Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:13][OH:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[S:27](Cl)([C:30]1[CH:36]=[CH:35][C:33]([CH3:34])=[CH:32][CH:31]=1)(=[O:29])=[O:28]>C(Cl)Cl>[CH3:34][C:33]1[CH:35]=[CH:36][C:30]([S:27]([O:14][CH2:13][C@H:12]([NH:11][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:29])=[O:28])=[CH:31][CH:32]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: O=C(N[C@@H](CO)c1ccccc1)OCc1ccccc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OC[C@H](NC(=O)OCc2ccccc2)c2ccccc2)cc1
Reaction time: 8 h

Procedure:
53.9 g of (R)-2-benzyloxycarbonylamino-2-phenylethanol (198.7 mmol) were dissolved in a mixture of 500 ml of methylene chloride and 80.3 ml (993.5 mmol) of pyridine. 45.5 g (238.4 mmol) of tosyl chloride in 240 ml of methylene chloride were added at 0° C. with stirring and the mixture was stirred at room temperature for 7 hours. A further 11.36 g of tosyl chloride (59.61 mmol) were added. The mixture was stirred at 0° C. for 5 hours. The batch was then allowed to stand overnight at room temperature and concentrated in vacuo. The residue was taken up in ethyl acetate. The organic phase was washed three times with 10% strength aqueous citric acid solution and twice with water, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated with diethyl ether, filtered off with suction, washed with diethyl ether and dried over phosphorus pentoxide. Yield: 60.9 g (72%). The mother liquor was concentrated, taken up in n-heptane/ethyl acetate (6/4) and chromatographed on silica gel to give an additional yield of 3.5 g (4.2%).
Reaction SMILES: Cl.[CH2:2]([O:9][NH2:10])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:11]N(P(N(C)C)(N(C)C)=O)C.CI>O.[Cl-].[Na+].O>[CH2:2]([O:9][NH:10][CH3:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CN(C)P(=O)(N(C)C)N(C)C
Reactant: NOCc1ccccc1
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: CI
Solvent: O
Product: CNOCc1ccccc1

Procedure:
To a stirred solution of O-benzylhydroxyl amine hydrochloride (1.59 g, 10 mmole) in 15 ml of dry HMPA containing dry sodium bicarbonate (3.36 g, 40 mmole) was added methyl iodide (1.5 g, 11 mmole). After 5 hours the resulting mixture was diluted with 30 ml of water and 20 ml of brine and extracted three times with ethyl ether. The extracts were combined, washed, dried and evaporated to produce the crude product as an oil. The oil was chromatographed to afford 800 mg of title C compound, with consistent spectral data.
Reaction SMILES: [Li+].CC([N-]C(C)C)C.C1CCCCC1.[C:15]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])(=[O:17])[CH3:16].I[CH2:24][CH2:25][CH2:26][Si:27]([O:32][CH3:33])([O:30][CH3:31])[O:28][CH3:29]>C1COCC1>[CH3:29][O:28][Si:27]([O:32][CH3:33])([O:30][CH3:31])[CH2:26][CH2:25][CH2:24][CH2:16][C:15]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17]
Reactant: CO[Si](CCCI)(OC)OC
Reactant: CC(=O)OC(C)(C)C
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: C1CCCCC1
Product: CO[Si](CCCCC(=O)OC(C)(C)C)(OC)OC
Temperature: -78 °C
Reaction time: 1 h
Yield: 96.4 %

Procedure:
To an 1.5 M solution of LDA.THF in cyclohexane (53.33 mL, 80.00 mmol) and THF (160 mL), cooled to −78° C. in a dry ice/acetone bath, t-butyl acetate (9.29 g, 80.00 mmol) was added dropwise over 15 min. After 1 h at −78° C., 3-iodopropyltrimethoxysilane (23.21 g, 80.00 mmol) was added dropwise over 15 min. The reaction mixture was allowed to stir at −78° C. for 1 h, sealed with a teflon stopper, and kept in a freezer at −15° C. for 3 days. The cold reaction mixture was vacuum filtered through silica gel (300 mL), eluted with 1:1 hexanes/THF (600 mL), and concentrated to provide 21.48 g of a pale yellow oil. A quick distillation produced the volatile components, and 17.76 g of a colorless oil was recovered: bp 55-85° C. (0.2 mm). This material was purified by fractional distillation to provide 6.26 g (28%) of a colorless oil: bp 62-3° C. (0.03 mm); 1 HNMR (CDCl3) δ 3.56 (s, OMe), 2.21 (t, CH2CO), 1.62 (quintet, CH2), 1.45 (m, CH2), 1.44 (s, tBu), 0.66 (m, CH2Si).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([C:9]([CH3:12])([CH3:11])[CH3:10])=[C:6]([OH:8])[CH:7]=1.[Br:13]C1C=CC(O)=CC=1.C(O)(C)(C)C.S(=O)(=O)(O)O>C(Cl)(Cl)(Cl)Cl>[Br:13][C:3]1[CH:2]=[CH:7][C:6]([OH:8])=[C:5]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:4]=1
Reactant: Oc1ccc(Br)cc1
Reactant: CC(C)(C)c1ccc(Br)cc1O
Agent: O=S(=O)(O)O
Solvent: CC(C)(C)O
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C)c1cc(Br)ccc1O
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Using the same general procedure as for the preparation of 5-bromo-2t-butylphenol (Compound D), but instead using 50.00 g (289.0 mmol) of 4-bromophenol, 21.40 g (27.25 ml, 289.0 mmol) of t-butanol, 14.0 ml of conc. sulfuric acid (added slowly) and 140 ml of distilled carbon tetrachloride, stirred at room temperature for 24 hours produced a dull green-colored solution and a white precipitate. At this time an additional 3.5 ml of conc. sulfuric acid was added and the solution was allowed to stir for 4 days at room temperature. After aqueous workup, a dark yellow oil was isolated. Purification by flash chromatography (silica, 2% ethyl acetate in hexane) yielded the title compound as a clear, light yellow oil. PMR (CDCl3): d 1.38 (9H, s), 4.79 (1H, s), 6.54 (1H, d, J=8.5 Hz), 7.16 (1H, dd, J=8.5, 2.5 Hz), 7.35 (1H, d, J=2.5 Hz).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[N:13][C:14]([C:15]([NH2:17])=[O:16])=[C:10]3[CH2:9][N:8]=[C:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[C:6]=2[CH:25]=1.CC(C)C(O)=O.[CH3:32][C:33]([N:35]([CH3:37])[CH3:36])=O>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[N:13][C:14]([C:15]([N:17]=[CH:32][CH2:33][N:35]([CH3:37])[CH3:36])=[O:16])=[C:10]3[CH2:9][N:8]=[C:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[C:6]=2[CH:25]=1
Reactant: CC(=O)N(C)C
Reactant: NC(=O)c1ncn2c1CN=C(c1ccccc1Cl)c1cc(Cl)ccc1-2
Solvent: CC(C)C(=O)O
Product: CN(C)CC=NC(=O)c1ncn2c1CN=C(c1ccccc1Cl)c1cc(Cl)ccc1-2
Temperature: 115 °C

Procedure:
A mixture of 0.0047 mole 8-chloro-6-(2-chlorophenyl)-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxamide and 3 ml of dimethyl acetamide dimethyl acetate was heated in an oil bath at a temperature of about 115° C. After cooling the crystals were collected on a glass filter and washed with dimethyl formamide (DMF) and ether.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([OH:14])=O)[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17].FC1C(OC(N(C)C)=[N+](C)C)=C(F)C(F)=C(F)C=1F.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[CH3:63][CH:64]1[CH2:69][CH2:68][NH:67][CH2:66][CH2:65]1>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([N:67]1[CH2:68][CH2:69][CH:64]([CH3:63])[CH2:65][CH2:66]1)=[O:14])[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17]
Reactant: CC(Nc1ncnc2cc(C(=O)O)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1
Reactant: CC1CCNCC1
Agent: CN(C)C(Oc1c(F)c(F)c(F)c(F)c1F)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CC1CCN(C(=O)c2cc3ncnc(NC(C)c4nc5cc(Cl)ccc5[nH]4)c3cc2Cl)CC1

Procedure:
Prepared analogously to Example 37a from 6-chloro-4-[1-(5-chloro-1H-benzimidazol-2-yl)-ethylamino]-7-hydroxycarbonyl-quinazoline, pentafluorophenyl-tetramethyluronium-hexafluorophosphate (PFTU), diisopropylethylamine and 4-methyl-piperidine in DMSO at ambient temperature.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]=[C:12]=[O:13])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:14][C:15]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:16]=1[C:17](O)=[O:18]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([N:11]2[C:17](=[O:18])[C:16]3[C:15](=[CH:23][CH:22]=[C:21]([O:24][CH3:25])[CH:20]=3)[NH:14][C:12]2=[O:13])(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: O=C=NS(=O)(=O)c1ccc(Cl)cc1
Reactant: COc1ccc(N)c(C(=O)O)c1
Product: COc1ccc2[nH]c(=O)n(S(=O)(=O)c3ccc(Cl)cc3)c(=O)c2c1
Yield: 64.7 %

Procedure:
1.00 g (4.59 mmol) of 4-chlorobenzenesulfonylisocyanate and 698 mg (4.18 mmol) of 2-amino-5-methoxybenzoic acid were treated in the same way as in Example 1 to obtain 992 mg of the above-identified compound (yield 64.8%). Properties: colorless crystal, Melting point: 192°-194° C., PMR (δppm, DMSO-d6): 3.79 (3H,s), 7.08 (1H,d), 7.30 (2H,m), 7.75 (2H,d), 8.16 (2H,d), 11.48 (1H,br).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[C:5](Cl)=[N:6][CH:7]=1.[CH3:12][O-:13].[Na+].O>CO>[Br:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[C:5]([O:13][CH3:12])=[N:6][CH:7]=1
Reactant: C[O-]
Reactant: O=[N+]([O-])c1cc(Br)cnc1Cl
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COc1ncc(Br)cc1[N+](=O)[O-]
Temperature: 20 °C

Procedure:
To a suspension of 5-bromo-2-chloro-3-nitropyridine (75.0 g, 1 wt, 1 eq) in methanol (300 mL, 4 vols), is added a solution of sodium methoxide in methanol (25 wt %, 88.6 g, 1.3 eq) over approximately 1 hour so as to maintain the internal temperature at 20±5° C. The mixture is stirred at 20° C. for at least 0.5 hr, then monitored for completion by HPLC. Water (375 mL, 5 vols) is then added to the mixture at such a rate as to maintain the internal temperature below 30° C., then aged at this temperature for at least 0.5 hr. The batch is then concentrated to 6 vols in vacuo. The resulting slurry is allowed to cool to 20-25° C., then collected by vacuum filtration, washed with water and dried in vacuo with a nitrogen bleed at 20-25° C. to constant weight to afford 5-bromo-2-methoxy-3-nitropyridine as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:8])=[N:6][CH:7]=1.[N-:9]([C:12]#[N:13])[C:10]#[N:11].[Na+]>>[C:10]([N:9]=[C:12]([NH2:13])[NH:1][C:2]1[CH:7]=[N:6][C:5]([F:8])=[CH:4][CH:3]=1)#[N:11]
Reactant: Nc1ccc(F)nc1
Reactant: N#C[N-]C#N
Agent: [Na+]
Product: N#CN=C(N)Nc1ccc(F)nc1

Procedure:
A solution of 5-amino-2-fluoropyridine and sodium dicyanamide was processed as described in Example 71A to provide the desired product.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([NH2:11])[C:7]=1[C:8]([NH2:10])=[O:9].Cl[C:13]1[S:14][C:15]([CH3:18])=[CH:16]N=1>>[CH3:18][C:15]1[S:14][C:13]2=[N:11][C:6]3[C:7]([C:8](=[O:9])[N:10]2[CH:16]=1)=[C:2]([F:1])[CH:3]=[CH:4][CH:5]=3
Reactant: Cc1cnc(Cl)s1
Reactant: NC(=O)c1c(N)cccc1F
Product: Cc1cn2c(=O)c3c(F)cccc3nc2s1
Yield: 82.3 %

Procedure:
10.8 g of 6-fluoroanthanilamide and 9.4 g of 2-chloro-5-methylthiazole were stirred for 7 hours at 150° C. After working up in the conventional manner there was obtained 13.5 g (83%) of the above compound; m.p. 245°-246° C.
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4](NCC2C=CC(OC)=CC=2)[N:3]=1.[H-].[Na+].I[CH:24]([CH3:26])[CH3:25].O>CN(C=O)C>[CH:24]([C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[CH:4][N:3]=1)([CH3:26])[CH3:25]
Reactant: CC(C)I
Reactant: COc1ccc(CNc2nc(Cl)nc3nc[nH]c23)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)c1ncc2[nH]cnc2n1
Reaction time: 0.5 h

Procedure:
2-chloro-6-(4-methoxybenzylamino)purine was suspended in dry DMF (5 ml) and treated with sodium hydride, 60% dispersion (82 mg, 2.06 mmol). The suspension was stirred for 30 min over which time it became a clear yellow/green solution. 2-Iodopropane (0.280 mL, 1.7 eq.) was added over 5 min and the resultant solution stirred for 2 days. Water was added and the solution and extracted with ethyl acetate. The organic layer was evaporated to give the product isopropyl purine.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.[N:10]1([CH2:15][C:16]2[CH:17]=[CH:18][C:19](Br)=[N:20][CH:21]=2)[CH:14]=[CH:13][N:12]=[CH:11]1>>[N:10]1([CH2:15][C:16]2[CH:17]=[CH:18][C:19]([C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)=[N:20][CH:21]=2)[CH:14]=[CH:13][N:12]=[CH:11]1
Reactant: OB(O)c1cccnc1
Reactant: Brc1ccc(Cn2ccnc2)cn1
Product: c1cncc(-c2ccc(Cn3ccnc3)cn2)c1

Procedure:
Synthesized using 3-pyridylboronic acid (206 mg, 1.68 mmol) and 1a (200 mg, 0.84 mmol) according to Method C. Yellow solid. Yield: 144 mg, 0.61 mmol, 73%. 1H NMR (CDCl3, 500 MHz): δH (ppm): 5.20 (s, 2H), 6.93 (t, J=1.5 Hz, 1H), 7.13 (t, J=0.9 Hz, 1H), 7.40 (ddd, J=7.9, 4.7, 0.9 Hz, 1H), 7.52 (dd, J=8.2, 2.2 Hz, 1H), 7.60 (s, 1H), 7.75 (d, J=8.2 Hz), 8.29-8.32 (m, 1H), 8.61 (m, 1H), 8.66 (dd, J=4.7, 1.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz): δC (ppm)=48.0, 119.0, 120.6, 123.6, 130.5, 131.0, 134.0, 134.3, 135.9, 137.3, 148.2, 148.9, 150.3, 155.0. MS (ESI): m/z=237.03 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9](=[O:18])[C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:4][CH:3]=1.Br[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=1>>[CH3:1][C:2]1[N:7]=[CH:6][C:5]([N:8]([CH2:20][CH2:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]([F:29])([F:30])[F:31])=[CH:26][CH:27]=2)[C:9](=[O:18])[C:10](=[O:17])[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[CH:4][CH:3]=1
Reactant: FC(F)(F)c1ccc(CCBr)cc1
Reactant: Cc1ccc(NC(=O)C(=O)c2ccccc2)cn1
Product: Cc1ccc(N(CCc2ccc(C(F)(F)F)cc2)C(=O)C(=O)c2ccccc2)cn1

Procedure:
In analogy to the procedure described for the synthesis example 43 (step 2), the title compound N-(6-methyl-pyridin-3-yl)-2-oxo-2-phenyl-N-[2-(4-trifluoromethyl-phenyl)-ethyl]-acetamide (MS m/e: 413.2 [M+H]+) was prepared from N-(6-methyl-pyridin-3-yl)-2-oxo-2-phenyl-acetamide and 1-(2-bromo-ethyl)-4-trifluoromethyl-benzene.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9].C(=O)([O-])[O-].[K+].[K+].Br[CH2:17][CH2:18][NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23]>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH2:17][CH2:18][NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23]
Reactant: COc1ccccc1O
Reactant: CC(C)(C)OC(=O)NCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccccc1OCCNC(=O)OC(C)(C)C
Reaction time: 24 h
Yield: 97.3 %

Procedure:
A mixture of 2-methoxyphenol (9.8 mL, 89.3 mmol), dimethylformamide (100 mL) and potassium carbonate (61.5 g, 445 mmol) was stirred at 23° C. while as tert-butyl 2-bromoethylcarbamate (20 g, 89.3 mmol) was added. The mixture was stirred for 24 hours and then poured into ethyl ether:hexanes (1:1, 400 mL) and was washed with water (5×50 mL). The aqueous layer was extracted with ethyl ether:hexanes (1:1, 3×40 mL) and the combined organic layers were dried (Na2SO4) and concentrated in vacuo to provide tert-butyl 2-(2-methoxyphenoxy)ethylcarbamate (23.22 g, 97% yield) as a yellow oil; MS (PB-PCI) C14H21NO4 m/e calc 267.32; found 268 (MH+).
Reaction SMILES: [C:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([OH:18])=[O:17])=[CH:13][CH:14]=3)[NH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.[C:19]([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C>[C:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[NH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1
Reactant: O=C(O)c1ccc2c(C3=CCCCC3)c[nH]c2c1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: COC(=O)c1ccc2c(C3=CCCCC3)c[nH]c2c1
Temperature: 20 °C
Reaction time: 18 h
Yield: 99 %

Procedure:
A solution (0.1 M) of 3-cyclohex-1-en-1-yl-1H-indole-6-carboxylic acid (prepared as described in International patent application publication WO2004/087714) in dry DMF was cooled to 0° C. and treated with K2CO3 (1.05 eq). A solution (3 M) of MeI (1.05 eq) in DMF was then added over 0.5 h, and the temperature was raised to 20° C. After 18 h, the reaction was quenched with aqueous HCl(1N) and diluted with EtOAc. The organic phase was separated and washed several times with aqueous HCl(1N), then with brine. The dried organics were concentrated to give the title compound (99%) as a solid; (ES+) m/z 256 (M+H)+.
Reaction SMILES: [CH2:1](O)/[CH:2]=[CH:3]/[CH:4]=[CH:5]/[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]CC.C1(P([N:28]=[N+:29]=[N-:30])(C2C=CC=CC=2)=O)C=CC=CC=1.C1CCN2C(=NCCC2)CC1>C1(C)C=CC=CC=1>[N:28]([CH2:1]/[CH:2]=[CH:3]/[CH:4]=[CH:5]/[CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])=[N+:29]=[N-:30]
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: CCCCCCC/C=C/C=C/CO
Solvent: C1CCC2=NCCCN2CC1
Solvent: Cc1ccccc1
Product: CCCCC/C=C/C=C/CN=[N+]=[N-]

Procedure:
(2E,4E)-Dodeca-2,4-dien-1-ol (4.95 g) was dissolved in dry toluene (110 ml) and diphenylphosphinyl azide (7.92 g) was added. DBU (4.91 ml) was added dropwise. The mixture turned opaque under evolution of heat. The solvent was evaporated and diethyl ether was added to the residue. The reaction mixture was washed with 1M HCl, 1M NaOH and brine and the organic layer was dried over sodium sulfate, filtered and concentrated to give a light yellow liquid. The crude product was filtered over silica gel.
Reaction SMILES: C([O:4][C:5]1([O:33][C@H:32]([CH2:34][O:35]C(=O)C)[C@@H:23]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:14]1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:6]([F:13])([F:12])[C:7]([O:9][CH2:10][CH3:11])=[O:8])(=O)C.[O-]CC.[Na+].C(O)(=O)C>C(O)C>[F:13][C:6]([F:12])([C:5]1([O:33][C@H:32]([CH2:34][OH:35])[C@@H:23]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:14]1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[OH:4])[C:7]([O:9][CH2:10][CH3:11])=[O:8]
Reactant: CCOC(=O)C(F)(F)C1(OC(C)=O)O[C@H](COC(C)=O)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Agent: CC[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCO
Product: CCOC(=O)C(F)(F)C1(O)O[C@H](CO)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Reaction time: 1.5 h

Procedure:
To a stirred solution of 1.83 g of 2-deoxy-2,2-difluoro-4,5-bis-O-(phenylmethyl)-D-arabino-3-heptulofuranosonic acid, ethyl ester diacetate in 5.1 ml of ethanol was added 3.4 ml of 1.5M sodium ethoxide in ethanol at 25° C. After 1.5 hours, the mixture was treated with 0.61 ml of glacial acetic acid and partitioned with ether and water. The organic layer was washed with water, sodium bicarbonate solution, and brine, dried and concentrated. The residue was subjected to column chromatography on silica gel to give an oil; CMR δ 100.1 (triplet, J=29.6 Hz, anomeric carbon)
Reaction SMILES: [F:1][C:2]1[C:7]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][C:3]=1[C:14](=[O:16])[CH3:15].C(=O)([O-])[O-].[K+].[K+].[CH2:23](Br)[CH:24]=[CH2:25]>C(#N)C>[CH2:25]([N:11]1[CH2:10][CH2:9][CH:8]([C:7]2[C:2]([F:1])=[C:3]([C:14](=[O:16])[CH3:15])[CH:4]=[CH:5][CH:6]=2)[CH2:13][CH2:12]1)[CH:24]=[CH2:23]
Reactant: C=CCBr
Reactant: CC(=O)c1cccc(C2CCNCC2)c1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: C=CCN1CCC(c2cccc(C(C)=O)c2F)CC1

Procedure:
Preparation according to Example 1: 1-(2-fluoro-3-piperidin-4-ylphenyl)ethanone (0.01 g), acetonitrile (2 ml), potassium carbonate (0.01 g) and allylbromide (0.01 g). MS m/z (rel. intensity, 70 eV) 261 (M+, 89), 260 (82), 234 (bp), 218 (25), 82 (32).
Reaction SMILES: [CH:1]([CH:3]1[CH2:20][CH2:19][C@@:18]2([CH3:21])[C@@H:5]([C@@H:6]([OH:23])[CH2:7][C@@H:8]3[C@@H:17]2[CH2:16][CH2:15][C@@:13]2([CH3:14])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[OH:22])[CH2:4]1)=O.[OH-].[Na+].Cl.Cl.[NH2:28][CH2:29][CH2:30][O:31][NH2:32]>O1CCOCC1.O.O>[NH2:28][CH2:29][CH2:30][O:31]/[N:32]=[CH:1]\[C@H:3]1[CH2:20][CH2:19][C@@:18]2([CH3:21])[C@@H:5]([C@@H:6]([OH:23])[CH2:7][C@@H:8]3[C@@H:17]2[CH2:16][CH2:15][C@@:13]2([CH3:14])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[OH:22])[CH2:4]1
Reactant: NCCON
Reactant: C[C@]12CCC(C=O)C[C@@H]1[C@@H](O)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)CC[C@@H]12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: C[C@]12CC[C@H](/C=N\OCCN)C[C@@H]1[C@@H](O)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)CC[C@@H]12
Reaction time: 0.25 h

Procedure:
A solution of 3-formyl-5α-androstan-6α,17β-diol (II-c, Prep. 3, 240 mg) in dioxane/water (2/1, 30 mL) was treated with sodium hydroxide (0.1 N) to pH=13-14 and stirred for 15 minutes, then a solution O-(2-aminoethyl)-hydroxylamine dihydrochloride (170 mg) in water (3 mL) was poured in. After 1 hr. the organic solvent was distilled off and the acqueous solution was extracted with chloroform (5×20 mL). The combined organic layers were dried over sodium sulfate and evaporated to dryness under reduced pressure. The residue was purified by flash chromatography (SiO2, chloroform/methanol/ammonia 90/10/1) to give (Z)-3β-(2-aminoethoxyiminomethyl)-5α-androstan-6α,17β-diol, which was dissolved in ethyl acetate/methanol 70/30 and treated with oxalic acid to give 85 mg of (Z)-3β-(2-aminoethoxyiminomethyl)-5α-androstan-6α,17β-diol oxalate (I-d) as a white solid mp 190-192° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:23]=[CH:24][C:25]=1[N:26]1[CH2:30][C:29](=[O:31])[NH:28][S:27]1(=[O:33])=[O:32])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][C:20]([OH:22])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(O[N:42]1N=N[C:44]2C=CC=N[C:43]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.C(N)C.Cl>CS(C)=O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:23]=[CH:24][C:25]=1[N:26]1[CH2:30][C:29](=[O:31])[NH:28][S:27]1(=[O:32])=[O:33])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][C:20]([NH:42][CH2:43][CH3:44])=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)Cc1ccccc1Cc1ccc(N2CC(=O)NS2(=O)=O)c(OCc2ccccc2)c1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: CCN
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CCNC(=O)Cc1ccccc1Cc1ccc(N2CC(=O)NS2(=O)=O)c(OCc2ccccc2)c1
Reaction time: 0.08 h

Procedure:
To a solution of {2-[3-benzyloxy-4-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-benzyl]-phenyl}-acetic acid (40 mg, 0.86 mmol) in DMSO (0.7 mL) is added HATU (49 mg, 0.129 mmol) and diisopropylethylamine (0.045 mL, 0.256 mmol). The mixture is stirred for 5 min then ethylamine (0.086 mL, 2M in THF) is added dropwise. Upon completion of the reaction, the mixture is acidified with 1N HCl and extracted with EtOAc. The organic phase is washed with brine and dried over magnesium sulfate. The solvent is removed under reduced pressure to give the title compound which is used directly in the next step.
Reaction SMILES: [O:1]1[CH2:3][CH:2]1[CH:4]([N:12]=[CH:13][B:14]=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[NH2:16][CH2:17][CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[CH2:20][CH2:19]1>C(O)(C)C>[OH:1][CH:2]([CH:4]([N:12]=[CH:13][B:14]=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:3][NH:16][CH2:17][CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[O:25])[CH2:20][CH2:19]1
Reactant: O=BC=NC(Cc1ccccc1)C1CO1
Reactant: NCC1CCN(C(=O)OCc2ccccc2)CC1
Solvent: CC(C)O
Product: O=BC=NC(Cc1ccccc1)C(O)CNCC1CCN(C(=O)OCc2ccccc2)CC1
Yield: 121.6 %

Procedure:
1-(oxiran-2-yl)-N-((oxoboryl)methylene)-2-phenylethanamine (1.61 mmol, 424 mg) and benzyl 4-(aminomethyl)piperidine-1-carboxylate (1.94 nmnol, 480 mg) in isopropanol (20 mL) was heated at 80° C. for overnight. Evaporated the solvent and purified by flash chromatography to get benzyl 4-((2-hydroxy-3-((oxoboryl)methyleneamino)-4-phenylbutylamino)methyl)piperidine-1-carboxylate (880 mg). 1H NMR (300 MHz, CDCl3), δ: 7.363-7.174 (m, 10H), 5.118 (s, 2H), 4.767 (br, 1H), 4.187 (m, 2H), 3.786 (m, 1H), 3.458 (m, 1H), 3.023-2.671 (m, 6H), 2.484 (d, J=6.6 Hz, 2H), 1.733 (m, 2H), 1.600 (m, 1H), 1.347 (s, 9H), 1.135 (m, 2H).