Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:15](=O)[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:17][CH3:18])[N:13]=2)[NH:8][CH:7]=1)=[O:5])[CH3:2].P(Br)(Br)[Br:20].O.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[Br:20])=[N:13][C:12]([O:17][CH3:18])=[CH:11][CH:10]=2)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1c[nH]c2ccc(OC)nc2c1=O
Reactant: BrP(Br)Br
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1cnc2ccc(OC)nc2c1Br
Reaction time: 0.5 h
Yield: 89.5 %

Procedure:
A suspension of 6-methoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acid ethyl ester (74.57 g, 300 mmol) in dry DMF (260 mL) under argon was stirred efficiently* in a water bath (to maintain approximately room temperature—may need slight ice-cooling on a large scale). Phosphorus tribromide (30.0 mL, 316 mmol) was added dropwise over 15 min and stirring was continued for an additional 30 min. Water (1 L) was added, followed by saturated sodium carbonate solution to pH 7. The solid was collected by suction filtration, washed with water and dried under vacuum over phosphorus pentoxide to give the title compound (83.56 g, 90%).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].[NH4+].[Cl-].[CH2:14](Br)[CH:15]=[CH2:16]>C1COCC1.[Zn]>[Cl:1][CH2:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([OH:5])[CH2:16][CH:15]=[CH2:14]
Reactant: O=C(CCCl)c1ccccc1
Reactant: C=CCBr
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: C1CCOC1
Product: C=CCC(O)(CCCl)c1ccccc1
Reaction time: 1 h
Yield: 97.3 %

Procedure:
A solution of 3-chloro-1-phenylpropan-1-one (100 g, 0.595 mol) in THF (280 ml) was added dropwise to a well-stirred mixture of zinc powder (need not be activated) (40 g, 1.231 mol, satd aq NH4Cl solution (1500 ml) and THF (400 ml). Allyl bromide (143 g, 1.19 mol) was dissolved in THF (200 ml) was slowly added to the reaction mixture. The reaction was mildly exothermic, and the mixture began to reflux spontaneously. After refluxing had ceased, the mixture was stirred for 1 h. The mixture was extracted with EtOAc, dried over anhydrous Na2SO4, and concentrated to give 1-chloro-3-phenylhex-5-en-3-ol (122 g, 97%). 1H NMR: (400 MHz, CDCl3): δ=2.24 (s, 1H), 2.34 (m, 2H), 2.53 (m, 1H), 2.75 (m, 1H), 3.20 (m, 1H), 3.58 (m, 1H), 5.18 (t, 1H), 5.51 (m, 1H), 7.26 (m, 1H), 7.26-7.39 (m, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH2:8][CH:7]([CH2:11]C=O)[N:6]1[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])=[O:4].[CH:24]([O:29][CH3:30])([O:27][CH3:28])OC.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>>[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH2:8][CH:7]([CH2:11][CH:24]([O:27][CH3:28])[O:29][CH3:30])[N:6]1[C:14]([O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:15])=[O:4]
Reactant: COC(OC)OC
Reactant: COC(=O)C1CCCC(CC=O)N1C(=O)OCc1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: COC(=O)C1CCCC(CC(OC)OC)N1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 96 %

Procedure:
6-(2-Oxo-ethyl)-piperidine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester (Compound 236, 0.4 g, 1.25 mmol), trimethyl orthoformate (5 mL) and p-toluenesulfonic acid monohydrate (0.03 g) were combined, and the reaction mixture was stirred at room temperature for 12 hours. Aqueous NaHCO3 (25 mL) was added and the reaction was extracted with CHCl3 (3×100 mL). The combined organic layer was dried over MgSO4 and concentrated. The residue was purified by flash chromatography (1:2 EtOAc/hexanes) to afford Compound 237 (0.441 g, 96%). Rf=0.75 (1:1 EtOAc/hexanes).
Reaction SMILES: C(N(CC)C(C)C)C.[F:9][C:10]1[CH:11]=[C:12]([C:16]2[N:21]=[C:20]([CH3:22])[C:19]([C:23]([OH:25])=O)=[CH:18][N:17]=2)[CH:13]=[CH:14][CH:15]=1.[N:26]1([NH2:35])[C:30]2=[CH:31][N:32]=[CH:33][CH:34]=[C:29]2[CH:28]=[CH:27]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.O>[N:26]1([NH:35][C:23]([C:19]2[C:20]([CH3:22])=[N:21][C:16]([C:12]3[CH:13]=[CH:14][CH:15]=[C:10]([F:9])[CH:11]=3)=[N:17][CH:18]=2)=[O:25])[C:30]2=[CH:31][N:32]=[CH:33][CH:34]=[C:29]2[CH:28]=[CH:27]1
Reactant: Cc1nc(-c2cccc(F)c2)ncc1C(=O)O
Reactant: Nn1ccc2ccncc21
Agent: CCN(CC)C(C)C
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: O
Product: Cc1nc(-c2cccc(F)c2)ncc1C(=O)Nn1ccc2ccncc21
Temperature: 80 °C
Reaction time: 8 h
Yield: 44.9 %

Procedure:
Diethyl-iso-propylamine (1.13 mmol) is added a solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (0.75 mmol), pyrrolo[2,3-c]pyridine-1-ylamine (0.75 mmol) and TBTU (0.9 mmol) in anhydrous DMF (7 mL) at rt, and the reaction mixture is stirred at 80° C. overnight. Water is added and the mixture is extracted with EtOAc. The organic layer is separated, washed with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 40-100% MeOH in DCM to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid pyrrolo[2,3-c]pyridin-1-ylamide (117 mg, 45%) as a solid. MS: 348 (M+H); 1H NMR (300 MHz, CD3OD): δ 2.84 (s, 3H), 6.72 (d, H), 7.29 (m, H), 7.55 (m, H), 7.71 (m, H), 8.14-8.29 (m, 2H), 8.36 (d, 3), 8.75 (s, H), 9.17 (s, H). IC50=28.5 nM.
Reaction SMILES: [CH3:1][N:2]([CH3:43])[C:3]1[CH:8]=[CH:7][C:6]([P:9]([C:34]2[CH:39]=[CH:38][C:37]([N:40]([CH3:42])[CH3:41])=[CH:36][CH:35]=2)([CH2:11][CH2:12][CH2:13][P:14]([C:25]2[CH:30]=[CH:29][C:28]([N:31]([CH3:33])[CH3:32])=[CH:27][CH:26]=2)([C:16]2[CH:21]=[CH:20][C:19]([N:22]([CH3:24])[CH3:23])=[CH:18][CH:17]=2)=O)=O)=[CH:5][CH:4]=1.C(N(CCCC)CCCC)CCC.C1([SiH](Cl)Cl)C=CC=CC=1>CC1C=CC=CC=1C>[CH3:33][N:31]([CH3:32])[C:28]1[CH:29]=[CH:30][C:25]([P:14]([C:16]2[CH:17]=[CH:18][C:19]([N:22]([CH3:24])[CH3:23])=[CH:20][CH:21]=2)[CH2:13][CH2:12][CH2:11][P:9]([C:6]2[CH:7]=[CH:8][C:3]([N:2]([CH3:1])[CH3:43])=[CH:4][CH:5]=2)[C:34]2[CH:39]=[CH:38][C:37]([N:40]([CH3:41])[CH3:42])=[CH:36][CH:35]=2)=[CH:26][CH:27]=1
Reactant: CN(C)c1ccc(P(=O)(CCCP(=O)(c2ccc(N(C)C)cc2)c2ccc(N(C)C)cc2)c2ccc(N(C)C)cc2)cc1
Agent: Cl[SiH](Cl)c1ccccc1
Solvent: Cc1ccccc1C
Solvent: CCCCN(CCCC)CCCC
Product: CN(C)c1ccc(P(CCCP(c2ccc(N(C)C)cc2)c2ccc(N(C)C)cc2)c2ccc(N(C)C)cc2)cc1
Temperature: 145 °C
Yield: 95 %

Procedure:
12.0 g (19.5 mmol) of 1,3-bis[bis(4-dimethylaminophenyl)phosphinyl]propane and 24 ml (100 mmol) of tri-n-butylamine are initially charged in 80 ml of o-xylene in an argon atmosphere while stirring. 14.4 ml (100 mmol) of phenyldichlorosilane are slowly added dropwise. The mixture is heated to 145° C., stirred for 6 hours and the solvent is distilled off under reduced pressure. Cooling the clear solution results in formation of colorless crystals which are filtered off. The crystals obtained are suspended in 100 ml of degassed o-xylene and extracted with 20 ml of 2N sodium hydroxide solution. The organic phase is separated off, dried with sodium sulphate and evaporated under reduced pressure. This gives 10.8 g of colorless solid, corresponding to a yield of 95%.
Reaction SMILES: [CH:1]12[CH2:6][CH:5]1[C:4](=[O:7])[O:3][C:2]2=[O:8].[NH2:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]2=[O:22])=[CH:12][C:11]=1[F:23]>C1COCC1>[F:23][C:11]1[CH:12]=[C:13]([N:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]2=[O:22])[CH:14]=[CH:15][C:10]=1[NH:9][C:4]([CH:5]1[CH2:6][CH:1]1[C:2]([OH:3])=[O:8])=[O:7]
Reactant: O=C1OC(=O)C2CC12
Reactant: Nc1ccc(-n2ccccc2=O)cc1F
Solvent: C1CCOC1
Product: O=C(O)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
Temperature: 25 °C
Yield: 31.9 %

Procedure:
A solution of 3-oxabicyclo[3.1.0]hexane-2,4-dione (160 mg) in THF (5 ml) was treated with 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one (321 mg; CAS 536747-52-1, prepared according to C. F. Bigge et al., patent application WO 2003045912). The suspension was stirred over night at r.t. The solid was collected by filtration, triturated with 1N HCl (5 ml), again collected by filtration, washed with 1N HCl, H2O, then cyclohexane and dried to give (1RS,2SR)-2-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-cyclopropanecarboxylic acid (144 mg) as off-white solid. MS: 315.3 ([M−H]−)
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[C:3]=1[NH:10][S:11]([C:14]1[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=1)(=[O:13])=[O:12].OC1C2N=NNC=2C=CC=1.[OH:33][CH:34]([CH:37]1[CH2:41][O:40][C:39]([CH3:43])([CH3:42])[O:38]1)[CH2:35][NH2:36].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O>[OH:33][CH:34]([CH:37]1[CH2:41][O:40][C:39]([CH3:43])([CH3:42])[O:38]1)[CH2:35][NH:36][C:18](=[O:19])[C:17]1[CH:21]=[CH:22][C:14]([S:11](=[O:13])(=[O:12])[NH:10][C:3]2[C:4]([F:9])=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[CH:15][CH:16]=1
Reactant: O=C(O)c1ccc(S(=O)(=O)Nc2c(F)cc(F)cc2F)cc1
Reactant: CC1(C)OCC(C(O)CN)O1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Oc1cccc2[nH]nnc12
Solvent: CN(C)C=O
Product: CC1(C)OCC(C(O)CNC(=O)c2ccc(S(=O)(=O)Nc3c(F)cc(F)cc3F)cc2)O1
Temperature: -10 °C
Reaction time: 10 h

Procedure:
4.97 g (15 mmol) of 4-[N-(2,4,6-trifluorophenyl)sulfamoyl]-benzoic acid is dissolved in 50 ml of dry dimethylformamide under argon atmosphere, 2.03 g (15 mmol) of hydroxybenzotriazole and 2.42 g (15 mmol) of 2-hydroxy-2-(2,2-dimethyl-1,3-dioxolan-4-yl)-ethylamine are added and the solution is cooled to -10° C. At this temperature, 3.09 g (15 mmol) of dicyclohexylcarbodiimide is added to the solution. Then it is stirred for 1 hour at -10° C. and 10 hours at room temperature. The turbid reaction solution is filtered and the filtrate is concentrated by evaporation in a vacuum. The residue is dissolved in 100 ml of ethyl acetate, the solution is shaken out five times with saturated sodium bicarbonate solution and twice with water, the organic phase is dried on sodium sulfate, filtered and concentrated by evaporation. 3.46 g (7.29 mmol)=48.6% of the theoretical yield is obtained as a solid.
Reaction SMILES: [CH3:1][C@H:2]1[C@H:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[O:5][C:4](=[O:13])[N:3]1[C:14](=[O:24])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[O:22][CH3:23].[CH3:25]I>O1CCCC1.C(OCC)(=O)C>[CH3:1][C@H:2]1[C@H:6]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[O:5][C:4](=[O:13])[N:3]1[C:14](=[O:24])[C@H:15]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[O:22][CH3:23])[CH3:25]
Reactant: CI
Reactant: COc1ccccc1CC(=O)N1C(=O)O[C@@H](c2ccccc2)[C@@H]1C
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COc1ccccc1[C@H](C)C(=O)N1C(=O)O[C@@H](c2ccccc2)[C@@H]1C
Reaction time: 0.75 h

Procedure:
19.1 g of sodium 1,1,1,3,3,3-hexamethyldisilazanate are added to a solution, cooled to −50° C., of 10 g of (4S,5S)-4-methyl-5-phenyl-3-[(2-methoxyphenyl)acetyl]oxazolidin-2-one in 150 cm3 of tetrahydrofuran, the mixture is stirred for 45 minutes at this temperature and then 7.72 cm3 of methyl iodide are added. The reaction mixture is then stirred for 15 hours at room temperature, then diluted with ethyl acetate, washed with 50 cm3 of water and then with 50 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is crystallized from isopropyl ether, filtered off and dried. There are obtained 4.2 g of (4S,5S)-4-methyl-5-phenyl-3-[(S)-2-(2-methoxyphenyl)propionyl]oxazolidin-2-one in the form of a white solid.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1B(O)O.Br[C:10]1[S:18][C:17]2[C:12](=[N:13][CH:14]=[CH:15][C:16]=2[NH:19][C:20]2[CH:21]=[C:22]3[C:26](=[CH:27][CH:28]=2)[NH:25][CH:24]=[CH:23]3)[CH:11]=1>>[NH:25]1[C:26]2[C:22](=[CH:21][C:20]([NH:19][C:16]3[CH:15]=[CH:14][N:13]=[C:12]4[CH:11]=[C:10]([C:2]5[S:1][CH:5]=[CH:4][CH:3]=5)[S:18][C:17]=34)=[CH:28][CH:27]=2)[CH:23]=[CH:24]1
Reactant: OB(O)c1cccs1
Reactant: Brc1cc2nccc(Nc3ccc4[nH]ccc4c3)c2s1
Product: c1csc(-c2cc3nccc(Nc4ccc5[nH]ccc5c4)c3s2)c1

Procedure:
The title compound was prepared from thiophene-2-boronic acid and (2-bromo-thieno[3,2-b]pyridin-7-yl)-(1H-indol-5-yl)-amine by a procedure analogous to example 17. 1H NMR (400 MHz, DMSO) d 11.1 (s, 2H), 8.27 (d, 1H), 7.73 (s, 1H), 7.48 (m, 5H), 7.19 (m, 1), 7.03 (d, 1H), 6.50 (s, 1H); LC-MS: 348 (MH+); HPLC RT: 5.11 minutes.
Reaction SMILES: [CH2:1]([N:8]1[CH2:16][C:15]2[C:14](Cl)=[N:13][C:12]([Cl:18])=[N:11][C:10]=2[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1>C(O)(C)C>[CH2:1]([N:8]1[CH2:16][C:15]2[C:14]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[N:13][C:12]([Cl:18])=[N:11][C:10]=2[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C1COCCN1
Reactant: O=C1c2nc(Cl)nc(Cl)c2CN1Cc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: O=C1c2nc(Cl)nc(N3CCOCC3)c2CN1Cc1ccccc1
Reaction time: 0.5 h

Procedure:
6-benzyl-2,4-dichloro-5H-pyrrolo[3,4-d]pyrimidin-7(6H)-one (cw) (0.125 g, 0.000425 mol), isopropyl alcohol (2.90 mL), N,N-diisopropylethylamine (0.150 mL, 0.861 mmol) and morpholine (0.0556 mL, 0.638 mmol) were mixed and the mixture was stirred for 30 minutes. The reaction mixture was concentrated. The resulting residue was chromatographed through silica gel (40 g, 0-5% MeOH in dichloromethane) to give the compound cx (0.126 g, 86%).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH3:12])(=[O:11])=[O:10])=[CH:5][CH:4]=1)#[CH:2].C(N(CC)CC)C.Br[C:21]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:22]=1[CH:23]=[O:24]>ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[F:29][C:27]1[CH:28]=[CH:21][C:22]([CH:23]=[O:24])=[C:25]([C:2]#[C:1][C:3]2[CH:4]=[CH:5][C:6]([S:9]([CH3:12])(=[O:10])=[O:11])=[CH:7][CH:8]=2)[CH:26]=1
Reactant: C#Cc1ccc(S(C)(=O)=O)cc1
Reactant: O=Cc1ccc(F)cc1Br
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)c1ccc(C#Cc2cc(F)ccc2C=O)cc1
Temperature: 80 °C
Reaction time: 3.5 h
Yield: 79.2 %

Procedure:
A degassed mixture of 1-ethynyl-4-methanesulfonyl-benzene (2.5 g, 13.87 mmol), bis(triphenylphosphine)palladium(II) chloride (0.49 g, 0.69 mmol), copper(I) iodide (0.13 g, 0.69 mmol), triethylamine (28 mL), and 2-bromo-4-fluorobenzaldehyde (3.38 g, 16 mmol) in dichloromethane (10 mL) was stirred at 80° C. for 3.5 hours, then at room temperature overnight. The reaction mixture was partitioned between dichloromethane and water. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (RediSep® Flash column, 230-400 mesh, 15-35% ethyl acetate in hexane) gave 4-fluoro-2-(4-methanesulfonyl-phenylethynyl)-benzaldehyde (3.32 g, 79%). MS (ESI+) cald. for C16H11FO3S [(M+H)+] 302, obsd. 302.
Reaction SMILES: [F:1][C:2]1[CH:22]=[C:21]([N:23]2[CH:27]=[CH:26][CH:25]=[N:24]2)[CH:20]=[CH:19][C:3]=1[CH2:4][C:5]1[C:6]([CH3:18])=[C:7]([CH3:17])[C:8]([CH:15]=C)=[C:9]([CH:14]=1)[C:10]([O:12][CH3:13])=[O:11].CC(C)=[O:30].C(#N)C.I([O-])(=O)(=O)=O.[Na+]>[Os]=O.O>[F:1][C:2]1[CH:22]=[C:21]([N:23]2[CH:27]=[CH:26][CH:25]=[N:24]2)[CH:20]=[CH:19][C:3]=1[CH2:4][C:5]1[C:6]([CH3:18])=[C:7]([CH3:17])[C:8]([CH:15]=[O:30])=[C:9]([CH:14]=1)[C:10]([O:12][CH3:13])=[O:11]
Reactant: CC(C)=O
Reactant: C=Cc1c(C(=O)OC)cc(Cc2ccc(-n3cccn3)cc2F)c(C)c1C
Agent: O=[Os]
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: O
Solvent: CC#N
Product: COC(=O)c1cc(Cc2ccc(-n3cccn3)cc2F)c(C)c(C)c1C=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of methyl 5-(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)-3,4-dimethyl-2-vinylbenzoate (0.40 g) in a mixed solvent of acetone (5.00 mL)-acetonitrile (5.00 mL)-water (5.00 mL) were added osmium oxide (fixed catalyst I) (0.14 g) and sodium periodate (1.17 g), and the mixture was stirred overnight at room temperature. The reaction mixture was filtered, and the filtrate was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give the title compound (0.40 g) as a crude product. This compound was used in the next step without an additional purification.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[NH:4][C:3]=1[C:8](=[C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][C:13]1=[O:21])[C:9]([OH:11])=O.[F:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][CH:29]=1)[NH2:26]>>[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[NH:4][C:3]=1[C:8](=[C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][C:13]1=[O:21])[C:9]([NH:26][C:25]1[CH:27]=[CH:28][CH:29]=[C:23]([F:22])[CH:24]=1)=[O:11]
Reactant: Cc1cc(C)c(C(C(=O)O)=C2C(=O)Nc3ccccc32)[nH]1
Reactant: Nc1cccc(F)c1
Product: Cc1cc(C)c(C(C(=O)Nc2cccc(F)c2)=C2C(=O)Nc3ccccc32)[nH]1
Yield: 21.1 %

Procedure:
(3,5-Dimethyl-1H-pyrrol-2-yl)-(2-oxo-1,2-dihydroindol-3-ylidene)-acetic acid (90 mg) was reacted with 3-fluoroaniline (35 mg) using method B to give 25 mg (21%) of the title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[OH:11].Cl[Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].C(N(CC)CC)C>ClCCl>[Si:13]([O:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[NH2:1])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]
Reactant: Nc1ccc([N+](=O)[O-])cc1O
Reactant: CC(C)(C)[Si](C)(C)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](C)(C)Oc1cc([N+](=O)[O-])ccc1N
Temperature: 25 °C
Reaction time: 4 h
Yield: 84.2 %

Procedure:
To a magnetically stirred solution of 2-amino-5-nitrophenol (5.62 g, 36.5 mmol) and chloro-t-butyldimethylsilane (5.00 g, 33.2 mmol) in dry dichloromethane (66 mL) was added triethylamine (5.55 mL, 39.8 mmol) at 25° C. The reaction mixture was stirred at ambient temperature for 4 hours and partitioned between diethyl ether (200 mL) and saturated ammonium chloride. The aqueous layer was separated and the ether layer washed (saturated ammonium chloride, 1x; water, 1x; brine, 1x), dried (MgSO4), filtered, and evaporated in vacuo. Crystallization from ethyl acetate/hexanes gave 7.5 g (84%) of O-t-butyldimethylsilyl-2-amino-5-nitrophenol
Reaction SMILES: [C:1](#[N:5])[CH:2]([CH3:4])[CH3:3].[CH2:6]([Mg][Cl:14])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[BH4-].[Na+].Cl>CO>[ClH:14].[NH2:5][CH:1]([CH:2]([CH3:4])[CH3:3])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: CC(C)C#N
Reactant: Cl[Mg]Cc1ccccc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(C)C(N)Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 93.9 %

Procedure:
To 13.8 g (0.2 mol) of isobutyronitrile dissolved in 50 ml of anhydrous tetrahydrofuran(THF) was added 110 ml (0.22 mol) of 2.0M benzylmagnesiumchloride at room temperature, and the resulting mixture was refluxed for 1 hour and cooled to room temperature. Subsequently, 200 ml of methanol and 11.4 g (0.3 mol) of NaBH4 were added thereto and stirred for 1 hour at room temperature. The resultant was adjusted to about pH 11 by adding 1N HCl. The above mixture was extracted with chloroform and dried over anhydrous Na2SO4, and methanolic HCl was added to obtain 37.5 g of the title compound(yield 94%).
Reaction SMILES: C([O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:18]2[C:17](Cl)=[N:16][CH:15]=[N:14][C:13]=2[CH:12]=[CH:11]1)(=O)C.[Cl:20][C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][C:27]=1[O:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=1)[NH2:24].[OH-].[Na+].Cl>C(O)(C)C>[Cl:20][C:21]1[CH:22]=[C:23]([NH:24][C:17]2[C:18]3[N:10]([CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][OH:4])[CH:11]=[CH:12][C:13]=3[N:14]=[CH:15][N:16]=2)[CH:25]=[CH:26][C:27]=1[O:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:37])([F:38])[F:36])[CH:30]=1
Reactant: Nc1ccc(Oc2cccc(C(F)(F)F)c2)c(Cl)c1
Reactant: CC(=O)OCCCCCn1ccc2ncnc(Cl)c21
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Product: OCCCCCn1ccc2ncnc(Nc3ccc(Oc4cccc(C(F)(F)F)c4)c(Cl)c3)c21
Temperature: 25 °C
Reaction time: 1 h
Yield: 78.9 %

Procedure:
A solution of 5-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)pentyl acetate (200 mg) and 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (265 mg) in isopropyl alcohol (3.5 mL) was stirred at 80° C. for 14 hrs. 1N Aqueous sodium hydroxide solution (2.1 mL) was added at 0° C., and the mixture was stirred at room temperature for 1 hr. 1N Hydrochloric acid (2.0 mL) was added to the reaction system, and the mixture was extracted with ethyl acetate. The organic layer washed with aqueous sodium hydrogen carbonate and saturated brine and dried over magnesium sulfate. After concentration under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate→ethyl acetate:methanol=1:19) to give a colorless solid. Recrystallization from ethyl acetate-hexane gave the title compound (275 mg) as colorless crystals.
Reaction SMILES: [C:1](=[O:6])([O:4][CH3:5])[O:2][CH3:3].[C:7]1(O)[CH:12]=[CH:11]C=[CH:9][CH:8]=1>>[C:1](=[O:6])([O:4][C:5]1[CH:11]=[CH:12][CH:7]=[CH:8][CH:9]=1)[O:2][CH3:3]
Reactant: Oc1ccccc1
Reactant: COC(=O)OC
Product: COC(=O)Oc1ccccc1

Procedure:
A transesterification reaction was performed between dimethyl carbonate and phenol to obtain methyl phenyl carbonate. The obtained methyl phenyl carbonate was subjected to a disproportionation reaction to obtain a diphenyl carbonate product containing about 90 ppm by weight of methyl phenyl carbonate.
Reaction SMILES: C[O:2][C:3]1[N:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:7]([C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]3[CH2:25][CH2:24][CH:23]([C:26]4[N:30]=[C:29]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=5)[NH:28][N:27]=4)[CH2:22][CH2:21]3)=[CH:15][CH:14]=1)=[N:8]2.Cl.N1C=CC=CC=1>O.C([O-])(O)=O.[Na+]>[C:37]1([C:6]2[C:7]([C:13]3[CH:18]=[CH:17][C:16]([CH2:19][N:20]4[CH2:25][CH2:24][CH:23]([C:26]5[N:30]=[C:29]([C:31]6[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=6)[NH:28][N:27]=5)[CH2:22][CH2:21]4)=[CH:15][CH:14]=3)=[N:8][C:9]3[CH:10]=[CH:11][NH:12][C:3](=[O:2])[C:4]=3[CH:5]=2)[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1
Reactant: COc1nccc2nc(-c3ccc(CN4CCC(c5n[nH]c(-c6ccccn6)n5)CC4)cc3)c(-c3ccccc3)cc12
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: O
Product: O=c1[nH]ccc2nc(-c3ccc(CN4CCC(c5n[nH]c(-c6ccccn6)n5)CC4)cc3)c(-c3ccccc3)cc12
Temperature: 150 °C

Procedure:
A mixture of 5-methoxy-3-phenyl-2-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-1,6-naphthyridine (725 mg, 1.31 mmol) and pyridine hydrochloride (6.9 gm, ˜60 mmol) was heated at 150° C. for ten minutes. The cooled residue was dissolved in the minimum amount of water and neutralized with aqueous NaHCO3. The precipitated solid was collected by filtration and purified by column chromatography on silica gel eluting with 1-14% methanol/ethyl acetate (sat'd NH4OH). The isolated product was digested in methanol/acetonitrile to give pure product. 1H NMR (500 MHz, DMSO-d6): δ 11.58 (1H, d, J=4.8 Hz), 8.68 (1H, br s), 8.39 (1H, s), 8.03 (1H, d, J=7.3 Hz), 7.50 (2H, t, J=6.5 Hz), 7.31-7-33 (5H, m), 7.24-7.25 (4H, m), 6.79 (2H, d, J=7.3 Hz), 3.50 (2H, s), 2.84 (2H, br d, J=10.5 Hz), 2.72 (1H, m), 2.08 (2H, br t, J=11 Hz), 1.95 (2H, br d, J=11.6 Hz), 1.77 (2H, m). m/e (m+1): 540.3, 270.9 [(m+2)/2].