. The solid was filtered and dried to afford the title compound (400 mg, 51%). This material was taken to the next step without further purification.
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:10][C@H:9]([CH3:11])[CH2:8][CH2:7][C@H:6]1[C:12]([OH:14])=O)(=[O:3])[CH3:2].C(Cl)(=O)C([Cl:18])=O>ClCCl.CN(C)C=O>[C:1]([O:4][CH:5]1[CH2:10][CH:9]([CH3:11])[CH2:8][CH2:7][CH:6]1[C:12]([Cl:18])=[O:14])(=[O:3])[CH3:2]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CC(=O)O[C@H]1C[C@H](C)CC[C@H]1C(=O)O
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(=O)OC1CC(C)CCC1C(=O)Cl
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of (1R,2S,4R)-2-Acetoxy-4-methyl-cyclohexanecarboxylic acid (109 mg, 0.54 mmol) in dichloromethane (2.7 ml) was added oxalyl chloride (545 ul, 1.09 mmol) followed by 1 drop of dimethylformamide. The reaction mixture was stirred for 4 h at room temperature. The solvents were then removed to obtain 119 mg (99%) of (1R*,2S*, 4R*)-2-Acetoxy-4-methyl-cyclohexanecarboxylic acid chloride. NMR 1H (CDCl3, 400 MHz): 5.45 ppm (s, 1H); 2.46-2.42 ppm (m, 1H); 2.02 ppm (s, 3H); 2.02-1.96 ppm (m, 1H); 1.91-1.76 ppm (m, 3H); 1.70-1.61 ppm (m, 1H); 1.16-1.08 ppm (m, 1H); 0.99-0.88 ppm (m, 1H); 0.87 ppm (d, 3H).
Reaction SMILES: [CH2:1]([CH:3]([NH2:6])[CH2:4][CH3:5])[CH3:2].[C:7]([NH:10][C:11]1[S:12][C:13]([S:16](Cl)(=[O:18])=[O:17])=[N:14][N:15]=1)(=[O:9])[CH3:8].Cl>O>[C:7]([NH:10][C:11]1[S:12][C:13]([S:16]([NH:6][CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])(=[O:17])=[O:18])=[N:14][N:15]=1)(=[O:9])[CH3:8]
Reactant: CCC(N)CC
Reactant: CC(=O)Nc1nnc(S(=O)(=O)Cl)s1
Agent: Cl
Solvent: O
Product: CCC(CC)NS(=O)(=O)c1nnc(NC(C)=O)s1
Temperature: 20 °C
Reaction time: 2 h

Procedure:
1-Ethylpropylamine (0.1 mole) and water (50 ml) are charged into a glass reaction vessel fitted with a mechanical stirrer and thermometer. The solution is cooled to 20° C. and stirred while 2-acetamido-5-chlorosulfonyl-1,3,4-thiadiazole (0.1 mole) is added slowly while holding the reaction temperature between 0° C. and 20° C. At the conclusion of the addition, stirring is continued for a period of about 2 hours at room temperature. The reaction mixture is then neutralized with 6 N hydrochloric acid. Solids are filtered out, water washed and dried to yield the desired product 2-acetamido-5-[N-(1-ethylpropyl)aminosulfonyl]-1,3,4-thiadiazole.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:13][C:14](=[S:26])[NH:15][C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:25])[CH3:24])=[CH:18][CH:17]=2)[CH:5]=[C:6]([Cl:12])[C:7]=1[O:8][CH2:9][CH2:10][OH:11].[CH3:27][S:28](Cl)(=[O:30])=[O:29]>N1C=CC=CC=1.O1CCCC1.C(OCC)(=O)C>[C:23]([NH:22][C:19]1[CH:20]=[CH:21][C:16]([NH:15][C:14](=[S:26])[NH:13][C:4]2[CH:3]=[C:2]([Cl:1])[C:7]([O:8][CH2:9][CH2:10][O:11][S:28]([CH3:27])(=[O:30])=[O:29])=[C:6]([Cl:12])[CH:5]=2)=[CH:17][CH:18]=1)(=[O:25])[CH3:24]
Reactant: CC(=O)Nc1ccc(NC(=S)Nc2cc(Cl)c(OCCO)c(Cl)c2)cc1
Reactant: CS(=O)(=O)Cl
Solvent: C1CCOC1
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CC(=O)Nc1ccc(NC(=S)Nc2cc(Cl)c(OCCOS(C)(=O)=O)c(Cl)c2)cc1
Temperature: 0 °C
Reaction time: 0.75 h

Procedure:
To an ice cooled solution of N-(4-{3-[3,5-dichloro-4-(2-hydroxy-ethoxy)-phenyl]-thioureido}-phenyl)-acetamide (0.20 g) in pyridine (2 mL) and tetrahydrofuran (0.5 mL) is added methanesulfonyl chloride (0.11 g) and the solution is stirred at 0° C. for 45 minutes. The reaction mixture is then diluted with ethyl acetate, washed successively twice with 2% aqueous hydrochloric acid, once with saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. After removing the solvents by evaporation under reduced pressure the resulting residue is recrystallized from acetone-hexanes to give the desired product as a white powder.
Reaction SMILES: [CH2:1]([C@H:8]([NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:9](=[O:15])[NH:10][CH2:11][CH2:12][CH:13]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:27][C@@H:28]([C@H:36]([C@@H:38]1[C@@H:42]([O:43][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45])[C@@H:41]([O:51][Si:52]([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53])[C@H:40]([N:59]2[CH:64]=[CH:63][C:62](=[O:65])[N:61]([CH2:66][C:67]3[CH:72]=[CH:71][C:70]([O:73][CH3:74])=[CH:69][CH:68]=3)[C:60]2=[O:75])[O:39]1)[OH:37])[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.O1CCCC1>[CH2:1]([C@@H:8]([C:9](=[O:15])[NH:10][CH2:11][CH2:12][CH2:13][NH:27][C@@H:28]([C@H:36]([CH:38]1[C@@H:42]([O:43][Si:44]([C:47]([CH3:48])([CH3:49])[CH3:50])([CH3:46])[CH3:45])[C@@H:41]([O:51][Si:52]([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:53])[CH3:54])[C@H:40]([N:59]2[CH:64]=[CH:63][C:62](=[O:65])[N:61]([CH2:66][C:67]3[CH:72]=[CH:71][C:70]([O:73][CH3:74])=[CH:69][CH:68]=3)[C:60]2=[O:75])[O:39]1)[OH:37])[C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1ccc(Cn2c(=O)ccn([C@@H]3O[C@H]([C@H](O)[C@H](N)C(=O)OC(C)(C)C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]3O[Si](C)(C)C(C)(C)C)c2=O)cc1
Reactant: O=CCCNC(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: COc1ccc(Cn2c(=O)ccn([C@@H]3OC([C@H](O)[C@H](NCCCNC(=O)[C@H](Cc4ccccc4)NC(=O)OCc4ccccc4)C(=O)OC(C)(C)C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]3O[Si](C)(C)C(C)(C)C)c2=O)cc1
Yield: 21 %

Procedure:
By using an analogous procedure to that described for Example 1, a solution of benzyl (1S)-1-benzyl-2-oxo-2-[(3-oxopropyl)amino]ethylcarbamate (61 mg, 0.173 mmol, obtained from Reference Example 22), tert-butyl (2S,3R)-2-amino-3-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl-(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)-tetrahydro-2-furanyl]-3-hydroxypropanoate (100 mg, 0.139 mmol, obtained from Reference Example 6), acetic acid (1 drop), and sodium triacetoxyborohydride (59 mg, 0.277 mmol) in anhydrous tetrahydrofuran (4 ml) was stirred at room temperature under nitrogen for 5 hours. The product was purified by chromatography (flash column, silica gel, 2.5% methanol in methylene chloride) to provide tert-butyl (5S,12S)-5-benzyl-12-[(R)-[(3R,4R,5R)-3,4-bis{[tertbutyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate (31 mg, 21%) as a white solid.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([C:9]1[N:13]2[CH2:14][CH2:15][CH2:16][CH:17]([C:18]([O:20]C(C)C)=[O:19])[C:12]2=[CH:11][CH:10]=1)=[O:8].C(=O)([O-])[O-].[K+].[K+]>CO.O>[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([C:9]1[N:13]2[CH2:14][CH2:15][CH2:16][CH:17]([C:18]([OH:20])=[O:19])[C:12]2=[CH:11][CH:10]=1)=[O:8]
Reactant: CC(C)OC(=O)C1CCCn2c(C(=O)c3cccn3C)ccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: Cn1cccc1C(=O)c1ccc2n1CCCC2C(=O)O

Procedure:
A mixture of 0.314 g. of isopropyl 3-(N-methyl-2-pyrroyl)-5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate, 0.28 g. of potassium carbonate and 10 ml. of a (1:1) methanol-water mixture is refluxed under nitrogen atmosphere for 3 hours, cooled, and evaporated to dryness. The residue is taken up in 50 ml. of water and extracted with ethyl acetate (3×10 ml.). The aqueous solution is acidified with 10% hydrochloric acid and extracted with ethyl acetate (10×15 ml.). The combined extracts are washed with saturated sodium chloride solution dried with anhydrous sodium sulfate and evaporated to dryness under reduced pressure, to afford 3-(N-methyl-2-pyrroyl)-5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylic acid, (XIVa, R=H, Q=CH3, n=2).
Reaction SMILES: [C:1]([O-:4])([O-])=O.[K+].[K+].[C:7]([OH:11])(C)(C)C.O.C([CH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=C>[Fe-3](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+].O=[Os](=O)(=O)=O.C1(C)C=CC=CC=1.C(Cl)Cl>[O:18]1[CH2:19][CH2:20][CH:15]([C@@H:1]([OH:4])[CH2:7][OH:11])[CH2:16][CH2:17]1
Reactant: C=CC1CCOCC1
Reactant: O=C([O-])[O-]
Reactant: CC(C)(C)O
Agent: N#C[Fe-3](C#N)(C#N)(C#N)(C#N)C#N
Agent: O=[Os](=O)(=O)=O
Agent: [K+]
Solvent: ClCCl
Solvent: Cc1ccccc1
Solvent: O
Product: OC[C@H](O)C1CCOCC1
Temperature: 0 °C

Procedure:
A 500-mL, round-bottomed flask was charged with potassium ferricyanide (III) (15.0 g, 45.6 mmol), 2,5-diphenyl-4,6-bis(9-O-dihydroquinidyl)pyrimidine ((DHQD)2-PYR) (132 mg, 0.15 mmol) and K2CO3 (6.29 g, 45.6 mmol). A 1:1 mixture of tert-butyl alcohol/H2O (150 mL) was added and the suspension was stirred under N2. A 0.25 M solution of OsO4 in toluene (0.60 mL, 0.15 mmol) was then added the mixture was cooled to 0° C. After stirring for 60 minutes, 4-vinyltetrahydro-2H-pyran (1.70 g, 15.2 mmol) was added and the mixture was stirred overnight. Solid Na2S2O5 (22.5 g) was then added and the reaction mixture was allowed to warm to ambient temperature. CH2Cl2 (150 mL) was then added and the layers were separated. The aqueous layer was extracted with CH2Cl2 (3×30 mL) and the combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. Chromatography (SiO2, 10% methanol/CHCl3) gave 2.11 g of (1R)-1-tetrahydro-2H-pyran-4-ylethane-1,2-diol as a colorless oil.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C@H:6]2[C@H:15]3[CH2:16][CH2:17][N:18]([C:19]([C@H:21]4[CH2:26][CH2:25][CH2:24][CH2:23][C@H:22]4[NH:27][C:28](=[O:35])[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:20])[C@H:14]3[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[NH:7]2)=[CH:2]1.S1C=CC([C@H]2[C@@H]3CCN(C([C@H]4CCCC[C@H]4NC(=O)C4C=CC=CC=4)=O)[C@@H]3C3C=CC=CC=3N2)=C1>C1(C)C=CC=CC=1.[O-2].[O-2].[Mn+4]>[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[C:15]3[CH2:16][CH2:17][N:18]([C:19]([C@H:21]4[CH2:26][CH2:25][CH2:24][CH2:23][C@H:22]4[NH:27][C:28](=[O:35])[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:20])[C:14]=3[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N:7]=2)=[CH:2]1
Reactant: O=C(N[C@@H]1CCCC[C@@H]1C(=O)N1CC[C@@H]2[C@H](c3ccsc3)Nc3ccccc3[C@@H]21)c1ccccc1
Agent: [Mn+4]
Agent: O=C(N[C@@H]1CCCC[C@@H]1C(=O)N1CC[C@@H]2[C@H]1c1ccccc1N[C@H]2c1ccsc1)c1ccccc1
Agent: [O-2]
Solvent: Cc1ccccc1
Product: O=C(N[C@@H]1CCCC[C@@H]1C(=O)N1CCc2c(-c3ccsc3)nc3ccccc3c21)c1ccccc1
Yield: 17 %

Procedure:
A mixture of N-((1R,2S)-2-{[(3aR*,4R*,9bR*)-4-(3-thienyl)-2,3,3a, 4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)benzamide and N-((1R,2S)-2-{[(3aS*,4R*,9bS*)-4-(3-thienyl)-2,3,3a, 4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)benzamide (422 mg, 0.87 mmol) was dissolved in toluene (30 ml), manganese dioxide (7.6 g, 87 mmol) was added and the mixture was refluxed overnight. The reaction mixture was filtered through celite and washed with methanol. The filtrate was concentrated under reduced pressure. The residue was subjected to column chromatography using silica gel (30 g), and eluted with hexane-ethyl acetate (9:1-2:1, v/v). Crystallization from diisopropy ether gave the title compound (70 mg, 17%) as pale-brown crystals.
Reaction SMILES: C(OC([N:7]1[C@H:11]([CH:12]([OH:21])[C:13]2[N:14]3[CH:20]=[N:19][CH:18]=[C:15]3[S:16][CH:17]=2)[CH2:10][C@H:9]([S:22][C:23]2[C@H:24]([CH3:40])[C@@H:25]3[C@@H:35]([C@H:36]([OH:38])[CH3:37])[C:34](=[O:39])[N:26]3[C:27]=2[C:28]([O:30]CC=C)=[O:29])[CH2:8]1)=O)C=C.CNC1C=CC=CC=1.O>ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:38][C@@H:36]([C@H:35]1[C:34](=[O:39])[N:26]2[C:27]([C:28]([OH:30])=[O:29])=[C:23]([S:22][C@H:9]3[CH2:10][C@@H:11]([CH:12]([OH:21])[C:13]4[N:14]5[CH:20]=[N:19][CH:18]=[C:15]5[S:16][CH:17]=4)[NH:7][CH2:8]3)[C@H:24]([CH3:40])[C@H:25]12)[CH3:37]
Reactant: C=CCOC(=O)C1=C(S[C@H]2C[C@@H](C(O)c3csc4cncn34)N(C(=O)OCC=C)C2)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: O
Solvent: CNc1ccccc1
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(S[C@@H]3CN[C@H](C(O)c4csc5cncn45)C3)[C@H](C)[C@H]12
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 20.8 %

Procedure:
Tetrakis(triphenylphosphine)palladium(0) (13.8 mg) is added to a solution of 70 mg of allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-3-yl)methyl]pyrrolidin-3-yl]thio-6-((1R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate (stereoisomer A) and 0.077 ml of N-methylaniline in 1.0 ml of dry dichloromethane, and the mixture is stirred in an argon atmosphere at room temperature for 45 min. Distilled water (3 ml) is added thereto, and the mixture is washed three times with 5 ml of ethyl acetate. The water layer is filtered, followed by concentration under reduced pressure and freeze drying to give a colorless flocculent material. The flocculent material is purified by column chromatography (water-methanol) on Cosmosil 40C18-PREP to give 11.5 mg of the title compound as a colorless flocculent material.