Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH2:3][C:4]([NH2:6])=[O:5])#[N:2].CC([O-])(C)C.[K+].[CH3:13][CH:14]([CH3:20])[CH:15]=[CH:16][C:17](=O)[CH3:18].N#N.O=O>CS(C)=O.O.Cl>[CH3:18][C:17]1[NH:6][C:4](=[O:5])[C:3]([C:1]#[N:2])=[C:15]([CH:14]([CH3:20])[CH3:13])[CH:16]=1
Reactant: CC(=O)C=CC(C)C
Reactant: N#CCC(N)=O
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: N#N
Solvent: CS(C)=O
Solvent: O
Product: Cc1cc(C(C)C)c(C#N)c(=O)[nH]1
Temperature: 23 °C
Reaction time: 0.5 h
Yield: 39.8 %

Procedure:
To a solution of 2-cyanoacetamide (35.1 g, 417 mmol) and t-BuOK (42.5 g, 379 mmol) in DMSO (631 ml) was added 5-methyl-3-hexen-2-one (50.0 ml, 379 mmol) under N2 atmosphere. The mixture was stirred at 23° C. for 30 min and then additional t-BuOK (127 g, 1137 mmol) was added. The N2 gas was displaced by O2 gas and the mixture was stirred for 45 h at 23° C. under oxygen. The mixture was cooled to 0° C., diluted with H2O (200 ml) and HCl (5N, 227 ml, slowly added). The mixture was stirred for 15 min at 0° C. and the solid was filtered with Buchner funnel. The solid was washed with H2O (1500 ml) and dried with hot-air (55° C., 16 h) to give 6-methyl-2-oxo-4-(propan-2-yl)-1,2-dihydropyridine-3-carbonitrile (26.6 g, 40% yield). 1H NMR (400 MHz, CDCl3): δ 6.14 ppm (s, 1H), 3.25-3.29 (m, 1H), 2.45 (s, 3H), 1.26 (d, J=6.8 Hz, 6H); LC-MS: m/z 177.1 [M+1], 198.9 [M+23].
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:23]([NH2:25])=O)=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]21.S(Cl)(Cl)=O.C(=O)([O-])O.[Na+]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:23]#[N:25])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]21
Reactant: NC(=O)c1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(Cl)cc1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: N#Cc1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(Cl)cc1Cl
Yield: 90.6 %

Procedure:
To a solution of 9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxamide (1.73 g, 4.37 mmol) in N,N-dimethylformamide (20 mL) was added thionyl chloride (1.05 mL, 14.4 mmol). The resultant mixture was stirred at 50° C. for 1.5 hr and poured into saturated aqueous sodium hydrogen carbonate at 0° C. The resultant precipitate was collected by filtration, washed with water and diisopropyl ether to give the title compound as a pale white solid (1.496 g, 3.96 mmol, 91%).
Reaction SMILES: [O:1]1[CH:6]=[CH:5][CH2:4][CH2:3][CH2:2]1.C([Li])(C)(C)C.[O:12]1[C:14]([CH2:18][CH3:19])([CH2:15][CH2:16]I)[CH2:13]1>CCCCCC.O1CCCC1.CN(C)P(N(C)C)(N(C)C)=O>[CH2:15]([C:14]1([O:12][CH2:13]1)[CH2:18][CH2:19][C:2]1[O:1][CH2:6][CH2:5][CH2:4][CH:3]=1)[CH3:16]
Reactant: C1=COCCC1
Reactant: CCC1(CCI)CO1
Agent: [Li]C(C)(C)C
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CCC1(CCC2=CCCCO2)CO1
Temperature: 25 °C
Reaction time: 2 h
Yield: 86.5 %

Procedure:
To a stirred solution of 3.2 g of dihydropyran and 1.4 g of dry tetrahydrofuran at 0° C. was added dropwise 50 ml 2 M tert-butyl lithium. The reaction was allowed to warm to room temperature, then cooled to -10° to -20° C., and 10 g of 1,2-epoxy-2-(ethyl)-4-iodobutane and 0.7 g of hexamethylphosphoramide was added dropwise over 10 minutes. After stirring for 2 hours at -15° to -20° C., 6-8 ml of dry tetrahydrofuran was added. The reaction mixture was allowed to warm to room temperature, stirred for a total of 2 hours, 40-50 ml of hexane was added, and the mixture was washed with water and then with a saturated sodium chloride and sodium bisulfite mixture, dried and vacuum stripped to give 6 g of the desired material as an oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[N:11]=[N:12][C:13]([CH:16]([NH:18][C:19]([C:21]3O[CH:23]=[CH:24][CH:25]=3)=[O:20])[CH3:17])=[CH:14][N:15]=2)=[CH:5][CH:4]=1.NC(C1N=NC(NC2C=CC(OC)=CC=2)=NC=1)C.[F:44][C:45]1C=C(C=C[CH:53]=1)C(Cl)=O>>[F:44][C:45]1[CH:53]=[C:21]([CH:25]=[CH:24][CH:23]=1)[C:19]([NH:18][CH:16]([C:13]1[N:12]=[N:11][C:10]([NH:9][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)=[N:15][CH:14]=1)[CH3:17])=[O:20]
Reactant: O=C(Cl)c1cccc(F)c1
Reactant: COc1ccc(Nc2ncc(C(C)NC(=O)c3ccco3)nn2)cc1
Agent: COc1ccc(Nc2ncc(C(C)N)nn2)cc1
Product: COc1ccc(Nc2ncc(C(C)NC(=O)c3cccc(F)c3)nn2)cc1

Procedure:
In a similar manner as described for Intermediate 59, using 6-(1-aminoethyl)-N-[4-(methyloxy)phenyl]-1,2,4-triazin-3-amine (Intermediate 47) (100 mg, 0.41 mmol), and 3-fluorobenzoyl chloride (0.059 mL, 0.45 mmol) to afford 3-fluoro-N-[1-(3-{[4-(methyloxy)phenyl]amino}-1,2,4-triazin-6-yl)ethyl]benzamide (130 mg) as a yellow solid. MS m/z 368 (M+1).
Reaction SMILES: [CH2:1]([C@H:6]1[CH2:11][CH2:10][C@H:9](/[CH:12]=[CH:13]/[C:14](OCC)=[O:15])[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5].[H-].C([Al+]CC(C)C)C(C)C.Cl.O>ClCCl.CCCCCC>[CH2:1]([C@H:6]1[CH2:11][CH2:10][C@H:9](/[CH:12]=[CH:13]/[CH2:14][OH:15])[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCC[C@H]1CC[C@H](/C=C/C(=O)OCC)CC1
Agent: CC(C)C[Al+]CC(C)C
Agent: Cl
Agent: [H-]
Solvent: CCCCCC
Solvent: O
Solvent: ClCCl
Product: CCCCC[C@H]1CC[C@H](/C=C/CO)CC1
Reaction time: 1 h

Procedure:
A solution of 13.5 g of ethyl (E)-3-(trans-4-pentylcyclohexyl)acrylate in 100 ml of dichloromethane was treated dropwise at -78° C. and while gassing with nitrogen with a 20% solution of diisobutylaluminium hydride in hexane. After completion of the addition the slightly yellow solution was stirred for a further 1 hour and then treated cautiously with 10 ml of 25% hydrochloric acid. The reaction mixture was poured into 100 ml of water and the organic phase was separated. The aqueous phase was back-extracted twice with 100 ml of dichloromethane each time. The combined organic phases were washed with 500 ml of water, 500 ml of concentrated potassium hydrogen carbonate solution and again with 500 ml of water and subsequently dried over magnesium sulphate, filtered and concentrated. Distillation of the residue gave 10 g of (E)-3-(trans-4-pentylcyclohexyl)allyl alcohol with b.p. 174°-175° C./15 mmHg.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11](O)[CH2:10][C@H:9]1[CH2:14][O:15][C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(Cl)(Cl)(Cl)[Cl:46]>C(Cl)(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([Cl:46])[CH2:10][C@H:9]1[CH2:14][O:15][C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: ClC(Cl)(Cl)Cl
Reactant: COC(=O)c1ccc(OC[C@@H]2C[C@@H](O)CN2C(=O)OC(C)(C)C)cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClC(Cl)Cl
Product: COC(=O)c1ccc(OC[C@@H]2C[C@H](Cl)CN2C(=O)OC(C)(C)C)cc1
Temperature: 50 °C
Reaction time: 24 h
Yield: 92 %

Procedure:
To a stirred solution of methyl 4-(trans-1-tert-butoxycarbonyl-4-hydroxy-(2S)-pyrrolidinyl)methoxybenzoate (351 mg, 1.0 mmol) and Ph3P (393 mg, 1.5 mmol) in CHCl3 (5.0 ml) was added CCl4 (5.0 ml) at room temperature. The reaction mixture was stirred at 50° C. for 24 hr. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography on silica gel with n-hexane to n-hexane-EtOAc (4:1, v/v) as eluent to give methyl 4-(cis-1-tert-butoxycarbonyl-4-chloro-(2S)-pyrrolidinyl)methoxybenzoate (340 mg, 92%) as a pale yellow oil. 1H-NMR (CDCl3) δ1.48 (s, 9H), 2.38-2.65 (m, 2H), 3.50-3.60 (m, 1H), 3.88 (s, 3H), 3.89-4.05 (m, 1H), 4.26-4.41 (m, 4H), 6.95-6.97 (m, 2H), 7.98 (d, J=8.5 Hz, 2H).
Reaction SMILES: C1(=O)[N:5]([CH2:6][CH2:7][CH2:8][CH:9]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[CH:13]=[CH:12][C:11]3[CH:20]=[CH:21][CH:22]=[CH:23][C:10]2=3)C(=O)C2=CC=CC=C12.O.NN>C(O)C>[NH2:5][CH2:6][CH2:7][CH2:8][CH:9]1[C:10]2[CH:23]=[CH:22][CH:21]=[CH:20][C:11]=2[CH:12]=[CH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]1=2
Reactant: O=C1c2ccccc2C(=O)N1CCCC1c2ccccc2C=Cc2ccccc21
Agent: NN
Solvent: CCO
Solvent: O
Product: NCCCC1c2ccccc2C=Cc2ccccc21

Procedure:
5-(3-Phthalimidopropyl)-5H-dibenzo[a,d]cycloheptene, 2.15 g. (0.0054 mole), is dissolved in 50 ml. of hot 95% ethanol. Hydrazine hydrate, 0.6 ml., is added and the solution heated to refluxing for 2 hours. The solution then is cooled, acidified, and the precipitate of phthalhydrazide removed by filtration. Ethanol is distilled from the filtrate under reduced pressure and the residue dissolved in 40 ml. of water. The filtered solution is evaporated by heating under reduced pressure to a volume of approximately 20 ml. Upon cooling, the hydrochloride salt of 5-(3-aminopropyl)-5H-dibenzo[a,d]cycloheptene is precipitated in a yield of 1.35 g. (87.5%). After recrystallization from a mixture of ethanol and ether and from isopropyl alcohol, an analytical sample melted at 263°-265° C., dec.
Reaction SMILES: [C:1]1([CH:9]=[CH:8][CH:7]=[C:5]([OH:6])[C:3]=1[OH:4])[OH:2].[CH:10](OCC)(OCC)[O:11][CH2:12][CH3:13].OC1C(O)=C(C)C=CC=1C=O>C1(C)C=CC=CC=1>[CH2:12]([O:11][CH:10]1[O:2][C:1]2[CH:9]=[CH:8][CH:7]=[C:5]([OH:6])[C:3]=2[O:4]1)[CH3:13]
Reactant: CCOC(OCC)OCC
Reactant: Oc1cccc(O)c1O
Agent: Cc1ccc(C=O)c(O)c1O
Solvent: Cc1ccccc1
Product: CCOC1Oc2cccc(O)c2O1
Temperature: 150 °C
Yield: 72.6 %

Procedure:
A 500 mL round bottom flask was charged with pyrogallol (25 g, 0.198 mol), triethyl orthoformate (40 mL, 35.6 g, 0.240 mol), toluene (250 mL) and Amberlyst-15 (2.40 g). A 40 cm long B24 reflux condenser was attached and on top of this a distillation head was connected to a condenser, receiver adaptor and 100 mL collecting flask. The reaction mixture was stirred and heated under reflux at a metal block temperature of 150° C. for 1 h. The water flow to the is reflux condenser was stopped and the water to the distillation condenser was turned on. Distillate boiling point up to 78° C. was collected over 4 h, after which the block temperature was increased to 260° C. for 30 min and finally 170° C. for 30 min. The toluene/ethanol azeotrope (43 mL) was collected and contained 68% ethanol. The red mixture was filtered through celite and the filtrate was evaporated to dryness. The residue was absorbed onto 60 mL of flash silica then applied to a column of 300 mL flash silica made up in heptane/EtOAc (9:1). Elution with this solvent mixture afforded 37 (26.2 g, 73%) as a very pale yellow oil:
Reaction SMILES: [C:1]([N:9]1[CH2:13][CH2:12][C:11]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=2)([CH2:14][CH2:15]S(C)(=O)=O)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[S:30]1[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[N:32]=[C:31]1[CH:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1.C(=O)(O)[O-].[Na+].C(OCC)(=O)C.CO>O1CCCC1.O.ClCCl>[C:1]([N:9]1[CH2:13][CH2:12][C:11]([CH2:14][CH2:15][N:42]2[CH2:43][CH2:44][CH:39]([C:31]3[S:30][C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=4[N:32]=3)[CH2:40][CH2:41]2)([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=2)[CH2:10]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(C2(CCS(C)(=O)=O)CCN(C(=O)c3ccccc3)C2)cc1OC
Reactant: c1ccc2sc(C3CCNCC3)nc2c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc(C2(CCN3CCC(c4nc5ccccc5s4)CC3)CCN(C(=O)c3ccccc3)C2)cc1OC
Temperature: 25 °C
Reaction time: 48 h

Procedure:
Combine 1-benzoyl-3-(3,4-dimethoxy-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidine (0.63 g, 1.45 mmol) and 4-(benzothiazol-2-yl)-piperidine (0.35 g, 1.60 mmol), and sodium bicarbonate (0.24 g, 2.9 mmol) in tetrahydrofuran/water (15/4) (30 mL). Heat to reflux. After 48 hours, cool to ambient temperature and evaporate in vacuo to obtain a residue. Partition the residue between dichloromethane and 5% sodium bicarbonate solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 5/1 ethyl acetate/methanol to give a solid. Combine the solid with dichloromethane and extract with 5% sodium bicarbonate solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Dry the residue in vacuo at 65° C. to give the title compound: Rf=0.24 (silica gel, 5/1 ethyl acetate/methanol); mp; 60-62° C. Elemental Analysis calculated for C33H37N3O3S·0.25 H1O: C 70.75; H 6.75; N 7.50; Found: C 70.79; H 6.70; N 7.39.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]2[S:10][C:9]3[CH2:11][CH2:12][CH:13]([C:15](OCC)=[O:16])[CH2:14][C:8]=3[C:7]=2[CH:20]=1)#[N:2].[Li+].[BH4-]>C1COCC1>[OH:16][CH2:15][CH:13]1[CH2:14][C:8]2[C:7]3[CH:20]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]=3[S:10][C:9]=2[CH2:11][CH2:12]1
Reactant: CCOC(=O)C1CCc2sc3ccc(C#N)cc3c2C1
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: N#Cc1ccc2sc3c(c2c1)CC(CO)CC3
Temperature: 25 °C
Yield: 39 %

Procedure:
To a room temperature solution of ethyl 8-cyano-1,2,3,4-tetrahydrodibenzo[b,d]thiophene-2-carboxylate (0.72 g, 2.53 mmol) in THF (4 mL) was added LiBH4 (6.33 mL of 2 N solution in THF, 12.66 mmol). The reaction was heated at reflux for 5.5 hour, then was cooled in ice water, and quenched with 7 mL of 1 N NaOH (aq) solution. After stirring for a few minutes at room temperature, the mixture was extracted with EtOAc. The organic layer was washed with water, then brine, then was dried over MgSO4, filtered, and concentrated. Purification by chromatography on silica gel (50% EtOAc in hexane) afforded 0.24 g (39%) of the title compound as a white solid: mp 165-166° C.; MS (ES) m/z=243 [M]+.
Reaction SMILES: C([O:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]=1[C:19]1[N:20]=[C:21]([NH2:24])[O:22][CH:23]=1)C1C=CC=CC=1.[H][H]>C(O)C.[Pd]>[NH2:24][C:21]1[O:22][CH:23]=[C:19]([C:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:17]=[CH:18][C:9]=2[OH:8])[N:20]=1
Reactant: Nc1nc(-c2c(OCc3ccccc3)ccc3ccccc23)co1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: Nc1nc(-c2c(O)ccc3ccccc23)co1
Yield: 40.6 %

Procedure:
4-(2-Benzyloxy-naphthalen-1-yl)-oxazol-2-ylamine (12, 1.0 g) was dissolved in ethanol and then palladium, 10% on carbon (390 mg) was added. The mixture was stirred under 1 atmosphere of hydrogen for 48 hours. The mixture was filtered through a pad of hyflo and washed with industrial methylated spirits. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography to afford 1-(2-amino-oxazol-4-yl)-naphthalen-2-ol (22) (290 mg, 41%) as a glassy orange foam. 1H NMR (DMSO-D6): 6.6 (2H, br s), 6.85 (1H, s), 7.2 (1H, d, J=9.0 Hz), 7.25 (1H, m), 7.4 (1H, m), 7.75 (2H, m), 7.9 (1H, m), 9.9 (1H, br s). Mass Spectrum (m/z): 227 (M+H)+.
Reaction SMILES: [H-].[Na+].[C:3]([O:10][CH3:11])(=[O:9])[CH2:4][C:5]([O:7][CH3:8])=[O:6].I[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH3:27]>CN1CCCN(C)C1=O.Cl>[CH3:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[O:20][CH2:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH:4]([C:3]([O:10][CH3:11])=[O:9])[C:5]([O:7][CH3:8])=[O:6]
Reactant: Cc1ccccc1OCc1ccccc1I
Reactant: COC(=O)CC(=O)OC
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN1CCCN(C)C1=O
Product: COC(=O)C(C(=O)OC)c1ccccc1COc1ccccc1C
Reaction time: 0.33 h
Yield: 79 %

Procedure:
To a suspension of sodium hydride (60% oil dispersion) (15.4 g) in 90 mL of 1,3-dimethyl-3,4,5,6-tetrahydro-2 [1H]-pyrimidinone (DMPU), cooled in an ice-water bath, was added dropwise a solution of dimethyl malonate (44 mL) in DMPU (150 mL). The mixture was stirred 20 minutes after the addition was completed, and then 1-iodo-2- [(2-methylphenoxy)methyl]benzene (62.5 g) and cuprous iodide (73.3 g) were added. The resulting mixture was stirred at 100° C. for 5 h, then stirred at 25° C. overnight. The mixture was diluted with 1 N, HCl (~150 mL) and extracted with diethyl ether (3×400 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure to a semi-solid, which was purified by flash chromatography on silica gel (5:2 hexane: ethyl acetate as eluant). The major material was collected and concentrated to a white solid, which was triturated in hexane and collected by filtration to yield 56.9 g (79%) of the title compound of Step C as a white solid, mp 99-103° C.
Reaction SMILES: [CH2:1]([C:4]1[NH:5][CH:6]=[C:7]([CH2:9][OH:10])[N:8]=1)[CH2:2][CH3:3].[N+]([O-])(O)=O>>[CH2:1]([C:4]1[NH:5][CH:6]=[C:7]([CH:9]=[O:10])[N:8]=1)[CH2:2][CH3:3]
Reactant: CCCc1nc(CO)c[nH]1
Solvent: O=[N+]([O-])O
Product: CCCc1nc(C=O)c[nH]1

Procedure:
A solution of 108.6 gm. of 2-n-propyl-4-imidazolemethanol in 107 ml. of concentrated HNO3 is reacted as in Example 15, giving the desired product, m.p. 103.5°-105.5° C.
Reaction SMILES: [C:1]([N:5]1[C:10]2([CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[O:9][C:8]2[CH:16]=[CH:17][CH:18]=[CH:19][C:7]=2[C:6]1=[O:20])(=[O:4])[CH2:2][CH3:3].C([Mg]Cl)CCC.C(O[C@H:31]1[NH:34][C:33](=[O:35])[C@@H:32]1[C@H:36]([O:38][Si:39]([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40])[CH3:37])(=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.C(OCC)(=O)C>[Si:39]([O:38][C@@H:36]([C@@H:32]1[C@@H:31]([C@@H:2]([CH3:3])[C:1]([N:5]2[C:10]3([CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)[O:9][C:8]3[CH:16]=[CH:17][CH:18]=[CH:19][C:7]=3[C:6]2=[O:20])=[O:4])[NH:34][C:33]1=[O:35])[CH3:37])([C:42]([CH3:43])([CH3:44])[CH3:45])([CH3:40])[CH3:41]
Reactant: CC(=O)O[C@H]1NC(=O)[C@@H]1[C@@H](C)O[Si](C)(C)C(C)(C)C
Reactant: CCC(=O)N1C(=O)c2ccccc2OC12CCCCC2
Agent: CCCC[Mg]Cl
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N[C@@H]1[C@@H](C)C(=O)N1C(=O)c2ccccc2OC12CCCCC2
Temperature: 5 °C
Reaction time: 0.25 h
Yield: 53 %

Procedure:
Under a nitrogen atmosphere, 273 mg (1.0 mmol) of 3-propionyl-spiro[2,3-dihydro-4H-1,3-benzoxazine-2,1′-cyclohexan]-4-one was charged in a 30-ml three-necked flask to dissolve it in 2 ml of tetrahydrofuran. To the resulting solution, 2.44 ml (2.2 mmol) of a tetrahydrofuran solution (0.9M) of n-butylmagnesium chloride was slowly added dropwise at room temperature. The resulting mixture was reacted for 25 minutes under the same conditions. After cooling to 5° C., 2 ml of a tetrahydrofuran solution of 287 mg (1.0 mmol) of (3R,4R)-4-acetoxy-3-[(R)-1-tert-butyldimethylsilyloxyethyl]azetidin-2-one was added at the same temperature. The resulting mixture was stirred for 15 minutes, added with 10 ml of ethyl acetate and then added dropwise with 2 ml of a 10% aqueous solution of citric acid. After separation, the organic layer was washed with 2 ml of a saturated aqueous solution of sodium bicarbonate and 2 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and distilled to remove the solvent. The residue was purified by column chromatography, whereby 263 mg (0.53 mmol) of a condensation product was obtained (yield: 53%, β:α=92:8).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([CH2:9][N:10]2[C:18]3[C:13](=[C:14]([N+:19]([O-])=O)[CH:15]=[CH:16][CH:17]=3)[C:12]([CH:22]=[CH2:23])=[N:11]2)=[CH:7][CH:6]=[C:5]([CH3:24])[N:4]=1>[OH-].[OH-].[Pd+2].CO>[CH2:22]([C:12]1[C:13]2[C:14]([NH2:19])=[CH:15][CH:16]=[CH:17][C:18]=2[N:10]([CH2:9][C:8]2[C:3]([O:2][CH3:1])=[N:4][C:5]([CH3:24])=[CH:6][CH:7]=2)[N:11]=1)[CH3:23]
Reactant: C=Cc1nn(Cc2ccc(C)nc2OC)c2cccc([N+](=O)[O-])c12
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CCc1nn(Cc2ccc(C)nc2OC)c2cccc(N)c12
Reaction time: 7 h
Yield: 29.9 %

Procedure:
To 1-((2-methoxy-6-methylpyridin-3-yl)methyl)-4-nitro-3-vinyl-1H-indazole (395 mg, 1.22 mmol) in a Parr flask was added palladium hydroxide on carbon (171 mg, 20% wt) and MeOH (6 mL) for solubility. The Parr flask was attached to the shaker and applied with 40 psi H2 for seven hours. The reaction mixture was evacuated, purged with nitrogen, filtered through Celite, and the filter pad was rinsed with MeOH. The filtrate was concentrated to a yellow oily residue under reduced pressure. Silica gel chromatography eluting with 1% MeOH, 0.5% NH4OH in DCM gave the product (108 mg).
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:16]2[CH:21]=[CH:20][C:19]([S:22][CH3:23])=[CH:18][CH:17]=2)[C:8]([NH:10][C:11]2[S:12][CH:13]=[CH:14][N:15]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.ClC1C=C(C=CC=1)C(OO)=[O:29]>C(Cl)Cl>[CH:1]1([CH2:6][CH:7]([C:16]2[CH:17]=[CH:18][C:19]([S:22]([CH3:23])=[O:29])=[CH:20][CH:21]=2)[C:8]([NH:10][C:11]2[S:12][CH:13]=[CH:14][N:15]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CSc1ccc(C(CC2CCCC2)C(=O)Nc2nccs2)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CS(=O)c1ccc(C(CC2CCCC2)C(=O)Nc2nccs2)cc1
Yield: 31.9 %

Procedure:
A solution 3-cyclopentyl-2-(4-methylsulfanyl-phenyl)-N-thiazol-2-yl-propionamide (75 mg, 0.216 mmol) in methylene chloride (1 mL) was treated with 3-chloroperoxybenzoic acid (75% grade, 50 mg, 0.216 mmol). The reaction mixture was immediately monitored by thin layer chromatography, and the results indicated the immediate absence of starting material. The reaction mixture was partitioned between water and methylene chloride and then washed with a saturated aqueous sodium bicarbonate solution. The organic layer was further washed with water and then dried over magnesium sulfate, filtered, and concentrated in vacuo. Recrystallization from 1/1 hexanes/ethyl acetate afforded 3-cyclopentyl-2-(4-methanesulfinyl-phenyl)-N-thiazol-2-yl-propionamide (25 mg, 32%) as a white solid: mp 170–173° C.; EI-HRMS m/e calcd for C18H22N2O2S2 (M+) 362.1123, found 362.1121.
Reaction SMILES: [C:1]([CH:5]1[CH2:16][CH2:15][C:8]2([O:12][CH:11]([CH2:13]Cl)[CH2:10][O:9]2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[C:17]1(=[O:27])[NH:21][C:20](=[O:22])[C:19]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:18]12.[K]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[C:1]([CH:5]1[CH2:16][CH2:15][C:8]2([O:12][CH:11]([CH2:13][N:21]3[C:20](=[O:22])[C:19]4=[CH:23][CH:24]=[CH:25][CH:26]=[C:18]4[C:17]3=[O:27])[CH2:10][O:9]2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CC(C)(C)C1CCC2(CC1)OCC(CCl)O2
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Agent: [K]
Solvent: CN(C)C=O
Product: CC(C)(C)C1CCC2(CC1)OCC(CN1C(=O)c3ccccc3C1=O)O2
Reaction time: 6 h
Yield: 101.4 %

Procedure:
A mixture of 8-t-butyl-2-chloromethyl-1,4-dioxaspiro(4,5)decane (10 g, 40 mmol) (prepared as described in EP 281842; see also the references cited in this document for related compounds), potassium phthalimide (8.9 g, 48 mmol) and a catalytic amount of tetra-n-butyl ammonium iodide in DMF (80 ml) were heated to 120° C. for 3 hours. Additional potassium phthalimide (2.8 g, 16 mmol) was then added and heating was continued for 6 hours. The solvent was then evaporated in vacuo and toluene (150 ml) was added. After filtration from insoluble material the organic phase was washed two times with brine (100 ml), dried (MgSO4) and evaporated in vacuo. The resulting residue (22 g) was purified by flash chromatography on silica (toluene/ethylacetate 3:1) yielding the title compound as light yellow crystals (14.5 g, Fp. 97°-115° C.).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].I[CH2:16][CH2:17][OH:18]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][N:5]([CH2:16][CH2:17][OH:18])[C:4](=[O:8])[CH:3]=1
Reactant: O=c1cc(Br)cc[nH]1
Reactant: OCCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: O=c1cc(Br)ccn1CCO
Temperature: 80 °C
Reaction time: 48 h
Yield: 13.8 %

Procedure:
To a solution of 4-bromopyridin-2(1H)-one (174 mg, 1.00 mmol) in THF (3.5 mL) was added K2CO3 (1.38 g, 10.0 mmol) and 2-iodoethanol (156 μL, 2.00 mmol). The reaction was stirred at 80° C. for 2 days before being cooled to room temperature and filtered. The filtrate was concentrated and purified by column chromatography (0-10% MeOH—CH2Cl2) to yield 4-bromo-1-(2-hydroxyethyl)pyridin-2(1H)-one as a pale yellow solid (30 mg, 7%). ESI-MS m/z calc. 217.0. found 218.3 (M+1)+. Retention time 0.33 minutes. 1H NMR (400 MHz, DMSO-d6) δ 7.57 (d, J=7.2 Hz, 1H), 6.70 (d, J=2.2 Hz, 1H), 6.44 (dd, J=2.2, 7.2 Hz, 1H), 4.89 (t, J=5.4 Hz, 1H), 3.91 (t, J=5.4 Hz, 2H), 3.59 (q, J=5.4 Hz, 2H).