Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][CH:14]=2)[CH:10]=O)=[CH:4][CH:3]=1.[C:17]([CH2:20]P(=O)(OC)OC)(=[O:19])[CH3:18].C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[F:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][C:7]2[CH:8]=[C:9](/[CH:10]=[CH:18]/[C:17](=[O:19])[CH3:20])[CH:12]=[CH:13][CH:14]=2)=[CH:4][CH:3]=1
Reactant: COP(=O)(CC(C)=O)OC
Reactant: O=Cc1cccc(Oc2ccc(F)cc2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(=O)/C=C/c1cccc(Oc2ccc(F)cc2)c1

Procedure:
A mixture of the product from step (c) (8.9 g). dimethyl acetylmethylphosphonate (6.84 g), anhy. potassium carbonate (11.37 g) and dry THF (100 ml) was heated under N2 at 50°-55° C. for 20 hours. The mixture was then cooled and filtered, the residue washed with THF, and the filtrate and washings combined and stripped to give a pale orange oil which was eluted through a silica gel column using ether/40-60 pet. ether (1:2) and the eluate stripped and dried under high vacuum to give the desired product as a very pale yellow, viscous oil (5.59 g).
Reaction SMILES: C([O:3][C:4](=[O:29])[C:5]([NH:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)=[C:15]([O:24][CH2:25][CH:26]2[CH2:28][CH2:27]2)[N:14]=1)=[O:12])([CH2:8][CH3:9])[CH2:6][CH3:7])C.[OH-].[Na+]>>[CH:26]1([CH2:25][O:24][C:15]2[N:14]=[C:13]([C:11]([NH:10][C:5]([CH2:6][CH3:7])([CH2:8][CH3:9])[C:4]([OH:29])=[O:3])=[O:12])[CH:18]=[CH:17][C:16]=2[N:19]2[CH2:20][CH2:21][CH2:22][CH2:23]2)[CH2:27][CH2:28]1
Reactant: CCOC(=O)C(CC)(CC)NC(=O)c1ccc(N2CCCC2)c(OCC2CC2)n1
Agent: [Na+]
Agent: [OH-]
Product: CCC(CC)(NC(=O)c1ccc(N2CCCC2)c(OCC2CC2)n1)C(=O)O

Procedure:
In analogy to the procedure described in Example 252 b, 2-[(6-cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carbonyl)-amino]-2-ethyl-butyric acid ethyl ester (Example 289) was treated with sodium hydroxide to give the title compound as colorless oil. MS: 376.3 [M+H]+.
Reaction SMILES: CC1C=CC(S(O[C:12]2[C:21]3[C:20](=[O:22])[N:19]([CH3:23])[CH:18]=[N:17][C:16]=3[N:15]([CH3:24])[C:14](=[O:25])[CH:13]=2)(=O)=O)=CC=1.[F:26][C:27]1[CH:33]=[C:32]([I:34])[CH:31]=[CH:30][C:28]=1[NH2:29]>>[F:26][C:27]1[CH:33]=[C:32]([I:34])[CH:31]=[CH:30][C:28]=1[NH:29][C:12]1[C:21]2[C:20](=[O:22])[N:19]([CH3:23])[CH:18]=[N:17][C:16]=2[N:15]([CH3:24])[C:14](=[O:25])[CH:13]=1
Reactant: Cc1ccc(S(=O)(=O)Oc2cc(=O)n(C)c3ncn(C)c(=O)c23)cc1
Reactant: Nc1ccc(I)cc1F
Product: Cn1cnc2c(c(Nc3ccc(I)cc3F)cc(=O)n2C)c1=O

Procedure:
3,8-dimethyl-4,7-dioxo-3,4,7,8-tetrahydropyrido[2,3-d]pyrimidin-5-yl 4-methylbenzenesulfonate (compound 1D, 80 mg of 60% pure material) and 2-fluoro-4-iodoaniline (300 mg, large excess) were heated at 125° C. for 2 hours to yield 5-(2-fluoro-4-iodophenylamino)-3,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (Example 1). The product was confirmed by LC-MS and isolated by HPLC to give the title compound as a tan solid (17 mg). 1H NMR (400 MHz, MeOD) δ ppm 3.57 (s, 3 H) 3.64 (s, 3 H) 5.76 (s, 1 H) 7.30 (t, J=8.34 Hz, 1 H) 7.61 (dt, J=8.34, 1.01 Hz, 1 H) 7.66 (dd, J=9.85, 1.77 Hz, 1 H) 8.48 (s, 1 H); [M+H] calc'd for C15H12FIN4O2, 427; found, 427.
Reaction SMILES: [C:1]1([C:7]2[N:12]=[C:11]([CH:13]=O)[CH:10]=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[BH4-].[Na+].C[OH:18]>>[CH3:13][C:11]1[C:10]([OH:18])=[CH:9][CH:8]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:12]=1
Reactant: O=Cc1cccc(-c2ccccc2)n1
Reactant: CO
Agent: [BH4-]
Agent: [Na+]
Product: Cc1nc(-c2ccccc2)ccc1O
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 99 %

Procedure:
To a solution of 0.250 g (1.36 mmol) of 6-phenyl-2-pyridine aldehyde in 5 mL of methanol was added sodium borohydride (0.08 g, 2.05 mmol) portionwise with stirring under N2 at ambient temperature. After 10 min, the reaction was quenched with 5 mL of saturated aqueous ammonium chloride solution. This solution was extracted with 3×50 mL EtOAc. The organic fractions were pooled, dried over Na2SO4 and concentrated. After removing the volatiles in vacuo, the resultant yellow oil was chromatographed on silica with 10% EtOAc/hexanes. Clean fractions were combined and the volatiles were removed to provide 0.250 g of 2-methylhydroxyl-6-phenyl pyridine as a clear oil (>99%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C@H:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[C:13]([OH:15])=[O:14])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.C(OC(=O)[C@H](CC1C=CC(O)=CC=1)N)(C)(C)C>>[F:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C@@H:12]([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([OH:23])=[CH:21][CH:22]=2)[C:13]([OH:15])=[O:14])(=[O:9])=[O:10])[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)[C@@H](Cc1ccc(O)cc1)NS(=O)(=O)c1cccc(F)c1
Agent: CC(C)(C)OC(=O)[C@@H](N)Cc1ccc(O)cc1
Product: O=C(O)[C@H](Cc1ccc(O)cc1)NS(=O)(=O)c1cccc(F)c1

Procedure:
Following 18a synthetic method, using B2 (118.65 mg, 0.5 mmol) instead of A2 gave 18b as a colorless oil; (56.33 mg, 49.8%). [α]D25: −14.4 (c=0.27, CHCl3); 1H-NMR (300 MHz, acetone-d6): δ 8.20 (s, 1H), 7.56-7.48 (m, 2H), 7.44-7.35 (m, 2H), 7.03-6.95 (m, 3H), 6.70-6.65 (m, 2H), 4.18-4.11 (m, 1H), 3.06-2.81 (m, 2H); 13C NMR (300 MHz, acetone-d6): δ 171.53, 163.77, 160.48, 156.28, 143.54, 131.00, 130.36, 126.92, 122.75, 119.25, 115.07, 113.89, 113.57, 57.63, 37.74; HRMS (ESI): calcd for: C15H14FNO5S [M+Na]+=362.0469, obsd [M+Na]+=362.0485.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][C:9](=[O:13])[CH2:10]2)=[CH:5][CH:4]=1.[H-].[Na+].Br[CH2:17][CH2:18][O:19][CH2:20][CH2:21]Br.[Cl-].[NH4+]>C1COCC1>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][C:9](=[O:13])[C:10]32[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:5][CH:4]=1
Reactant: BrCCOCCBr
Reactant: COc1ccc2c(c1)CC(=O)CC2
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: COc1ccc2c(c1)C1(CCOCC1)C(=O)CC2
Reaction time: 0.17 h
Yield: 51 %

Procedure:
To the THF (300 ml) solution of 7-methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound A1, 20 g, 0.11 mol), sodium hydride (9.9 g, 3.7 eq.) was added at 0° C. After stirring for 10 min, 1-bromo-2-(2-bromo-ethoxy)-ethane (19 ml, 12 eq.) was added dropwise thereto, and the mixture was stirred at 80° C. for 3 hr. To the reaction solution, saturated aqueous solution of ammonium chloride was added and the extraction was carried out twice with ethyl acetate. The organic layer was dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (white solid, 13 g, 51%).
Reaction SMILES: [H-].[Na+].Cl[CH2:4][CH2:5][S:6](Cl)(=[O:8])=[O:7].[F:10][C:11]([F:31])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([NH2:24])=[N:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1>C1COCC1>[F:31][C:11]([F:10])([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[C:12]1[CH:13]=[CH:14][C:15]([C:18]2[C:19]3=[N:24][S:6](=[O:8])(=[O:7])[CH2:5][CH2:4][N:20]3[CH:21]=[CH:22][CH:23]=2)=[CH:16][CH:17]=1
Reactant: O=S(=O)(Cl)CCCl
Reactant: Nc1ncccc1-c1ccc(C(F)(F)c2ccccc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=S1(=O)CCN2C=CC=C(c3ccc(C(F)(F)c4ccccc4)cc3)C2=N1
Reaction time: 0.17 h

Procedure:
To a suspension of NaH (60%, 196 mg) in THF (dry) (20 mL) was added 2-chloroethanesulfonyl chloride (0.310 mL) at 0° C. and the mixture was stirred for 10 min at the same temperature. A solution of 3-(4-(difluoro(phenyl)methyl)phenyl)pyridin-2-amine (291 mg) in THF (dry) (10 mL) was added at 0° C. and the mixture was stirred at room temperature under a dry atmosphere with anhydrous calcium chloride tube for 2 hr. The mixture was quenched with water/THF then water at 0° C. and extracted with EtOAc/THF. Silica-gel was added to the organic phase and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (silica gel, eluted with MeOH in EtOAc) and concentrated in vacuo. The residue was washed with IPE to give the title compound (49 mg) as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][NH:8][C:9]2[N:14]=[C:13]([O:15][C:16]3[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][C:17]=3[F:23])[CH:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.[F:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][C:34]([N:36]=[C:37]=[O:38])=[O:35])=[CH:29][CH:28]=1.COC1C=CC(CNC2N=CN=C(OC3C=CC(NC(NC(=O)CC4C=CC(F)=CC=4)=O)=CC=3F)C=2)=CC=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9]2[N:14]=[C:13]([O:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:37]([NH:36][C:34](=[O:35])[CH2:33][C:30]4[CH:31]=[CH:32][C:27]([F:26])=[CH:28][CH:29]=4)=[O:38])=[CH:18][C:17]=3[F:23])[CH:12]=[CH:11][N:10]=2)=[CH:24][CH:25]=1
Reactant: O=C=NC(=O)Cc1ccc(F)cc1
Reactant: COc1ccc(CNc2nccc(Oc3ccc(N)cc3F)n2)cc1
Agent: COc1ccc(CNc2cc(Oc3ccc(NC(=O)NC(=O)Cc4ccc(F)cc4)cc3F)ncn2)cc1
Solvent: C1CCOC1
Product: COc1ccc(CNc2nccc(Oc3ccc(NC(=O)NC(=O)Cc4ccc(F)cc4)cc3F)n2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 62 %

Procedure:
A solution of N-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)pyrimidin-2-amine (Compound C of Example 14, 34 mg, 0.10 mmol) in THF (1 ml) was treated with 0.36 M 2-(4-fluorophenyl)acetyl isocyanate in toluene (Compound D of Example 11, 0.31 mL, 0.11 mmol) and the mixture stirred at RT for 1 h. The mixture was concentrated in vacuo and the solid obtained was triturated first with 3:1 isopropyl ether/EtOAc and then CH2Cl2 to give the title compound (32 mg, 62%) as an off-white solid. 1H NMR (DMSO-d6) δ 10.47 (s, 1H), 10.26 (s, 1H), 8.15 (s, 1H), 7.76 (d, 1H, J=12.6 Hz), 7.61 (dd, 3H, J=9.1, 5.0 Hz), 7.29 (s, 2H), 7.31-7.21 (m, 3H), 6.81 (s, 3H), 6.24 (s, 1H), 4.32 (s, 1H), 3.96 (s, 1H), 3.68 (s, 3H), 3.48 (s, 2H); MS(ESI+) m/z 520.14 (M+H)+.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[NH:12]=[C:13]1[N:17]([CH2:18][CH2:19][S:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:16]2[CH:27]=[CH:28][C:29]([O:31][C:32]([F:35])([F:34])[F:33])=[CH:30][C:15]=2[S:14]1>C(O)C>[NH:12]=[C:13]1[N:17]([CH2:18][CH2:19][S:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:9])[C:16]2[CH:27]=[CH:28][C:29]([O:31][C:32]([F:34])([F:35])[F:33])=[CH:30][C:15]=2[S:14]1
Reactant: N=c1sc2cc(OC(F)(F)F)ccc2n1CCSc1ccccc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: CCO
Product: N=c1sc2cc(OC(F)(F)F)ccc2n1CCS(=O)c1ccccc1
Temperature: 0 °C
Reaction time: 3 h
Yield: 52.1 %

Procedure:
m-Chloroperbenzoic acid (0.6 g) is added in the course of approximately 10 minutes to 2-imino-3-(2-phenylthioethyl)-6-trifluoromethoxybenzothiazoline (1.3 g) in absolute ethanol (20 cc) cooled to 0° C. The reaction is continued for 3 hours at a temperature in the region of 20° C. The reaction medium is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) and the residue obtained purified by chromatography on a silica column with ethyl acetate as eluent. (RS)-2-Imino-3-(2-phenylsulphinylethyl)-6-trifluoromethoxybenzothiazoline (0.7 g) is obtained in the form of a yellowish oil, which is converted to a hydrochloride, m.p. 210° C.
Reaction SMILES: [Cl:1][C:2]1[C:3]([OH:18])=[CH:4][C:5]2[CH:9]=[C:8]([CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)[S:7][C:6]=2[C:16]=1[Cl:17].Br[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22].CN(C)C=O.C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[Cl:1][C:2]1[C:3]([O:18][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:4][C:5]2[CH:9]=[C:8]([CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)[S:7][C:6]=2[C:16]=1[Cl:17]
Reactant: CCOC(=O)CBr
Reactant: Oc1cc2cc(C3CCCCC3)sc2c(Cl)c1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCC(C)=O
Product: CCOC(=O)COc1cc2cc(C3CCCCC3)sc2c(Cl)c1Cl
Reaction time: 3 h

Procedure:
To a mixture of 6,7-dichloro-2-cyclohexyl-5-hydroxybenzo[b]thiophene and 110 ml of 2-butanone is added 11.5 g of ethyl bromoacetate in 60 ml of 2-butanone, followed by 10 ml dimethylformamide and 9.5 g of potassium carbonate. The reaction mixture is stirred under nitrogen at 90°-95° for 3 hrs, allowed to cool and filtered. The filtrate is poured into a mixture of 100 ml water and 100 ml ether. The layers are separated and the aqueous layer is extracted with 200 ml of ether. The organic layers are combined dried over anhydrous magnesium sulfate, filtered and the solvent is removed to give a solid which is recrystallized in ether-hexane to give 14.8 g of ethyl [(6,7-dichloro-2-cyclohexylbenzo[b]thien-5-yl)oxy]acetate, mp 73°-75°.
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16]C2C=CC=CC=2)[C@@H:13]([O:23][CH2:24]C2C=CC=CC=2)[C@@:12]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH2:48][C:49]([F:52])([F:51])[F:50])=[CH:43][CH:42]=3)[CH:34]=2)(OC)[O:11][C:10]1([CH2:55][OH:56])[CH2:53][OH:54])C1C=CC=CC=1.F[C:58](F)(F)[C:59](O)=O>ClCCl>[CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C@@H:13]([O:23][CH2:24][C:59]2[CH:58]=[CH:14][CH:9]=[CH:10][CH:53]=2)[C@:12]2([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[CH:42]=[CH:43][C:44]([O:47][CH2:48][C:49]([F:50])([F:52])[F:51])=[CH:45][CH:46]=4)[CH:34]=3)[O:11][C@@:10]1([CH2:55][OH:56])[CH2:53][O:54]2)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: CO[C@@]1(c2ccc(Cl)c(Cc3ccc(OCC(F)(F)F)cc3)c2)OC(CO)(CO)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Reactant: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: OC[C@@]12CO[C@@](c3ccc(Cl)c(Cc4ccc(OCC(F)(F)F)cc4)c3)(O1)[C@H](OCc1ccccc1)[C@@H](OCc1ccccc1)[C@@H]2OCc1ccccc1
Reaction time: 1 h

Procedure:
[(3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-yl]methanol 7k (100 mg, 0.13 mmol) was dissolved in 10 mL dichloromethane, followed by addition of 0.1 mL trifluoroacetic acid. The reaction mixture was stirred for 1 hour. Thereafter, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography with elution system D to obtain the title compound [(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]methanol 7m (22 mg, white solid), yield: 22.9%. MS m/z (ESI): 778.3 [M+18].
Reaction SMILES: [CH:1]([N:4]([CH:18]([CH3:20])[CH3:19])[CH2:5][CH2:6][N:7]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:10](=O)[C:8]1=[O:9])([CH3:3])[CH3:2].Cl.[CH2:22]([NH:29][C:30](=[O:33])[NH:31][NH2:32])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(O)C.C(=O)(O)[O-].[Na+]>O>[CH2:22]([NH:29][C:30](=[O:33])[NH:31]/[N:32]=[C:10]1/[C:8](=[O:9])[N:7]([CH2:6][CH2:5][N:4]([CH:18]([CH3:20])[CH3:19])[CH:1]([CH3:3])[CH3:2])[C:17]2[C:12]/1=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CC(C)N(CCN1C(=O)C(=O)c2ccccc21)C(C)C
Reactant: NNC(=O)NCc1ccccc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CC(C)N(CCN1C(=O)/C(=N/NC(=O)NCc2ccccc2)c2ccccc21)C(C)C
Temperature: 25 °C
Reaction time: 11 h
Yield: 69.8 %

Procedure:
A suspension of 137 mg of 1-(2-diisopropylaminoethyl)isatin and 120 mg of 4-benzylsemicarbazide hydrochloride in 2 ml of a mixture of ethanol and water (2:1) was stirred for 11 hours at room temperature, and an aqueous sodium bicarbonate solution was added to the reaction mixture. The precipitates were collected by filtration, washed with water and recrystallized from aqueous ethanol to obtain 147 mg of (E)-1-(2-diisopropylaminoethyl)isatin 3-(4-benzylsemicarbazone). Chemical properties of the product were identical with those of the product obtained by Example 5.
Reaction SMILES: [CH2:1]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]([O:14]C2C=CC3C(=CC=C(C#N)C=3)C=2)=O)[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5].C([C@H]1CC[C@H](C(O)=O)CC1)CCCC.S(Cl)([Cl:43])=O>>[CH2:1]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]([Cl:43])=[O:14])[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCC[C@H]1CC[C@H](C(=O)Oc2ccc3cc(C#N)ccc3c2)CC1
Reactant: O=S(Cl)Cl
Agent: CCCCC[C@H]1CC[C@H](C(=O)O)CC1
Product: CCCCC[C@H]1CC[C@H](C(=O)Cl)CC1

Procedure:
Preparation of 6-cyano-2-naphthyl trans-4-n-pentylcyclohexane-1-carboxylate by the following route: ##STR17## trans-4-n-Pentylcyclohexane-1-carboxylic acid chloride is prepared (step A9) by the standard procedure of heating a solution of trans-4-n-pentylcyclohexane-1-carboxylic acid (0.01 mole) in an excess of thionyl chloride for 2 hours. Removal of the excess of thionyl chloride gives a residue of the acid chloride which is mixed with dry pyridine (40 ml) and cooled to 0°-5° C. 6-Cyano-2-naphthol (0.012 mole), as prepared in Example 4 above, is then added and the solution stirred at room temperature for 20 hours; during this time the reaction mixture is protected from atmospheric moisture by a calcium chloride guard tube. The pyridine is then removed by rotary evaporation. The residual solid is purified by column chromatography on silica gel, using chloroform or chloroform:hexane (2:1) mixture as eluent. The purified ester is isolated and crystallised from hexane or methanol until constant transition temperatures are obtained: crystal-nematic liquid crystal (C-N); 86.5° C.; nematic liquid crystal-isotropic liquid (N-I), 168.3° C.
Reaction SMILES: Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]([C:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([C:20]4[C:28]5[O:27][CH2:26][O:25][C:24]=5[CH:23]=[CH:22][C:21]=4[O:29][CH2:30][CH:31]4[CH2:33][CH2:32]4)[C:14]=3[NH:13][CH:12]=2)=[O:10])[CH2:4][CH2:3]1.[CH3:34][O:35][CH2:36][C:37](Cl)=[O:38]>>[CH3:34][O:35][CH2:36][C:37]([N:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]([C:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([C:20]4[C:28]5[O:27][CH2:26][O:25][C:24]=5[CH:23]=[CH:22][C:21]=4[O:29][CH2:30][CH:31]4[CH2:32][CH2:33]4)[C:14]=3[NH:13][CH:12]=2)=[O:10])[CH2:4][CH2:3]1)=[O:38]
Reactant: COCC(=O)Cl
Reactant: O=C(NC1CCNCC1)c1c[nH]c2c(-c3c(OCC4CC4)ccc4c3OCO4)ncnc12
Agent: Cl
Product: COCC(=O)N1CCC(NC(=O)c2c[nH]c3c(-c4c(OCC5CC5)ccc5c4OCO5)ncnc23)CC1

Procedure:
Starting from 4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example A138) and methoxy-acetyl chloride the title compound is obtained as colorless solid.
Reaction SMILES: [CH3:1][C:2]1([C:5]#[C:6][C:7]2[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[CH:11]=[CH:10][C:8]=2[NH2:9])[CH2:4][CH2:3]1.N1C=CC=CC=1.[C:23](Cl)(=[O:27])[CH2:24][CH2:25][CH3:26]>C(Cl)Cl>[CH3:1][C:2]1([C:5]#[C:6][C:7]2[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[CH:11]=[CH:10][C:8]=2[NH:9][C:23](=[O:27])[CH2:24][CH2:25][CH3:26])[CH2:4][CH2:3]1
Reactant: CC1(C#Cc2cc([N+](=O)[O-])ccc2N)CC1
Reactant: CCCC(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCC(=O)Nc1ccc([N+](=O)[O-])cc1C#CC1(C)CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 80.3 %

Procedure:
To a solution of 2-((1-methylcyclopropyl)ethynyl)-4-nitroaniline (220 mg, 1.0 mmol) and pyridine (160 mg, 2.0 mol) in CH2Cl2 (20 mL) was added butyryl chloride (140 mg, 1.3 mmol) at 0° C. The mixture was warmed to room temperature and stirred for 3 h. The mixture was poured into ice-water. The organic layer was separated and the aqueous phase was extracted with CH2Cl2 (30 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and evaporated under reduced pressure to obtain N-[2-(1-methyl-cyclopropyl-ethynyl)-4-nitro-phenyl]-butyramide (230 mg, 82%), which was directly used in the next step.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH:40]=[CH:41][CH:42]=1)[CH2:8][N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([C:24]3[C:25]([C:30]4[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=4)=[CH:26][CH:27]=[CH:28][CH:29]=3)=[O:23])=[CH:17][CH:16]=2)[CH2:11][CH2:10]1)([O:3]C)=[O:2].[OH-].[Na+].Cl>CCO>[F:39][C:36]([F:37])([F:38])[C:33]1[CH:34]=[CH:35][C:30]([C:25]2[C:24]([C:22]([NH:21][C:18]3[CH:17]=[CH:16][C:15]([N:12]4[CH2:11][CH2:10][N:9]([CH2:8][C:7]5[CH:6]=[C:5]([CH:42]=[CH:41][CH:40]=5)[C:1]([OH:3])=[O:2])[CH2:14][CH2:13]4)=[CH:20][CH:19]=3)=[O:23])=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:31][CH:32]=1
Reactant: COC(=O)c1cccc(CN2CCN(c3ccc(NC(=O)c4ccccc4-c4ccc(C(F)(F)F)cc4)cc3)CC2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1cccc(CN2CCN(c3ccc(NC(=O)c4ccccc4-c4ccc(C(F)(F)F)cc4)cc3)CC2)c1
Temperature: 25 °C
Yield: 89.7 %

Procedure:
To a solution of 4′-trifluoromethyl-biphenyl-2-carboxylic acid [4-[4-(3-carbomethoxy-benzyl)-piperazin-1-yl]-phenyl]-amide (1.6 g) in EtOH (100 mL) was added 1N sodium hydroxide (5.6 mL) and the mixture was stirred under reflux for 16 hours. The solution was cooled at room temperature and acidified with 1N hydrochloric acid (5.6 mL). The white precipitate obtained was filtered and recristallized from EtOH to give the title compound (1.4 g) as white crystals. m.p.: 225-227° C.
Reaction SMILES: ClCC([NH:5][C:6]1[S:7][CH:8]=[C:9]([C:11](=[N:28][O:29][CH3:30])[C:12]([NH:14][C@H:15]2[C@H:18]([C:19]([O:21][CH3:22])=[O:20])[N:17]([S:23]([O-:26])(=[O:25])=[O:24])[C:16]2=[O:27])=[O:13])[N:10]=1)=O.[Na+:31].CSC(=S)N.[Na]>O>[NH2:5][C:6]1[S:7][CH:8]=[C:9]([C:11](=[N:28][O:29][CH3:30])[C:12]([NH:14][C@H:15]2[C@H:18]([C:19]([O:21][CH3:22])=[O:20])[N:17]([S:23]([O-:26])(=[O:24])=[O:25])[C:16]2=[O:27])=[O:13])[N:10]=1.[Na+:31]
Reactant: CON=C(C(=O)N[C@@H]1C(=O)N(S(=O)(=O)[O-])[C@H]1C(=O)OC)c1csc(NC(=O)CCl)n1
Agent: CSC(N)=S
Agent: [Na+]
Agent: [Na]
Solvent: O
Product: CON=C(C(=O)N[C@@H]1C(=O)N(S(=O)(=O)[O-])[C@H]1C(=O)OC)c1csc(N)n1

Procedure:
In 2 ml of water is dissolved 50 mg of sodium trans-3-[2-(2-chloroacetamido-4-thiazolyl)-2-methoxyiminoacetamido]-4-methoxycarbonyl-2-oxoazetidine-1-sulfonate (syn-isomer) as obtained in Example 24C, followed by addition of 15 mg of sodium monomethyldithiocarbamate under ice-water cooling and stirring. The mixture is stirred at room temperature for 30 minutes and after further addition of 15 mg of sodium monomethyldithiocarbamate, the mixture is stirred for 30 minutes. The reaction mixture is filtered and the filtrate is washed with ether. The aqueous layer is chromatographed on an Amberlite XAD-II column and lyophilized to give sodium trans-3-[2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-4-methoxycarbonyl-2-oxoazetidine-1-sulfonate (syn-isomer).
Reaction SMILES: C([O:5][C:6]([CH2:8][O:9][N:10]=[C:11]([C:37]1[N:41]=[C:40]([NH2:42])[S:39][N:38]=1)[C:12]([NH:14][CH:15]1[C:35](=[O:36])[N:17]2[C:18]([C:32]([OH:34])=[O:33])=[C:19]([CH2:22][S:23][C:24]3[N:28]([CH2:29][C:30]#[CH:31])[N:27]=[N:26][N:25]=3)[CH2:20][S:21][C@H:16]12)=[O:13])=[O:7])(C)(C)C.C(O)=O.Cl>C(=O)(O)[O-].[Na+]>[C:6]([CH2:8][O:9][N:10]=[C:11]([C:37]1[N:41]=[C:40]([NH2:42])[S:39][N:38]=1)[C:12]([NH:14][CH:15]1[C:35](=[O:36])[N:17]2[C:18]([C:32]([OH:34])=[O:33])=[C:19]([CH2:22][S:23][C:24]3[N:28]([CH2:29][C:30]#[CH:31])[N:27]=[N:26][N:25]=3)[CH2:20][S:21][C@H:16]12)=[O:13])([OH:7])=[O:5]
Reactant: C#CCn1nnnc1SCC1=C(C(=O)O)N2C(=O)C(NC(=O)C(=NOCC(=O)OC(C)(C)C)c3nsc(N)n3)[C@H]2SC1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=CO
Product: C#CCn1nnnc1SCC1=C(C(=O)O)N2C(=O)C(NC(=O)C(=NOCC(=O)O)c3nsc(N)n3)[C@H]2SC1
Temperature: 25 °C
Yield: 31.3 %

Procedure:
A mixture of 7-[2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (syn isomer)(3.5 g), formic acid (35 ml) and conc. hydrochloric acid (1.0 ml) was stirred for an hour at room temperature. The reaction mixture was evaporated and the residue was pulverized with diethyl ether and dried. Thus obtained product (3.2 g) was dissolved in an aqueous solution of sodium bicarbonate and ethyl acetate was added thereto. The mixture was adjusted to pH 1 with 6N hydrochloric acid and then filtered. The ethyl acetate layer was separated from the filtrate, washed with a saturated aqueous solution of sodium chloride, treated with activated charcoal, dried over magnesium sulfate and then evaporated. The residue was pulverized with diethyl ether and dried to give a crude product (2.0 g). The product was dissolved in an aqueous solution of sodium bicarbonate and the solution was acidified with 6N hydrochloric acid. The precipitates were collected by filtration, washed with water and then dried to give 7-[2-carboxymethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (1.0 g), mp 160° to 165° C. (dec.).