Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH:2]([C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[N:27]([CH3:31])[CH:26]=[C:25]2[CH2:32][CH2:33][CH2:34][O:35][CH3:36])[CH:3]([CH:19]([CH3:21])[CH3:20])[CH2:4][CH:5]1[CH2:9][O:8][C:7]([CH3:11])([CH3:10])[N:6]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].N1C=CC=CC=1.[CH3:43][O:44][CH2:45][C:46](Cl)=[O:47].Cl>C1(C)C=CC=CC=1.CN(C)C1C=CN=CC=1>[CH3:43][O:44][CH2:45][C:46]([O:1][CH:2]([C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[N:27]([CH3:31])[CH:26]=[C:25]2[CH2:32][CH2:33][CH2:34][O:35][CH3:36])[CH:3]([CH:19]([CH3:21])[CH3:20])[CH2:4][CH:5]1[CH2:9][O:8][C:7]([CH3:11])([CH3:10])[N:6]1[C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])=[O:47]
Reactant: COCC(=O)Cl
Reactant: COCCCc1cn(C)c2ccc(C(O)C(CC3COC(C)(C)N3C(=O)OC(C)(C)C)C(C)C)cc12
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: COCCCc1cn(C)c2ccc(C(OC(=O)COC)C(CC3COC(C)(C)N3C(=O)OC(C)(C)C)C(C)C)cc12
Temperature: 0 °C
Reaction time: 3.5 h

Procedure:
A solution of 2.48 g of tert-butyl 4-(2-{hydroxy-[3-(3-methoxypropyl)-1-methyl-1H-indol-5-yl]methyl}-3-methylbutyl)-2,2-dimethyloxazolidine-3-carboxylate (diastereomer mixture) in 70 ml of toluene is admixed at 0° C. successively with 1.04 ml of pyridine, 1.11 ml of methoxyacetyl chloride and 0.62 g of 4-dimethylaminopyridine. The reaction mixture is stirred at 0° C. over 3.5 hours. The resulting mixture is poured onto 0.1N HCl (cold) and extracted with tert-butyl methyl ether (2×). The combined organic phases are washed successively with water, 1M sodium hydrogencarbonate solution and brine, dried over sodium sulphate and filtered, and the filtrate is concentrated by evaporation. The title compound (diastereomer mixture) is obtained as a white foam from the residue by means of flash chromatography (SiO2 60F). Rf=0.32 (1:1 EtOAc-heptane). Rt=26.14 (gradient II).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][S:6]([C:8]1[N:13]2[CH:14]=[CH:15][N:16]=[C:12]2[CH:11]=[CH:10][CH:9]=1)=[O:7].ClC1C=CC=C(C(OO)=[O:25])C=1.C(=O)([O-])O.[Na+]>ClCCl>[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][S:6]([C:8]1[N:13]2[CH:14]=[CH:15][N:16]=[C:12]2[CH:11]=[CH:10][CH:9]=1)(=[O:25])=[O:7]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=S(CCCCCl)c1cccc2nccn12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=S(=O)(CCCCCl)c1cccc2nccn12
Temperature: 25 °C
Reaction time: 64 h

Procedure:
To a solution of 0.88 g (3.47 mmol) of 5-(4-chlorobutylsulfinyl)imidazo[1,2-a]pyridine in 15 ml of dichloromethane, 0.90 g (5.20 mmol) of m-chloroperbenzoic acid was added at 0° C., followed by stirring at room temperature for 64 hours. 0.6 g (3.47 mmol) of m-chloroperbenzoic acid was further added to the reaction mixture, followed by stirring for 5 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate, extracted with dichloromethane and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent, n-hexane/ethyl acetate=1/4) to yield 0.28 g (29.7%, yellow oily substance) of the desired product.
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2([CH2:32][CH2:33][CH2:34][NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[N:19]([C:20]([NH:22][NH2:23])=[S:21])[N:18]=[C:17]([C:24]3[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=3[F:31])[S:16]2)[CH:12]=[CH:13][CH:14]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CO[C:45](OC)(OC)[CH3:46]>CC1C=CC(S(O)(=O)=O)=CC=1>[Si:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2([CH2:32][CH2:33][CH2:34][NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[N:19]([C:20]3[S:21][C:45]([CH3:46])=[N:23][N:22]=3)[N:18]=[C:17]([C:24]3[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=3[F:31])[S:16]2)[CH:12]=[CH:13][CH:14]=1)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)NCCCC1(c2cccc(O[Si](C)(C)C(C)(C)C)c2)SC(c2cc(F)ccc2F)=NN1C(=S)NN
Reactant: COC(C)(OC)OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: Cc1nnc(N2N=C(c3cc(F)ccc3F)SC2(CCCNC(=O)OC(C)(C)C)c2cccc(O[Si](C)(C)C(C)(C)C)c2)s1
Temperature: 80 °C
Yield: 72.2 %

Procedure:
Tert-butyl 3-(2-(3-(tert-butyldimethylsilyloxy)phenyl)-5-(2,5-difluorophenyl)-3-(hydrazinecarbonothioyl)-2,3-dihydro-1,3,4-thiadiazol-2-yl)propylcarbamate (100 mg, 0.157 mmol) was weighed into a 25 mL flask and suspended in 5.0 mL of 1,1,1-trimethoxyethane (5 mL, 0.157 mmol). 4-methylbenzenesulfonic acid (0.540 mg, 0.00314 mmol) was then added, and the reaction heated to 80° C. for 1 hour. The reaction mixture was concentrated in vacuo, and the residue was purified by flash column chromatography (20-50% ethyl acetate/hexanes), to afford 75 mg (72% yield) of the desired product as a yellow solid on standing.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[CH3:5][O:6][C:7](=[O:16])[CH2:8][CH2:9][CH2:10][C:11]1[S:12][CH:13]=[CH:14][CH:15]=1>C(OC(=O)C)(=O)C>[CH3:5][O:6][C:7](=[O:16])[CH2:8][CH2:9][CH2:10][C:11]1[S:12][C:13]([N+:1]([O-:4])=[O:2])=[CH:14][CH:15]=1
Reactant: COC(=O)CCCc1cccs1
Reactant: O=[N+]([O-])O
Solvent: CC(=O)OC(C)=O
Product: COC(=O)CCCc1ccc([N+](=O)[O-])s1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To 8 mL of acetic anhydride at −20° C. is added 1.2 mL of nitric acid (d=1.5). The mixture is kept at −20° C., and a solution of 4-thiophen-2-yl-butyric acid methyl ester (1.84 g, 10.0 mmol) in 12 mL of acetic anhydride is added dropwise. The reaction mixture is stirred for 10 minutes after completion of addition, and poured into an ice-water mixture. The product is extracted with ethyl acetate and the organic layer is washed with 10 N aqueous sodium hydroxide solution, dried and concentrated. The residue is purified by flash column chromatography eluting with 1:4 ethyl acetate:hexane to provide 1.32 g of 4-(5-nitro-thiophen-2-yl)-butyric acid methyl ester as a yellow oil; 1H NMR (DMSO-d6) δ 1.93 (quintet, J=7 Hz, 2H), 2.41 (t, J=7 Hz, 2H), 2.88 (t, J=7 Hz, 2H), 3.59 (s, 3H), 7.04 (d, J=5 Hz, 1H), 8.01 (d, J=5 Hz, 1H); MS 229.0 (M)+.
Reaction SMILES: Cl[C:2]1[N:27]=[CH:26][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=4)=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.C([Sn](CCCC)(CCCC)[C:33]1[O:37][CH:36]=[C:35]([CH:38]=[O:39])[CH:34]=1)CCC>O1CCOCC1>[F:25][C:21]1[CH:20]=[C:19]([CH:24]=[CH:23][CH:22]=1)[CH2:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([NH:10][C:9]2[C:4]3[CH:3]=[C:2]([C:33]4[O:37][CH:36]=[C:35]([CH:38]=[O:39])[CH:34]=4)[N:27]=[CH:26][C:5]=3[N:6]=[CH:7][N:8]=2)=[CH:12][CH:13]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cc(C=O)co1
Reactant: Fc1cccc(COc2ccc(Nc3ncnc4cnc(Cl)cc34)cc2)c1
Solvent: C1COCCO1
Product: O=Cc1coc(-c2cc3c(Nc4ccc(OCc5cccc(F)c5)cc4)ncnc3cn2)c1

Procedure:
(6-Chloropyrido[3,4-d]pyrimidin-4-yl)-(4-(3-fluorobenzyloxy)-phenyl)-amine (1 g) and 5-(tributylstannyl)-furan-3-carbaldehyde (J. Org. Chem. (1992), 57(11), 3126-31) (1.84 g) in dioxan (35 ml) were reacted together as in Procedure B. The solvent was evaporated and the residue suspended in dichloromethane. The mixture was filtered through Celite® and then evaporated. The residue was triturated with hexane giving a beige solid (1 g); m/z 441 (M+1)+.
Reaction SMILES: Cl[C:2]1[N:7]=[N:6][C:5]([CH2:8][N:9]2[CH:13]=[CH:12][N:11]=[C:10]2[C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[C:4]([CH2:21][CH3:22])[CH:3]=1.[CH3:23][O-:24].[Na+].O>CO>[CH2:21]([C:4]1[CH:3]=[C:2]([O:24][CH3:23])[N:7]=[N:6][C:5]=1[CH2:8][N:9]1[CH:13]=[CH:12][N:11]=[C:10]1[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1)[CH3:22]
Reactant: C[O-]
Reactant: CCc1cc(Cl)nnc1Cn1ccnc1-c1cccc(F)c1
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CCc1cc(OC)nnc1Cn1ccnc1-c1cccc(F)c1

Procedure:
A solution of 6-chloro-4-ethyl-3-[2-(3-fluoro-phenyl)-imidazol-1-ylmethyl]-pyridazine (73.3 mg, 0.23 mmol) and sodium methoxide (40 mg, 0.74 mmol) in methanol (5 mL) is heated under N2 for 5 hours. After cooling, water (10 mL) is added, followed by extraction with ethyl acetate (3×30 mL). The solvent is removed in vacuo and PTLC separation gives the title compound. LC-MS (M+1) 313.1 (retention time: 0.99 min).
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]([O:9]CC)=[O:8])=[CH:5][C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:3]1.[OH-].[Na+].Cl>C(O)C>[CH3:1][N:2]1[C:6]([C:7]([OH:9])=[O:8])=[CH:5][C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:3]1
Reactant: CCOC(=O)c1cc(-c2ccccc2)nn1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cn1nc(-c2ccccc2)cc1C(=O)O
Yield: 104.4 %

Procedure:
0.12 g of ethyl 1-methyl-3-phenyl-1H-5-pyrazolecarboxylate was dissolved in 5 ml ethanol. 1 ml of 5N aqueous sodium hydroxide solution was added thereto, followed by heating under reflux for 1 hour. The reaction solution was ice-cooled, neutralized with 2N hydrochloric acid and then extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and evaporated, to give 0.11 g of 1-methyl-3-phenyl-1H-5-pyrazolecarboxylic acid.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=2[Cl:22])=[CH:4][C:5]([N+:9]([O-])=O)=[C:6]([CH:8]=1)[NH2:7].Cl>C(O)C.[Zn]>[Cl:1][C:2]1[CH:8]=[C:6]([NH2:7])[C:5]([NH2:9])=[CH:4][C:3]=1[C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:19])[F:20])=[CH:14][C:13]=1[Cl:22]
Reactant: Nc1cc(Cl)c(-c2ccc(C(F)(F)F)cc2Cl)cc1[N+](=O)[O-]
Agent: Cl
Agent: [Zn]
Solvent: CCO
Product: Nc1cc(Cl)c(-c2ccc(C(F)(F)F)cc2Cl)cc1N
Reaction time: 2 h
Yield: 36.5 %

Procedure:
To a solution of [2-chloro-4-(trifluoromethyl)phenyl]boronic acid (4.5 g, 20.06 mmol) in water (30 mL) and dioxane (200 mL) was added K3PO4 (5.7 g, 26.85 mmol), 5-chloro-4-iodo-2-nitroaniline (4 g, 13.40 mmol) and Pd(PPh3)4 (800 mg, 0.69 mmol) maintained with an inert atmosphere of nitrogen and stirred overnight at 95° C. The resulting mixture was concentrated under vacuum to give a residue, which was purified by a silica gel column with 10% ethyl acetate in petroleum ether to produce 5-chloro-4-[2-chloro-4-(trifluoromethyl)phenyl]-2-nitroaniline as a yellow solid (3 g, 32%). Next, to a solution of 5-chloro-4-[2-chloro-4-(trifluoromethyl)phenyl]-2-nitroaniline (3 g, 8.54 mmol) in ethanol (80 mL) was added hydrochloric acid (2 mL) and Zn powder (3.4 g, 52.3 mmol) in portions. The resulting solution was stirred for 2 h at reflux. The resulting mixture was concentrated under vacuum and dissolved in water (100 ml) adjusted to pH 8 with sodium carbonate and extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum to give the residue, which was purified by a silica gel column with 20% ethyl acetate in petroleum ether to produce 4-chloro-5-[2-chloro-4-(trifluoromethyl)phenyl]benzene-1,2-diamine as brown oil (1 g, 36%). Finally, the solution of 4-chloro-5-[2-chloro-4-(trifluoromethyl)phenyl]benzene-1,2-diamine (100 mg, 0.31 mmol) in TFA (5 mL) and hydrochloric acid (conc, 1 mL) was stirred overnight at 80° C. and quenched with water (100 ml), adjusted pH to 8 with saturated aqueous sodium carbonate and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum to give a residue, which was purified by a silica gel column with 10% ethyl acetate in petroleum ether to produce 5-chloro-6-[2-chloro-4-(trifluoromethyl)phenyl]-2-(trifluoromethyl)-1H-1,3-benzodiazole as a white solid (107.8 mg, 87%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([C:20]1[CH:21]=[CH:22][C:23](=[O:27])[N:24]([CH3:26])[CH:25]=1)[CH2:9][C:10]([C:12]1[CH:13]=[CH:14][C:15](=[O:19])[N:16]([CH3:18])[CH:17]=1)=O.Cl.[NH2:29][OH:30].C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([C:20]1[CH:21]=[CH:22][C:23](=[O:27])[N:24]([CH3:26])[CH:25]=1)[CH2:9]/[C:10](/[C:12]1[CH:13]=[CH:14][C:15](=[O:19])[N:16]([CH3:18])[CH:17]=1)=[N:29]\[OH:30]
Reactant: NO
Reactant: Cn1cc(C(=O)CC(c2ccc(=O)n(C)c2)c2ccccc2Cl)ccc1=O
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: Cn1cc(/C(CC(c2ccc(=O)n(C)c2)c2ccccc2Cl)=N/O)ccc1=O

Procedure:
In analogy to example 151, step 3, 5,5′-[1-(2-chlorophenyl)-3-oxopropane-1,3-diyl]bis(1-methylpyridin-2(1H)-one) was reacted with hydroxylamine hydrochloride in the presence of NaHCO3 to give the title compound containing less than 10% of the corresponding Z isomer as an off-white solid, MS (ESI+): m/z=398.1 [M+H]+.
Reaction SMILES: C[O:2][C:3]([C:5]1[N:6]([CH3:22])[S:7](=[O:21])(=[O:20])[C:8]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][C:9]=2[C:10]=1[OH:11])=O.[Br:23][C:24]1[CH:25]=[C:26]([CH:28]=[CH:29][CH:30]=1)[NH2:27].C1(C)C(C)=CC=CC=1>C1(C)C=CC=CC=1>[Br:23][C:24]1[CH:25]=[C:26]([NH:27][C:3]([C:5]2[N:6]([CH3:22])[S:7](=[O:21])(=[O:20])[C:8]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH:13]=[CH:12][C:9]=3[C:10]=2[OH:11])=[O:2])[CH:28]=[CH:29][CH:30]=1
Reactant: COC(=O)C1=C(O)c2ccc3ccccc3c2S(=O)(=O)N1C
Reactant: Nc1cccc(Br)c1
Solvent: Cc1ccccc1
Solvent: Cc1ccccc1C
Product: CN1C(C(=O)Nc2cccc(Br)c2)=C(O)c2ccc3ccccc3c2S1(=O)=O
Yield: 77 %

Procedure:
N-(3-Bromophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide was prepared analogous to Example 1 from 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methylester-1,1-dioxide and 3-bromoaniline in toluene. Yield: 77% of theory; m.p.268°-269° C (decomp.; from xylene).
Reaction SMILES: C[Si](C)(C)[O-].[Na+].O.C([O:10][C:11]([C:13]1([CH2:28][O:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]3[CH:41]=[CH:40][C:39]([C:42]#[N:43])=[CH:38][CH:37]=3)=[CH:32][CH:31]=2)[CH2:17][CH2:16][N:15]([C:18](=[O:27])[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[CH2:14]1)=[O:12])C>C(#N)C>[C:42]([C:39]1[CH:40]=[CH:41][C:36]([C:33]2[CH:32]=[CH:31][C:30]([O:29][CH2:28][C:13]3([C:11]([OH:12])=[O:10])[CH2:17][CH2:16][N:15]([C:18](=[O:27])[C:19]4[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=4)[CH2:14]3)=[CH:35][CH:34]=2)=[CH:37][CH:38]=1)#[N:43]
Reactant: CCOC(=O)C1(COc2ccc(-c3ccc(C#N)cc3)cc2)CCN(C(=O)c2ccc(OC)cc2)C1
Agent: C[Si](C)(C)[O-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: COc1ccc(C(=O)N2CCC(COc3ccc(-c4ccc(C#N)cc4)cc3)(C(=O)O)C2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 54.8 %

Procedure:
Sodium trimethyl silanolate (72.1 g) and water (7.72 mL, 428.6 mmol) were added to a stirred solution of 3-(4′-cyano-biphenyl-4-yloxymethyl)-1-(4-methoxy-benzoyl)-pyrrolidine-3-carboxylic acid ethyl ester (see Preparation 28) (207.7 g, 428.6 mmol) in acetonitrile (2090 mL). The resulting mixture was stirred at RT for 18 hours. The reaction mixture was filtered and the solid was partitioned between ethyl acetate (2000 mL) and aqueous hydrogen chloride solution (2000 mL, 2M). The organic layer was washed with water (1000 mL) then concentrated under reduced pressure to afford a pale orange foam. This was recrystallised twice, from ethyl acetate (700 mL) then isopropyl alcohol (700 mL) to afford the title compound as a white solid (107.2 g, 55%).
Reaction SMILES: COC[O:4][C@@H:5]1[CH2:18][C@@H:17]2[C@H:8]([C@H:9]3[C@H:14]([CH2:15][CH2:16]2)[CH2:13][C@:12]2([CH3:24])[C@@H:19]([C:22]#[N:23])[CH2:20][CH2:21][C@H:11]2[CH2:10]3)[CH2:7][CH2:6]1.Cl>CO.ClCCl>[OH:4][C@@H:5]1[CH2:18][C@@H:17]2[C@H:8]([C@H:9]3[C@H:14]([CH2:15][CH2:16]2)[CH2:13][C@:12]2([CH3:24])[C@@H:19]([C:22]#[N:23])[CH2:20][CH2:21][C@H:11]2[CH2:10]3)[CH2:7][CH2:6]1
Reactant: COCO[C@H]1CC[C@@H]2[C@H](CC[C@@H]3C[C@@]4(C)[C@@H](CC[C@@H]4C#N)C[C@H]32)C1
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: C[C@]12C[C@H]3CC[C@@H]4C[C@@H](O)CC[C@H]4[C@@H]3C[C@@H]1CC[C@@H]2C#N
Reaction time: 14 h
Yield: 93.9 %

Procedure:
To compound 9 (165 mg, 0.5 mmol) in methanol (9 mL) and dichloromethane (3 mL) was added 6 N HCl (10 ml) at room temperature. After 14 h, the product was extracted into EtOAc (50 mL×2). The combined extracts were dried, filtered, and concentrated. The residue was purified by flash column chromatography (silica gel eluted with 25% EtOAc in hexanes) to afford compound 10 (135 mg, 94%): mp 162-164° C.; [α]D20 +33.9 (c 0.31, CHCl3); 1H NMR (CDCl3) δ 4.06 (s, br, 1H), 0.86 (s, 3H); 13C NMR (CDCl3) δ 121.3, 66.1, 48.3, 47.9, 46.9, 44.9, 44.2, 40.2, 39.8, 38.1, 36.0, 33.8, 33.7, 32.6, 28.4, 26.3 (2C), 23.1, 14.2; IR νmax 3456, 2235, 1447 cm−1. Anal. Calcd for (C19H29NO): C, 79.39; H, 10.17; N, 4.87. Found: C, 79.60; H, 10.26; N, 4.92.
Reaction SMILES: [CH3:1][N:2]([CH3:9])[CH2:3][CH2:4][O:5][CH2:6][CH2:7][OH:8].[Cl-].[CH2:11]([O:13][C:14](=[O:20])/[CH:15]=[CH:16]/[C:17](O)=[O:18])[CH3:12].C([O-])(O)=O.[Na+]>CN(C)C1C=CN=CC=1.C1(C)C=CC=CC=1>[CH2:11]([O:13][C:14](=[O:20])[CH:15]=[CH:16][C:17]([O:8][CH2:7][CH2:6][O:5][CH2:4][CH2:3][N:2]([CH3:9])[CH3:1])=[O:18])[CH3:12]
Reactant: CN(C)CCOCCO
Reactant: CCOC(=O)/C=C/C(=O)O
Agent: CN(C)c1ccncc1
Agent: O=C([O-])O
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: CCOC(=O)C=CC(=O)OCCOCCN(C)C
Temperature: 25 °C
Reaction time: 5 h
Yield: 49.8 %

Procedure:
To the solution of 2-[2-(dimethylamino)-ethoxy]ethanol (13.35 g, 100 mmol, 1.9 equiv.) and 4-dimethylaminopyridine (50 mg) in toluene (80 ml) is added a solution of fumaric acid monoethylester monochloride (8.50 g, 52 mmol, 1.0 equiv.) in toluene (20 ml) at 23° C. over 25 min. The temperature rises to 34° C. and an orange suspension is formed. After 5 h stirring at room temperature, the mixture is poured on ice-cooled saturated aqueous NaHCO3 solution and the product is extracted with ethyl acetate. The organic layer is washed 3 times with H2O, then twice with brine. It is then dried over MgSO4 and concentrated in a rotary evaporator. The residue is dissolved in methyl t-butyl ether and SiO2 (6.0 g) is added to the solution. The suspension is shaken vigorously, then filtered and again concentrated and dried under high vacuum (23° C., 0.05 mbar). This yields the product (6.71 g, 50%) as a yellow liquid.
Reaction SMILES: [ClH:1].[OH:2][C@@H:3]([C:14]1[N:19]=[CH:18][CH:17]=[CH:16][N:15]=1)[CH2:4][N:5](C)[C:6](=O)OC(C)(C)C>>[ClH:1].[ClH:1].[CH3:6][NH:5][CH2:4][C@H:3]([C:14]1[N:15]=[CH:16][CH:17]=[CH:18][N:19]=1)[OH:2]
Reactant: CN(C[C@@H](O)c1ncccn1)C(=O)OC(C)(C)C
Agent: Cl
Product: CNC[C@@H](O)c1ncccn1
Temperature: 50 °C
Reaction time: 2.5 h

Procedure:
A 6 N solution of aq. HCl (5 mL) was added to tert-butyl (2R)-2-hydroxy-2-pyrimidin-2-ylethyl(methyl)carbamate (1.17 g) at room temperature. After 2.5 h, reaction mixture was concentrated in vacuo using 3×10 mL portions of ethanol to assist in water removal. The oil was dissolved in ethanol, heated to ca. 50° C. and THF was added until slightly turbid at this temperature. The solution was allowed to cool to room temperature. The resulting solid was collected by filtration and washed with ethanol/THF (50/50) followed by diethyl ether to afford 0.78 g of the title compound.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][CH:14]([O:18][CH2:19][CH:20]=[CH2:21])[CH2:15]C=C)[CH2:11][O:10][C:9]1([CH3:23])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]>ClCCl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][CH:14]2[CH2:15][CH:21]=[CH:20][CH2:19][O:18]2)[CH2:11][O:10][C:9]1([CH3:22])[CH3:23])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: C=CCOC(CC=C)C[C@H]1COC(C)(C)N1C(=O)OC(C)(C)C
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)=Cc2ccccc2)c(C)c1
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1[C@@H](CC2CC=CCO2)COC1(C)C
Temperature: 25 °C
Reaction time: 4 h
Yield: 92 %

Procedure:
To a solution of (S)-4-(2-allyloxy-pent-4-enyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester (1.38 g, 4.24 mmol) in dichloromethane (10 mL) was added benzylidene[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro-(tricyclohexylphosphine)ruthenium (144 mg, 4% equivalent). The mixture was stirred at room temperature for 4 h. Solvents were evaporated and the residue was purified through flash column chromatography (silica gel, 0-20% ethyl acetate/hexanes) to afford (S)-4-(3,6-dihydro-2H-pyran-2-ylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid t-butyl ester (1.16 g, 92%) as a brown oil: 1H NMR (300 MHz, CDCl3) δ ppm 1.48 (s, 12H), 1.56, 16.0 (2×s, 3H), 1.69 (br. s., 1H), 1.81-2.20 (m, 3H), 3.55 (br. s., 1H), 3.83-4.02 (m, 2H), 4.00-4.28 (m, 3H), 5.61-5.93 (m, 2H).
Reaction SMILES: C(C1N=C(N2CCC(F)(F)C2)C2C(=NN(CC)N=2)N=1)(C)(C)C.[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][CH2:39][C:38]([F:42])([F:41])[CH2:37]2)[C:30]2[N:35]=[N:34][NH:33][C:31]=2[N:32]=1)([CH3:26])([CH3:25])[CH3:24].FC(F)(F)S(O[CH2:49][C:50]([F:53])([F:52])[F:51])(=O)=O>>[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][CH2:39][C:38]([F:41])([F:42])[CH2:37]2)[C:30]2[C:31](=[N:33][N:34]([CH2:49][C:50]([F:53])([F:52])[F:51])[N:35]=2)[N:32]=1)([CH3:26])([CH3:24])[CH3:25]
Reactant: CC(C)(C)c1nc(N2CCC(F)(F)C2)c2nn[nH]c2n1
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Agent: CCn1nc2nc(C(C)(C)C)nc(N3CCC(F)(F)C3)c2n1
Product: CC(C)(C)c1nc(N2CCC(F)(F)C2)c2nn(CC(F)(F)F)nc2n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoro-pyrrolidin-1-yl)-2-ethyl-2H-[1,2,3]triazolo[4,5-d]pyrimidine (example 3, step b), the title compound was prepared from 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 2,2,2-trifluoroethyl trifluoromethanesulfonate and isolated as light-yellow solid (3.0 mg, 20%). MS (m/e): 365.3 (MH+).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:31]=[CH:30][C:12]2[CH2:13][CH2:14][C:15]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[C:16]=3[CH2:17][N:18]([CH3:21])[CH2:19][CH2:20][C:11]=2[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OCC)(=[O:34])C>N1C=CC=CC=1.[O-2].[O-2].[O-2].[Cr+6]>[CH2:1]([O:8][C:9]1[CH:31]=[CH:30][C:12]2[CH2:13][CH2:14][C:15]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[C:16]=3[CH2:17][N:18]([CH:21]=[O:34])[CH2:19][CH2:20][C:11]=2[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1ccc2c(c1OC)CN(C)CCc1cc(OCc3ccccc3)ccc1CC2
Reactant: CCOC(C)=O
Agent: [Cr+6]
Agent: [O-2]
Solvent: c1ccncc1
Product: COc1ccc2c(c1OC)CN(C=O)CCc1cc(OCc3ccccc3)ccc1CC2
Reaction time: 2 h

Procedure:
To a chromium trioxide - pyridine complex freshly prepared from 28 g of chromium trioxide and 280 ml of anhydrous pyridine is added dropwise a solution of 21 g of 10-benzyloxy-3,4-dimethoxy-6-methyl-5,6,7,8,13,14-hexahydrodibenz[c,g]azecine in 140 ml of pyridine at 10° - 15°C over a period of 35 minutes, and the mixture is allowed to stand at the same temperature for 2 hours and then at room temperature for 15 hours. The mixture is then diluted with 600 ml of ethyl acetate, stirred well, and filtered to remove the inorganic precipitate. The filtrate is passed through a column of alumina and celite (kiesel-guhr) and evaporated to dryness. The resulting residue (14.3 g) is dissolved in 286 ml of methanol, treated with 7 g of sodium borohydride, and chromatographed on 140 g of silica gel. The benzene - ethyl acetate (10 : 1) elution (2.45 g) is recrystallized from methylene chloride - ether to yield 2.11 g of 10-benzyloxy-3,4-dimethoxy-6-formyl-5,6,7,8,13,14-hexahydrodibenz[c,g]azecine as colorless needles having mp. 140° - 141°C. IR: νmaxCHCl 3 1654 cm-1. Anal. Calcd. for C27H29O4N: C, 75.15%; H, 6.77%; N, 3.25%. Found: C, 75.20%; H, 7.02%; N, 3.23%.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[O:8])[O:5][CH:6]=1.[CH2:9](OB(C=C)OCCCC)[CH2:10]CC.C(C1OC(C=O)=CC=1)C1C=CC=CC=1>CN(C)C=O>[CH:9]([C:2]1[CH:3]=[C:4]([CH:7]=[O:8])[O:5][CH:6]=1)=[CH2:10]
Reactant: C=CB(OCCCC)OCCCC
Reactant: O=Cc1cc(Br)co1
Agent: O=Cc1ccc(Cc2ccccc2)o1
Solvent: CN(C)C=O
Product: C=Cc1coc(C=O)c1

Procedure:
The title compound was synthesized from 4-bromo-furan-2-carbaldehyde (1.1 g, 6.29 mmol) and vinylboronic acid dibutyl ester (1.67 mL, 7.54 mmol) using the same conditions used to synthesize 5-benzyl-furan-2-carbaldehyde, with the exception that the reaction was run in N,N-dimethylformamide (DMF) (20 mL). Purification by flash chromatography (0-30% EtOAc in heptane) provided 4-vinylfuran-2-carbaldehyde as an orange oil; Yield 282 mg (37%). 1H NMR (400 MHz, CDCl3) δ ppm 5.31 (dd, J=10.88, 0.93 Hz, 1 H), 5.61 (dd, J=17.57, 0.54 Hz, 1 H), 6.56 (dd, J=17.55, 10.91 Hz, 1 H), 7.37 (s, 1 H), 7.67 (s, 1 H), 9.66 (d, J=0.59 Hz, 1 H).