Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O1CCCC1.COP([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])(OC)=O.[H-].[Na+].[CH:22]([C:26]1[CH2:27][C@@H:28]2[C@H:31]([CH:32]=1)[C:30](=O)[CH2:29]2)([CH2:24][CH3:25])[CH3:23]>O>[CH:22]([C:26]1[CH2:32][C@@H:31]2[C@H:28]([CH:27]=1)[C:29](=[CH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:30]2)([CH2:24][CH3:25])[CH3:23]
Reactant: COP(=O)(CC(=O)OC(C)(C)C)OC
Reactant: CCC(C)C1=C[C@@H]2C(=O)C[C@@H]2C1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCC(C)C1=C[C@@H]2C(=CC(=O)OC(C)(C)C)C[C@@H]2C1
Temperature: 0 °C
Reaction time: 0.33 h

Procedure:
A tetrahydrofuran (15 mL) solution of tert-butyl dimethylphosphonoacetate (3.70 g, 16.5 mmol) was added dropwise at 0° C. over 20 minutes to a tetrahydrofuran (15 mL) suspension of sodium hydride (0.68 g, 63%, 18.0 mmol), and the mixture was stirred at 0° C. for 20 minutes. To this solution, a tetrahydrofuran (15 mL) solution of (±)-(1S,5R)-3-sec-butylbicyclo[3.2.0]hept-3-en-6-one (2.48 g, 15.1 mmol) was added dropwise at 0° C. over 15 minutes, and the mixture was stirred at room temperature for 2 hours. The mixture was treated with water, followed by extraction with diethyl ether. The organic layer was dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the compound of interest as a yellow oil substance (3.10 g, 78%).
Reaction SMILES: [CH:1]([O:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]3[CH:19]=[CH:18]S[CH:16]=3)[CH:13]=2)[N:8]=[CH:7][N:6]=1)([CH3:3])[CH3:2].BrC1[CH:22]=[C:23]2C(=CC=1)N=[CH:26][N:25]=[C:24]2[O:31]C(C)C.CNC(C1C=CC(B(O)O)=CC=1)=O>>[CH:1]([O:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]3[CH:19]=[CH:18][C:23]([C:24]([NH:25][CH3:26])=[O:31])=[CH:22][CH:16]=3)[CH:13]=2)[N:8]=[CH:7][N:6]=1)([CH3:3])[CH3:2]
Reactant: CC(C)Oc1ncnc2ccc(-c3ccsc3)cc12
Reactant: CC(C)Oc1ncnc2ccc(Br)cc12
Agent: CNC(=O)c1ccc(B(O)O)cc1
Product: CNC(=O)c1ccc(-c2ccc3ncnc(OC(C)C)c3c2)cc1

Procedure:
The title compound was prepared in an analogous method to 4-isopropoxy-6-thiophene-3-yl-quinazoline, starting with 6-Bromo-4-isopropoxy-quinazoline and using 4-(N-methylaminocarbonyl)phenyl boronic acid. The product was characterized by its mass spectrum MS and HPLC retention time: MS (m/z) 321.03 [M+H]+; HPLC Rt=1.66 minutes (Method A).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([NH:14][CH2:15][CH2:16][C:17]3[N:18]=[N:19][N:20]([CH:22](C)[CH3:23])[N:21]=3)=[O:13])[N:10]=2)[CH:7]=1.Cl.C(N1N=NC(CCN)=N1)(C)C.C(N1N=NC(CCN)=N1)C>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([NH:14][CH2:15][CH2:16][C:17]3[N:18]=[N:19][N:20]([CH2:22][CH3:23])[N:21]=3)=[O:13])[N:10]=2)[CH:7]=1
Reactant: CC(C)n1nnc(CCNC(=O)Nc2cn3cc(Br)ccc3n2)n1
Agent: CC(C)n1nnc(CCN)n1
Agent: CCn1nnc(CCN)n1
Agent: Cl
Product: CCn1nnc(CCNC(=O)Nc2cn3cc(Br)ccc3n2)n1

Procedure:
This compound is prepared analogously to Intermediate E1 (described in preparation of intermediates section) by replacing 2-(2-isopropyl-2H-tetrazol-5-yl)-ethylamine hydrochloride (Intermediate D1) with 2-(2-ethyl-2H-tetrazol-5-yl)-ethylamine (Intermediate D2).
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]1([CH:17]([CH3:21])[C:18]([OH:20])=[O:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.Br[CH2:23][CH2:24][C@@H:25]([CH3:28])[CH2:26][CH3:27]>O1CCCC1>[CH3:21][C:17]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([CH2:23][CH2:24][C@@H:25]([CH3:28])[CH2:26][CH3:27])[C:18]([OH:20])=[O:19]
Reactant: CC(C(=O)O)c1ccccc1
Reactant: CC[C@H](C)CCBr
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CC[C@H](C)CCC(C)(C(=O)O)c1ccccc1
Reaction time: 17 h
Yield: 90 %

Procedure:
Lithium bis(trimethylsilyl)amide (3.23 g, 19.3 mmol) was added to 8 mL of tetrahydrofuran and the resulting solution was cooled in an ice bath. Addition of a solution of 2-phenyl-propionic acid (1.16 g, 7.73 mmol) in 1 mL of tetrahydrofuran to the reaction solution was followed by addition of (S)-1-bromo-3-methyl-pentane (2.05 g, 12.4 mmol). The reaction vessel was removed from the cooling bath, placed in a 50° C. oil bath, and the reaction solution was stirred for 17 hours. After concentration, the resulting residue was dissolved in 25 mL of 1 N NaOH, washed with 25 mL of 2:1 hexane/iso-propyl acetate, acidified to pH 1 with 6 N HCl, and extracted with ethyl acetate (3×30 mL). The combined organic layers were dried over Na2SO4 and concentrated to give 1.63 g (90%) of a clear oil. 1H NMR (300 MHz, CDCl3): δ ppm 0.83 m, 6 H) 1.20 m, 5 H) 1.57 (s, 3 H) 1.98 m, 2 H) 7.35 m, 5 H).
Reaction SMILES: C(Cl)Cl.[CH3:4][O:5][C:6]1[C@@:7]2([CH2:31][CH:32]=[C:33]([CH3:35])[CH3:34])[CH2:13][CH:11]3[O:12][C@@:8]2([O:29][CH3:30])[C@H:9]([C:21](=[O:28])[C:22]=1[CH2:23][CH:24]=[C:25]([CH3:27])[CH3:26])[C@:10]3([CH3:20])[CH2:14][CH2:15][CH:16]=[C:17]([CH3:19])[CH3:18].BrB(C)C.CCCCCC.CC[O:48]C(C)=O>>[OH:12][C@@H:11]1[C@@:10]([CH3:20])([CH2:14][CH2:15][CH:16]=[C:17]([CH3:18])[CH3:19])[C@@H:9]2[C@:8]([OH:48])([O:29][CH3:30])[C@@:7]([CH2:31][CH:32]=[C:33]([CH3:34])[CH3:35])([C:6]([O:5][CH3:4])=[C:22]([CH2:23][CH:24]=[C:25]([CH3:26])[CH3:27])[C:21]2=[O:28])[CH2:13]1
Reactant: COC1=C(CC=C(C)C)C(=O)[C@H]2[C@]3(OC)OC(C[C@]13CC=C(C)C)[C@@]2(C)CCC=C(C)C
Reactant: CCOC(C)=O
Agent: CB(C)Br
Solvent: CCCCCC
Solvent: ClCCl
Product: COC1=C(CC=C(C)C)C(=O)[C@@H]2[C@](C)(CCC=C(C)C)[C@@H](O)C[C@@]1(CC=C(C)C)[C@@]2(O)OC
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 88 %

Procedure:
A DCM (2 mL) solution of 15 (29 mg, 6.6 μmol, 1 equiv.) was cooled to −78° C. in a 10-mL teardrop-shaped flask, and a DCM solution of bromodimethylborane (2.65 M, 0.25 mL, 0.66 mmol, 10 equiv.) was added dropwise. After stirring the bright yellow solution at −78° C. for 10 min, it was quenched sequentially at −78° C. with 1.25 mL NEt3 and saturated aqueous NaHCO3. The mixture was warmed to room temperature and extracted thrice with EtOAc. The organic extracts were combined, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to yield a yellow residue. Flash column chromatography (30 mL SiO2, 9:1 hexane:EtOAc) afforded 26.7 mg (58 μmol, 88% yield) of 17 as a yellow oil. TLC Rf 0.38 (7:3 hexane:EtOAc). 1H NMR (600 MHz; C6D6): δ 5.55 (dq, J=11.5, 1.3 Hz, 1H), 5.35 (t, J=7.3 Hz, 1H), 5.28 (t, J=6.6 Hz, 1H), 3.71 (s, 1H), 3.67 (dd, J=11.8, 5.3 Hz, 1H), 3.53 (s, 3H), 3.34 (dd, J=15.2, 6.4 Hz, 1H), 3.16 (m, 1H), 3.14 (s, 1H), 3.06 (s, 3H), 2.92 (dd, J=14.1, 11.5 Hz, 1H), 2.86 (tdd, J=12.8, 7.7, 5.0 Hz, 1H), 2.26 (d, J=14.1 Hz, 1H), 2.08 (tt, J=12.5, 6.1 Hz, 1H), 2.00 (dd, J=12.8, 12.0 Hz, 1H), 1.84 (s, 3H), 1.72 (s, 3H), 1.72-1.68 (m, 1H), 1.62 (s, 6H), 1.60-1.58 (m, 1H), 1.56 (s, 3H), 1.42 (s, 3H), 1.27 (td, J=12.7, 4.4 Hz, 1H), 1.12 (s, 3H). 13C NMR (126 MHz; C6D6): δ 197.3, 171.2, 136.5, 131.8, 131.1, 125.8, 124.5, 123.36, 123.23, 100.2, 73.4, 61.8, 57.5, 52.4, 48.2, 40.9, 39.7, 37.5, 30.8, 26.0, 25.76, 25.72, 23.7, 22.2, 18.01, 17.90, 17.7, 17.3. FTIR (thin film) νmax: 3464 (br), 2969, 2928, 2859, 1665, 1615, 1450, 1376, 1329, 1235, 1087, 1040, 986, 928, 907, 858, 737 cm-1. HRMS-ESI (m/z): [M+H]+ calculated for C28H44O5, 461.3262. found, 461.3254.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[NH:4][C@@H:5]1[C@@H:9]([NH2:10])[CH2:8][N:7]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6]1.[F:19][C:20]([F:28])([CH2:26][Cl:27])[CH2:21][CH2:22][C:23](O)=[O:24].C(N(CC)CC)C>CCOC(C)=O>[CH3:1][O:2][C:3](=[O:18])[NH:4][C@@H:5]1[C@@H:9]([NH:10][C:23](=[O:24])[CH2:22][CH2:21][C:20]([F:28])([F:19])[CH2:26][Cl:27])[CH2:8][N:7]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6]1
Reactant: COC(=O)N[C@H]1CN(Cc2ccccc2)C[C@@H]1N
Reactant: O=C(O)CCC(F)(F)CCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COC(=O)N[C@H]1CN(Cc2ccccc2)C[C@@H]1NC(=O)CCC(F)(F)CCl
Temperature: 25 °C
Yield: 99.9 %

Procedure:
A solution of the product from Step 3 (2.20 g, 8.82 mmol), 4,4-difluoro-5-chloropentanoic acid (1.52 g, 8.82 mmol) and triethylamine (3.57 g, 35.3 mmol) in EtOAc (25 mL) was stirred as propanephosphonic acid cyclic anhydride (5.25 mL of a 50% solution of in EtOAc, 8.82 mmol) was added in one portion. After heating at reflux overnight, the reaction was cooled to room temperature, diluted with EtOAc (300 mL) and washed with saturated sodium carbonate solution. The organic layer was dried over sodium sulfate and concentrated to an oil that was separated by silica gel chromatography (Biotage 25+S (A Dynax Corp.; Charlottesville, Va.) eluting with a dichloromethane/methanol/ammonium hydroxide gradient (100:0:0-95:5:0.25). The desired fractions were concentrated and triturated with di-isopropylether to afford 3.56 g (70%) of the product as a white solid. 1H NMR (400 MHz, Chloroform-d) δ 7.36-7.22 (m, 5H), 6.14-6.00 (br s, 1H), 5.17-5.04 (br s, 1H), 4.17-4.04 (br m, 1H), 4.00-3.86 (br m, 1H), 3.74-3.49 (m, 4H), 3.65 and 3.63 (s, 3H), 3.12-2.94 (m, 2H), 2.49-2.43 (m, 1H), 2.42-2.49 (m, 4H). MS 404.2 (AP+, 100).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[O:18][C:19]3[C:25]([C:26]([O:28]C)=O)=[CH:24][CH:23]=[CH:22][C:20]=3[N:21]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[NH3:31]>CO>[C:26]([C:25]1[C:19]2[O:18][C:17]([CH:14]3[CH2:13][CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[O:10])[CH2:16][CH2:15]3)=[N:21][C:20]=2[CH:22]=[CH:23][CH:24]=1)(=[O:28])[NH2:31]
Reactant: N
Reactant: COC(=O)c1cccc2nc(C3CCN(C(=O)OCc4ccccc4)CC3)oc12
Solvent: O
Solvent: CO
Product: NC(=O)c1cccc2nc(C3CCN(C(=O)OCc4ccccc4)CC3)oc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Methyl 2-(1-(benzyloxycarbonyl)piperidin-4-yl)benzo[d]oxazole-7-carboxylate (102 mg, 0.26 mmol) was added to a mixture of methanol (5 mL) and ammonia water (10 mL) and the mixture was stirred at room temperature for overnight. Then the solid was filtered. 98 mg of solid of benzyl 4-(7-carbamoylbenzo[d]oxazol-2-yl)piperidine-1-carboxylate was obtained. LC-MS (ESI) m/z: 380 (M+1)+.
Reaction SMILES: C([O:3][C:4](=[O:44])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[C:18]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[CH:17]=[C:16]([C:31]#[C:32][C:33]3[CH:38]=[CH:37][C:36]([S:39]([CH3:42])(=[O:41])=[O:40])=[CH:35][CH:34]=3)[CH:15]=2)=[CH:9][C:8]=1[CH3:43])C.[OH-].[Na+].Cl>C(O)C>[CH3:42][S:39]([C:36]1[CH:37]=[CH:38][C:33]([C:32]#[C:31][C:16]2[CH:15]=[C:14]([S:13][C:10]3[CH:11]=[CH:12][C:7]([O:6][CH2:5][C:4]([OH:44])=[O:3])=[C:8]([CH3:43])[CH:9]=3)[CH:19]=[C:18]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:29])([F:30])[F:28])[CH:22]=3)[CH:17]=2)=[CH:34][CH:35]=1)(=[O:41])=[O:40]
Reactant: CCOC(=O)COc1ccc(Sc2cc(C#Cc3ccc(S(C)(=O)=O)cc3)cc(Oc3cccc(C(F)(F)F)c3)c2)cc1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cc1cc(Sc2cc(C#Cc3ccc(S(C)(=O)=O)cc3)cc(Oc3cccc(C(F)(F)F)c3)c2)ccc1OCC(=O)O
Reaction time: 16 h

Procedure:
{4-[3-(4-Methanesulfonyl-phenylethynyl)-5-(3-trifluoromethyl-phenoxy)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid ethyl ester (140 mg; 0.22 mmol) was dissolved in ethanol (15 mL), and aqueous 1 N sodium hydroxide (3 mL) was added. The reaction mixture was stirred for 16 h. acidified with 1 N aqueous hydrochloric acid and extracted with ethyl acetate, dried and evaporated to dryness. The organic phase was purified by preparative HPLC (method B). Yield: 100 mg (75%). HPLC-MS: m/z: 635.1 (M+Na); Rt: 2.62 min.
Reaction SMILES: C([N:8](CC1C=CC=CC=1)[CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][C:17]([O:20][CH3:21])([CH3:19])[CH3:18])[CH2:12][CH2:11]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CO.O.[Pd]>[CH3:21][O:20][C:17]([CH3:19])([CH3:18])[CH2:16][N:13]1[CH2:14][CH2:15][CH:10]([CH2:9][NH2:8])[CH2:11][CH2:12]1
Reactant: COC(C)(C)CN1CCC(CN(Cc2ccccc2)Cc2ccccc2)CC1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CO
Solvent: O
Product: COC(C)(C)CN1CCC(CN)CC1
Temperature: 80 °C
Yield: 74.2 %

Procedure:
To a solution of N,N-dibenzyl-N-{[1-(2-methoxy-2-methylpropyl)piperidin-4-yl]methyl}amine (EXAMPLE 4, Step 5, 756 mg, 1.85 mmol) and ammonium formate (583 mg, 9.24 mmol) in methanol (40 mL) and water (15 mL) was added 10% palladium on carbon (185 mg) at ambient temperature. The mixture was heated at 80° C. for 6 h. After cooling, the mixture was filtered through a pad of Celite and the filtrate was concentrated in vacuo. The obtained residue was partitioned between dichlorometane and aqueous ammonia. After extraction with dichloromethane, the combined organic extract was dried over magnesium sulfate and concentrated to give 275 mg (66%) of the title compound as a pale yellow oil.
Reaction SMILES: [CH2:1]([N:4]([CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1)[C:5]([C:7]1[S:11][CH:10]=[N:9][CH:8]=1)=O)[CH2:2][CH3:3].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:31])=CC=1>O>[CH2:1]([N:4]([CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1)[C:5]([C:7]1[S:11][CH:10]=[N:9][CH:8]=1)=[S:31])[CH2:2][CH3:3]
Reactant: CCCN(CCOc1ccc(Cl)cc1)C(=O)c1cncs1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: O
Product: CCCN(CCOc1ccc(Cl)cc1)C(=S)c1cncs1
Temperature: 25 °C
Yield: 73.3 %

Procedure:
A mixture of the N-propyl-N-[2-(4-chlorophenoxy)ethyl]thiazole-5-carboxamide (0.9 g, 3 mmol) obtained in Example 2B and Lawesson's Reagent (2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulphide, 1.2g, 3 mmol) was refluxed for 20 hours and then cooled to room temperature. Water (100 ml) was added and the residue was extracted into ether (2×200 ml). The combined organic extract was washed with saturated sodium chloride solution (50 ml) and dried over magnesium sulphate. Evaporation of the solvent left an oil which, after flash chromatography on silica gel using 1:1 ethyl acetate: petroleum ether as the eluant, yielded the desired product as a yellow oil (0.75 g), M+ found: 340
Reaction SMILES: [C:1]([NH:8][C@H:9]1[CH2:14][CH2:13][C@@H:12]([C:15]([O:17][C:18]2[CH:27]=[CH:26][C:21]([C:22]([O:24]C)=[O:23])=[C:20]([O:28][CH3:29])[CH:19]=2)=[O:16])[CH2:11][CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].O.O[Li].O>C1COCC1>[C:1]([NH:8][C@H:9]1[CH2:14][CH2:13][C@@H:12]([C:15]([O:17][C:18]2[CH:27]=[CH:26][C:21]([C:22]([OH:24])=[O:23])=[C:20]([O:28][CH3:29])[CH:19]=2)=[O:16])[CH2:11][CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: COC(=O)c1ccc(OC(=O)[C@H]2CC[C@@H](NC(=O)OC(C)(C)C)CC2)cc1OC
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Product: COc1cc(OC(=O)[C@H]2CC[C@@H](NC(=O)OC(C)(C)C)CC2)ccc1C(=O)O
Temperature: 45 °C

Procedure:
To a stirred solution of methyl 4-[N-Boc-cis-1-amino-4-cyclohexanoyloxy]-2-methoxybenzoate (220 mg, 0.52 mmol) in THF:H2O (5 mL: 1 mL) was added LiOH.H2O (67.6 mg, 1.59 mmol). The reaction was heated to 45° C. over 12 h and then cooled to ambient temperature. The solvent was removed under reduced pressure. The crude solid passed through a plug of silca gel packed in 50:50 MeOH:CH2Cl2 and eluted with same. The solvent was removed under reduced pressure to afford 4-[N-Boc-cis-1-amino-4-cyclohexanoyloxy]-2-methoxybenzoic acid as a white solid.
Reaction SMILES: [CH:1](=[CH:8][C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[C:18]([CH2:21][N+]1C=CC=CC=1)(=[O:20])[NH2:19].[OH-].[Na+]>CO.O>[C:11]1([C:9]2[CH:8]=[C:1]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[NH:19][C:18](=[O:20])[CH:21]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: NC(=O)C[n+]1ccccc1
Reactant: O=C(C=Cc1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=c1cc(-c2ccccc2)cc(-c2ccccc2)[nH]1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of benzylideneacetophenone (41.6 g) and N-carbamoylmethylpyridinium chloride (34.4 g) (prepared according to the method of O. ALBRECHT et al., Helv. Chim. Acta 24, 241E (1941)) in methanol (600 cc), is added, at room temperature, a 1N aqueous solution of sodium hydroxide (200 cc). The initially yellow solution takes on an orange colour and a yellow solid precipitates. The mixture is stirred at room temperature for 15 minutes and acetic acid (400 cc) is then added. The green solution obtained is stirred for 1 hour at room temperature. The solvent is then distilled in 4 hours under atmospheric pressure. The solid residue obtained is taken up in distilled water (500 cc). After stirring for 1 hour at more temperature, the solid is separated by filtration, washed with distilled water (3×100 cc) and dried under reduced pressure at 60° C. (whitish solid; m.p.=209°-212° C.)
Reaction SMILES: [O:1]=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.OP([O-])(O)=O.[K+].OP([O-])([O-])=O.[K+].[K+].[Cl-].[K+].[OH:28][C@H:29]1[CH2:34][CH2:33][C@H:32]2[C@H:35]3[C@H:44]([CH2:45][CH2:46][C@:30]12[CH3:31])[C@@H:43]1[C:38](=[CH:39][C:40](=[O:47])[CH2:41][CH2:42]1)[CH2:37][C@H:36]3[CH3:48]>CN(C=O)C>[OH:1][C@@H:45]1[CH2:46][C@@:30]2([CH3:31])[C@@H:32]([CH2:33][CH2:34][C@@H:29]2[OH:28])[C@H:35]2[C@H:44]1[C@@H:43]1[C:38]([CH2:37][C@H:36]2[CH3:48])=[CH:39][C:40](=[O:47])[CH2:41][CH2:42]1
Reactant: C[C@@H]1CC2=CC(=O)CC[C@@H]2[C@H]2CC[C@]3(C)[C@@H](O)CC[C@H]3[C@@H]21
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: O=P([O-])(O)O
Agent: O=P([O-])([O-])O
Agent: [Cl-]
Solvent: CN(C)C=O
Product: C[C@@H]1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CC[C@H](O)[C@@]1(C)C[C@H]2O
Temperature: 28 °C
Reaction time: 0.5 h
Yield: 73 %

Procedure:
A 2 l Erlenmeyer flask that contained 1000 ml of a nutrient solution, sterilized for 30 minutes at 121° C. in an autoclave and consisting of 3% by weight of glucose, 1% by weight of corn steep liquor, 0.2% by weight of NaNO3, 0.1% by weight of KH2PO4, 0.2% by weight of K2HPO4, 0.05% by weight of KCl, 0.05% by weight of MgSO47H2O, and 0.002% by weight of FeSO47H2O (pH 6,0), was inoculated with a slant rod culture of the strain Glomerella cingulata (IFO 6425) and shaken for 72 hours at 28° C. in a rotary shaker at 165 rpm. With this preculture, a 20 l fermenter was inoculated, and said fermenter was coated with 19 l of a sterile medium of the same final composition as described for the preculture. In addition, before the sterilization, another 1.0 ml of silicone oil and 1.0 ml of synperonic were added for foam abatement. After a growth phase of 12 hours at 0.7 bar of overpressure, a temperature of 28° C., an aeration of 10 l/minute and a stirring speed of 350 rpm, a solution of 2.0 g of 17β-hydroxy-7α-methylestr-4-en-3-one in 30 ml DMF was added. Stirring was continued, and it was aerated. After 19 hours, the culture broth was harvested and extracted for 16 hours with 20 l of methyl isobutyl ketone and for 23 hours with 20 l of methyl isobutyl ketone. The combined organic phases were evaporated to the dry state. The residue was dissolved to a large extent in methanol. The silicone oil was filtered off. It was concentrated by evaporation, and after chromatography on silica gel with a gradient that consists of dichloromethane and acetone, 1.55 g (73%) of 11α, 17β-dihydroxy-7α-methylestr-4-en-3-one was isolated. After recrystallization from acetone/diisopropyl ether, 827 mg (39%) of white crystals with a melting point of 163° C. and [α]D=−16° (CHCl3, c=0.501) was isolated.
Reaction SMILES: [CH3:1][O:2][CH2:3][N:4]1[C:9]2[CH:10]=[C:11]([CH:14]=[O:15])[CH:12]=[CH:13][C:8]=2[S:7][C:6]2[N:16]=[CH:17][CH:18]=[N:19][C:5]1=2.[CH3:20][Li]>O1CCCC1.C(OCC)C.ClCCl.[O-2].[O-2].[Mn+4]>[CH3:20][C:14]([C:11]1[CH:12]=[CH:13][C:8]2[S:7][C:6]3[N:16]=[CH:17][CH:18]=[N:19][C:5]=3[N:4]([CH2:3][O:2][CH3:1])[C:9]=2[CH:10]=1)=[O:15]
Reactant: [Li]C
Reactant: COCN1c2cc(C=O)ccc2Sc2nccnc21
Agent: [Mn+4]
Agent: [O-2]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: ClCCl
Product: COCN1c2cc(C(C)=O)ccc2Sc2nccnc21
Temperature: 25 °C
Reaction time: 17 h

Procedure:
Into a solution of 16 g of 10-(methoxymethyl)-10H-pyrazino[2,3-b][1,4]benzothiazine-8-carboxaldehyde in 200 ml of tetrahydrofuran was dropped at −78° C. 60 ml of a 1.4 M solution of methyllithium in diethyl ether. Next, the resulting mixture was heated to room temperature over 2 hours. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, 16 g of a yellow oily substance was obtained. To a solution of 16 g of this oily substance in dichloromethane (300 ml) was added 100 g of manganese dioxide and the resulting mixture was stirred at room temperature for 17 hours. After the completion of the reaction, the manganese dioxide was filtered off. The filtrate was concentrated and the residue thus obtained was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate) to thereby give 9. 4 g of the title compound. as yellow. crystals.
Reaction SMILES: [N:1]([CH2:4][CH:5]1[O:9][C:8](=[O:10])[N:7]([C:11]2[CH:16]=[C:15]([F:17])[C:14]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)=[C:13]([F:24])[CH:12]=2)[CH2:6]1)=[N+]=[N-]>CO.[Pd]>[NH2:1][CH2:4][CH:5]1[O:9][C:8](=[O:10])[N:7]([C:11]2[CH:12]=[C:13]([F:24])[C:14]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)=[C:15]([F:17])[CH:16]=2)[CH2:6]1
Reactant: [N-]=[N+]=NCC1CN(c2cc(F)c(-c3cccnc3)c(F)c2)C(=O)O1
Agent: [Pd]
Solvent: CO
Product: NCC1CN(c2cc(F)c(-c3cccnc3)c(F)c2)C(=O)O1
Reaction time: 16 h

Procedure:
(±)-5-(Azidomethyl)-3-[4-(3-pyridyl)-3,5-difluorophenyl]-2-oxazolidinone (PREPARATION 6, 354 mg, ~1.07 mmol) in methanol (40 ml) and palladium on carbon (10%, 50 mg) are mixed. The mixture is purged with nitrogen and then placed under an atmosphere of hydrogen (1 atm). The reaction is allowed to stir at 20°-25° for 16 hrs. After this time, the reaction is filtered and concentrated under reduced pressure to a solid amine. The crude amine is suitable for acetylation without further purification. An analytical sample is prepared by preparative TLC (SG) methanol/chloroform (10/90). The title compound is recovered as a solid, mp 143°-145°; FTIR (neat) cm-1 3368, 1757, 1646, 1412, 1244, 1025 and 714; MS (El, m/z) 305, 276, 233, 219, 44 and 29; NMR (CDCl3) 8.71, 8.62, 7.79, 7.39, 7.33, 4.79-4.70, 4.06, 3.92, 3.18. 2.98 and 1.52 δ.
Reaction SMILES: C([Si]([O:8][CH2:9][C:10]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:11]=1[N:19]=[C:20]=S)(C)C)(C)(C)C.[CH:22]1([C:25]2[CH:26]=[C:27]([NH2:31])[CH:28]=[CH:29][CH:30]=2)[CH2:24][CH2:23]1>>[CH:22]1([C:25]2[CH:26]=[C:27]([NH:31][C:20]3[O:8][CH2:9][C:10]4[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:11]=4[N:19]=3)[CH:28]=[CH:29][CH:30]=2)[CH2:24][CH2:23]1
Reactant: CC(C)(C)[Si](C)(C)OCc1cc([N+](=O)[O-])ccc1N=C=S
Reactant: Nc1cccc(C2CC2)c1
Product: O=[N+]([O-])c1ccc2c(c1)COC(Nc1cccc(C3CC3)c1)=N2
Yield: 73.6 %

Procedure:
Prepared from tert-butyl-(2-isothiocyanato-5-nitro-benzyloxy)-dimethyl-silane (Example C1) (5.8 g, 18 mmol) and 3-cyclopropyl-phenylamine (2.5 g, 19 mmol) according to the procedure described for Example 1. Obtained the title compound as a yellow foam (4.1 g, 74%), MS (ISP) m/e=310.5 [(M+H)+].