Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][C:3](Br)=[O:4].[NH:6]([CH2:8][C:9]([OH:11])=[O:10])[CH3:7].C(N(CC)CC)C>C1COCC1>[CH3:7][N:6]1[C:3](=[O:4])[CH2:2][O:10][C:9](=[O:11])[CH2:8]1
Reactant: O=C(Br)CBr
Reactant: CNCC(=O)O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CN1CC(=O)OCC1=O
Temperature: 50 °C
Reaction time: 0.25 h

Procedure:
Bromacetyl bromide (202 g, 1.0 moles) is dissolved in THF (400 ml) and rapidly added to a cooled (15° C.), vigorously stirred sarcosine (178.2, 2.0 moles)-THF (900 ml) mixture. After two hours of thorough mixing at room temperature the reaction mixture is filtered. Triethylamine (101 g, 1.0 moles) is added to the filtrate. This reaction mixture is stirred at 50° C. for 0.25 hours and then filtered. Evaporation of this filtrate's solvent produces roughly 80 g of crude, liquid N-methyl-2,5-morpholinedione. Vacuum distillation of this oil yields 60 g of N-methyl-2,5-morpholinedione (B.P. 114°-116° C. at 0.1 mm, ND23 =1.4967). Proton NMR analysis of the distillate shows chemical shifts at 2.952, 2.985, 3.94, 4.16, and 4.74 PPM. Elemental analysis of the compound is as follows--calculated for C5H7NO3 : C, 46.50; H, 5.48; N, 10.84; O, 37.17%. Found: C, 46.78; H, 5.80; N, 11.16; O, 36.47%.
Reaction SMILES: [OH:1][C@H:2]1[CH2:6][C:5](=[O:7])[C:4]([CH2:8][C:9]#[CH:10])=[C:3]1[CH3:11].[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl>[O:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]1[O:1][C@H:2]1[CH2:6][C:5](=[O:7])[C:4]([CH2:8][C:9]#[CH:10])=[C:3]1[CH3:11]
Reactant: C#CCC1=C(C)[C@@H](O)CC1=O
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: O
Product: C#CCC1=C(C)[C@@H](OC2CCCCO2)CC1=O
Yield: 86.5 %

Procedure:
1 To a solution of (S)-4-hydroxy-3-methyl-2(2-propynyl)cyclopent-2-ene-l-one (20.0 g) in dichloromethane (200 ml) were added with stirring 3,4-dihydro-2H-pyran (12.5 g) and a catalytic amount of p-toluenesulfonic acid hydrate under ice-water cooling, then the solution was stirred at room temperature for 1.5 hours. This solution was partitioned between diethyl ether and brine, and the organic layer was washed twice with brine. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The resultant residue was subjected to silica gel column chromatography (eluent; n-hexane:ethyl acetate=5:1) to afford (S)-4-(2-tetrahydropyranyloxy)-3-methyl-2-(2-propynyl)cyclopent-2-ene-1-one (27 g, yield 86.6%) pale yellow oil.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]=[C:15]([CH3:20])[CH:14]=[C:13]2[OH:21])=[O:5])[CH3:2].[Br:22][CH2:23][CH2:24][CH2:25]Br.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:1]([O:3][C:4]([CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]=[C:15]([CH3:20])[CH:14]=[C:13]2[O:21][CH2:25][CH2:24][CH2:23][Br:22])=[O:5])[CH3:2]
Reactant: BrCCCBr
Reactant: CCOC(=O)CCCOc1ccc2nc(C)cc(O)c2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)CCCOc1ccc2nc(C)cc(OCCCBr)c2c1

Procedure:
A reaction between 6-(3-ethoxycarbonylpropoxy)-2-methylquinolin-4-ol (1.157 g, 4 mmol), 1,3-dibromopropane (3.230 g, 16 mmol) and anhydrous potassium carbonate (0.663 g, 4.8 mmol) in acetone was performed similar to that described in Example 5b. The expected compound was obtained as a white solid (0.903 g, 55%). 1H NMR (400 MHz, CDCl3): 1.25 (3H, t, J=7.2 Hz), 2.18 (2H, m), 2.56 (4H, m), 2.65 (3H, s), 3.67 (2H, t, J=6.3 Hz), 4.14 (4H, m), 4.31 (2H, t, J=5.8 Hz), 6.61 (s, 1H), 7.29 (1H, dd, J=9.1, 2.6 Hz), 7.36 (1H, d, J=2.6 Hz), 7.85 (1H, d, J=9.1 Hz).
Reaction SMILES: [F:1][CH:2]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][N:24]([CH2:36][CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:25]3[S:26][CH:27]=[C:28]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[N:29]=3)=[CH:19][CH:18]=2)=[CH:11][CH:10]=1)[C:3]([O:5]CC)=[O:4].O1CCCC1.O.[OH-].[Li+].Cl>O.CO>[F:1][CH:2]([CH2:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][N:24]([CH2:36][CH2:37][C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:25]3[S:26][CH:27]=[C:28]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:29]=3)=[CH:19][CH:18]=2)=[CH:13][CH:14]=1)[C:3]([OH:5])=[O:4]
Reactant: CCOC(=O)C(F)Cc1ccc(OCc2ccc(CN(CCc3ccccc3)c3nc(-c4ccccc4)cs3)cc2)cc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)C(F)Cc1ccc(OCc2ccc(CN(CCc3ccccc3)c3nc(-c4ccccc4)cs3)cc2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 68 %

Procedure:
A mixture of ethyl 2-fluoro-3-{4-[(4-{[(2-phenylethyl)(4-phenyl-1,3-thiazol-2-yl)amino]methyl}benzyl)oxy]phenyl}-propanoate (740 mg, 1.31 mmol), tetrahydrofuran (15 mL), methanol (10 mL), water (10 mL) and lithium hydroxide monohydrate (165 mg, 3.92 mmol) was stirred at room temperature for 3 hr. The reaction mixture was neutralized with 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was recrystallized from hexane-diisopropyl ether to give the title compound (505 mg, yield 68%) as colorless crystals.
Reaction SMILES: C([O:8][C:9](=O)[C@@H:10]([O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)([C:30]([F:33])([F:32])[F:31])[C:26]([F:29])([F:28])[F:27])=[CH:21][C:20]=1[CH3:44])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)C1C=CC=CC=1.[BH4-].[Na+].O>CO.C1COCC1>[CH3:44][C:20]1[CH:21]=[C:22]([C:25]([O:34][CH2:35][C:36]2[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=2)([C:26]([F:27])([F:28])[F:29])[C:30]([F:32])([F:33])[F:31])[CH:23]=[CH:24][C:19]=1[O:18][C@@H:10]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:9][OH:8]
Reactant: COc1ccc(COC(c2ccc(O[C@@H](Cc3ccccc3)C(=O)OCc3ccccc3)c(C)c2)(C(F)(F)F)C(F)(F)F)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: COc1ccc(COC(c2ccc(O[C@H](CO)Cc3ccccc3)c(C)c2)(C(F)(F)F)C(F)(F)F)cc1
Temperature: 0 °C
Yield: 67.3 %

Procedure:
1.7 g (2.7 mmol) of (S)-2-{2-methyl-4-[2,2,2-trifluoro-1-(4-methoxy-benzyloxy)-1-trifluoromethyl-ethyl]-phenoxy}-3-phenyl-propionic acid benzyl ester was dissolved in a mixture of 11 mL of methanol and 11 mL of THF and cooled to 0° C. To this solution 1.0 g (26.9 mmol) of NaBH4 were added in portions, and the mixture was slowly warmed to room temperature overnight. Water was added, the phases were separated and the inorganic one was extracted with dichloromethane. The combined organic phases were washed with brine, dried (Na2SO4), filtered and evaporated. Purification by column chromatography with CH2Cl2/MeOH 95:5 yielded 960 mg (68%) (S)-2-{2-methyl-4-[2,2,2-trifluoro-1-(4-methoxy-benzyloxy)-1-trifluoromethyl-ethyl]-phenoxy}-3-phenyl-propan-1-ol as a light yellow oil, MS: 528 (M)+.
Reaction SMILES: [NH:1]([C:3]1[N:4]=[N:5][C:6]([Cl:12])=[CH:7][C:8]=1[C:9]([NH2:11])=[O:10])[NH2:2].[N:13]([O-])=O.[Na+]>C(O)(=O)C.O>[Cl:12][C:6]1[CH:7]=[C:8]([C:9]([NH2:11])=[O:10])[C:3]2[N:4]([N:13]=[N:2][N:1]=2)[N:5]=1
Reactant: O=N[O-]
Reactant: NNc1nnc(Cl)cc1C(N)=O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: NC(=O)c1cc(Cl)nn2nnnc12
Temperature: 0 °C
Reaction time: 1 h
Yield: 77.1 %

Procedure:
To an ice-cold solution of 3-hydrazino-4-aminocarbonyl-6-chloro-pyridazine (4.2 g; 0.0244 mole) [obtained as reported in J. Het. Chemistry, 7, 465 (1970)] in 15% acetic acid, a solution of sodium nitrite (1.55 g) in water (10 ml) was added dropwise. After stirring for one hour at 5°-10° C., the separated precipitate was filtered, crystallized from water, filtered again and dried under vacuum at 50° C. to give 3.44 g (77.5%) of the title compound, m.p. 226° C. (dec.).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[C:6]([CH:9]=1)[CH:7]=O.[N:16]1([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[C:6]([CH2:7][N:19]2[CH2:18][CH2:17][N:16]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20]2)[CH:9]=1
Reactant: O=Cc1cc(Cl)ccc1N1CCOCC1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: O
Product: CC(C)(C)OC(=O)N1CCN(Cc2cc(Cl)ccc2N2CCOCC2)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 113.9 %

Procedure:
A round-bottom flask was charged with 5-chloro-2-(morpholin-4-yl)benzaldehyde (1.60 g, 7.09 mmol, 1.00 equiv), tert-butyl piperazine-1-carboxylate (1.20 g, 6.43 mmol, 0.910 equiv), 1,2-dichloromethane (20 mL). The mixture was stirred at room temperature for 0.5 hour. Sodium triacetoxyborohydride (4.09 g, 19.3 mmol, 2.72 equiv) was added. The resulting solution was stirred overnight at room temperature and diluted with H2O (50 mL). The resulting solution was extracted with dichloromethane (2×20 mL), the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/4) to yield 2.90 g (crude) of tert-butyl 4-[[5-chloro-2-(morpholin-4-yl)phenyl]methyl]piperazine-1-carboxylate as yellow oil. LCMS (ESI, m/z): 396 [M+H]+.
Reaction SMILES: [CH3:1][C:2]([CH3:21])([CH3:20])[C:3]([C:5]1[O:6][C:7]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:8]=2[C:9]=1[CH2:10][C:11]([OH:13])=O)=[O:4].C1C=CC2N(O)N=NC=2C=1.[CH2:32]([C@H:35]1[CH2:39][CH2:38][C@H:37]([CH2:40][CH2:41][CH3:42])[NH:36]1)[CH2:33][CH3:34].CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)CCl>[CH2:32]([C@H:35]1[CH2:39][CH2:38][C@H:37]([CH2:40][CH2:41][CH3:42])[N:36]1[C:11](=[O:13])[CH2:10][C:9]1[C:8]2[CH:14]=[C:15]([O:18][CH3:19])[CH:16]=[CH:17][C:7]=2[O:6][C:5]=1[C:3](=[O:4])[C:2]([CH3:20])([CH3:1])[CH3:21])[CH2:33][CH3:34]
Reactant: COc1ccc2oc(C(=O)C(C)(C)C)c(CC(=O)O)c2c1
Reactant: CCC[C@H]1CC[C@H](CCC)N1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCC[C@H]1CC[C@H](CCC)N1C(=O)Cc1c(C(=O)C(C)(C)C)oc2ccc(OC)cc12
Temperature: 40 °C

Procedure:
Dissolve a mixture of 17 mg [2-(2,2-dimethylpropanoyl)-5-methoxy-1-benzofuran-3-yl]acetic acid from the Step B Example 1 and 18.5 mg HOBt in 1 mL dry DMF. Add 13.7 mg trans-2,5-dipropylpyrrolidine from the Step D above followed by 23.0 mg EDC and 35 μL DIEA. This solution was heated at 40° C. for 2 hours. It was purified directly on RP-HPLC using 70-100% MeCN gradient. The fractions containing pure product were pooled and lyophilized to give the title compound. LC-MS: 4.58 min. (m/Z 428.3, 344.2, 450.3).
Reaction SMILES: [CH3:1][C:2]1([CH3:36])[CH2:7][CH:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[C:23]4[C:18](=[CH:19][C:20]([CH2:24][OH:25])=[CH:21][CH:22]=4)[N:17]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[CH:16]=3)[CH:12]=[CH:11][N:10]=2)[CH2:5][C:4]([CH3:35])([CH3:34])[NH:3]1.CCN(CC)CC.P([O-])(O)(O)=[O:45].[Na+].Cl([O-])=O.[Na+]>CS(C)=O.O.CCOC(C)=O>[CH3:1][C:2]1([CH3:36])[CH2:7][CH:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[C:23]4[C:18](=[CH:19][C:20]([C:24]([OH:45])=[O:25])=[CH:21][CH:22]=4)[N:17]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:32])([CH3:31])[CH3:33])[CH:16]=3)[CH:12]=[CH:11][N:10]=2)[CH2:5][C:4]([CH3:35])([CH3:34])[NH:3]1
Reactant: CC1(C)CC(Nc2nccc(-c3cn(COCC[Si](C)(C)C)c4cc(CO)ccc34)n2)CC(C)(C)N1
Reactant: O=P([O-])(O)O
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: O
Product: CC1(C)CC(Nc2nccc(-c3cn(COCC[Si](C)(C)C)c4cc(C(=O)O)ccc34)n2)CC(C)(C)N1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of [3-[2-(2,2,6,6-Tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-6-yl]-methanol (7.20 g, 14.1 mmol) in DMSO (35 ml) and Et3N (31.4 ml, 226 mmol) was added a solution of sulfur trioxide pyridine complex (6.73 g, 42.3 mmol) in DMSO (35 ml). After stirring for 2 h at room temperature, the reaction mixture was poured into EtOAc and the organic phase was washed with water. The organic layer was dried and concentrated. The crude product was dissolved in tert-butanol (645 ml) and 2-methyl-2-butene (100 ml). Then sodium dihydrogenphosphate (4.19 g, 35.0 mmol) dissolved in water (50 ml) was added followed by sodium chlorite (7.91 g, 70.0 mmol) dissolved in water (75 ml) The reaction mixture was stirred overnight and concentrated and diluted with EtOAc upon which a yellow solid was obtained which was used without further purification. Yield: 5.00 g (69%).
Reaction SMILES: [OH-].[K+].[C:3]([CH:7]1[CH2:12][CH2:11][C:10](=[O:13])[CH2:9][CH2:8]1)([CH3:6])([CH3:5])[CH3:4].O.C(O)(C)C>C(O)(C)C.O.CC(C)=O>[C:3]([CH:7]1[CH2:8][CH2:9][CH:10]([OH:13])[CH2:11][CH2:12]1)([CH3:6])([CH3:4])[CH3:5]
Reactant: CC(C)(C)C1CCC(=O)CC1
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)=O
Solvent: CC(C)O
Solvent: O
Product: CC(C)(C)C1CCC(O)CC1

Procedure:
1 mg (2×10-5 moles) of [Ir(3,4,7,8 Me4 phen)COD]Cl oxidized with air in 50 ml of isopropanol-H2O (1%) were treated with 0.56 ml of an aqueous solution of KOH (100 mg in 50 ml of H2O) and successively heated at reflux for 1 hour. 5 g of 4-terbutyl-cyclohexanone were then added and it was heated at reflux for 30 minutes. The gaschromatographic analysis revealed a conversion of 100% and a trans/cis ratio=22.1 (95.5% of trans isomer). By addition of water and vacuum removal of the isopropanol and of the acetone which had formed, the reaction product 4-terbutyl-cyclohexanol was isolated. Ratios: [KOH]/[cat.]=1; [substratum]/[cat.]=1630. This example points out the possibility of obtaining, with a ratio KOH/cat.=1, the reduction of 4-terbutyl-cyclohexanone with a high stereoselectivity. In fact, when repeating the test under the same operative conditions as employed before, higher amounts of KOH were used, precisely 5.6 ml and 11.2 ml of aqueous solution, corresponding to a KOH/cat. ratio equal to 5 and 10, respectively. Equal conversions of 100% were obtained, while the trans/cis ratios decreased to 4.5 and 4, respectively.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[OH:16])([CH3:4])([CH3:3])[CH3:2].[CH3:17][O-:18].[Na+].Cl>Cl([O-])(=O)(=O)=O.C([N+](CC)(CC)CC)C.C(#N)C>[C:12]([C:7]1[CH:8]=[C:9]([CH2:11][CH2:11][C:9]2[CH:8]=[C:7]([C:12]([CH3:14])([CH3:13])[CH3:15])[C:17]([OH:18])=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:10]=2)[CH:10]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[C:6]=1[OH:16])([CH3:15])([CH3:14])[CH3:13]
Reactant: Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Reactant: C[O-]
Agent: CC[N+](CC)(CC)CC
Agent: Cl
Agent: [Na+]
Solvent: CC#N
Product: CC(C)(C)c1cc(CCc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)cc(C(C)(C)C)c1O
Reaction time: 8 h
Yield: 442.2 %

Procedure:
The electrolysis cell was charged with 300 milliliters of 10 percent aqueous acetonitrile and 6.9 grams (0.03 mole) of tetraethylammonium perchlorate. Nitrogen gas was passed through the system while 4.4 grams (0.02 mole) of 2,6-di-t-butyl-4-methylphenol, and 0.108 gram (0.002 mole) of sodium methoxide were added. The electrolysis was conducted at ambient temperatures under a nitrogen atmosphere at an anode potential of +0.35 volt (versus the saturated calomel electrode). The initial current of 210 milliamperes decreased to 16 milliamperes over the 10-hour electrolysis period. Upon completion of the electrolysis, the reaction mixture was acidified with 2.0 milliliters of concentrated hydrochloric acid and allowed to stand overnight (about 15 hours). The graphite felt anode was washed with two 50-milliliter portions of chloroform to remove the precipitate which had collected thereon during both the electrolysis and the standing period. The chloroform solution was dried over anhydrous magnesium sulfite and evaporated in vacuo to yield pure crystals of 1,2-bis(3,5-di-t-butyl-4-hydroxyphenyl)ethane (3.88 grams, 88.6 percent), melting point 170°-171° C.
Reaction SMILES: [CH2:1]([C:4]1([C:15]2[CH:20]=[CH:19][C:18](Br)=[CH:17][CH:16]=2)[O:8][C:7]2=[N:9][C:10]([N+:12]([O-:14])=[O:13])=[CH:11][N:6]2[CH2:5]1)[CH:2]=[CH2:3].[F:22][C:23]1[CH:24]=[C:25]([N:38]2[CH2:42][CH:41]([CH2:43][NH:44][C:45](=[O:47])[CH3:46])[O:40][C:39]2=[O:48])[CH:26]=[CH:27][C:28]=1B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[K+].[K+]>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.CN(C=O)C.O>[CH2:1]([C:4]1([C:15]2[CH:20]=[CH:19][C:18]([C:28]3[CH:27]=[CH:26][C:25]([N:38]4[CH2:42][CH:41]([CH2:43][NH:44][C:45](=[O:47])[CH3:46])[O:40][C:39]4=[O:48])=[CH:24][C:23]=3[F:22])=[CH:17][CH:16]=2)[O:8][C:7]2=[N:9][C:10]([N+:12]([O-:14])=[O:13])=[CH:11][N:6]2[CH2:5]1)[CH:2]=[CH2:3]
Reactant: C=CCC1(c2ccc(Br)cc2)Cn2cc([N+](=O)[O-])nc2O1
Reactant: CC(=O)NCC1CN(c2ccc(B3OC(C)(C)C(C)(C)O3)c(F)c2)C(=O)O1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: C=CCC1(c2ccc(-c3ccc(N4CC(CNC(C)=O)OC4=O)cc3F)cc2)Cn2cc([N+](=O)[O-])nc2O1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
The title compound was synthesized according to the reaction scheme shown in FIG. 21. To a mixture of 2-Allyl-2-(4-bromo-phenyl)-6-nitro-2,3-dihydro-imidazo[2,1-b]oxazole (80 mg, 0.229 mmol), N-{3-[3-Fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (104 mg, 0.274 mmol), Pd(PPh3)4 (53 mg, 0.046 mmol) and K2CO3 (240 mg, 0.458 mmol) was added anhydrous DMF/H2O (4 mL/0.4 mL, 4.4 mL total) under N2. The reaction mixture was stirred for 2 h at 80° C., cooled to rt, quenched with water, diluted with EtOAc, washed with brine and water. The organic layers were separated, dried (MgSO4) and concentrated. Column chromatography provided 63 mg of yellow solid. 1H NMR (400 MHz, DMSO-d) δ 8.26 (t, J=5.8 Hz, 1H), 7.60 (m, 2H), 7.41 (m, 2H), 5.61 (m, 1H), 5.16 (m, 2H), 4.74 (m, 1H), 4.65 (d, J=11.2 Hz, 1H), 4.48 (d, J=11.2 Hz, 1H), 4.15 (d, J=9.0 Hz, 1H), 3.76 (m, 1H), 3.41 (d, J=1.3 Hz, 2H), 3.02 (m, 2H); ESI MS m/z 522 (M+H+)
Reaction SMILES: [Cl:1][C:2]1[CH:13]=[CH:12][C:5]([C:6](N(OC)C)=[O:7])=[CH:4][N:3]=1.[H-].C([Al+]CC(C)C)C(C)C.CCCCCC.[Na+].[Cl-]>O1CCCC1>[Cl:1][C:2]1[CH:13]=[CH:12][C:5]([CH:6]=[O:7])=[CH:4][N:3]=1
Reactant: CON(C)C(=O)c1ccc(Cl)nc1
Agent: CC(C)C[Al+]CC(C)C
Agent: [Cl-]
Agent: [H-]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: O=Cc1ccc(Cl)nc1
Temperature: -20 °C
Reaction time: 3 h

Procedure:
In tetrahydrofuran (8 ml), 6-chloro-N-methoxy-N-methylnicotinamide (500 mg) was dissolved, followed by the dropwise addition of diisobutylaluminum hydride (a 0.95M hexane solution, 2.88 ml) at −78° C. in an argon gas atmosphere. The resulting mixture was stirred for 3 hours and then, at room temperature, for 2 hours. After the reaction mixture was cooled to −20° C., saturated aqueous NaCl solution (2 ml) was added thereto, followed by stirring for 30 minutes. The insoluble matter was filtered off. The residue was washed with ethyl acetate. The filtrate and the washing were combined together. The mixture was washed with saturated aqueous NaCl solution and dried over anhydrous sodium sulfate. The solvent was then distilled off under reduced pressure, whereby the title compound (346 mg, 98%) was obtained as a crude product. The product was provided for the subsequent reaction without purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([NH:8]C2C=CC(C(F)(F)F)=CC=2)[CH:5]=[CH:4][C:3]=1[C:19]([C:21]1[CH:26]=[C:25]([N+:27]([O-:29])=[O:28])[CH:24]=[CH:23][C:22]=1[CH3:30])=[O:20].BrC1C=CC(C(C2C=C([N+]([O-])=O)C=CC=2C)=O)=C(Cl)C=1.[Cl:51][C:52]1[CH:57]=[CH:56][C:55](N)=[C:54]([CH3:59])[CH:53]=1>>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:55]2[CH:56]=[CH:57][C:52]([Cl:51])=[CH:53][C:54]=2[CH3:59])[CH:5]=[CH:4][C:3]=1[C:19]([C:21]1[CH:26]=[C:25]([N+:27]([O-:29])=[O:28])[CH:24]=[CH:23][C:22]=1[CH3:30])=[O:20]
Reactant: Cc1ccc([N+](=O)[O-])cc1C(=O)c1ccc(Nc2ccc(C(F)(F)F)cc2)cc1Cl
Reactant: Cc1cc(Cl)ccc1N
Agent: Cc1ccc([N+](=O)[O-])cc1C(=O)c1ccc(Br)cc1Cl
Product: Cc1cc(Cl)ccc1Nc1ccc(C(=O)c2cc([N+](=O)[O-])ccc2C)c(Cl)c1

Procedure:
The reaction was carried out similarly as described in the preparation of compound 414, using compound 402 (0.56 mmol) and 4-chloro-2-methyl-phenylamine (0.56 mmol). The crude product was purified by continuous gradient flash chromatography using EtOAc/petroleum ether (40-60) 0:100 to 25:75 as the eluent to afford the title compound as yellow foam.
Reaction SMILES: N.C([N:9]1[C@@H:13]([C@@H:14]([CH3:18])[CH:15]([F:17])[F:16])[CH2:12][O:11][C:10]1=[O:19])C1C=CC=CC=1.[Li]>C(OCC)C>[F:17][CH:15]([F:16])[C@@H:14]([C@H:13]1[CH2:12][O:11][C:10](=[O:19])[NH:9]1)[CH3:18]
Reactant: C[C@@H](C(F)F)[C@H]1COC(=O)N1Cc1ccccc1
Agent: N
Agent: [Li]
Solvent: CCOCC
Product: C[C@@H](C(F)F)[C@H]1COC(=O)N1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 88.1 %

Procedure:
To liquid ammonia at −50° C. under argon was slowly added a solution of (S)-3-benzyl-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-one (627 mg) (200 mg, 0.784 mmol) in diethylether (10 mL). Lithium (pellets; 54.4 mg, 7.84 mmol) were added in three portions. The reaction mixture became green then dark greenish blue over ˜10 min. The mixture was stirred for additional 15 min and then quenched slowly by the addition of saturated aqueous ammonium chloride solution (3 mL). The mixture was allowed to warm slowly to room temperature. The residue was diluted with diethylether (20 mL) and water (10 mL). The separated aqueous layer was extract with ether (2×25 mL) and DCM (3×20 mL). The DCM and ether layers were separately concentrated under reduced pressure. The residues were dissolved in DCM and combined. The organic layer was dried over magnesium sulfate, filtered off and concentrated under reduced pressure providing crude (S)-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-one (114 mg) as a colorless solid, which was directly used without further purification. MS m/z 166.1 (M+H)+; Rt-0.37 min.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([C:9]2[N:13]3[CH:14]=[CH:15][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[C:17]([F:18])[C:12]3=[N:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[N:23]1[CH:28]=[C:27](B(O)O)[CH:26]=[N:25][CH:24]=1>>[F:18][C:17]1[C:12]2[N:13]([C:9]([C:4]3[CH:5]=[CH:6][C:7]([F:8])=[C:2]([C:27]4[CH:28]=[N:23][CH:24]=[N:25][CH:26]=4)[CH:3]=3)=[CH:10][N:11]=2)[CH:14]=[CH:15][C:16]=1[C:19]([OH:22])([CH3:21])[CH3:20]
Reactant: CC(C)(O)c1ccn2c(-c3ccc(F)c(Cl)c3)cnc2c1F
Reactant: OB(O)c1cncnc1
Product: CC(C)(O)c1ccn2c(-c3ccc(F)c(-c4cncnc4)c3)cnc2c1F
Yield: 6 %

Procedure:
2-[3-(3-Chloro-4-fluorophenyl)-8-fluoroimidazo[1,2-α]pyridin-7-yl]-propan-2-ol and pyrimidine-5-boronic acid were coupled in the same way as in Example 30 to give 2-{8-fluoro-3-[4-fluoro-3-(pyrimidin-5-yl)phenyl]-imidazo[1,2-α]pyridin-7-yl}propan-2-ol as an off-white solid (7 mg, 6%): m/z (ES+) 367 [MH+].
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=2)(=[O:10])=[O:9])=[CH:4][C:3]=1[F:18].[F:19][C:20]1[CH:21]=[CH:22][C:23]([O:29][CH3:30])=[C:24](B(O)O)[CH:25]=1>>[F:18][C:3]1[CH:4]=[C:5]([S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=2)(=[O:10])=[O:9])[CH:6]=[CH:7][C:2]=1[C:22]1[CH:21]=[C:20]([F:19])[CH:25]=[CH:24][C:23]=1[O:29][CH3:30]
Reactant: O=S(=O)(c1cccc(Cl)c1)c1ccc(Br)c(F)c1
Reactant: COc1ccc(F)cc1B(O)O
Product: COc1ccc(F)cc1-c1ccc(S(=O)(=O)c2cccc(Cl)c2)cc1F

Procedure:
The subtitle compound was prepared by the method of example 2 step (ii) using the product of step (ii) and 5-fluoro-2-methoxybenzene boronic acid.