Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:11].[CH3:12]N(C=O)C.S(Cl)(Cl)=O>CO>[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH3:12])=[O:7])=[CH:4][C:3]=1[CH3:11]
Reactant: CN(C)C=O
Reactant: Cc1cc(C(=O)O)ccc1O
Solvent: O=S(Cl)Cl
Solvent: CO
Product: COC(=O)c1ccc(O)c(C)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96 %

Procedure:
To a solution of 4-hydroxy-3-methylbenzoic acid (10.00 g, 65.7 mmol) and DMF (100 μL) in MeOH (35 mL) was added dropwise thionyl chloride (4.8 mL, 65.7 mmol) at room temperature. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with the addition of aqueous saturated sodium bicarbonate solution (50 mL), and methanol was removed under reduced pressure. The residue was extracted with EtOAc (3×50 mL) and dried over sodium sulfate, filtered and concentrated in vacuo to provide methyl 4-hydroxy-3-methyl-benzoate (10.53 g, 96%) as a light brown solid. ESI-MS m/z calc. 166.0. found 167.1 (M+1)+; Retention time: 1.09 minutes (3 min run).
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[Br:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)=[CH:10][CH:9]=1.I[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]>CC(=O)CC>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[CH:16][CH:15]=2)=[CH:12][CH:13]=1
Reactant: Oc1ccc(-c2ccc(Br)cc2)cc1
Reactant: CCCCCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CCCCCOc1ccc(-c2ccc(Br)cc2)cc1
Temperature: 30 °C

Procedure:
Anhydrous K2CO3 (416g, 3 mol) was added to a mixture of 4-bromo-4′-hydroxybiphenyl (300 g, 1.2 mol), 1-iodopentane (234 ml, 1.79 mol) and 2-butanone (600 ml). The reaction mixture was refluxed for 44 h until TLC (85:15 hexanes/EtOAc) showed complete consumption of the bromo alcohol. The mixture was cooled to about 30° C., diluted with CH2C12 (600 ml) and then filtered. The filtrate was washed twice with H2O and twice with a saturated aqueous NaCl solution, dried over anhydrous Na2SO4, filtered and then dried at reduced pressure to provide a solid. This solid was isolated by filtration, washed repeatedly with a total of 2 L of ice-cold heptane to remove all traces of iodopentane and then dried overnight under high vacuum. Yield: 340 g (88%) of a white powder.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].ClCCl.[OH:8][N:9]=[C:10]([CH3:25])[CH2:11][N:12]([S:21]([CH3:24])(=[O:23])=[O:22])[C:13]1[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:20]>C(N(CC)CC)C>[C:1]([O:8][N:9]=[C:10]([CH3:25])[CH2:11][N:12]([S:21]([CH3:24])(=[O:23])=[O:22])[C:13]1[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:20])(=[O:3])[CH3:2]
Reactant: CC(=O)Cl
Reactant: CC(CN(c1c(C)cccc1C)S(C)(=O)=O)=NO
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)ON=C(C)CN(c1c(C)cccc1C)S(C)(=O)=O

Procedure:
Acetyl chloride (0.9 ml) was added to a dichloromethane (20 ml) solution of N-[2-hydroxyiminopropyl]-2',6'-dimethylmethanesulphonanilide (2.6 g) and triethylamine (1.6 ml). The mixture was stirred and boiled under reflux for 3 hours, then filtered, and the filtrate evaporated to a clear yellow oil. A solution of this oil in chloroform was percolated through a short column of silica gel, and the eluate evaporated to give analytically pure N-[2-(acetyloxyimino)propyl]-2',6'-dimethylmethanesulphonanilide. Yield 1.9 g (63%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2Cl.[NH:13]1[CH2:18][CH2:17][CH2:16][C@H:15]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:14]1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2[N:13]1[CH2:18][CH2:17][CH2:16][C@H:15]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[CH2:14]1
Reactant: Clc1ccnc2ccc(Br)cc12
Reactant: CC(C)(C)OC(=O)N[C@H]1CCCNC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN1CCCC1=O
Product: CC(C)(C)OC(=O)N[C@H]1CCCN(c2ccnc3ccc(Br)cc23)C1

Procedure:
A solution of 6-bromo-4-chloroquinoline (1.0 equiv.), (S)-tert-butyl piperidin-3-ylcarbamate (1.0 equiv.) and DIEA (1.5 equiv.) in NMP (0.1 M) was heated at 140° C. for 48 hours. Upon cooling the solution was poured onto ice and upon melting the solid was filtered, rinsed with H2O and pumped on to yield (S)-tert-butyl 1-(6-bromoquinolin-4-yl)piperidin-3-ylcarbamate. LC/MS=406.0/408.0 (M+H), LC=2.85 min.
Reaction SMILES: [C:1]([C:4]1[CH:15]=[CH:14][C:7]2[N:8]([CH3:13])[C:9]([CH2:11][OH:12])=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[Mn]([O-])(=O)(=O)=[O:17].[K+]>>[C:1]([C:4]1[CH:15]=[CH:14][C:7]2[N:8]([CH3:13])[C:9]([C:11]([OH:17])=[O:12])=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: CC(=O)c1ccc2c(c1)nc(CO)n2C
Agent: [K+]
Product: CC(=O)c1ccc2c(c1)nc(C(=O)O)n2C

Procedure:
In a manner analogous to that described in Example 12, 4.1 g of 5-acetyl-1-methyl-benzimidazole-2-methanol can be oxidised with 4 g of potassium permanganate to give 5-acetyl-1-methyl-benzimidazole-2-carboxylic acid with a melting point above 135°.
Reaction SMILES: Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH2:10])=[CH:5][CH:4]=1.C[O-].[Na+].[CH2:14]([O:16][CH:17]([O:22][CH2:23][CH3:24])[C:18](=[NH:21])OC)[CH3:15]>CO>[Br:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:18](=[NH:21])[CH:17]([O:22][CH2:23][CH3:24])[O:16][CH2:14][CH3:15])=[CH:5][CH:4]=1
Reactant: NCc1ccc(Br)cc1
Reactant: CCOC(OCC)C(=N)OC
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CCOC(OCC)C(=N)NCc1ccc(Br)cc1
Yield: 62.3 %

Procedure:
(4-Bromophenyl)methanamine hydrochloride (2.359 g, 10.39 mmol) and sodium methoxide (2.376 mL, 10.39 mmol) were added to a solution of methyl 2,2-diethoxyacetimidate (3.35 g, 20.78 mmol) in methanol (10 ml). The cloudy mixture was heated at 70 C for 1.5 h and the resulting yellow mixture was concentrated. The residue was purified by silica gel with 100% ethyl acetate to give a yellow viscous oil (2.04 g, 62%). 1H NMR (400 MHz, CDCl3) δ ppm 7.47 (2H, d, J=8.56 Hz), 7.23 (2H, d, J=8.06 Hz), 6.76 (1H, br. s.), 5.31 (1H, br. s.), 4.94 (1H, br. s.), 4.45 (2H, br. s.), 3.47-3.77 (4H, m), 1.26 (6H, t, J=7.05 Hz). LCMS:R.T.=2.12; [M+2]+=317.2.
Reaction SMILES: [OH:1][N:2]([CH:6](C1SC2C=CC(CC(C)C)=CC=2C=1)[CH3:7])[C:3]([NH2:5])=[O:4].[S:21]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[CH:23]=[CH:22]1>>[OH:1][N:2]([CH:6]([C:23]1[C:24]2[CH:29]=[C:28]([CH2:23][CH:24]([CH3:29])[CH3:25])[CH:27]=[CH:26][C:25]=2[S:21][CH:22]=1)[CH3:7])[C:3]([NH2:5])=[O:4]
Reactant: c1ccc2sccc2c1
Reactant: CC(C)Cc1ccc2sc(C(C)N(O)C(N)=O)cc2c1
Product: CC(C)Cc1ccc2scc(C(C)N(O)C(N)=O)c2c1

Procedure:
N-hydroxy-N-[1-(5-(2,2-dimethylethyl)benzo[b]thien-2-yl)-ethyl]urea. The desired compound was prepared according to the method of example 2, except using the material prepared as in step c, above, instead of benzothiophene. (R1 =NH2, A=CHCH3, X=S[2-isomer], Y=5-(CH3)3C).
Reaction SMILES: Cl[C:2]1[C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:15])[CH:8]=2)[N:3]=1.[NH2:16][C@H:17]([C:25]([OH:27])=[O:26])[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+].Cl>O>[C:25]([C@@H:17]([NH:16][C:2]1[C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:15])[CH:8]=2)[N:3]=1)[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([OH:27])=[O:26]
Reactant: N[C@@H](Cc1ccccc1)C(=O)O
Reactant: O=C(O)c1cc2cc(Cl)ccc2nc1Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: O=C(O)c1cc2cc(Cl)ccc2nc1N[C@@H](Cc1ccccc1)C(=O)O
Temperature: 135 °C
Reaction time: 24 h
Yield: 56.9 %

Procedure:
A mixture of 2,6-dichloroquinoline-3-carboxylic acid (243 mg, 1 mmol), L-phenylalanine (330 mg, 2 mmol) and potassium carbonate (415 mg, 3 mmol) in water (3 mL) is stirred for 24 h at 135° C. in closed reaction vial. After cooling, the reaction mixture is acidified by addition of 2N HCl, and the precipitated solid is collected on filter, washed with water and recrystallized from DMF-water to give the title compound (211 mg, 57%) as yellow needles.
Reaction SMILES: [OH-].[Li+].[F:3][C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10]C)=[O:9])=[CH:6][C:5]=1[S:14]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)(=[O:16])=[O:15]>O.CO>[F:3][C:4]1[CH:13]=[CH:12][C:7]([C:8]([OH:10])=[O:9])=[CH:6][C:5]=1[S:14]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)(=[O:15])=[O:16]
Reactant: COC(=O)c1ccc(F)c(S(=O)(=O)N2CCOCC2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)c1ccc(F)c(S(=O)(=O)N2CCOCC2)c1
Reaction time: 4 h
Yield: 87.7 %

Procedure:
A solution of lithium hydroxide (1.56 g, 37.3 mmol) in water (5 mL) was added to a stirred solution of 4-fluoro-3-(morpholine-4-sulfonyl)-benzoic acid, methyl ester (Example 5, 2.26 g, 7.45 mmol) in methanol (50 mL) / water (10 mL) at 0° C. After 4 hours, the clear solution was quenched with aqueous hydrochloric acid (2M, 10 mL). Concentration in vacuo to remove the methanol afforded a white precipitate. Filtration and drying afforded the title compound as a white powder (1.89 g, 88% yield): 1HNMR (CDCl3) δ3.21 (td, J=7, 1.5 Hz, 4H), 3.75 (td, , J=7, 1.5 Hz , 4H), 3.98 (s, 3H), 7.28 (dd, J=18, 15 Hz, 1H), 8.28 (ddd, J=7, 5, 2 Hz, 1H), 8.51 (dd, J=7, 2 Hz, 1H): MS (ESI) [M−H]− at m/z 303.
Reaction SMILES: [F:1][C:2]([F:9])([F:8])[C:3]1[N:4]=[CH:5][NH:6][CH:7]=1.[H-].[Na+].Br[CH2:13][C:14]([O:16][CH3:17])=[O:15]>C1COCC1>[F:1][C:2]([F:9])([F:8])[C:3]1[N:4]=[CH:5][N:6]([CH2:13][C:14]([O:16][CH3:17])=[O:15])[CH:7]=1
Reactant: FC(F)(F)c1c[nH]cn1
Reactant: COC(=O)CBr
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)Cn1cnc(C(F)(F)F)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 254.7 %

Procedure:
To a solution of 4-(trifluoromethyl)-1H-imidazole (10.0 g, 73.5 mmol) in THF (75 mL) at 0° C. was added sodium hydride (60% in mineral oil, 3.25 g, 80.8 mmol) under nitrogen. The mixture was stirred at 0° C. for 30 min. Methyl bromoacetate (1.67 mL, 17.6 mmol) was added and the reaction was stirred for 3 h at room temperature. LC-MS showed the reaction was complete. The solvent was removed under reduced pressure. The crude material was redissolved in diethyl ether and washed with sat. aq. ammonium chloride and 1N HCl aqueous solution. The combined aqueous layer was reextracted with ethyl acetate three times. The combined organic layer was dried over MgSO4, filtered, and evaporated to a mixture of solid and oil. The crude was filtered to remove most of the oil, and the solid was washed with heptane. This yellow solid was triturated in a minimum amount of diethyl ether to wash off the yellow impurities. The material was filtered and the solid was retriturated with diethyl ether again. The filtrate was concentrated and the previous trituration steps were repeated. This afforded (I-36a) as a white solid (9.33 g, 61%); 1H NMR (400 MHz, CDCl3): δ 7.53 (1H), 7.30 (1H), 4.73 (2H), 3.81 (3H); m/z 209.0 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[S:14][CH:13]=[N:12][C:11]=2[NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:4][CH:3]=1.[Li]CCCC.[Cl:28]N1C(=O)CCC1=O>C1COCC1.CCCCCC>[Cl:28][C:13]1[S:14][C:10]([C:9]#[C:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[C:11]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:19])([CH3:21])[CH3:20])[N:12]=1
Reactant: CC(C)(C)OC(=O)Nc1ncsc1C#Cc1ccc(F)cc1
Reactant: O=C1CCC(=O)N1Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC(C)(C)OC(=O)Nc1nc(Cl)sc1C#Cc1ccc(F)cc1
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 78.8 %

Procedure:
2.63 g (8.26 mmol) of tert-butyl N-{5-[2-(4-fluorophenyl)ethynyl]-1,3-thiazol-4-yl}carbamate are dissolved in 100 ml of dry THF in a dried Schlenk flask under nitrogen and cooled to −78° C. 11 ml of a 15% solution of n-BuLi in n-hexane are then slowly added dropwise, and the mixture is stirred at −78° C. for 20 min. 1120 mg (8.38 mmol) of N-chlorosuccinimide dissolved in 1 ml of dry THF are subsequently added dropwise, and the mixture is stirred at −78° C. for 15 min, then quenched using 10 ml of n-butanol and warmed to RT. The solvent is removed in vacuo, and the residue is purified directly by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 99/1), giving 2.3 g (6.51 mmol, 78%) of tert-butyl N-{2-chloro-5-[2-(4-fluorophenyl)ethynyl]-1,3-thiazol-4-yl}-carbamate as beige solid from PE; ESI-MS: m/e: 353 ([M+H]+).
Reaction SMILES: [O:1]1[C@H:3]2[CH2:4][C@@H:5]3[C@@H:21]([C@@:22]4([CH3:28])[CH2:23][CH2:24][C@H:25]([OH:27])[CH2:26][C:2]124)[CH2:20][CH2:19][C@@:18]1([CH3:29])[C@H:6]3[CH2:7][CH2:8][C@@H:9]1[C@H:10]([CH3:17])[CH2:11][CH2:12][CH2:13][CH:14]([CH3:16])[CH3:15].[NH2:30][CH2:31][CH2:32][CH2:33][CH2:34][NH2:35].C(O)CCC>COC(C)(C)C>[OH:1][C@:2]12[CH2:26][C@@H:25]([OH:27])[CH2:24][CH2:23][C@:22]1([CH3:28])[C@@H:21]1[C@H:5]([C@H:6]3[C@:18]([CH3:29])([CH2:19][CH2:20]1)[C@@H:9]([C@H:10]([CH3:17])[CH2:11][CH2:12][CH2:13][CH:14]([CH3:16])[CH3:15])[CH2:8][CH2:7]3)[CH2:4][C@H:3]2[NH:30][CH2:31][CH2:32][CH2:33][CH2:34][NH2:35]
Reactant: NCCCCN
Reactant: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3C[C@@H]4OC45C[C@@H](O)CC[C@]5(C)[C@H]3CC[C@]12C
Solvent: COC(C)(C)C
Solvent: CCCCO
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3C[C@@H](NCCCCN)[C@@]4(O)C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: 25 °C
Yield: 60.8 %

Procedure:
5,6α-epoxicholestan-3β-ol (8.9 g, 22.1 mmol, 1 eq) and putrescine (3.9 g, 44.1 mmol, 2 eq) were charged in a round-bottomed flask equipped with a magnetic stirrer bar. 1-Butanol (70 ml, 5 vol) was added and the mixture heated to reflux for 40 h. The reaction mixture was cooled at r.t., diluted with methyl-tertbutyl-ether (5 vol) and washed with water (5 vol) and with brine (5 vol). The organic layer was passed through a silica pad (40 g) eluted with methyl-tertbutyl-ether (3 vol) then 10% Methanol/ethyl acetate (60 vol). Fractions of interest were pooled and the solvent was removed under reduced pressure to give 5α-Hydroxy-6β-(4-aminobutylamino)-cholestan-3β-ol as a white solid (6.6 g, 61%). In same conditions, use of ethanol as solvent (40 vol) and Ca(OTf)2 as catalyst gave a 19% yield.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([OH:11])=[CH:9][CH:10]=1)=[O:4].[C:12](Cl)(=[O:24])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21](Cl)=[O:22]>>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12](=[O:24])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([O:11][C:8]2[CH:7]=[CH:6][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:10][CH:9]=2)=[O:22])=[CH:7][CH:6]=1)=[O:4]
Reactant: COC(=O)c1ccc(O)cc1
Reactant: O=C(Cl)CCCCCCCCC(=O)Cl
Product: COC(=O)c1ccc(OC(=O)CCCCCCCCC(=O)Oc2ccc(C(=O)OC)cc2)cc1

Procedure:
A similar procedure to Example 1 is carried out by using 15.2 g of methyl p-hydroxybenzoate and 12 g of sebacic acid dichloride to yield di(p-methyloxycarbonylphenyl)sebacate, m.p. 109.5°-110.5° C., as white crystals.
Reaction SMILES: [O:1]1[CH2:4][CH:3]([CH:5]=O)[CH2:2]1.[CH3:7][C:8]([S@@:11]([NH2:13])=[O:12])([CH3:10])[CH3:9]>ClCCl.S([O-])([O-])(=O)=O.[Cu+2]>[O:1]1[CH2:4][CH:3](/[CH:5]=[N:13]/[S@:11]([C:8]([CH3:10])([CH3:9])[CH3:7])=[O:12])[CH2:2]1
Reactant: CC(C)(C)[S@@](N)=O
Reactant: O=CC1COC1
Agent: [Cu+2]
Agent: O=S(=O)([O-])[O-]
Solvent: ClCCl
Product: CC(C)(C)[S@](=O)/N=C/C1COC1
Temperature: 25 °C
Reaction time: 48 h
Yield: 29 %

Procedure:
In a round-bottomed flask, oxetane-3-carbaldehyde (452 mg, 3.15 mmol) was dissolved in dichloromethane (18 ml) and (S)-2-methylpropane-2-sulfinamide (435 mg, 3.59 mmol) and anhydrous copper (II) sulfate (1.11 g, 6.93 mmol) were added. The reaction mixture was stirred at room temperature for 48 h then filtered through a glass microfiber filter, rinsing with dichloromethane. The filtrate was concentrated and the residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc) to afford 173 mg (29%) of (S)-2-methyl-propane-2-sulfinic acid 1-oxetan-3-yl-meth-(E)-ylideneamide as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.28 (d, J=4.9 Hz, 1H), 4.74-5.00 (m, 4H), 4.00-4.19 (m, 1H), 1.23 (s, 9H).
Reaction SMILES: [CH:1]([C:3]1[N:10]2[C:6]([S:7][C:8]([C:11]3[C@H:12]([CH3:35])[C@@H:13]4[C@@H:30]([C@H:31]([OH:33])[CH3:32])[C:29](=[O:34])[N:14]4[C:15]=3[C:16]([O:18]CC3C=CC([N+]([O-])=O)=CC=3)=[O:17])=[CH:9]2)=[CH:5][N:4]=1)=[O:2].F[C:37](F)(F)S(OC)(=O)=O>ClCCl>[CH:1]([C:3]1[N:4]([CH3:37])[CH:5]=[C:6]2[N+:10]=1[CH:9]=[C:8]([C:11]1[C@H:12]([CH3:35])[C@@H:13]3[C@@H:30]([C@H:31]([OH:33])[CH3:32])[C:29](=[O:34])[N:14]3[C:15]=1[C:16]([O-:18])=[O:17])[S:7]2)=[O:2]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(c3cn4c(C=O)ncc4s3)[C@H](C)[C@H]12
Reactant: COS(=O)(=O)C(F)(F)F
Solvent: ClCCl
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(c3c[n+]4c(C=O)n(C)cc4s3)[C@H](C)[C@H]12
Reaction time: 5 h

Procedure:
To a suspension of 33 mg of 4-nitrobenzyl (1S,5R,6S)-2-(5-formylimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in 1 ml of dichloromethane was added 0.017 ml of methyl trifluoromethanesulfonate under ice-cooling. The mixture was stirred for 5 hours, and concentrated under reduced pressure. The residual concentrate was dissolved in 2 ml of THF and 2 ml of 1/15 M sodium phosphate buffer (pH 6.6), and 47 mg of 10% Pd-C was added therto. The reactor was purged with hydrogen, and the reaction mixture was stirred at room temperature for 2 hours. The catalyst was collected by filtration on Celite, and washed with water. The filtrate was washed with ethyl acetate, and the aqueous layer was purified by column chromatography on DIAION HP-20 (20% methanol in water) and on COSMOSEAL 40C18-PREP (water:methanol=10:1) to give 2.5 mg of the title compound.
Reaction SMILES: [CH2:1]([O:7][C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1[O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH:11]=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C([O-])(=O)C.[NH4+].[N+:28]([CH3:31])([O-:30])=[O:29]>>[N+:28]([CH:31]=[CH:11][C:10]1[CH:13]=[CH:14][C:15]([O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[C:8]([O:7][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH:9]=1)([O-:30])=[O:29]
Reactant: C[N+](=O)[O-]
Reactant: CCCCCCOc1ccc(C=O)cc1OCCCCCC
Agent: CC(=O)[O-]
Agent: [NH4+]
Product: CCCCCCOc1ccc(C=C[N+](=O)[O-])cc1OCCCCCC

Procedure:
3,4-Dihexyloxybenzaldehyde (122.6 g; 0.4 mmol) is heated to 100° C. with ammonium acetate (23.12 g; 0.3 mol) and nitromethane (42.7 g; 0.7 mol). Working-up is analogous to Example 6b).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][N:11]([C:13]([CH3:18])([CH3:17])[C:14](O)=[O:15])[CH:12]=2)=[CH:4][C:3]=1[O:19][CH:20]([C:22]1[C:27]([Cl:28])=[CH:26][CH:25]=[C:24]([F:29])[C:23]=1[Cl:30])[CH3:21].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[CH3:45][N:46]([CH3:51])[CH2:47][CH2:48][CH2:49][NH2:50]>CN(C=O)C>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][N:11]([C:13]([CH3:18])([CH3:17])[C:14]([NH:50][CH2:49][CH2:48][CH2:47][N:46]([CH3:51])[CH3:45])=[O:15])[CH:12]=2)=[CH:4][C:3]=1[O:19][CH:20]([C:22]1[C:27]([Cl:28])=[CH:26][CH:25]=[C:24]([F:29])[C:23]=1[Cl:30])[CH3:21]
Reactant: CN(C)CCCN
Reactant: CC(Oc1cc(-c2cnn(C(C)(C)C(=O)O)c2)cnc1N)c1c(Cl)ccc(F)c1Cl
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: CC(Oc1cc(-c2cnn(C(C)(C)C(=O)NCCCN(C)C)c2)cnc1N)c1c(Cl)ccc(F)c1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 14.4 %

Procedure:
To a solution of 2-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-2-methyl-propionic acid (1.00 g, 2.20 mmol) in DMF (5.5 mL) were added HOBT (300 mg, 2.20 mmol), EDC (633 mg, 3.30 mmol), and N,N-dimethyl-propane-1,3-diamine (225 mg, 2.20 mmol). The reaction was stirred overnight at room temperature. The reaction was then purified by reversed phase C-18 prep HPLC eluting with acetonitrile/water with 0.1% acetic acid to afford 2-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-N-(3-dimethylamino-propyl)-isobutyramide (170 mg, 14% yield).
Reaction SMILES: [Cl:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([N+:11]([O-:13])=[O:12])=[CH:8][CH:9]=2)[N-:4][N:3]=1.[Na+].[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:24]=[CH:25][C:26]=1[CH2:27]Br)[C:20]([O:22][CH3:23])=[O:21]>CO>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([N+:11]([O-:13])=[O:12])=[CH:8][CH:9]=2)[N:4]([CH2:27][C:26]2[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][C:17]=2[O:16][CH3:15])[N:3]=1
Reactant: COC(=O)c1ccc(CBr)c(OC)c1
Reactant: O=[N+]([O-])c1ccc2c(Cl)n[n-]c2c1
Agent: [Na+]
Solvent: CO
Product: COC(=O)c1ccc(Cn2nc(Cl)c3ccc([N+](=O)[O-])cc32)c(OC)c1
Yield: 70 %

Procedure:
A mixture of 2.19 g. of sodium 3-chloro-6-nitroindazolide in 50 ml. methanol was stirred with 2.85 g methyl 3-methoxy-4-bromomethylbenzoate for 2 hours. After addition of 150 ml. water, the resultant precipitate was collected and recrystallised from ethyl acetate to give methyl 4-[3-chloro-6-nitroindazol-1-ylmethyl]-3-methoxybenzoate in 70% yield as a solid, m.p. 167°-168.5° C. A mixture of 1.25 g. of this solid was hydrogenated in the presence of 385 mg. 5% w/w palladium on calcium carbonate in 20 ml. ethyl acetate and 20 ml. methanol for 3 hours at a pressure of 1.1 bar. The catalyst was removed by filtration through diatomaceous earth. The filtrate was concentrated to low volume in vacuo and the residue (ca 3 ml.) was diluted with ether and petroleum ether (b.p. 40°-60° C.) and cooled to -20° C. The precipitated solid was collected and dried at 80° C. to give the ester L in 90% yield, m.p. 131°-131.5° C.
Reaction SMILES: [CH3:1][NH:2][C:3](C1N(CC2N3C=C(C)C=CC3=NC=2C2C=CC(C)=CC=2)N=CN=1)=O.[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2[N:36]=[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][N:38]3[C:43]=2[CH2:44][N:45]2[C:49]([C:50](OC)=[O:51])=[N:48][CH:47]=[N:46]2)=[CH:31][CH:30]=1.CNC>>[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([C:35]2[N:36]=[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][N:38]3[C:43]=2[CH2:44][N:45]2[C:49]([C:50]([N:2]([CH3:3])[CH3:1])=[O:51])=[N:48][CH:47]=[N:46]2)=[CH:33][CH:34]=1
Reactant: CNC(=O)c1ncnn1Cc1c(-c2ccc(C)cc2)nc2ccc(C)cn12
Reactant: COC(=O)c1ncnn1Cc1c(-c2ccc(Cl)cc2)nc2ccccn12
Agent: CNC
Product: CN(C)C(=O)c1ncnn1Cc1c(-c2ccc(Cl)cc2)nc2ccccn12

Procedure:
The title compound was prepared according to the procedure described for compound 68 from methyl 1-((2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)methyl)-1H-1,2,4-triazole-5-carboxylate and dimethylamine. 1H-NMR (400 MHz, CDCl3, δ) 8.21 (d, J=6.9 Hz, 1H), 7.97 (s, 1H), 7.71 (d, J=9.2 Hz, 1H), 7.68 (d, J=8.5 Hz, 2H), 7.49 (d, J=8.4 Hz, 1H), 7.34 (m, 1H), 6.94 (m, 1H), 5.80 (s, 2H), 3.21 (s, 3H), 3.13 (s, 3H) ppm; m/e 241, 243.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][NH:15]C(=O)C(F)(F)F)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][NH2:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCCC[C@H]1CNC(=O)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCCCC1CN
Reaction time: 16 h
Yield: 70.2 %

Procedure:
(S)-2-[(2,2,2-Trifluoro-ethanoylamino)-methyl]-piperidine-1-carboxylic acid tert butyl ester (18.2 g) was dissolved in methanol (500 ml) and treated with potassium carbonate (16.1 g). After stirring for 16 h solvent was removed at reduced pressure and the residue partitioned between dichloromethane/water. The organic phase was separated, washed with brine, dried and solvent removed at reduced pressure. the residue was column chromatographed (silica gel, 0-10% (9:1 methanol/ammonia) in dichloromethane eluant) to give the title compound (8.82 g) of description 1.