Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Se](=O)=O.[OH2:4].[CH3:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][C:8]=1[C:15](=[O:17])[CH3:16]>O1CCOCC1>[CH3:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][C:8]=1[C:15](=[O:17])[CH:16]=[O:4]
Reactant: COc1ccc(OC)c(C(C)=O)c1
Reactant: O
Agent: O=[Se]=O
Solvent: C1COCCO1
Product: COc1ccc(OC)c(C(=O)C=O)c1
Temperature: 60 °C

Procedure:
A mixture of 3.66 g (33 mmol) of selenium dioxide, 1 ml of water and 25 ml of dioxane is heated to 60° C. 5.4 g (30 mmol) of 2′,5′-dimethoxyacetophenone are added and the mixture is refluxed for 16 hours. The solvents are evaporated off (orange-coloured oil; 6 g) and the product obtained is purified by flash chromatography (dichloromethane) (3.1 g of yellow oil; 53%).
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2[N:12]([CH3:21])[N:13]=[C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:15]=2[Cl:16])=[O:10])[C:5]([N+:22]([O-:24])=[O:23])=[CH:4][CH:3]=1.[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl>COCCOC.O>[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2[N:12]([CH3:21])[N:13]=[C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:15]=2[Cl:16])=[O:10])[C:5]([N+:22]([O-:24])=[O:23])=[CH:4][CH:3]=1
Reactant: Cn1nc(C(C)(C)C)c(Cl)c1C(=O)Nc1nc(Br)ccc1[N+](=O)[O-]
Reactant: OB(O)c1ccccc1Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: COCCOC
Solvent: O
Solvent: ClCCl
Product: Cn1nc(C(C)(C)C)c(Cl)c1C(=O)Nc1nc(-c2ccccc2Cl)ccc1[N+](=O)[O-]
Reaction time: 0.17 h

Procedure:
A solution of 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (6-bromo-3-nitro-pyridin-2-yl)-amide (200 mg, 0.480 mmol, prepared as described in the previous step) in DME (20 mL) and water (5 mL) was treated with 2-chlorophenylboronic acid (78.8 mg, 0.504 mmol) and cesium carbonate (469 mg, 1.44 mmol). The resulting mixture was degassed via sonication, placed under Ar, treated with PdCl2(dppf).DCM (19.6 mg, 0.0240 mmol), and heated to 90° C. for 3 h. The cooled mixture was then diluted with water (40 mL) and extracted twice with EtOAc (50 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 24-g SEPRA Si 50 SPE column (Isco system: Flow rate=20 mL/min; Eluent=EtOAc/hexanes, 1:99 v/v for 10 min, then 1:99 to 3:17 v/v over 40 min) to yield 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [6-(2-chloro-phenyl)-3-nitro-pyridin-2-yl]-amide as a yellow solid. Mass Spectrum (LCMS, APCI pos.): Calculated for C20H19Cl2N5O3: 448.1 (M+H). Measured: 448.0.
Reaction SMILES: C([O:5][C:6]([C@@H:8]1[CH2:10][C@H:9]1[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[N:12]=1)=[O:7])(C)(C)C.[ClH:18]>C(Cl)Cl.O1CCOCC1>[F:17][C:13]1[N:12]=[C:11]([C@@H:9]2[CH2:10][C@H:8]2[C:6]([OH:7])=[O:5])[CH:16]=[CH:15][CH:14]=1.[ClH:18]
Reactant: CC(C)(C)OC(=O)[C@@H]1C[C@H]1c1cccc(F)n1
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: O=C(O)[C@@H]1C[C@H]1c1cccc(F)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of trans-2-(6-fluoro-pyridin-2-yl)-cyclopropanecarboxylic acid t-butyl ester (165 mg, 0.7 mmol) in DCM (3 mL) was added HCl in dioxane (4 M, 10 mL). The resulting mixture was stirred at rt for 3 h. The mixture was then concentrated to give the desired product as HCl salt (120 mg, 79%). MS (M−H 181).
Reaction SMILES: [Si:1]([NH:8][C:9]1[N:10]=[C:11]([Cl:18])[C:12]2[CH:17]=[CH:16][NH:15][C:13]=2[N:14]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].I[CH:20]([CH3:22])[CH3:21].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[Si:1]([NH:8][C:9]1[N:10]=[C:11]([Cl:18])[C:12]2[CH:17]=[CH:16][N:15]([CH:20]([CH3:22])[CH3:21])[C:13]=2[N:14]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Nc1nc(Cl)c2cc[nH]c2n1
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)n1ccc2c(Cl)nc(N[Si](C)(C)C(C)(C)C)nc21
Yield: 99.1 %

Procedure:
2-(t-Butyl-dimethylsilanyl)amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (CXXII) (5 g, 17.7 mmol), 2-iodopropane (4.5 g, 26.6 mmol) and K2CO3 (4.3 g, 26.6 mmol) in DMF (20 mL) were reacted at ambient temperature for 15 h. After addition of H2O (50 mL) to the reaction mixture, the aqueous solution was extracted with EtOAc (300 mL) and the organic layer was washed with a brine solution (50 mL) and dried with Na2SO4. The solvents were removed in vacuo and the residue was purified by flash column chromatography (pet ether/EtOAc=10/1 to 5/1) to afford 2-(t-butyl-dimethylsilyl)amino-4-chloro-7-i-propyl-pyrrolo[2,3-d]pyrimidine (CXXXIII, 5.7 g, 100%) as a light yellow oil. LCMS: (ESI) m/z=325 (M+H)+.
Reaction SMILES: [C:1]([O:6][CH2:7][CH:8]1[O:10][CH2:9]1)(=[O:5])[CH2:2][CH2:3][CH3:4].O>CC(O)=O.C1COCC1>[C:1]([O:6][CH2:7][C@H:8]1[O:10][CH2:9]1)(=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: CCCC(=O)OCC1CO1
Solvent: CC(=O)O
Solvent: C1CCOC1
Solvent: O
Product: CCCC(=O)OC[C@@H]1CO1
Yield: 44 %

Procedure:
Using the (R,R)-(salen)Co(II) precatalyst of 1 (91 mg, 0.15 mmol, 0.005equiv), (+/−)-glycidyl butyrate (4.32 g, 30.0 mmol), AcOH (32 mL, 0.6 mmol, 0.02 equiv), 0.3 mL THF, and H2O (297 ml,, 16.5 mmol, 0.55 equiv) and a procedure analogous to the one outlined for 5b, (S)-glycidyl butyrate 5d (1.90 g, 13.2 mmol, 44%) was obtained as a clear oil by vacuum distillation of the reaction mixture (30° C., 0.5 torr). The product was determined to be >99% ee by conversion to and analysis of the 2-napthylsulfide (obtained by ring opening with 2-napthalenethiol in methanol using 1 equiv TEA at 0° C.; Chiralcel OD, 97:3 hexanes:EtOH, 1 mL/min, 260 nm).
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[C:9]([NH2:12])[CH:8]=[CH:7][CH:6]=2.N1C=CC=CC=1.[C:19]1([O:25]C(Cl)=O)C=CC=CC=1.C(N(CC)CC)C.[CH2:36]([N:43]1[CH2:47][CH2:46][C@@H:45]([NH2:48])[CH2:44]1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>ClCCl>[CH2:36]([N:43]1[CH2:47][CH2:46][CH:45]([NH:48][C:19]([NH:12][C:9]2[CH:8]=[CH:7][CH:6]=[C:5]3[C:10]=2[CH:11]=[C:2]([CH3:1])[N:3]=[CH:4]3)=[O:25])[CH2:44]1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1
Reactant: N[C@@H]1CCN(Cc2ccccc2)C1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: Cc1cc2c(N)cccc2cn1
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1cc2c(NC(=O)NC3CCN(Cc4ccccc4)C3)cccc2cn1
Reaction time: 1 h
Yield: 69 %

Procedure:
To a stirred solution of (D2) (1.50 g, 10.30 mmol) and pyridine (0.91 mL,1 1.30 mmol) in dichloromethane (50 mL) was added phenylchloroformate (1.42 mL, 11.30 mmol) dropwise at 25° C. over 10 min. After 1 h, triethylamine (1.58 mL, 11.30 mmol) was added and the reaction left to stir for a further 20 min. After this period, (R)—N-benzyl-3-aminopyrrolidine (1.67 g, 10.30 mmol) was added in dichloromethane (50 mL) and the whole stirred at 25° C. for 18 h. The mixture was then diluted with dichloromethane (100 mL), washed with water (100 ml) and dried (Na2SO4). Evaporation in vacuo gave a solid, which on recrystallisation from dichloromethane/petroleum ether gave the title compound as a pale brown solid (2.56 g). 1H NMR (CDCl3)  : 2.20-2.40 (3H, m), 2.45-2.50 (1H, m), 2.63 (3H, s), 2.70-2.80 (1H, m), 2.90-3.00 (1H, m), 3.50-3.60 (2H, m), 4.25-4.35 (1H, m), 5.35 (1H, d, J=8.1 Hz), 7.15-7.20 (2H, m), 7.25-7.30 (3H, m), 7.45-7.55 (2H, m), 7.77 (2H, d, J=7.3 Hz), 9.17 (1H, s).
Reaction SMILES: CCOC(/N=N/C(OCC)=O)=O.[OH:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=[O:19])=[CH:16][CH:15]=1.[S:22]1[CH:26]=[CH:25][C:24]([CH2:27]O)=[CH:23]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[S:22]1[CH:26]=[CH:25][C:24]([CH2:27][O:13][C:14]2[CH:21]=[CH:20][C:17]([CH:18]=[O:19])=[CH:16][CH:15]=2)=[CH:23]1
Reactant: O=Cc1ccc(O)cc1
Reactant: OCc1ccsc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=Cc1ccc(OCc2ccsc2)cc1
Temperature: 25 °C
Reaction time: 7 h
Yield: 40.4 %

Procedure:
To a tetrahydrofuran (250 mL) solution of diethylazodicarboxylate (16.1 mL, 40.9 mmol) were added 4-hydroxybenzaldehyde (5 g, 40.9 mmol), 3-thiophene methanol (3.86 mL, 40.9 mmol) and PS-triphenylphosphine (29 g, 1.41 mmol/g, 40.9 mmol). This mixture was stirred for 7 hours at room temperature. This mixture was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=2:1) to obtain the title compound (3.61 g, 40%).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[S:10][C:9]([CH2:11]O)=[C:8]([CH3:13])[C:6]=2[N:7]=1.P(Br)(Br)[Br:21]>C1(C)C=CC=CC=1>[Br:21][CH2:11][C:9]1[S:10][C:5]2[C:4]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)=[N:3][C:2]([Cl:1])=[N:7][C:6]=2[C:8]=1[CH3:13]
Reactant: BrP(Br)Br
Reactant: Cc1c(CO)sc2c(N3CCOCC3)nc(Cl)nc12
Solvent: Cc1ccccc1
Product: Cc1c(CBr)sc2c(N3CCOCC3)nc(Cl)nc12
Temperature: 100 °C
Reaction time: 8 h

Procedure:
To a stirring suspension (2-chloro-7-methyl-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-yl)-methanol in toluene at 40° C. was added PBr3 and the reaction mixture stirred at 100° C. overnight. DCM/saturated aqueous NaHCO3 extraction of the cooled mixture gave 6-bromomethyl-2-chloro-7-methyl-4-morpholin-4-yl-thieno[3,2-d]pyrimidine.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([CH2:11][CH:12]([C:18]3[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=3)[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:8][C:7]=2[CH:25]=1)#[N:2].C(OC([C@H](CC)C(N)O)=O)(C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[C:70]([O:74][C:75]([NH:77][C@H:78]([CH2:81][CH3:82])[CH2:79]O)=[O:76])([CH3:73])([CH3:72])[CH3:71]>O1CCCC1>[C:70]([O:74][C:75]([NH:77][C@H:78]([CH2:81][CH3:82])[CH2:79][O:24][C:21]1[CH:20]=[CH:19][C:18]([CH:12]([CH2:11][C:9]2[O:10][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:25][C:7]=3[CH:8]=2)[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:23][CH:22]=1)=[O:76])([CH3:73])([CH3:72])[CH3:71]
Reactant: CC[C@H](CO)NC(=O)OC(C)(C)C
Reactant: CCOC(=O)C(Cc1cc2cc(C#N)ccc2o1)c1ccc(O)cc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: CC[C@@H](C(=O)OC(C)(C)C)C(N)O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCOC(=O)C(Cc1cc2cc(C#N)ccc2o1)c1ccc(OC[C@@H](CC)NC(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 39.7 %

Procedure:
In 300 ml of tetrahydrofuran were dissolved 1.1 g of ethyl 3-(5-cyano-2-benzofuranyl)-2-(4-hydroxyphenyl)-propionate, 1.24 g of (2R)-2-tert-butoxycarbonyl-amino-1-butanol and 1.72 g of triphenylphosphine. The thus prepared solution was mixed with 1.14 g of diethyl azodicarboxylate and stirred at room temperature for 18 hours. The resulting solution was further mixed with 0.83 g of (2R)-2-tert-butoxycarbonylamino-1-butanol, 1.2 g of triphenylphosphine and 0.76 g of diethyl azodicarboxylate, and the mixture was stirred at room temperature for 18 hours. After concentrating the thus prepared reaction solution to dryness, the resulting residue was purified by subjecting it to silica gel column chromatography using a toluene/ethyl acetate mixture as a developing solvent, thereby obtaining 660 mg of ethyl 2-[4-[((2R)-2-tert-butoxycarbonylamino-1-butyl)oxy]phenyl]-3-(5-cyano-2-benzofuranyl)propionate in a colorless and oily form.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].Cl.[CH2:13](O)[CH3:14]>>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([O:6][CH2:13][CH3:14])=[O:5]
Reactant: CCO
Reactant: O=C(O)c1ccc(F)cc1F
Agent: Cl
Product: CCOC(=O)c1ccc(F)cc1F
Yield: 100 %

Procedure:
A solution of 2,4-difluoro-benzoic acid (19.3 g) in dry ethanol (200 ml) was treated with gaseous hydrochloric acid for 0.25 hours, then heated to reflux for 4 hours. Evaporation gave a white solid (22.7 g, 100%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([S:11][CH3:12])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.C(O)(=O)C.[Br:17]Br>C(Cl)(Cl)(Cl)Cl>[Br:17][CH2:9][C:8]([C:6]1[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[S:11][CH3:12])=[O:10]
Reactant: BrBr
Reactant: CSc1ccc(F)cc1C(C)=O
Solvent: ClC(Cl)(Cl)Cl
Solvent: CC(=O)O
Product: CSc1ccc(F)cc1C(=O)CBr
Reaction time: 16 h
Yield: 67.7 %

Procedure:
To a stirring solution of 20c (2.07 g, 11.34 mmol), carbon tetrachloride (62 ml) and glacial acetic acid (2.07 ml) was added at room temperature a solution of bromine (μL 546.6, 10.66 mmol) in carbon tetrachloride (34 ml). The first drop was added and after 20 minutes the solution was added dropwise in 4 hours. After stirring for 16 hours the solvent was distilled and to the residue was added water and solid sodium bicarbonate (to pH 7), the organic phase was separated and water extracted with dichloromethane (3×30 ml), the organic layers were dried and evaporated. The crude product was chromatographed (70% petroleum ether 40-60° in dichloromethane) to give 1.90 g of 21c as a yellowish solid (64% yield). 1H NMR (CDCl3) δ7.47-7.42 (dd, 1H, J=8.85, 2.84 Hz); 7.38-7.18(m, 2H); 4.42 (s, 2H); 2.43 (s, 3H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[C:11]([CH2:13][O:14][CH2:15][C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:17])[N:12]=2)=[CH:4][CH:3]=1.[C:24](=O)([O:27]C)[O:25][CH3:26].[H-].[Na+].Cl>O1CCCC1.O.CO>[CH3:26][O:25][C:24]([CH:15]([O:14][CH2:13][C:11]1[N:12]=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[S:9][CH:10]=1)[C:16]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:17])=[O:27]
Reactant: COC(=O)OC
Reactant: O=C(COCc1csc(-c2ccc(F)cc2)n1)c1ccccc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: COC(=O)C(OCc1csc(-c2ccc(F)cc2)n1)C(=O)c1ccccc1
Yield: 93.4 %

Procedure:
A solution of 9.8 g (0.03 mol) of 2-[2-(4-fluorophenyl)-4-thiazolylmethyloxy]acetophenone in 80 ml of tetrahydrofuran is added dropwise to 3.0 g (0.033 mol) of dimethyl carbonate and 0.8 g (0.033 mol) of sodium hydride in 20 ml of tetrahydrofuran at 60° C. with stirring under nitrogen, and the mixture is then stirred at 60° C. for 1 hour. After cooling, first 5 ml of methanol and then 500 ml of water are added, and the mixture is acidified with dilute hydrochloric acid and extracted with methyl tert-butyl ether. The organic phase is washed with sodium bicarbonate solution, dried and concentrated. The result is 10.8 g (93% yield) of ω-methoxycarbonyl-2-[2-(4-fluorophenyl)-4-thiazolylmethyloxy]acetophenone as an ocher solid of melting point 86°-89° C.
Reaction SMILES: [CH3:1][C:2]([OH:7])([CH2:5][CH3:6])[CH2:3][CH3:4].[C:8](Cl)(=[O:12])[C:9]([CH3:11])=[CH2:10]>C(Cl)(Cl)(Cl)Cl>[C:8]([O:7][C:2]([CH3:1])([CH2:5][CH3:6])[CH2:3][CH3:4])(=[O:12])[C:9]([CH3:11])=[CH2:10]
Reactant: CCC(C)(O)CC
Reactant: C=C(C)C(=O)Cl
Solvent: ClC(Cl)(Cl)Cl
Product: C=C(C)C(=O)OC(C)(CC)CC
Temperature: 25 °C

Procedure:
Into a 100 ml long neck round bottom flask with a vacuum adapter is placed about 2 g of 3 A molecular sieves. The flask is connected to a vacuum line and placed under reduced pressure of about 0.02 mm of Hg. It is then heated, causing gas (air) to evolve from the sieves. Heating is continued until gas evolution ceases. Then the flask is allowed to cool to room temperature and the vacuum adapter is removed. Solvent in the form of 50 ml of carbon tetrachloride is then added to the flask along with 25 mmol of 3-methyl-3-pentanol and 25 mmol of methacryloyl chloride. A magnetic stirring bar is added to the contents of the flask and a condenser with a drying tube is attached to the neck of the flask. Then the flask and its contents are placed in a hot water bath and heated for 185 hours while being subjected to magnetic stirring. The contents of the flask are then cooled and filtered through a celite pad, filtered through a 20 cm Al2O3 column, the column washed with 100 ml of CH2Cl2 and the solvents are then evaporated under reduced pressure. The resulting product is pure monomeric 3-methyl-3-pentyl methacrylate ester.
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[OH-].[Na+].[CH:14]1([N:20]=[N:21][C:22]2(Cl)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.O>CN(C)C=O>[CH:22]1([N:21]=[N:20][C:14]2([N:5]3[C:1](=[O:11])[C:2]4=[CH:10][CH:9]=[CH:8][CH:7]=[C:3]4[C:4]3=[O:6])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1
Reactant: ClC1(N=NC2CCCCC2)CCCCC1
Reactant: O=C1NC(=O)c2ccccc21
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1C1(N=NC2CCCCC2)CCCCC1
Temperature: 40 °C
Reaction time: 0.25 h

Procedure:
To a stirred solution of 10.45 grams (.071 moles) phthalimide in 80 mls of N,N-dimethylformamide in a 250 ml 4-neck flask equipped with a magnetic stirrer, thermometer and addition funnel was added 4.0 grams (.05 moles) of 50% sodium hydroxide and the solution stirred for 15 minutes at 40° C. To this solution was added dropwise 11.45 grams (.05 moles) of 1-cyclohexylazo-1chlorocyclohexane (from Example 3-11) over 20 minutes at 40° to 45° C. After the addition was complete, the reaction was stirred an additional 60 minutes at 40° C, poured into 250 ml cold water and the white solid that formed was filtered off and dissolved in 100 ml of pentane. The insolubles were filtered off and the pentane filtrate washed with water and saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, filtered and the pentane evaporated under reduced pressure on a rotating evaporator. The product was a white solid and weighed 11.5 grams (68% crude yield). The infrared spectrum of the product was in agreement with the structure of 1-cyclohexylazo-1-phthalimidocyclohexane (absence of NH and OH bands and a strong carbonyl band at 1700-1730 cm-1).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([N:13]2[CH:17]=[CH:16][CH:15]=[CH:14]2)[CH:7]=[C:8]([N+:10]([O-:12])=[O:11])[CH:9]=1)([O-])=O.N1C=CC=CC=1.[NH4+]=S>C(O)C.O>[N+:10]([C:8]1[CH:9]=[C:4]([NH2:1])[CH:5]=[C:6]([N:13]2[CH:14]=[CH:15][CH:16]=[CH:17]2)[CH:7]=1)([O-:12])=[O:11]
Reactant: O=[N+]([O-])c1cc(-n2cccc2)cc([N+](=O)[O-])c1
Solvent: c1ccncc1
Solvent: CCO
Solvent: O
Product: Nc1cc(-n2cccc2)cc([N+](=O)[O-])c1
Reaction time: 4 h
Yield: 98 %

Procedure:
To a solution of 1-(3,5-dinitro-phenyl)-1H-pyrrole (8.2 g, 35.19 mmol) and pyridine (10 ml) in ethanol (100 ml), at 80° C., was added a 20% aqueous solution of ammonium sulfide (38.4 ml, 140.76 mmol, 4.0 eq.) in water (10 ml). The mixture was stirred at the same temperature for 4 h. The mixture was quenched with ice water (200 ml) and the precipitated solid was filtered. The filtered solid was dried under vacuum to afford the product in 98% yield (7.0 g).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:14]2[CH2:15][CH2:16][NH:17][CH2:18][CH:19]=2)[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1)([O-:3])=[O:2].C(O[C:23]1(O[Si](C)(C)C)[CH2:25][CH2:24]1)C.C([BH3-])#N.[Na+].C(O)(=O)C>C(O)C>[CH:23]1([N:17]2[CH2:16][CH:15]=[C:14]([C:6]3[CH:7]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[CH2:19][CH2:18]2)[CH2:25][CH2:24]1
Reactant: CCOC1(O[Si](C)(C)C)CC1
Reactant: O=[N+]([O-])c1cc(C2=CCNCC2)cc(C(F)(F)F)c1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Solvent: CC(=O)O
Product: O=[N+]([O-])c1cc(C2=CCN(C3CC3)CC2)cc(C(F)(F)F)c1
Yield: 78.6 %

Procedure:
Stir the mixture of 4-(3-nitro-5-(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyridine (150 mg, 0.55 mmol), (1-ethoxycyclopropoxy)trimethylsilane (700 mg, 2.4 mmol), sodium cyanoborohydride (200 mg, 3.3 mmol) and acetic acid (240 mg, 4.0 mmol) in ethanol (10 mL) at 60° C. overnight. Concentrate the mixture to get a residue, partition between EtOAc and water, collect the organic layer, wash with water and brine sequentially, and dry over anhydrous sodium sulfate. Concentrate under reduced pressure to give the product as a yellow solid (135 mg, 79%). MS: (M+1): 313.1.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:10]([O:20][C@H:21]3[CH2:30][O:29][C@H:28]4[C@@H:23]([O:24][CH:25]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)[O:26][CH2:27]4)[CH2:22]3)=[N:9][C:5]2=[N:6][C:7]=1I.[B:37]1([C:46]2[CH:51]=[CH:50][C:49](B3OC(C)(C)C(C)(C)O3)=[CH:48][CH:47]=2)[O:41][C:40]([CH3:43])([CH3:42])[C:39]([CH3:45])([CH3:44])[O:38]1>C1COCC1.CCOC(C)=O.C(=O)([O-])[O-].[Ag+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:10]([O:20][C@H:21]3[CH2:30][O:29][C@H:28]4[C@@H:23]([O:24][CH:25]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)[O:26][CH2:27]4)[CH2:22]3)=[N:9][C:5]2=[N:6][C:7]=1[C:49]1[CH:50]=[CH:51][C:46]([B:37]2[O:41][C:40]([CH3:43])([CH3:42])[C:39]([CH3:45])([CH3:44])[O:38]2)=[CH:47][CH:48]=1
Reactant: C[Si](C)(C)CCOCn1c(O[C@H]2CO[C@@H]3COC(c4ccccc4)O[C@H]3C2)nc2nc(I)c(Cl)cc21
Reactant: CC1(C)OB(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)OC1(C)C
Agent: [Ag+2]
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC1(C)OB(c2ccc(-c3nc4nc(O[C@H]5CO[C@@H]6COC(c7ccccc7)O[C@H]6C5)n(COCC[Si](C)(C)C)c4cc3Cl)cc2)OC1(C)C
Temperature: -78 °C
Reaction time: 21 h

Procedure:
To a stirred solution of 6-chloro-5-iodo-2-(((4aR,7R,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl)oxy)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine (4.29 g, 9.31 mmol) under nitrogen in anhydrous THF (30 mL) was added silver carbonate (3.08 g, 11.18 mmol), Pd(PPh3)4 (538 mg, 0.466 mmol), and 1,4-benzenediboronic acid bis(pinacol) ester (9.22 g, 27.9 mmol). The mixture was cooled to −78° C., a hard vacuum was pulled, and nitrogen was introduced (3×). The mixture was allowed to warm to room temperature, then heated to reflux. After 21 hours, the mixture was cooled to room temperature and diluted with EtOAc (80 mL). The mixture was filtered through celite with EtOAc rinse until filtrate was colorless. The filtrate was concentrated under reduced pressure. The resultant residue was chromatographed using a Biotage™ 150 g (100 g+50 g in series) silica gel cartridge eluted with 0-30% EtOAc in 1:1 Hexane/DCM over 15 column volumes. The product fractions were combined and concentrated under reduced pressure, then the resultant oil was dissolved in MeCN and water, frozen at −78° C., and lyophilized to dryness to provide the title compound as a yellow solid. LC-MS: calculated for C37H47BClN3O7Si 719.30, observed m/e: 720.43 (M+H)+ (Rt 3.25/4 min).
Reaction SMILES: [C:1]([N:8]1[C@H:12]([C:13]#[CH:14])[CH2:11][O:10]C1(C)C)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.O>[C:1]([NH:8][C@H:12]([C:13]#[CH:14])[CH2:11][OH:10])([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]
Reactant: C#C[C@@H]1COC(C)(C)N1C(=O)OC(C)(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: C#C[C@H](CO)NC(=O)OC(C)(C)C

Procedure:
A solution of (R)-N-Boc-2,2-dimethyl-4-ethynyl-oxazolidine (200 mg, 0.89 mmol) (Example 91A above) in a mixture of MeOH (10 mL) and water (1 mL) was treated with p-toluenesulfonic acid monohydrate (16 mg, 0.09 mmol). After stirring at reflux overnight a thermodynamic mixture of starting material and product was obtained (appr. 1:1). The solvent was concentrated and the product was separated from the starting material via silica gel column chromatography with a 0-60-100% EtOAc in hexanes gradient. The recovered starting material was subjected to the above process for two more times yielding (R)-N-Boc-2-amino-but-3-yn-1-ol. (Yield 150 mg, 91%).