Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([OH:8])([OH:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:9]1(O)CCCCC1.COC1CCCCC1O.C1(O)C=CC=CC=1.C1(OC)C(=CC=CC=1)O>CO>[CH3:9][O:7][C:1]1([OH:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: OC1CCCCC1
Reactant: OC1(O)CCCCC1
Agent: COC1CCCCC1O
Agent: COc1ccccc1O
Solvent: CO
Solvent: Oc1ccccc1
Product: COC1(O)CCCCC1

Procedure:
Ruthenium Catalyzed Hydrogenations. For guaiacol hydrogenation in the presence of ruthenium catalyst the products were similar to those identified earlier in our laboratory. At 150° C., 30% of the guaiacol had already been converted by the time the reactor reached temperature, time zero in FIG. 1. The primary product was that resulting from saturation of the phenolic ring, 2-methoxycyclohexanol (60% yield @ 4 h). Cyclohexanediol was the secondary product (11%), although cyclohexanol was also significant (6%). The methanol byproduct was found (1%). There was little phenol formed at this temperature. At 200° C. the initial conversion of guaiacol during heatup was 44%. As shown in FIG. 2 the methoxycyclohexanols were still the main product (54% yield @ 4 h), but cyclohexanediol became less important (4%) while more cyclohexanol was formed (12%). More methanol was present (2%), as was more phenol. At 250° C., 60% of the guaiacol was converted by the time the reactor reached temperature. As shown in FIG. 3 cyclohexanol almost surpassed methoxycyclohexanols as the main product. Methoxycyclohexanol yield peaked at 17% in the 1 to 2 h range before reacting on to secondary products. The maximum cyclohexanol yield was 13%. Cyclohexanediol was only a minor product (1%). More phenol was evident and cyclohexane became a significant product (2%); however, the hexane recovery is likely limited by its low solubility in the water. More cyclohexane may have been actually produced and remained in the reactor as a separate light phase, which could not be sampled by our method. Over the period of the test, the amount of aqueous phase products is reduced. A large methane gas product was produced in this test, as has been reported for processing at these conditions of temperature and catalyst wherein phenol was extensively gasified at as low as 250° C.xi At 300° C., phenol is the primary product that was recoverable. Cyclohexanol and methoxycyclohexanol are early products which are reduced to low levels within the first hour at temperature. All three isomers of methyl-phenol (cresols) are significant byproducts, as is benzene. Cyclohexane is present in the water product only at low concentration, but is likely present as a significant product in a separate phase. Because of the large amount of methane gas formation, this test was hydrogen limited with the reactor pressure surpassing the pressure set point after 1 h of operation and this factor is expected to have skewed the mechanism away from the high-use hydrogenation pathways, such as saturation of the aromatic ring. xiElliott, D. C.; Hart, T. R.; Neuenschwander, G. G. “Chemical Processing in High-Pressure Aqueous Environments. 8. Improved Catalysts for Hydrothermal Gasification.” Ind Eng. Chem. Res. 45(11) 3776-81, 2006.
Reaction SMILES: [CH2:1]1[CH2:8][NH:7][S:4](=[O:6])(=[O:5])[CH2:3][CH2:2]1.Br[C:10]1[N:19]=[C:18]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[O:21])[C:17]([OH:31])=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2>N1C=CC=CC=1>[O:5]=[S:4]1(=[O:6])[CH2:3][CH2:2][CH2:1][CH2:8][N:7]1[C:10]1[N:19]=[C:18]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[O:21])[C:17]([OH:31])=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2
Reactant: O=S1(=O)CCCCN1
Reactant: O=C(NCc1ccc(F)cc1)c1nc(Br)c2cccnc2c1O
Solvent: c1ccncc1
Product: O=C(NCc1ccc(F)cc1)c1nc(N2CCCCS2(=O)=O)c2cccnc2c1O
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a mixture of 1,4 butanesultam (prepared as in White et al, J. Org Chem. 1987, 52: 2162) (1.00 g, 7.40 mmol), 5-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide (3.06 g, 8.14 mmol), and Cu2O (1.06 g, 7.40 mmol) under an atmosphere of argon was added pyridine (50 mL), and the suspension was stirred at reflux for 16 hr. The reaction was allowed to cool to room temperature and filtered to remove the solids. The solids were washed with chloroform (500 mL). The resulting filtrate was evaporated to dryness and the residue was dissolved in chloroform (1L) and vigorously stirred with a slurry of EDTA (4.0 g) in water (150 mL). After a period of 16 hr, the chloroform extracts were dried (Na2SO4) and evaporated in vacuo. The residue was purified by reverse phase HPLC. (Waters PrePak 500 cartridge C18, Gradient elution with Water:Acetonitrile 95:5 to 5:95 with 0.1% TFA at 75 mL/min over 45 mins). Lyophilization of the pure fractions afforded the title compound as an off-white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([Si:13]([CH3:16])([CH3:15])[CH3:14])[C:3]=1[C:4]([NH:6][CH2:7][CH3:8])=[O:5].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Cl[CH2:28][S:29][CH3:30]>C1COCC1>[Cl:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([Si:13]([CH3:15])([CH3:14])[CH3:16])[C:3]=1[C:4]([N:6]([CH2:7][CH3:8])[CH2:28][S:29][CH3:30])=[O:5]
Reactant: CSCCl
Reactant: CCNC(=O)c1c(Cl)cccc1[Si](C)(C)C
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: CCN(CSC)C(=O)c1c(Cl)cccc1[Si](C)(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 44.6 %

Procedure:
To a solution of 2.0 g (7.8 mmol) of the compound of Example 45 in 30 mL dry THF was added 7.9 mL (7.9 mmol) sodium bis(trimethylsilyl)amide (1.0 M in THF). To the resulting mixture was added 1.0 g (10.4 mmol) chloromethyl methylsulfide. The mixture was stirred for 15 min and another 0.65 g (6.7 mmol) of chloromethyl methylsulfide was added. Stirring at RT was continued for 1 h and the mixture was then heated to reflux for 28 hours. The mixture was allowed to cool to RT and was then partitioned between ether and water. The organic layer was washed with brine, dried (MgSO4), and was filtered through silica gel. The filtrate was evaporated in vacuo and the residue was chromatographed (HPLC, 8% ethyl acetate/hexane) to yield 1.1 g (45%) of a colorless oil. nD25=1.5526.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:16]=[CH:15][C:7]([CH2:8][C@@H:9]([C:11]([O:13][CH3:14])=[O:12])[NH2:10])=[CH:6][CH:5]=1.C(N(CC)CC)C.[O:24]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[CH:26]=[C:25]1[C:33](O)=[O:34].CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[O:24]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[CH:26]=[C:25]1[C:33]([NH:10][C@H:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8][C:7]1[CH:6]=[CH:5][C:4]([O:3][CH3:2])=[CH:16][CH:15]=1)=[O:34]
Reactant: COC(=O)[C@@H](N)Cc1ccc(OC)cc1
Reactant: O=C(O)c1cc2ccccc2o1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@H](Cc1ccc(OC)cc1)NC(=O)c1cc2ccccc2o1
Yield: 94.6 %

Procedure:
The same procedures as in Example 2 were carried out from the compound obtained in Example 33 (2.5 g), triethylamine (1.7 mL), benzofuran-2-carboxylic acid (2.0 g), WSC.HCl (2.3 g), and methylene chloride (70 mL), to give the captioned compound (3.4 g, 96%) as an oily product.
Reaction SMILES: [C:1]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]=[CH:5][C:4](B(O)O)=[CH:3][CH:2]=1.[F:16][C:17]1[CH:18]=[C:19]([CH:29]([NH:31][C:32]([C:34]2[N:35]=[C:36](Cl)[O:37][CH:38]=2)=[O:33])[CH3:30])[CH:20]=[C:21]([F:28])[C:22]=1[NH:23][S:24]([CH3:27])(=[O:26])=[O:25].C([O-])([O-])=O.[Cs+].[Cs+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:28][C:21]1[CH:20]=[C:19]([CH:29]([NH:31][C:32]([C:34]2[N:35]=[C:36]([C:4]3[CH:5]=[CH:6][C:1]([C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=4)=[CH:2][CH:3]=3)[O:37][CH:38]=2)=[O:33])[CH3:30])[CH:18]=[C:17]([F:16])[C:22]=1[NH:23][S:24]([CH3:27])(=[O:26])=[O:25]
Reactant: OB(O)c1ccc(-c2ccccc2)cc1
Reactant: CC(NC(=O)c1coc(Cl)n1)c1cc(F)c(NS(C)(=O)=O)c(F)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: CC(NC(=O)c1coc(-c2ccc(-c3ccccc3)cc2)n1)c1cc(F)c(NS(C)(=O)=O)c(F)c1
Yield: 30.9 %

Procedure:
4-Biphenylboronic acid (51.5 mg, 0.26 mmol) and 2-chloro-oxazole-4-carboxylic acid [1-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-amide (50 mg, 0.13 mmol) was reacted using Pd(PPh3)2Cl2 (7 mg, 0.01 mmol), Cs2CO3 (127 mg, 0.39 mmol) as described above to give the title compound (20 mg, 31%) after purification by flash chromatography on silica gel (hexane: EtOAc=1:1).
Reaction SMILES: [CH3:1][N+:2]([CH2:5][C@H:6]([NH2:11])[CH2:7][C:8]([O-:10])=[O:9])([CH3:4])[CH3:3].C(N(C(C)C)CC)(C)C.[N:21]([C:24]1[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])=[CH:26][CH:25]=1)=[C:22]=[O:23]>CO>[CH2:30]([C:27]1[CH:26]=[CH:25][C:24]([NH:21][C:22](=[O:23])[NH:11][C@@H:6]([CH2:5][N+:2]([CH3:3])([CH3:4])[CH3:1])[CH2:7][C:8]([O-:10])=[O:9])=[CH:29][CH:28]=1)[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]
Reactant: C[N+](C)(C)C[C@H](N)CC(=O)[O-]
Reactant: CCCCCCCCc1ccc(N=C=O)cc1
Solvent: CO
Solvent: CCN(C(C)C)C(C)C
Product: CCCCCCCCc1ccc(NC(=O)N[C@H](CC(=O)[O-])C[N+](C)(C)C)cc1
Reaction time: 18 h

Procedure:
To a solution of (R)-aminocarnitine (22 mg, 0.14 mmol) and diisopropylethylamine (71 uL, 0.41 mmol) in MeOH (2 mL) was added 1-isocyanato-4-octylbenzene (63 uL, 0.27 mmol) and the reaction stirred for 18 h. The MeOH was removed in vacuo and the residue stirred with 1:1 ether/EtOAc. Impurities dissolved into the ether/EtOAc which were discarded and the remaining material taken up into 90:10 CH2Cl2/MeOH and then loaded onto a short SiOH plug. The title compound was eluted by increasing MeOH content in 10% steps to 60%. The compound was then taken up into 90:10 CH2Cl2/MeOH and filtered through a plug of celite which gave after drying the title compound as a white powder (9 mg, 17%). 1H NMR (400 MHz, CD3OD) δ 7.27 (d, 2H, J=8.4 Hz), 7.09 (d, 2H, J=8.4 Hz), 4.73-4.71 (m, 1H), 3.78-3.53 (m, 2H), 3.25 (s, 9H), 2.75-2.72 (m, 2H), 2.55 (t, 2H, J=8.0 Hz), 1.60-1.29 (m, 12H), 0.90 (t, 3H, J=6.8 Hz); MS ESI 392.3 [M+H]+, calcd for [C22H37N3O3+H]+ 392.55.
Reaction SMILES: [Cl-].[NH4+].[Br:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]([CH3:14])[CH2:11][CH2:12][OH:13])=[C:6]([N+:15]([O-])=O)[CH:5]=1>O.CCOC(C)=O.[Fe]>[NH2:15][C:6]1[CH:5]=[C:4]([Br:3])[CH:9]=[CH:8][C:7]=1[N:10]([CH3:14])[CH2:11][CH2:12][OH:13]
Reactant: CN(CCO)c1ccc(Br)cc1[N+](=O)[O-]
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCOC(C)=O
Product: CN(CCO)c1ccc(Br)cc1N
Temperature: 25 °C
Yield: 76.3 %

Procedure:
Iron (1.5 g, 26.2 mmol) and ammonium chloride (0.39 g, 1.0 eq) in water (8 mL) was heated to reflux for 0.5 hours. 2-((4-bromo-2-nitrophenyl)(methyl)amino)ethanol (25B) (2.0 g, 7.27 mmol) was slowly added. The reaction mixture was heated to reflux for 14 hours, cooled to rt, diluted with water and EtOAc and filtered through Celite. The aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel eluting with a gradient of PE:EtOAc 60:40-40:60, to provide 1.36 g (76%) of the desired product 2-((2-amino-4-bromophenyl)(methyl)amino)ethanol (25C): 1H NMR (300 MHz, CDCl3) δ 6.92-6.82 (3H, m), 3.68 (2H, t), 3.04 (2H, t), 2.70 (3H, s).
Reaction SMILES: Cl[C:2]1[C:7]([C:8](=[O:10])[CH3:9])=[C:6]([O:11][C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=2)[N:5]=[CH:4][N:3]=1.[CH:22]([C:25]1[N:29]=[C:28]([CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[O:27][N:26]=1)([CH3:24])[CH3:23].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH:22]([C:25]1[N:29]=[C:28]([CH:30]2[CH2:35][CH2:34][N:33]([C:2]3[C:7]([C:8](=[O:10])[CH3:9])=[C:6]([O:11][C:12]4[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=4)[N:5]=[CH:4][N:3]=3)[CH2:32][CH2:31]2)[O:27][N:26]=1)([CH3:24])[CH3:23]
Reactant: CC(=O)c1c(Cl)ncnc1Oc1ccc(S(C)(=O)=O)cc1
Reactant: CC(C)c1noc(C2CCNCC2)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(=O)c1c(Oc2ccc(S(C)(=O)=O)cc2)ncnc1N1CCC(c2nc(C(C)C)no2)CC1
Yield: 19.6 %

Procedure:
To a solution of 1-[4-chloro-6-(4-methanesulfonyl-phenoxy)-pyrimidin-5-yl]-ethanone (0.21 mmol, 70 mg) and 4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidine (0.21 mmol, 49 mg) in N,N-dimethyl formamide (500 uL) was added potassium carbonate (0.21 mmol, 29 mg). The mixture was microwaved at 100° C. for 150 seconds. Its progress was monitored by thin layer chromatography and LCMS. The reaction was treated with water and the desired compound was extracted in ethyl acetate. Organic layer was evaporated in vacuo. Purification by HPLC provided Compound A165 as a white solid (20 mg, 20%). 1H-NMR (400 MHz, CDCl3) δ(ppm): 8.24 (s, 1H); 8.01 (d, 2H); 7.32 (d, 2H); 4.02 (m, 2H); 3.22 (m, 3H); 3.10 (m, 1H); 3.08 (s, 3H); 2.69 (s, 3H), 2.18 (m, 2H), 2.02 (m, 2H); 1.35 (d, 6H). LCMS (ESI), m/z 486.3 (M+H+, 100%).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[Cl:6][C:7]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][C@H:29]([OH:32])[CH2:30][OH:31])=[CH:23][C:8]=1[C:9]([NH:11][CH2:12][C:13]12[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH2:14]1)[CH2:20]2)=[O:10].C(N(CC)CC)C>ClCCl>[Cl:6][C:7]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][C@H:29]([OH:32])[CH2:30][O:31][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:23][C:8]=1[C:9]([NH:11][CH2:12][C:13]12[CH2:20][CH:19]3[CH2:18][CH:17]([CH2:16][CH:15]([CH2:21]3)[CH2:14]1)[CH2:22]2)=[O:10]
Reactant: CS(=O)(=O)Cl
Reactant: O=C(NCC12CC3CC(CC(C3)C1)C2)c1cc(CC[C@H](O)CO)ccc1Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OC[C@@H](O)CCc1ccc(Cl)c(C(=O)NCC23CC4CC(CC(C4)C2)C3)c1

Procedure:
Methanesulfonylchloride (0.08 mL) was added to a solution of 2-chloro-5-[(3S)-3,4-dihydroxybutyl]-N-(tricyclo(3.3.1.13,7]dec-1-ylmethyl)benzamide (Example 1b) (0.33 g) and triethylamine (0.33 ml) in dichloromethane (10 mL). After 1 hour the reaction mixture was concentrated, redissolved in ethyl acetate and the organic layer washed with water, brine, dried over anhydrous magnesium sulfate, filtered and evaporated. Purification by normal phase HPLC (gradient 0–5% ethanol (EtOH) in dichloromethane on silica Novapak™ column), gave the sub-titled compound (0.14 g).
Reaction SMILES: [C:1]([C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:17]=1[NH:16][CH:15]=[C:14]2Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(=O)(O)(O)[OH:20]>>[C:1]([C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:17]=1[NH:16][C:15](=[O:20])[CH2:14]2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(c1ccccc1)c1cccc2c(Cl)c[nH]c12
Reactant: O=P(O)(O)O
Product: O=C1Cc2cccc(C(=O)c3ccccc3)c2N1

Procedure:
The process as defined in claim 7 wherein 7-benzoyl-3-chloro-indole is hydrolyzed with phosphoric acid in a solvent at reflux temperature to produce 7-benzoylindolin-2-one.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]2.C1([O:19][C:20](=O)[NH:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=2)C=CC=CC=1>CS(C)=O>[OH:12][CH:9]1[CH2:10][C:11]2[C:2]([NH:1][C:20]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:30])([F:31])[F:32])=[CH:24][CH:23]=3)=[O:19])=[CH:3][CH:4]=[CH:5][C:6]=2[CH2:7][CH2:8]1
Reactant: Nc1cccc2c1CC(O)CC2
Reactant: O=C(Nc1ccc(OC(F)(F)F)cc1)Oc1ccccc1
Solvent: CS(C)=O
Product: O=C(Nc1ccc(OC(F)(F)F)cc1)Nc1cccc2c1CC(O)CC2
Temperature: 100 °C
Reaction time: 1.5 h
Yield: 21.2 %

Procedure:
A mixture of 8-amino-1,2,3,4tetrahydro-naphthalen-2-ol (32.6 mg, 0.20 mmol) and (4trifluoromethoxy-phenyl)-carbamic acid phenyl ester (59.5 mg, 0.20 mmol) in DMSO (1.0 ml) was stirred at 100° C. for 1.5 hours. The mixture-was concentrated under reduced pressure, and then purified by preparatory HPLC to obtain N-(7-hydroxy-5,6,7,8-tetrahydro-naphthalen-1-yl)-N′-(4-trifluoromethoxy-phenyl)-urea (15.5 mg, 21% yield).
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH2:4][CH:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[OH:6].F[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:20]>CN1CCN(C)C1=O>[CH3:1][NH:2][CH2:3][CH2:4][CH:5]([O:6][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:20])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: Cc1ccccc1F
Reactant: CNCCC(O)c1ccccc1
Solvent: CN1CCN(C)C1=O
Product: CNCCC(Oc1ccccc1C)c1ccccc1

Procedure:
reacting an alkoxide of N-methyl-3-phenyl-3-hydroxypropylamine with 2-fluorotoluene in 1,3-dimethyl-2-imidazolidinone to give N-methyl-3-(2-methylphenoxy)-3-phenylpropylamine;
Reaction SMILES: [C:1]1([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]=[C:9]([CH2:17][CH2:18][C:19]([OH:21])=[O:20])[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)O.N.[CH2:28](O)[CH3:29]>O>[C:1]1([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]=[C:9]([CH2:17][CH2:18][C:19]([O:21][CH2:28][CH3:29])=[O:20])[N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCO
Reactant: O=C(O)CCc1cc2ccccc2c(-c2ccccc2)n1
Agent: N
Agent: O=S(=O)(O)O
Solvent: O
Product: CCOC(=O)CCc1cc2ccccc2c(-c2ccccc2)n1

Procedure:
1-Phenyl-3-isoquinolinepropanoic acid (2 g) and concentrated sulphuric acid (2 cc) in absolute ethanol (20 cc) are stirred for 20 hours at room temperature (approximately 20° C.). The mixture is diluted with water (100 cc), alkalinised to pH 9 with concentrated ammonia solution and extracted with methylene chloride (3×50 cc). The organic phase is dried over magnesium sulphate, filtered and evaporated to dryness under reduced pressure. Ethyl 1-phenyl-3-isoquinolinepropionate (1.9 g) is obtained in the form of an oil, the proton NMR spectrum of which, in deuterated chloroform, has the following characteristics:
Reaction SMILES: O.C(=O)([O-])[O-].[Na+].[Na+].O.CC1(C)C(C)(C)OB([C:17]2[CH:29]=[CH:28][C:20]3[N:21]=[C:22]([NH:24][C:25](=[O:27])[CH3:26])[S:23][C:19]=3[CH:18]=2)O1.Br[C:32]1[CH:33]=[C:34]([O:38][CH2:39][CH2:40][NH:41][C:42](=[O:46])[CH2:43][O:44][CH3:45])[CH:35]=[N:36][CH:37]=1>[Pd].C1COCC1>[C:25]([NH:24][C:22]1[S:23][C:19]2[CH:18]=[C:17]([C:32]3[CH:33]=[C:34]([O:38][CH2:39][CH2:40][NH:41][C:42](=[O:46])[CH2:43][O:44][CH3:45])[CH:35]=[N:36][CH:37]=3)[CH:29]=[CH:28][C:20]=2[N:21]=1)(=[O:27])[CH3:26]
Reactant: CC(=O)Nc1nc2ccc(B3OC(C)(C)C(C)(C)O3)cc2s1
Reactant: COCC(=O)NCCOc1cncc(Br)c1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COCC(=O)NCCOc1cncc(-c2ccc3nc(NC(C)=O)sc3c2)c1
Reaction time: 0.17 h
Yield: 26 %

Procedure:
A Biotage high recovery microwave vessel was charged with sodium carbonate hydrate (0.048 g, 0.38 mmol), 0.15 mL water and a stirbar. The slurry was sonicated and stirred for 10 minutes. An inert atmosphere inlet was placed over the vessel and the remaining reagents were added under a flow of nitrogen. To the vessel was added N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-yl)acetamide (0.043 g, 0.14 mmol), 100 mg Pd FibreCat® palladium catalyst, and N-(2-(5-bromopyridin-3-yloxy)ethyl)-2-methoxyacetamide (0.0247 g, 0.085 mmol) dissolved in 1 mL THF. The vessel was sealed, and irritated using a Biotage personal chemistry microwave reactor to 130° C. for 25 minutes. The cooled reaction was diluted with 5 mL THF, and filtered through a 0.22 μm PTFE membrane. The catalyst was washed with THF (2×5 mL), and the combined filtrates were concentrated in vacuo. The residue was sonicated in 2 mL water, and filtered. The precipitate was then dissolved in 3 mL MeOH, filtered, and concentrated in vacuo. The crude was purified using a 19×150 mm Waters Xterra Prep C18 OBD column (100 Å pore diameter, 5 μm particle size, spherical shape, PN 186002381; Gradient: 0→5 min@20 mL/min, 10% B; 5.0→35 min@20 mL/min, linear gradient to 40% B; 35→45@20 mL/min, isocratic at 40% B, 45→55 min@20 mL/min, step to 100% B; 55→60 min@20 mL/min, step to 10% B; 60 min end; A=10.7 mM NH4HCO3 in water, pH adjusted to 8.6 with concentrated NH4OH; B acetonitrile). A band that eluted from 24.2 to 26.0 minutes was isolated. The solvent was removed in vacuo to afford N-(2-(5-(2-(N-actyl)aminobenzo[d]thiazol-6-yl)pyridin-3-yloxy)ethyl)-2-methoxyacetamide. (0.0090 g, 26% yield). 1H NMR (400 MHz, DMF) δ ppm 2.34 (s, 3H) 3.37 (s, 3H) 3.70 (q, J=5.84 Hz, 2H) 3.89 (s, 2H) 4.35 (t, J=5.97 Hz, 2H) 7.81 (dd, J=2.54, 1.96 Hz, 1H) 7.83 (s, 1H) 7.85 (s, 1H) 7.86-7.90 (m, J=8.41, 1.86 Hz, 1H) 8.32 (d, J=2.25 Hz, 1H) 8.47 (d, J=1.47 Hz, 1H) 8.62 (br. s., 1H) 12.35 (br. s., 1H). 13C NMR (101 MHz, DMF) δ ppm 22.46 (s, 1 C) 38.02 (s, 1 C) 58.54 (s, 1 C) 66.92 (s, 1 C) 71.91 (s, 1 C) 118.91 (s, 1 C) 120.35 (s, 1 C) 121.07 (s, 1 C) 125.49 (s, 1 C) 132.82 (s, 1 C) 133.22 (s, 1 C) 136.79 (s, 1 C) 137.04 (s, 1 C) 140.37 (s, 1 C) 149.26 (s, 1 C) 155.35 (s, 1 C) 159.21 (s, 1 C) 169.69 (s, 1 C) 169.72 (s, 1 C). HPLC-MS: retention time=1.12 min (99.3%@215 nm; 98.1% @254 nm; m/z=401.1, calculated for C19H20N4O4S+H+=401.1).
Reaction SMILES: [OH:1][CH:2]([C:19]1[S:20][CH:21]=[CH:22][CH:23]=1)[C:3]([NH:5][CH:6]1[C:17](=[O:18])[N:8]2[C:9]([C:14]([O-:16])=[O:15])=[C:10]([CH3:13])[CH2:11][S:12][C@H:7]12)=[O:4].FC(F)(F)C(O)=O>C1(OC)C=CC=CC=1>[OH:1][CH:2]([C:19]1[S:20][CH:21]=[CH:22][CH:23]=1)[C:3]([NH:5][CH:6]1[C:17](=[O:18])[N:8]2[C:9]([C:14]([OH:16])=[O:15])=[C:10]([CH3:13])[CH2:11][S:12][C@H:7]12)=[O:4]
Reactant: CC1=C(C(=O)[O-])N2C(=O)C(NC(=O)C(O)c3cccs3)[C@H]2SC1
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Product: CC1=C(C(=O)O)N2C(=O)C(NC(=O)C(O)c3cccs3)[C@H]2SC1
Yield: 90.6 %

Procedure:
Diphenylmethyl (6R,7R,2'R and S)-7-(2'-hydroxy-2'-[thien-2-yl]-acetamido)-3-methylceph-3-em-4-carboxylate (543mg, 1.05mmole) was dissolved in anisole (4ml) and stirred with trifluoroacetic acid (4 ml) at +20° to +25° for 7 mins. The anisole and trifluoroacetic acid were evaporated and the residue partitioned between 3%-aqueous sodium bicarbonate solution (ca 50ml) and ethyl acetate (ca 50ml). The aqueous layer was washed with ethyl acetate (3xca 50ml), layered with ethyl acetate and adjusted to pH 2.5. The ethyl acetate layer was combined with the ethyl acetate backwash of the aqueous layer, dried, and evaporated to give (6R,7R,2'R and S)-7-(2'-hydroxy-2'-[thien-2-yl] -acetamido)- 3-methylceph-3-em-4-carboxylic acid as a foam (337mg, 91%). This foam was dissolved in acetone (3ml) and stirred with a solution of sodium 2-ethylhexanoate (186mg, 1.05mmole) in acetone (2ml) and ether (2ml). The precipitated material was filtered off, washed with ether, and dried to give the title compound containing 2mole-equivalents of water (i.r., microanalysis) and one-sixth mole-equivalents of ether (n.m.r., microanalysis) as a pale-brown solid (183mg, 0.486 mmole, 46.4%); λmax (pH6-buffer) 237.5nm, inflexion at 255nm (ε12,640 and 9,250 respectively); νmax (nujol) 3380 (NH,H2O), 1760 (azetidin-2-one), 1680 and 1528 (CONH), and 1600 cm-1 (CO2 -); τ (Me2SO-D6) 1.48 and 1.63 (total 1H, 2d,J9Hz,NH), 2.54 to 3.10 (3H, m, thiophene protons), 4.46 (ca 1H, m, C7 -H), 4.60 and 4.62 (total ca 1H, 2S, CHOH), 5.00 (1H,d,J4.5Hz, C7 -H), 6.49 and 6.87 (2H, ABq, J18Hz, C2 -H2), 8.01 (3H,s, C3 -CH3). A signal at τ 8.89 revealed the presence of one-sixth mole-equivalent of diethyl ether. (Found: C,41.1, 41.4; H,3.6,3.8; N,6.6, 7.0; S,14.5. C14H13N2NaO5S2. One-sixth C2H5OC2H5. 2H2O (424.7) requires C,41.5; H,4.4; N,6.5; S,15.1%).