Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:19]([NH:21][CH:22]([C:26]([O:28][CH3:29])=[O:27])[CH:23]([OH:25])[CH3:24])=[O:20])[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)([O-])O.[Na+]>ClCCl>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:19]([NH:21][CH:22]([C:26]([O:28][CH3:29])=[O:27])[C:23](=[O:25])[CH3:24])=[O:20])[CH2:11][C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COC(=O)C(NC(=O)[C@H](CCCC1CCCCC1)CC(=O)OC(C)(C)C)C(C)O
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Solvent: ClCCl
Product: COC(=O)C(NC(=O)[C@H](CCCC1CCCCC1)CC(=O)OC(C)(C)C)C(C)=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 75.3 %

Procedure:
A solution of tert-butyl (3R)-6-cyclohexyl-3-({[2-hydroxy-1-(methoxycarbonyl)propyl]amino}carbonyl)hexanoate (Preparation 171) (6.48 g, 15.69 mmol) in dichloromethane (60 ml) was treated with Dess-Martin periodinane [1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one] (7.32 g, 17.26 mmol) and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. A solution of sodium thiosulphate (6 g in 50 ml water) and a saturated aqueous sodium hydrogen carbonate solution (50 ml) were then added to the mixture which was stirred for a further 10 minutes. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were sequentially washed with water and brine, dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of pentane: ethyl acetate (100:0 to 90:10) to afford the title compound as a colourless oil (4.86 g)
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([OH:14])=O)[CH:9]=[CH:8][C:7]=2[N:15]2[CH2:18][C:17]([F:20])([F:19])[CH2:16]2)[CH2:3][CH2:2]1.[CH:21]1([CH2:24][C@H:25]([NH2:32])[C:26]2[N:30]=[C:29]([CH3:31])[O:28][N:27]=2)[CH2:23][CH2:22]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>>[CH:21]1([CH2:24][C@H:25]([NH:32][C:12]([C:10]2[CH:9]=[CH:8][C:7]([N:15]3[CH2:18][C:17]([F:20])([F:19])[CH2:16]3)=[C:6]([O:5][CH2:4][CH:1]3[CH2:2][CH2:3]3)[N:11]=2)=[O:14])[C:26]2[N:30]=[C:29]([CH3:31])[O:28][N:27]=2)[CH2:23][CH2:22]1
Reactant: Cc1nc([C@@H](N)CC2CC2)no1
Reactant: O=C(O)c1ccc(N2CC(F)(F)C2)c(OCC2CC2)n1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc([C@H](CC2CC2)NC(=O)c2ccc(N3CC(F)(F)C3)c(OCC3CC3)n2)no1

Procedure:
In analogy to the procedure described in Example 47 b), 6-cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (Example 1 b)) was reacted with (S)-2-cyclopropyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethylamine in the presence of TBTU and DIEA to obtain the title compound; MS (EI): m/e=434.2 [MH+].
Reaction SMILES: Cl.[NH2:2][C:3]1([CH3:22])[CH2:7][CH2:6][CH2:5][CH:4]1[NH:8][C:9](=[O:21])[O:10][C@@H:11]1[CH2:16][C@H:15]([CH3:17])[CH2:14][CH2:13][C@H:12]1[CH:18]([CH3:20])[CH3:19].Cl[C:24]1[N:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=1.CCN(C(C)C)C(C)C>CS(C)=O>[CH3:22][C:3]1([NH:2][C:24]2[N:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=2)[CH2:7][CH2:6][CH2:5][CH:4]1[NH:8][C:9](=[O:21])[O:10][C@@H:11]1[CH2:16][C@H:15]([CH3:17])[CH2:14][CH2:13][C@H:12]1[CH:18]([CH3:19])[CH3:20]
Reactant: CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)NC1CCCC1(C)N
Reactant: FC(F)(F)c1cnc(Cl)nc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)NC1CCCC1(C)Nc1ncc(C(F)(F)F)cn1

Procedure:
A solution of (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl N-(2-amino-2-methylcyclopentyl)carbamate hydrochloride (Intermediate 27; 2.0 g, 6.01 mmol), 2-chloro-5-(trifluoromethyl)pyrimidine (CAS number 69034-12-4; 1.21 g, 6.61 mmol) and DIPEA (3.15 ml, 18.02 mmol) in dry DMSO (15 ml) was subjected to microwave irradiation at 140° C. for 4 hours. The reaction was partitioned between ethyl acetate and brine. The aqueous layer was extracted further with ethyl acetate (2×100 ml). The combined organics were washed with brine (3×125 ml), dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (silica, 0-30% diethyl ether/petrol) to afford the title compound as a single trans-enantiomer.
Reaction SMILES: [Cl:1][C:2]1[C:3]([N:9]=[C:10]=[S:11])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:12][NH2:13]>C1C=CC=CC=1.C(O)C>[Cl:1][C:2]1[C:3]([NH:9][C:10]([NH:13][CH3:12])=[S:11])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CN
Reactant: S=C=Nc1ncc(Cl)cc1Cl
Solvent: CCO
Solvent: c1ccccc1
Product: CNC(=S)Nc1ncc(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A solution of 3,5 dichloro-2-pyridylisothiocyanate (5.13 g.) in benzene (20 ml.) was added to a solution of methylamine in ethanol (5 ml., 33%) and the mixture was stirred for 18 hours at ambient temperature. Petroleum ether (60°-80° C., 30 ml.) was added and the resulting precipitate was filtered off and recrystallised from benzene-light petroleum to give colourless microcrystals of 1-(3,5-dichloro-2-pyridyl)-3-methyl-2-thiourea (4.18 g.) m.pt. 105°-109° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])=[C:6]([C:8]2[C:9]([O:16][CH2:17][CH3:18])=[CH:10][C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=1.[N:28]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([O:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:32]=1)=[C:29]=[O:30]>>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[O:19][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:29]([NH:28][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([O:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH:32]=2)=[O:30])=[CH:7][C:6]=1[C:8]1[C:9]([O:16][CH2:17][CH3:18])=[CH:10][C:11](=[O:15])[N:12]([CH3:14])[CH:13]=1
Reactant: O=C=Nc1cccc(Oc2ccccc2)c1
Reactant: CCOc1cc(=O)n(C)cc1-c1cc(N)ccc1Oc1ccc(F)cc1F
Product: CCOc1cc(=O)n(C)cc1-c1cc(NC(=O)Nc2cccc(Oc3ccccc3)c2)ccc1Oc1ccc(F)cc1F

Procedure:
A stock solution of Example 1G (0.73 M in pyridine, 458 μL, 0.033 mmol, 1.0 equivalent) and 1-isocyanato-3-phenoxybenzene (0.40 M in DMA, 108 μL, 0.043 mmol, 1.3 equivalents) were aspirated from their respective source vials, mixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter), and loaded into an injection loop. The reaction segment was injected into the flow reactor (Hastelloy coil, 0.75 mm inner diameter, 2.32 mL internal volume) set at 100° C., and passed through the reactor at 232 μL min−1 (10 minute residence time). Upon exiting the reactor, the reaction was loaded directly into an injection loop and purified by preparative HPLC on a Phenomenex Luna C8(2) 5 um 100 Å AXIA column (50 mm×21.2 mm). A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 30 mL/min (0-0.5 min 5% A, 0.5-6.5 min linear gradient 30-70% A, 6.5-7.0 min linear gradient 70-100% A, 7.0-8.5 min 100% A, 8.5-9.0 min linear gradient 100-5% A, 9.0-10 min 5% A) to yield the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 7.56 (s, 1H), 7.45-7.37 (m, 3H), 7.39-7.22 (m, 4H), 7.20-7.12 (m, 1H), 7.11 (ddd, J=8.0, 2.0, 1.0 Hz, 1H), 7.05-6.92 (m, 4H), 6.89 (d, J=8.7 Hz, 1H), 6.63 (ddd, J=8.1, 2.4, 0.9 Hz, 1H), 5.82 (s, 1H), 3.92 (q, J=6.9 Hz, 2H), 3.36 (s, 3H), 1.13 (t, J=6.9 Hz, 3H). MS (APCI+) m/z 583.7 (M+H)+.
Reaction SMILES: Cl.CN(C)[CH2:4][CH:5]([CH3:15])[C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[OH:14])=[O:7].[C-:17]#[N:18].[K+]>O>[C:17]([CH2:4][CH:5]([CH3:15])[C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[OH:14])=[O:7])#[N:18]
Reactant: [C-]#N
Reactant: CC(CN(C)C)C(=O)c1ccccc1O
Agent: Cl
Agent: [K+]
Solvent: O
Product: CC(CC#N)C(=O)c1ccccc1O
Yield: 93 %

Procedure:
A mixture of 2-(3-dimethylamino-2-methylpropionyl)phenol hydrochloride (2.70 g), potassium cyanide (1.3 g) and water (50 ml) was heated under reflux for 2 hours. The mixture was cooled, neutralised and extracted with chloroform. The extracts were dried (MgSO4) and the solvent was evaporated and purified by chromatography on a silica column to give 2-(3-cyano-2-methylpropionyl)phenol as an orange oil (1.95 g).
Reaction SMILES: [C:1]1([CH2:7][C:8]([NH:10][CH:11]2[C:42](=[O:43])[N:13]3[C:14]([C:26]([O:28][CH:29]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:27])=[C:15](OS(C(F)(F)F)(=O)=O)[CH2:16][S:17][C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:44][O:45][C:46]1[CH:51]=[CH:50][C:49]([Sn](CCCC)(CCCC)CCCC)=[CH:48][CH:47]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>CN1CCCC1=O.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.[Pd]>[C:1]1([CH2:7][C:8]([NH:10][CH:11]2[C:42](=[O:43])[N:13]3[C:14]([C:26]([O:28][CH:29]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)[C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[O:27])=[C:15]([C:49]4[CH:50]=[CH:51][C:46]([O:45][CH3:44])=[CH:47][CH:48]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(Cc1ccccc1)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(OS(=O)(=O)C(F)(F)F)CS[C@H]12
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(OC)cc1
Agent: [Pd]
Agent: O=C(C=Cc1ccccc1)C=Cc1ccccc1
Agent: [Cl-]
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: COc1ccc(C2=C(C(=O)OC(c3ccccc3)c3ccccc3)N3C(=O)C(NC(=O)Cc4ccccc4)[C@H]3SC2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 56.9 %

Procedure:
A mixture of 0.1029 g ((0.000163 mole) of diphenylmethyl 7-phenylacetamido-3-(trifluoromethylsulfonyloxy)-3-cephem- -4-carboxylate, 0.0775 g (0.000195 mole) of (p-methoxyphenyl)tri-n-butylstannane, 0.044 g (0.00032 mole) of zinc chloride and 0.00378 g (0.000016 mole) of tri(2-furyl)-phosphine in 4 mL of dry 1-methyl-2-pyrrolidinone, under an argon atmosphere, was degassed for 30 seconds. Then 0.0047 g (0.000008 mole) of palladium(0) bis(dibenzylidene acetone) was added all at once. The reaction mix was stirred at 50° for 5.5 hrs and room temperature for 16 hrs. The reaction mix was then diluted with ethyl acetate and the organic solution washed with dilute ammonium chloride. The ethyl acetate was removed at reduced pressure and replaced with acetonitrile. The organic phase was washed with n-pentane and the acetonitrile removed at reduced pressure. The residue was chromatographed on silica gel to yield 0.0548 g (57%) of diphenylmethyl 7-phenylacetamido-3-(p-methoxyphenyl)-3cephem-4-carboxylate. The nuclear magnetic resonance spectrum was consistent for the desired structure.
Reaction SMILES: [C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4])[OH:2].C(O[Si:12](OCC)(OCC)OCC)C>C1(C)C=CC=CC=1>[C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4])[OH:2].[Si:12]
Reactant: CCO[Si](OCC)(OCC)OCC
Agent: Oc1ccccc1O
Solvent: Cc1ccccc1
Product: [Si]

Procedure:
A solution of catechol (22.0 g, 0.20 mmol) and toluene (220 mL) was dehydrated by distilling 20 mL of the solution. Thereafter, 20.8 g (0.10 mmol) of tetraethoxysilane (TEOS) was added to the solution while stirring. The mixed solution was refluxed for 1 hour, and then, while the distillation temperature was 100° C. or higher, distilled at a liquid flow rate of 15 mL/h until the amount of the solution became 100 mL. As a result, catechol-silicon complex toluene was obtained. To 2 mL of catechol-silicon complex toluene, 2 mL of acetylacetone was added to produce a coating liquid.
Reaction SMILES: [ClH:1].[CH:2]1([C@H:8]2[N:13]3[CH:14]=[C:15]([C:20]([N:22]4[C@H:27]([CH3:28])[CH2:26][N:25](CC5C=CC=CC=5)[CH2:24][C@@H:23]4[CH3:36])=[O:21])[C:16]4[CH:17]=[CH:18][CH:19]=[C:11]([C:12]=43)[O:10][CH2:9]2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1>C(O)C.[Pd]>[ClH:1].[CH:2]1([C@H:8]2[N:13]3[CH:14]=[C:15]([C:20]([N:22]4[C@H:23]([CH3:36])[CH2:24][NH:25][CH2:26][C@@H:27]4[CH3:28])=[O:21])[C:16]4[CH:17]=[CH:18][CH:19]=[C:11]([C:12]=43)[O:10][CH2:9]2)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1
Reactant: C[C@@H]1CN(Cc2ccccc2)C[C@H](C)N1C(=O)c1cn2c3c(cccc13)OC[C@H]2C1CCCCC1
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: C[C@@H]1CNC[C@H](C)N1C(=O)c1cn2c3c(cccc13)OC[C@H]2C1CCCCC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 61.9 %

Procedure:
To a solution of (R)-3-cyclohexyl-2,3-dihydro-6-[(cis)-4-benzyl-2,6-dimethylpiperazin-1-ylcarbonyl]pyrrolo[1,2,3-de]-1,4-benzoxazine hydrochloride salt (200 mg, 0.42 mmol) in ethanol (5 ml) was added 10% palladium on charcoal (10 mg). The mixture was stirred under a hydrogen atmosphere for 16 h at room temperature. The mixture was filtered and the solvent removed in vacuo to afford the title compound as a white solid (100 mg, 0.26 mmol).
Reaction SMILES: [OH:1][CH:2]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:3]1[O:7][N:6]=[C:5]([C:8]([O:10]CC)=O)[CH:4]=1.Cl.[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][CH:25]=[C:24]2[CH2:30][CH2:31][NH2:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>O1CCCC1.[OH-].[Na+].O.CN(C=O)C.C(OCC)(=O)C>[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][CH:25]=[C:24]2[CH2:30][CH2:31][NH:32][C:8]([C:5]1[CH:4]=[C:3]([CH:2]([OH:1])[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[O:7][N:6]=1)=[O:10]
Reactant: CCOC(=O)c1cc(C(O)c2ccccc2)on1
Reactant: NCCc1c[nH]c2ccc(Cl)cc12
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: O=C(NCCc1c[nH]c2ccc(Cl)cc12)c1cc(C(O)c2ccccc2)on1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.6 %

Procedure:
A mixture of ethyl 5-(hydroxy(phenyl)methyl)isoxazole-3-carboxylate (0.534 g; 2.16 mmol) in tetrahydrofurane (6 mL) and sodium hydroxide in water (2M, 5.4 mL) was stirred at room temperature for 1 hour and diluted in water, extracted with dichloromethane and the waters acidified with HCl 6N in water to pH 2 extracted with ethyl acetate, the organic layer was dried and concentrated under reduced pressure. The residue was added to a mixture of 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.5 g; 2.16 mmol), HATU (0.822 g; 2.16 mmol), N,N diisopropylethylamine (0.932 mL; 5.41 mmol), in DMF (12 mL) and was stirred at room temperature overnight. The reaction mixture was diluted in ethyl acetate, washed with sodium disulphate, sodium carbonate and brine, dried and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane) to yield 0.817 g (95%) of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(hydroxy(phenyl)methyl)isoxazole-3-carboxamide as a white solid.
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[NH2:12][C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[C:4]([C:3]1[C:2]([NH:12][C:13]2[CH:14]=[CH:15][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:21][CH:22]=2)=[N:10][C:9]([Cl:11])=[CH:8][CH:7]=1)(=[O:5])[NH2:6]
Reactant: NC(=O)c1ccc(Cl)nc1Cl
Reactant: COC(=O)c1ccc(N)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)c1ccc(Nc2nc(Cl)ccc2C(N)=O)cc1
Reaction time: 0.17 h
Yield: 106.1 %

Procedure:
To a solution of 2,6-dichloronicotinamide (1 g, 5.24 mmol) and methyl 4-aminobenzoate (0.950 g, 6.28 mmol) in THF (30 mL) was added lithium bis(trimethylsilyl)amide (18.32 mL, 18.32 mmol) at −78° C. The reaction mixture was stirred for 10 min. The dry ice bath was removed and the reaction mixture was stirred at rt for 3.5 h. The reaction mixture was diluted with water and the resulting yellow precipitate was filtered to give 1.7 g of methyl 4-(3-carbamoyl-6-chloropyridin-2-ylamino)benzoate as a yellow solid.
Reaction SMILES: [OH:1][C:2]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[CH:14][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1)=[O:5].[CH3:24][O:25][CH2:26][CH2:27]Br>>[CH3:24][O:25][CH2:26][CH2:27][O:1][C:2]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]([F:23])([F:21])[F:22])=[CH:14][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1)=[O:5]
Reactant: O=C(NCc1ccccn1)c1cc(OCC(F)(F)F)ccc1O
Reactant: COCCBr
Product: COCCOc1ccc(OCC(F)(F)F)cc1C(=O)NCc1ccccn1
Yield: 67.6 %

Procedure:
Using the general method of Example I Part A, 6.5 g (0.02 mole) of 2-hydroxy-N-(2-pyridylmethyl)-5-(2,2,2-trifluoroethoxy)benzamide was reacted with 3.9 g (0.028 mole) of 2-bromoethyl methyl ether to give 5.2 g of white crystalline 2-(2-methoxyethoxy)-N-(2-pyridylmethyl)-5-(2,2,2-trifluoroethoxy)benzamide, m.p. 104°-107° C.
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=1)[CH:11]=[N:12][OH:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClN1C(=O)CCC1=O.[CH:25]([P:27](=[O:32])([O:30][CH3:31])[O:28][CH3:29])=[CH2:26].C(N(CC)CC)C>>[O:1]([C:8]1[CH:9]=[C:10]([C:11]2[CH2:26][CH:25]([P:27](=[O:32])([O:30][CH3:31])[O:28][CH3:29])[O:13][N:12]=2)[CH:14]=[CH:15][CH:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C=CP(=O)(OC)OC
Reactant: ON=Cc1cccc(Oc2ccccc2)c1
Agent: O=C1CCC(=O)N1Cl
Solvent: CCN(CC)CC
Product: COP(=O)(OC)C1CC(c2cccc(Oc3ccccc3)c2)=NO1
Yield: 95.6 %

Procedure:
In analogy to Example 1, 42.65 g (0.2 mol) of 3-phenoxybenzaldoxime, 29.4 g (0.22 mol) of N-chlorosuccinimide, 29.2 ml (0.22 mol) of dimethyl vinylphosphonate and 30.6 ml (0.22 mol) of triethylamine are reacted, and 66.4 g of oily product are obtained.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]=2)=[CH:4][C:3]=1[O:21][CH3:22]>[Pd].CO>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:12][CH2:13]2)=[CH:4][C:3]=1[O:21][CH3:22]
Reactant: COc1cc(C2=CCN(C(=O)OC(C)(C)C)CC2)ccc1N
Agent: [Pd]
Solvent: CO
Product: COc1cc(C2CCN(C(=O)OC(C)(C)C)CC2)ccc1N
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of 10% palladium on carbon (0.1 g) in methanol (30 mL) was added the product of Example 62A (0.8 g, 2.6 mmol) and the mixture was stirred at ambient temperature under hydrogen for 8 hours. The mixture was filtered and concentrated to yield the title compound. MS: 307 (M+H+).
Reaction SMILES: [Li+].[Cl-].FC(F)(F)S(O[C:9]([CH:11]([CH2:16][OH:17])[CH2:12][CH:13]([CH3:15])[CH3:14])=[CH2:10])(=O)=O.[Si:20]([CH2:24][Mg]Cl)([CH3:23])([CH3:22])[CH3:21].[NH4+].[Cl-]>CCOCC.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>[CH3:14][CH:13]([CH3:15])[CH2:12][CH:11]([C:9]([CH2:21][Si:20]([CH3:24])([CH3:23])[CH3:22])=[CH2:10])[CH2:16][OH:17]
Reactant: C[Si](C)(C)C[Mg]Cl
Reactant: C=C(OS(=O)(=O)C(F)(F)F)C(CO)CC(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CCOCC
Product: C=C(C[Si](C)(C)C)C(CO)CC(C)C
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 94.1 %

Procedure:
LiCl (7.00 mg, 0.159 mmol) and Pd(PPh3)4 (2.30 mg, 0.002 mmol) were added to anhydrous Et2O (1 mL), and then the resulting solution was cooled to 0° C. A solution obtained by dissolving 3-(hydroxymethyl)-5-methylhex-1-ene-2-yl trifluoromethanesulfonate (11 mg, 0.0398 mmol) in anhydrous Et2O (1 mL) was slowly added thereto and the resulting solution was stirred for 10 min. TMSCH2MgCl (0.119 mL, 0.119 mmol, 1.0 M/Et2O solution) was slowly added thereto, the resulting solution was stirred for 1 hr, and then a saturated NH4Cl aqueous solution (1 mL) was added thereto to complete the reaction. The temperature was increased to normal temperature, extraction was performed by using ethyl acetate (3×3 mL), distillation was performed under reduced pressure, and then column chromatography was used to obtain 8.03 mg (yield 94%) of the title compound.
Reaction SMILES: CCOC(/N=N/C(OCC)=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:32]([O:37][CH2:38][CH3:39])(=[O:36])[C@@H:33]([CH3:35])[OH:34].[Br:40][C:41]1[CH:46]=[CH:45][C:44](O)=[CH:43][CH:42]=1>O1CCCC1>[Br:40][C:41]1[CH:46]=[CH:45][C:44]([O:34][C@@H:33]([CH3:35])[C:32]([O:37][CH2:38][CH3:39])=[O:36])=[CH:43][CH:42]=1
Reactant: CCOC(=O)[C@@H](C)O
Reactant: Oc1ccc(Br)cc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCOC(=O)[C@H](C)Oc1ccc(Br)cc1

Procedure:
Prepared according to the method described in Example 1a) from diethylazodicarboxylate (6.7 ml), triphenylphosphine (13.11 g), (R)-(+)-ethyl lactate (5.67 ml) and 4-bromophenol (8.65 g) in dry tetrahydrofuran (125 ml). The residue obtained after work-up was purified by column chromatography over silica eluting with isohexane:dichloromethane (2:3) to give the sub-title compound as an oil (12.2 g).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[OH:9].CN1CCCCC1.[OH-:17].[Na+].Cl>C(Cl)(Cl)Cl>[CH3:8][C:5]1[C:6](=[O:17])[CH:7]=[C:2]([CH3:1])[C:3](=[O:9])[CH:4]=1
Reactant: [OH-]
Reactant: Cc1ccc(C)c(O)c1
Agent: Cl
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CN1CCCCC1
Product: CC1=CC(=O)C(C)=CC1=O

Procedure:
12.2 g of 2,5-dimethylphenol (0.1 mole), 1.98 g of cobalt di-(3-methylsalcylal)-3,3'-diimino-di-n-propylamine (0.0005 mole) and 0.5 g of N-methylpiperidine were dissolved in 200 ml of chloroform and then air was bubbled through the resulting solution at 15°C for 10 hours during which time the reaction was completed. After completion of the reaction, the reaction mixture was rendered basic by adding a 2% aqueous solution of sodium hydroxide to decompose peroxides present in the mixture followed by addition of dilute hydrochloric acid to render the solution acidic. The resulting solution was extracted with ether which was then distilled off to obtain 12.1 g of 2,5-dimethyl-parabenzoquinone (0.09 mole).
Reaction SMILES: [NH:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]([C:14]([OH:16])=[O:15])=[C:8]2[CH2:17][CH2:18][CH2:19][NH:20]C(OC(C)(C)C)=O)[C:2]([NH2:4])=[O:3].[ClH:28]>O1CCOCC1>[ClH:28].[NH:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]([C:14]([OH:16])=[O:15])=[C:8]2[CH2:17][CH2:18][CH2:19][NH2:20])[C:2]([NH2:4])=[O:3]
Reactant: CC(C)(C)OC(=O)NCCCc1c(C(=O)O)[nH]c2ccc(NC(N)=O)cc12
Agent: Cl
Solvent: C1COCCO1
Product: NCCCc1c(C(=O)O)[nH]c2ccc(NC(N)=O)cc12
Reaction time: 0.75 h

Procedure:
The above carboxylic acid (31 mg) was dissolved in 10 mL of 4N HCl in dioxane. The mixture was spun on the rotovap without vacuum for 45 min. The solid was filtered with a filter-tipped cannula and washed with 2×10 mL of methylene chloride. The solid was dried under vacuum to yield the title compound (21 mg); MS, electrospray, 278 (M+H).
Reaction SMILES: C[O-].[Na+].[CH:4]([O:6][CH3:7])=[O:5].[Cl:8][C:9]1[N:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH2:23][C:24](OC)=[O:25])[CH:12]=[CH:11][CH:10]=1.O>C1(C)C=CC=CC=1>[Cl:8][C:9]1[N:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2/[C:23](=[CH:24]\[OH:25])/[C:4]([O:6][CH3:7])=[O:5])[CH:12]=[CH:11][CH:10]=1
Reactant: COC=O
Reactant: COC(=O)Cc1ccccc1COc1cccc(Cl)n1
Agent: C[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: COC(=O)/C(=C/O)c1ccccc1COc1cccc(Cl)n1
Yield: 98.6 %

Procedure:
Sodium methoxide (0.39 g, 6.9 mmol) and methyl formate (1 ml, 16 mmol) were added portionwise to a stirred solution of methyl 2-(6-chloropyrid-2-yloxymethyl)phenylacetate (1.0 g, 3.3 mmol) in dry toluene (15 ml) under a nitrogen atmosphere at room temperature. After 3 hours at room temperature the mixture was poured into water and extracted with ethyl acetate. The ethyl acetate extracts were washed with water, dried and the ethyl acetate removed to give (E)-methyl 2-[2-(6-chloropyrid-2-yloxymethyl)phenyl]-3-hydroxyacrylate (1.04 g, 95%) as a brown gum which was used in the final stage without further purification; 1H NMR(270 MHz)δ: 3.75(3H,s), 5.29(2H,s), 6.65(1H,d), 6,90(1H,d), 7.15-7.60(6H,m), 11.98(1H,d) ppm.