Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Na].[CH:2]1([N:7]2[C:11]([NH2:12])=[C:10]([C:13]([NH2:15])=[O:14])[C:9]([CH2:16][CH3:17])=[N:8]2)[CH2:6][CH2:5][CH2:4][CH2:3]1.[F:18][C:19]([F:33])([F:32])[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27](OCC)=O)=[CH:22][CH:21]=1.Cl>C(O)C.O>[CH:2]1([N:7]2[C:11]3=[N:12][C:27]([CH2:26][C:23]4[CH:22]=[CH:21][C:20]([C:19]([F:18])([F:32])[F:33])=[CH:25][CH:24]=4)=[N:15][C:13](=[O:14])[C:10]3=[C:9]([CH2:16][CH3:17])[NH:8]2)[CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CCOC(=O)Cc1ccc(C(F)(F)F)cc1
Reactant: CCc1nn(C2CCCC2)c(N)c1C(N)=O
Agent: Cl
Agent: [Na]
Solvent: CCO
Solvent: O
Product: CCc1[nH]n(C2CCCC2)c2nc(Cc3ccc(C(F)(F)F)cc3)nc(=O)c1-2
Temperature: 25 °C
Yield: 57.5 %

Procedure:
Sodium (622 mg) was dissolved in ethanol (45 mL) and then 1-cyclopentyl-3-ethyl-5-amino-1H-pyrazole-4-carboxamide (3.0 g, 13.5 mmol), followed by ethyl 4-trifluoromethylphenylacetate (6.27 g, 27 mmol) were added. The reaction mixture was refluxed overnight, cooled to room temperature, and the solvent was stripped. Water, followed by 2N HCl were added to the residue and the product was collected by filtration, recrystallized from ether and dried at 110° C. and 0.2 mm Hg to afford 3.03 g of 1-cyclopentyl-3-ethyl-6-(4-trifluoromethylphenylmethyl)pyrazolo[3,4-d]pyrimidin-4-one, m.p. 212-213° C.
Reaction SMILES: [CH2:1]([C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][CH:4]=1)[CH3:2].Cl.[C:11](OC(=O)C)(=[O:13])[CH3:12].C([O-])(=O)C.[Na+]>O>[CH3:2][CH2:1][C:3]1[CH:9]=[CH:8][C:6]([NH:7][C:11]([CH3:12])=[O:13])=[CH:5][CH:4]=1
Reactant: CC(=O)OC(C)=O
Reactant: CCc1ccc(N)cc1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CCc1ccc(NC(C)=O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 45.7 %

Procedure:
Into a 10-liter reaction flask were introduced 243.8 g (2.01 mol) of 4-ethylaniline, 2 liters of water, 230 g of concentrated hydrochloric acid, and 250 g of acetic anhydride. A solution prepared by dissolving 200 g of sodium acetate in 800 ml of water was added dropwise thereto at 10 to 20° C. This mixture was stirred overnight at room temperature, and the resultant precipitate was taken out by filtration. The crystals were washed with water and recrystallized from methanol (200 ml) to obtain 150 g of the target compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:32])[NH:7][CH2:8][C:9]1[N:10]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:11](=[O:27])[C:12]2[C:17]([C:18]=1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[CH:16][C:15]([CH2:25][NH2:26])=[CH:14][CH:13]=2)([CH3:4])([CH3:3])[CH3:2].Cl[C:34]([O:36][CH2:37][CH3:38])=[O:35].C(N(CC)CC)C>O1CCCC1>[C:1]([O:5][C:6]([NH:7][CH2:8][C:9]1[N:10]([CH2:28][CH:29]([CH3:30])[CH3:31])[C:11](=[O:27])[C:12]2[C:17]([C:18]=1[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[CH:16][C:15]([CH2:25][NH:26][C:34](=[O:35])[O:36][CH2:37][CH3:38])=[CH:14][CH:13]=2)=[O:32])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)Cn1c(CNC(=O)OC(C)(C)C)c(-c2ccccc2)c2cc(CN)ccc2c1=O
Reactant: CCOC(=O)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCOC(=O)NCc1ccc2c(=O)n(CC(C)C)c(CNC(=O)OC(C)(C)C)c(-c3ccccc3)c2c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 71.1 %

Procedure:
To a solution of crude tert-butyl[6-(aminomethyl)-2-isobutyl-1-oxo-4-phenyl-1,2-dihydro-3-isoquinolinyl]methylcarbamate (0.16 g) (Example 285) in tetrahydrofuran (2 mL) were added ethyl chloroformate (0.035 mL, 0.36 mmol) and triethylamine (0.050 mL, 0.36 mmol), and the mixture was stirred at room temperature for 4 h. The reaction mixture was washed with water (4 mL) and concentrated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1 (v/v)) to give ethyl (3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-1-oxo-4-phenyl-1,2-dihydro-6-isoquinolinyl)methylcarbamate (0.13 g, 87%) as pale yellow powder.
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([CH2:5][NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:2]1.CCN(C(C)C)C(C)C.Cl[C:24]([O:26][CH:27]1[CH:34]2[CH2:35][CH:30]3[CH2:31][CH:32]([CH2:36][CH:28]1[CH2:29]3)[CH2:33]2)=[O:25].C(Cl)Cl.Cl>>[C:9]([O:8][C:7]([NH:6][CH2:5][CH:3]1[CH2:4][N:1]([C:24]([O:26][CH:27]2[CH:28]3[CH2:36][CH:32]4[CH2:31][CH:30]([CH2:35][CH:34]2[CH2:33]4)[CH2:29]3)=[O:25])[CH2:2]1)=[O:13])([CH3:10])([CH3:12])[CH3:11]
Reactant: O=C(Cl)OC1C2CC3CC(C2)CC1C3
Reactant: CC(C)(C)OC(=O)NCC1CNC1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCC1CN(C(=O)OC2C3CC4CC(C3)CC2C4)C1
Reaction time: 0.08 h
Yield: 23 %

Procedure:
A vial was charged with tert-butyl azetidin-3-ylmethylcarbamate (25 mg, 0.12 mmol), i-Pr2NEt (31 μL, 0.17 mmol) and a flea stir bar. A solution of 2-adamantyl chloroformate in CH2Cl2 (1.5 mL, 17 mg mL−1, 0.12 mmol) was added. The mixture was stirred overnight at rt. A 10-mL ChemElut cartridge (Varian Inc. catalog number 12198007) was wetted with 5% aq HCl (5 mL) and allowed to stand for 5 min. The reaction mixture was applied to the cartridge and eluted with ether (20 mL). The eluate was evaporated to dryness and the residue was purified by preparative HPLC to afford the title compound (10 mg, 23%). 1H NMR (CDCl3) δ 1.42 (s, 9H), 1.5-2.0 (14H), 2.76 (m, 1H), 3.35 (m, 2H), 3.67 (m, 2H), 4.03 (m, 2H), 4.68 (m, 1H), 4.78 (s, 1H); LC-MS Method 1 tR=2.08 min, m/z=387, 365, 309.
Reaction SMILES: [C:1]([N:9]1[CH2:14][CH2:13][N:12]([C:15](=[O:27])[C:16]([C:18]2C3C(=NC=CC=3)[NH:20][CH:19]=2)=[O:17])[C@H:11](C)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:29][C:30]1[N:31]=[CH:32][C:33]([O:44][CH3:45])=[C:34]2[C:38]=1NC=C2C(=O)C([O-])=O.[K+]>>[C:1]([N:9]1[CH2:14][CH2:13][N:12]([C:15](=[O:27])[C:16]([C:18]2[C:34]3[C:38](=[C:30]([Cl:29])[N:31]=[CH:32][C:33]=3[O:44][CH3:45])[NH:20][CH:19]=2)=[O:17])[CH2:11][CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C[C@@H]1CN(C(=O)c2ccccc2)CCN1C(=O)C(=O)c1c[nH]c2ncccc12
Reactant: COc1cnc(Cl)c2[nH]cc(C(=O)C(=O)[O-])c12
Agent: [K+]
Product: COc1cnc(Cl)c2[nH]cc(C(=O)C(=O)N3CCN(C(=O)c4ccccc4)CC3)c12

Procedure:
Compound 5an, N-(benzoyl)-N′-[(7-chloro-4-methoxy-6-azaindol-3-yl)-oxoacetyl]-piperazine was prepared by the same method which was used to prepare compound 5a except that Potassium (7-chloro-4-methoxy-6-azaindol-3-yl)-oxoacetate was employed as the starting material to give a white solid. The compound was purified by silica gel chromatography using EtOAc as the eluting solvent. MS m/z: (M+H)+ calcd for C21H20ClN4O4: 427.12; found 427.12. HPLC retention time: 1.28 minutes (column A).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:33])[C:25]4[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=4[F:32])[CH:20]=[CH:21][CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.[NH2:34][C:35]1[CH:36]=[C:37]2[C:41](=[CH:42][CH:43]=1)[CH2:40][CH:39]([N:44]([CH3:46])[CH3:45])[CH2:38]2.Cl>C(O)(C)C>[CH3:45][N:44]([CH3:46])[CH:39]1[CH2:38][C:37]2[C:41](=[CH:42][CH:43]=[C:35]([NH:34][C:2]3[N:7]=[C:6]([C:8]4[C:9]([C:17]5[CH:18]=[C:19]([NH:23][C:24](=[O:33])[C:25]6[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=6[F:32])[CH:20]=[CH:21][CH:22]=5)=[N:10][N:11]5[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=45)[CH:5]=[CH:4][N:3]=3)[CH:36]=2)[CH2:40]1
Reactant: CN(C)C1Cc2ccc(N)cc2C1
Reactant: O=C(Nc1cccc(-c2nn3ccccc3c2-c2ccnc(Cl)n2)c1)c1c(F)cccc1F
Agent: Cl
Solvent: CC(C)O
Product: CN(C)C1Cc2ccc(Nc3nccc(-c4c(-c5cccc(NC(=O)c6c(F)cccc6F)c5)nn5ccccc45)n3)cc2C1
Temperature: 180 °C

Procedure:
The title compound was synthesized by combining N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide (152 mg, 0.33 mmol), (5-amino-2,3-dihydro-1H-inden-2-yl)dimethylamine (70 mg, 0.40 mmol), hydrochloric acid (0.033 mmol, 33 uL 1M HCl/diethylether) and 3 mL isopropanol in a sealed vessel. The vial and contents were heated at 180° C. for 30 mins. The reaction was cooled and concentrated. The residue was partitioned between EtOAc and saturated aqueous NaHCO3. The organic layer was washed with brine, dried with MgSO4 and concentrated. The crude material was purified by silica gel column chromatography (0-100% gradient; (90% CH2Cl2:9% MeOH:1% NH4OH/CH2Cl2)) Purification provided 28 mg (14%) of the coupled adduct. ESIMS (M+H)+=603.30.
Reaction SMILES: [Cl:1][C:2]1[C:14]([Cl:15])=[CH:13][C:5]2[N:6]([CH2:10][CH2:11]O)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1.[BrH:16]>O>[Br:16][CH2:11][CH2:10][N:6]1[C:5]2[CH:13]=[C:14]([Cl:15])[C:2]([Cl:1])=[CH:3][C:4]=2[NH:8][C:7]1=[O:9]
Reactant: O=c1[nH]c2cc(Cl)c(Cl)cc2n1CCO
Reactant: Br
Solvent: O
Product: O=c1[nH]c2cc(Cl)c(Cl)cc2n1CCBr
Yield: 87 %

Procedure:
A mixture of 55 parts of 5,6-dichloro-1,3-dihydro-1-(2-hydroxyethyl)-2-H-benzimidazol-2-one and 450 parts of a hydrobromic acid solution 48% in water is stirred and refluxed for 4 hours. The reaction mixture is poured onto ice-water and stirred to room temperature. The precipitated product is filtered off, stirred in water, filtered off again and dried, yielding 55.5 parts (87%) of 1-(2-bromoethyl)-5,6-dichloro-1,3-dihydro-2H-benzimidazol-2-one.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([S:22]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)(=[O:24])=[O:23])[C:10]1[C:11]([CH3:21])=[CH:12][C:13]([C:16]([NH:18][CH2:19][OH:20])=[O:17])=[N:14][CH:15]=1.[C:32](OC(=O)C)(=[O:34])[CH3:33]>N1C=CC=CC=1>[C:32]([O:20][CH2:19][NH:18][C:16]([C:13]1[CH:12]=[C:11]([CH3:21])[C:10]([CH:9]([C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[F:1])[S:22]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)(=[O:24])=[O:23])=[CH:15][N:14]=1)=[O:17])(=[O:34])[CH3:33]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1cc(C(=O)NCO)ncc1C(c1cc(F)ccc1F)S(=O)(=O)c1ccc(F)cc1
Solvent: c1ccncc1
Product: CC(=O)OCNC(=O)c1cc(C)c(C(c2cc(F)ccc2F)S(=O)(=O)c2ccc(F)cc2)cn1
Temperature: 25 °C
Reaction time: 3 h
Yield: 39 %

Procedure:
To a solution of 5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-N-(1-hydroxymethyl)-4-methylpyridine-2-carboxamide (200 mg, 0.44 mmol) obtained in Example 85 in pyridine (2 ml), acetic anhydride (2 ml) was added, and the mixture was stirred for 3 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and then the residue was dissolved in ethyl acetate, and was washed with water. The solution was dried over anhydrous sodium sulfate and filtered, then the filtrate was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography. The fraction obtained from an elution with hexane:ethyl acetate=10:3 was concentrated under reduced pressure, washed with diethyl ether, and was collected by filtration, to obtain the title compound (86 mg, 0.17 mmol, 39%) as a white solid.
Reaction SMILES: CO.[Na].[O:4]=[C:5]([CH3:29])[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:19](=[O:20])[C:18]2[N:17](C(=O)C(C)(C)CC)[CH:16]=[N:15][C:14]=2[N:13]([CH3:28])[C:11]1=[O:12].O>CO>[O:4]=[C:5]([CH3:29])[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:19](=[O:20])[C:18]2[NH:17][CH:16]=[N:15][C:14]=2[N:13]([CH3:28])[C:11]1=[O:12]
Reactant: CCC(C)(C)C(=O)n1cnc2c1c(=O)n(CCCCC(C)=O)c(=O)n2C
Agent: [Na]
Solvent: O
Solvent: CO
Product: CC(=O)CCCCn1c(=O)c2[nH]cnc2n(C)c1=O
Reaction time: 0.25 h

Procedure:
A sodium methanol solution (prepared by adding sodium (20 mg, 0.9 mmol) to 1 ml of methanol) was added to a solution of 1-(5-oxohexyl)-3-methyl-7(methylpivaloyl)xanthine (270 mg, 0.7 mmol) in 4 ml of methanol and stirred for 15 min. The reaction mixture was poured into water (20 ml), then extracted with 25% ethanol/dichloromethane (4×50 ml). The organic extracts were combined, dried with sodium sulfate, and evaporated to give a yellow solid. The solid was washed with ether to remove impurities and give CT1505 (1-(5-oxohexyl)-3-methylxanthine) as a white solid (120 mg, 0.45 mmol, 65% yield).
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[Si:6]([O:13][C:14]1[C:15]([F:22])=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH:17]=O)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>ClCCl>[Si:6]([O:13][C:14]1[C:15]([F:22])=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH2:17][N:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]
Reactant: C1CCNC1
Reactant: CC(C)(C)[Si](C)(C)Oc1cccc(C=O)c1F
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)Oc1cccc(CN2CCCC2)c1F
Yield: 90.9 %

Procedure:
Pyrrolidine (6.8 mL, 82 mmol) was added to a solution of intermediate 32, 3-{[tert-butyl(dimethyl)silyl]oxy}-2-fluorobenzaldehyde (16.7 g, 66 mmol) in dichloromethane (200 mL). The reaction mixture was cooled on ice bath, and sodium triacetoxyborohydride (17.4 g, 82 mmol) was added in portions under stirring. The reaction mixture was intensively stirred for 12 h at RT. Water (100 mL) was added. The organic layer was separated. The aqueous one was extracted with CH2Cl2 (2×100 mL). The organic layer was washed with brine, dried over Na2SO4 and evaporated in vacuo to give the title compound (19 g, 94%, 60 mmol). 1H NMR data (DMSO-d6): 6.92-7.03 (m, 2H, H—Ar), 6.83-6.91 (m, 1H, H—Ar), 3.58 (d, 2H, J=1.7 Hz, Ar—CH2); 2.38-2.46 (m, 4H), 1.63-1.70 (m, 4H) 0.97 (s, 9H, t-Bu), 0.16 (s, 6H, 2CH3).
Reaction SMILES: [CH2:1]([NH:3][CH2:4][CH:5]([N:7]1[C:20]2[CH:19]=[C:18]([C:21]#[N:22])[CH:17]=[CH:16][C:15]=2[S:14][C:13]2[C:8]1=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH3:6])C.C(=O)([O-])[O-].[Na+].[Na+].Br[CH2:30][CH:31]1[CH2:33][CH2:32]1>CN(C)C=O>[CH:33]1([CH2:32][N:3]([CH3:1])[CH2:4][CH:5]([N:7]2[C:20]3[CH:19]=[C:18]([C:21]#[N:22])[CH:17]=[CH:16][C:15]=3[S:14][C:13]3[C:8]2=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH3:6])[CH2:31][CH2:30]1
Reactant: BrCC1CC1
Reactant: CCNCC(C)N1c2ccccc2Sc2ccc(C#N)cc21
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(CN(C)CC1CC1)N1c2ccccc2Sc2ccc(C#N)cc21
Temperature: 150 °C

Procedure:
A mixture of 10-(1-ethylamino-2-propyl)-2-phenothiazinecarbonitrile, L series (3.1 g), sodium carbonate (1.19 g) and bromomethylcyclopropane (2.7 g) in dimethylformamide (32 cc) is heated to 150° C. for 9 hours. After cooling, the reaction mixture is poured into distilled water (300 cc) and extracted with ethyl acetate (3×150 cc). The combined organic phases are washed with distilled water (4×100 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. The brown oily residue (3.38 g) is purified by chromatography on a column (height: 30 cm; diameter: 2.5 cm) of silica gel (0.06-0.20 mm), eluting with a mixture (80:20 by volume) (2 liters) of methylene chloride and ethyl acetate and collecting 60-cc fractions. Fractions 4 to 12 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. 10-{1-[N-(Cyclopropylmethyl)-methylamino]-2-propyl}-2-phenothiazinecarbonitrile, L series (1.83 g) is thereby obtained in the form of a yellow oil.
Reaction SMILES: [CH3:1][C:2]#[N:3].[Li]CCCC.[F:9][C:10]1([F:20])[CH2:12][CH:11]1[C:13](OCCCC)=[O:14]>C1COCC1>[F:9][C:10]1([F:20])[CH2:12][CH:11]1[C:13](=[O:14])[CH2:1][C:2]#[N:3]
Reactant: CC#N
Reactant: CCCCOC(=O)C1CC1(F)F
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: N#CCC(=O)C1CC1(F)F
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a solution of MeCN (1.1 g, 16.8 mmol) in THF (60 mL) was added dropwise n-BuLi in THF (11.2 mL, 40.3 mmol) at −78° C., and the reaction mixture was stirred at −78° C. under N2 for 30 min. Butyl 2,2-difluorocyclopropanecarboxylate (3.0 g, 16.8 mmol) was added at −78° C., and the reaction mixture was allowed to warm to RT over 3 h. The reaction mixture was quenched with water and adjusted to pH 7 with 1N HCl. The mixture was extracted with EtOAc, and the organic layer was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to afford crude 3-(2,2-difluorocyclopropyl)-3-oxopropanenitrile. A mixture of crude 3-(2,2-difluorocyclopropyl)-3-oxopropanenitrile and hydrazine (2.0 g, 50.4 mmol, 85% pure) in EtOH (30 mL) was stirred at reflux for 16 h. The reaction mixture was concentrated to dryness under reduced pressure. The crude residue was purified by chromatography eluting with an EtOAc/petroleum ether gradient (12.5 to 100% EtOAc) to afford 2.1 g (78.5%) of 45 as a yellow solid: 1H NMR (400 MHz, DMSO-d6): δ 11.40 (br s, 1H), 5.26 (s, 1H), 4.80 (br s, 2H), 2.78-2.66 (m, 1H), 2.04-1.75 (m, 1H), 1.73-1.21 (m, 1H); MS (ESI+) m/z=160.1 [M+1]+.
Reaction SMILES: Br[Si](C)(C)C.[CH2:6]([O:13][C@H:14]1[C@H:19]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C@H:18]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@H:17]([CH3:36])[O:16][C@@H:15]1[CH2:37][P:38](=[O:45])([O:42]CC)[O:39]CC)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C(Cl)Cl>[CH2:6]([O:13][C@H:14]1[C@H:19]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C@H:18]([O:28][CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C@H:17]([CH3:36])[O:16][C@@H:15]1[CH2:37][P:38](=[O:39])([OH:42])[OH:45])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: CCOP(=O)(C[C@H]1O[C@@H](C)[C@@H](OCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1)OCC
Agent: C[Si](C)(C)Br
Solvent: ClCCl
Product: C[C@@H]1O[C@H](CP(=O)(O)O)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 21 h
Yield: 104.1 %

Procedure:
Bromotrimethylsilane (0.255 mL, 1.93 mmol, commercially available from Sigma Aldrich) was added dropwise to a stirred solution of diethyl (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonate (0.110 g, 0.193 mmol) in DCM (6 mL) at 0° C. The cooling bath was removed, and the reaction mixture was allowed to warm to room temperature and stir for 21 h. The reaction mixture was concentrated in vacuo. The resulting residue was dissolved in MeOH and stirred for 2 h. The solution was then concentrated in vacuo to give (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonic acid as a light orange oil (0.103 g, 104% yield). The material thus obtained was taken on without further purification.
Reaction SMILES: C(=O)([O-])[O-].[Cs+:5].[Cs+].[C:7]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:18])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16]>O.CO>[C:7]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:18])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([O-:17])=[O:16].[Cs+:5]
Reactant: O=C(O)CCCCCCCC(=O)OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CO
Product: O=C([O-])CCCCCCCC(=O)OCc1ccccc1

Procedure:
Aqueous cesium carbonate (1M, 6.3 ml) is added dropwise to a solution of benzyl hydrogen azelate (3.00 g, 10.77 mmol) in 75 ml water/methanol (1:15) until the pH reaches approximately 7, whereupon the solvent is removed under reduced pressure and the residue dried under vacuum overnight. The oily, yellowish semicrystalline residue is dispersed in dry dimethylformamide (50 ml) and evaporated to dryness in vacuo. This procedure is repeated twice, yielding an off-white crystalline product. The product is used without further characterization.
Reaction SMILES: [Na].[N+](C(C)C)([O-])=[O:3].Br[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]2[N:20]=[C:19]([CH3:21])[C:18]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[N:17]2)=[CH:12][CH:11]=1.CN(C)C=O>O>[CH:9]([C:10]1[CH:15]=[CH:14][C:13]([N:16]2[N:20]=[C:19]([CH3:21])[C:18]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[N:17]2)=[CH:12][CH:11]=1)=[O:3]
Reactant: CCOC(=O)c1nn(-c2ccc(CBr)cc2)nc1C
Reactant: CC(C)[N+](=O)[O-]
Agent: [Na]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1nn(-c2ccc(C=O)cc2)nc1C
Temperature: 18 °C

Procedure:
4.6 g of sodium are dissolved in 330 ml of absolute alcohol, with stirring and whilst passing a vigorous stream of nitrogen over the mixture. After cooling to 18° C., 23.2 g of 2-nitropropane are added dropwise in the course of 15 minutes and the reaction mixture is stirred for a further one hour at room temperature. 64.8 g of 2-(p-bromomethylphenyl)-4-methyl-5-carboethoxy-2H-1,2,3-triazole are then introduced, 330 ml of dimethylformamide are added and the reaction mixture is stirred for 22 hours at room temperature. The reaction mixture is then discharged into 2 liters of water and the product which has crystallised out is filtered off with suction, dried in vacuo at 50° to 60° C. and recrystallised from 1 liter of hexane with the aid of bleaching earth. This gives 25.8 g of 2-(p-formyl-phenyl)-4-methyl-5-carboethoxy-2H-1,2,3-triazole with a melting point of 97° to 99° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:24])[CH:4]=[C:5]1[C:14]2[C:9](=[CH:10][C:11]([S:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)(=[O:17])=[O:16])=[CH:12][CH:13]=2)[CH2:8][CH2:7][CH2:6]1.[H][H]>CCOC(C)=O.[Pd]>[CH3:1][O:2][C:3](=[O:24])[CH2:4][CH:5]1[C:14]2[C:9](=[CH:10][C:11]([S:15]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)(=[O:16])=[O:17])=[CH:12][CH:13]=2)[CH2:8][CH2:7][CH2:6]1
Reactant: COC(=O)C=C1CCCc2cc(S(=O)(=O)c3ccccc3)ccc21
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COC(=O)CC1CCCc2cc(S(=O)(=O)c3ccccc3)ccc21
Yield: 92.2 %

Procedure:
(6-Benzenesulfonyl-3,4-dihydro-2H-naphthalen-1-ylidene)-acetic acid methyl ester (5.63 g, 15.8 mmol) was dissolved in 300 mL EtOAc in a 1 L Parr vessel, and 1.0 g of palladium/activated carbon was added. The reaction mixture was shaken for 8 hours under 50 psi of hydrogen, after which the mixture was filtered through a CELITE™ plug. The filtrate was evaporated under reduced pressure to give an oil, which was dissolved in hexanes:EtOAc (3:2) and eluted through silica gel to afford 5.22 g (14.56 mmol, 92.2%) of (6-benzenesulfonyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-acetic acid methyl ester. MS: 359 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][CH:4]=[CH:5][CH2:6][CH2:7][CH:8]1[CH2:13][CH:12]2[CH2:14][CH:9]1[CH:10]=[CH:11]2)[CH3:2].C(O)C[OH:17].C1(C)C=CC(S(O)(=O)=O)=CC=1.O.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[CH:9]12[CH2:14][CH:12]([CH:11]=[CH:10]1)[CH2:13][CH:8]2[CH2:7][CH2:6][CH2:5][CH:4]1[O:17][CH2:2][CH2:1][O:3]1
Reactant: CCOC=CCCC1CC2C=CC1C2
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: C1=CC2CC1CC2CCCC1OCCO1
Yield: 85 %

Procedure:
Next, the thus obtained 5-(4-ethoxy-3-buten-1-yl)-2-norbornene was mixed with 90 g of ethylene glycol, 1.0 g of p-toluenesulfonic acid and 300 ml of toluene and heated under reflux for one hour. The reaction mixture was allowed to cool down and poured into 100 ml of saturated sodium bicarbonate water. The resulting mixture separated into two layers. The organic layer was washed with water and saturated sodium chloride water, dried over anhydrous sodium sulfate, and concentrated in vacuum. It was further purified by vacuum distillation, obtaining 177 g of 2-{3-(5-norbornen-2-yl)-1-propyl}-1,3-dioxolane (boiling point 92° C./27 Pa, yield 85%).
Reaction SMILES: [NH:1]1[CH:5]=[N:4][C:3]([C:6]([NH2:8])=[O:7])=[N:2]1.[C:9](OC(=O)C)(=[O:11])[CH3:10]>>[C:9]([C:5]1[NH:1][N:2]=[C:3]([C:6]([NH2:8])=[O:7])[N:4]=1)(=[O:11])[CH3:10]
Reactant: CC(=O)OC(C)=O
Reactant: NC(=O)c1nc[nH]n1
Product: CC(=O)c1nc(C(N)=O)n[nH]1

Procedure:
A mixture of 0.2 g. of 1,2,4-triazole-3-carboxamide and 0.5 ml. of acetic anhydride is heated on an oil bath at a temperature of 150° C. for 20 minutes. The wet solid mass is triturated with diethyl ether and collected and washed with diethyl ether yielding 0.2 g. of colorless solid. This solid is recrystallized from acetonitrile giving a colorless solid, m.p. 212°-215° C. (dec).