Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13](B2OC(C)(C)C(C)(C)O2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:25])[CH:11]=2)[CH:6]=1.Br[C:28]1[CH:33]=[CH:32][C:31]([S:34][C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=2[F:42])=[CH:30][CH:29]=1.C(=O)(O)[O-].[Na+].O>C(COC)OC.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>[CH3:1][O:2][C:3](=[O:26])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:28]2[CH:29]=[CH:30][C:31]([S:34][C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=3[F:42])=[CH:32][CH:33]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:25])[CH:11]=2)[CH:6]=1
Reactant: COC(=O)Cc1cc2ccc(Cl)cc2c(B2OC(C)(C)C(C)(C)O2)c1C
Reactant: Fc1ccc(Sc2ccc(Br)cc2)c(F)c1
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: [Na+]
Solvent: O
Solvent: COCCOC
Product: COC(=O)Cc1cc2ccc(Cl)cc2c(-c2ccc(Sc3ccc(F)cc3F)cc2)c1C
Yield: 16.1 %

Procedure:
A stirred solution of [6-chloro-3-methyl-4-(4,4,5,5-tetra methyl-[1,3,2]-dioxaborolan-2-yl)-naphthalen-2-yl]-acetic acid methyl ester (0.2 g, 0.53 mmol) in dimethoxyethane (5 mL) was purged with argon for 5 minutes at room temperature. Tetrakis(triphenylphosphine)palladium(0) (0.031 g, 0.027 mmol), crude 1-(4-bromo-phenylsulfanyl)-2,4-difluorobenzene (0.176 g) and 1.0 M aqueous sodium bicarbonate (5 mL, 5 mmol) were added simultaneously to the reaction mixture under argon. The reaction mixture was refluxed for 2 hours and then brought to room temperature. Water was added and the resulting mixture was extracted twice with ethyl acetate. The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the crude product, which was finally purified using flash chromatography (0-3% ethyl acetate in hexanes) to give {6-chloro-4-[4-(2,4-difluoro-phenylsulfanyl)-phenyl]-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (0.04 g, 16%) as a solid.
Reaction SMILES: [NH2:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[NH:13][C:14](=[O:16])[NH:15][C:8]=23)=[CH:4][CH:3]=1.[C:19]1([N:25]=[C:26]=[O:27])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(Cl)Cl>N1C=CC=CC=1>[O:16]=[C:14]1[NH:13][C:9]2=[N:10][CH:11]=[CH:12][C:7]([O:6][C:5]3[CH:17]=[CH:18][C:2]([NH:1][C:26]([NH:25][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[O:27])=[CH:3][CH:4]=3)=[C:8]2[NH:15]1
Reactant: Nc1ccc(Oc2ccnc3[nH]c(=O)[nH]c23)cc1
Reactant: O=C=Nc1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(Nc1ccccc1)Nc1ccc(Oc2ccnc3[nH]c(=O)[nH]c23)cc1
Temperature: 50 °C
Yield: 68.7 %

Procedure:
Method H1 (in Pyridine). 7-(4-Aminophenoxy)-2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridine (65 mg, 0.27 mmol) was suspended in dry pyridine (3 mL) and heated at 50° C. Phenyl isocyanate (30 μL, 0.28 mmol) was added; the solution became clear. The reaction mixture was heated at reflux for 2 hours, then it was allowed to cool at room temperature. DCM (20 mL) was added, the precipitate formed was recovered by filtration and washed with more DCM, to afford 1-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl-oxy)phenyl)-3-phenyl-urea (67 mg, 69%). 1H-NMR (δ, ppm, DMSO-d6): 6.34 (d, 1H, HPy,5, J=7.5 Hz), 6.98 (t, 1H, Harom,Ph′,4, J=7.5 Hz), 7.13 (d, 2H, Harom,Ph,3+5, J=8.75 Hz), 7.29 (t, 2H, Harom,Ph′,3+5), 7.46 (d, 2H, Harom,Ph′,2+6), 7.53 (d, 2H, Harom,Ph,2+6), 7.76 (d, 1H, HPy,6) 8.67 (s, 1H, NHurea,1), 8.76 (s, 1H, NHurea,3), 11.19 (s, 1H, NHPy3), 11.35 (s, 1H, NHPy2). LC-MS (m/z): 362 (M+H, 100).
Reaction SMILES: [N:1]1([CH2:6][C:7]2[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:9][C:8]=2[OH:17])[CH:5]=[N:4][CH:3]=[N:2]1.F[C:19]1[CH:20]=[CH:21][C:22]([N+:27]([O-:29])=[O:28])=[C:23]([CH:26]=1)[NH:24][CH3:25].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH3:25][NH:24][C:23]1[CH:26]=[C:19]([O:17][C:8]2[CH:9]=[CH:10][C:11]([C:13]([F:16])([F:15])[F:14])=[CH:12][C:7]=2[CH2:6][N:1]2[CH:5]=[N:4][CH:3]=[N:2]2)[CH:20]=[CH:21][C:22]=1[N+:27]([O-:29])=[O:28]
Reactant: CNc1cc(F)ccc1[N+](=O)[O-]
Reactant: Oc1ccc(C(F)(F)F)cc1Cn1cncn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CNc1cc(Oc2ccc(C(F)(F)F)cc2Cn2cncn2)ccc1[N+](=O)[O-]
Yield: 59.4 %

Procedure:
The solution of 2-(1H-1,2,4-triazol-1-ylmethyl)-4-(trifluoromethyl)phenol (1.0 g) from Example 62, 5-fluoro-N-methyl-2-nitroaniline (700 mg) and K2CO3 (0.57 g) in DMF (10 ml) was heated at 100° C. for 90 minutes. After the solution was left to stand at room temperature, water was added to the solution, the aqueous layer was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by chromatography on a silica gel column (methylene chloride:methanol=99:1), to give the title compound (960 mg; 59%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][C:11]([C:13]2[CH:17]=[C:16]([N+:18]([O-])=O)[NH:15][N:14]=2)=[O:12])=[CH:4][CH:3]=1.[Cl-].[NH4+]>O1CCCC1.C(O)C.[Fe]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][C:11]([C:13]2[CH:17]=[C:16]([NH2:18])[NH:15][N:14]=2)=[O:12])=[CH:4][CH:3]=1
Reactant: O=C(NCCc1ccc(Cl)cc1)c1cc([N+](=O)[O-])[nH]n1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCO
Product: Nc1cc(C(=O)NCCc2ccc(Cl)cc2)n[nH]1
Temperature: 105 °C
Reaction time: 16 h
Yield: 7 %

Procedure:
To a solution of 5-nitro-1H-pyrazole-3-carboxylic acid [2-(4-chloro-phenyl)-ethyl]amide (160 mg, 5.42 mmol, 1 eq) in tetrahydrofuran and ethanol (1 mL/3 mL) was added a saturated solution of ammonium chloride (1 mL) and iron (97 mg, 1.73 mmol, 3.2 eq). The mixture was stirred at 105° C. for 16 h. After cooling, the mixture was filtrated on a short pad of celite and washed with ethanol (10 mL), tetrahydrofuran (10 mL) and water (10 mL). The filtrate was evaporated, water (10 mL) was added and the aqueous phase was extracted with dichloromethane (2×15 mL). The organic layers were dried over magnesium sulfate, filtered and evaporated in vacuo to afford 5-amino-1H-pyrazole-3-carboxylic acid [2-(4-chloro-phenyl)-ethyl]-amide as beige powder (100 mg, 70% yield).
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[CH2:7][CH:6]([N:8]2[C:12]([C:13]([OH:15])=[O:14])=[CH:11][N:10]=[CH:9]2)[C:5]2[CH:16]=[CH:17][CH:18]=[CH:19][C:4]=2[O:3]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[Na].[CH:34]1(O)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1.C1(O)CCCCC1>CN(C)C=O>[CH3:1][C:2]1([CH3:20])[CH2:7][CH:6]([N:8]2[C:12]([C:13]([O:15][CH:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)=[O:14])=[CH:11][N:10]=[CH:9]2)[C:5]2[CH:16]=[CH:17][CH:18]=[CH:19][C:4]=2[O:3]1
Reactant: OC1CCCCC1
Reactant: CC1(C)CC(n2cncc2C(=O)O)c2ccccc2O1
Agent: O=C(n1ccnc1)n1ccnc1
Agent: [Na]
Solvent: CN(C)C=O
Product: CC1(C)CC(n2cncc2C(=O)OC2CCCCC2)c2ccccc2O1
Temperature: 25 °C
Reaction time: 1 h
Yield: 20.5 %

Procedure:
3.3 Parts of 1-(2,3-dihydro-2,2-dimethyl-4H-1-benzopyran-4-yl)-1H-imidazole-5-carboxylic acid were dissolved in 45 parts of warm N,N-dimethylformamide. After cooling to room temperature, 2 parts of 1,1'-carbonylbis[1H-imidazole] were added and the whole was stirred for 1 hour at this temperature. The whole was heated to ±80° C. and a mixture of 0.1 parts of a cyclohexanol sodium salt solution and 3 parts of cyclohexanol was added. After stirring for 5 days at ±80° C., the mixture was evaporated. The residue was taken up trichloromethane and water and the organic layer was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using trichloromethane as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from hexane. The product was filtered off and dried, yielding 0.91 parts (20.5%) of cyclohexyl 1-(2,3-dihydro-2,2-dimethyl-4H-1-benzopyran-4-yl)-1H-imidazole-5-carboxylate; mp. 128.1° C. (compound 1.139).
Reaction SMILES: [O:1]=[C:2]1[C:11]2([CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]2)[CH2:10][C:9]2[C:4](=[N:5][CH:6]=[C:7](/[CH:24]=[CH:25]/[C:26](=[O:39])[N:27]3[CH2:32][CH2:31][C:30]([CH2:33][C:34]4[S:35][CH:36]=[CH:37][N:38]=4)=[CH:29][CH2:28]3)[CH:8]=2)[NH:3]1.[F:40][C:41]([F:46])([F:45])[C:42]([OH:44])=[O:43]>C(Cl)Cl>[F:40][C:41]([F:46])([F:45])[C:42]([OH:44])=[O:43].[O:39]=[C:26]([N:27]1[CH2:32][CH2:31][C:30]([CH2:33][C:34]2[S:35][CH:36]=[CH:37][N:38]=2)=[CH:29][CH2:28]1)/[CH:25]=[CH:24]/[C:7]1[CH:8]=[C:9]2[C:4](=[N:5][CH:6]=1)[NH:3][C:2](=[O:1])[C:11]1([CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)[CH2:10]2
Reactant: CC(C)(C)OC(=O)N1CCC2(CC1)Cc1cc(/C=C/C(=O)N3CC=C(Cc4nccs4)CC3)cnc1NC2=O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(/C=C/c1cnc2c(c1)CC1(CCNCC1)C(=O)N2)N1CC=C(Cc2nccs2)CC1
Temperature: 27.5 °C
Reaction time: 4 h
Yield: 58.4 %

Procedure:
To a stirred solution of (E)-tert-butyl 2-oxo-6-(3-oxo-3-(4-(thiazol-2-ylmethyl)-5,6-dihydropyridin-1(2H)-yl)prop-1-en-1-yl)-2,4-dihydro-1H-spiro[[1,8]naphthyridine-3,4′-piperidine]-1′-carboxylate (Compound 1) (0.6 g, 1.52 mmol) in CH2Cl2 (15 mL) was added trifluoro acetic acid (0.58 mL, 7.61 mmol) at 20-35° C. and the reaction mixture was allowed to stir at 20-35° C. for 4 h. Then the reaction mixture was rotary evaporated under vacuum to get residue which was triturated with diethyl ether to get the desired compound as a yellow solid (500 mg, 82%); 1H NMR (400 MHz, DMSO-d6) δ 10.88 (s, 1H), 8.50-8.32 (m, 3H), 8.07 (s, 1H), 7.71 (d, J=3.4 Hz, 1H), 7.61 (d, J=3.4 Hz, 1H), 7.46 (d, J=15.7 Hz, 1H), 7.28-7.14 (m, 1H), 5.68-5.65 (m, 1H), 4.26-4.20 (m, 1H), 4.08-4.02 (m, 1H), 3.78-3.72 (m, 3H), 3.68-3.62 (m, 1H), 3.16-3.06 (m, 4H), 2.97 (s, 2H), 2.20-2.04 (m, 2H), 2.03-1.92 (m, 2H), 1.62-1.48 (m, 2H); ES-MS: 450.2 (M+1)+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([Cl:10])=[CH:4][C:3]=1[CH2:11][C:12]([OH:14])=O.S(Cl)([Cl:17])=O>C(Cl)(Cl)(Cl)Cl>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([Cl:10])=[CH:4][C:3]=1[CH2:11][C:12]([Cl:17])=[O:14]
Reactant: COc1cc(Cl)cc(CC(=O)O)c1Cl
Reactant: O=S(Cl)Cl
Solvent: ClC(Cl)(Cl)Cl
Product: COc1cc(Cl)cc(CC(=O)Cl)c1Cl

Procedure:
By the method of Example 1, Step E, 10.92 grams (0.046 mole) of 2,5-dichloro-3-methoxyphenylacetic acid and 40 mL of thionyl chloride were reacted in approximately 200 mL of carbon tetrachloride, yielding 11.92 grams of 2,5-dichloro-3-methoxyphenylacetyl chloride as a black oil. The IR spectrum was consistent with the proposed structure.
Reaction SMILES: O[CH2:2][CH:3]1[O:17][C:6]2=[C:7]3[C:12](=[C:13]([CH3:15])[CH:14]=[C:5]2[CH2:4]1)[NH:11][C:10](=[O:16])[CH:9]=[CH:8]3.C(N(S(F)(F)[F:24])CC)C>C(Cl)Cl>[F:24][CH2:2][CH:3]1[O:17][C:6]2=[C:7]3[C:12](=[C:13]([CH3:15])[CH:14]=[C:5]2[CH2:4]1)[NH:11][C:10](=[O:16])[CH:9]=[CH:8]3
Reactant: Cc1cc2c(c3ccc(=O)[nH]c13)OC(CO)C2
Reactant: CCN(CC)S(F)(F)F
Solvent: ClCCl
Product: Cc1cc2c(c3ccc(=O)[nH]c13)OC(CF)C2
Temperature: -78 °C
Yield: 32.3 %

Procedure:
2-Hydroxymethyl-5-methyl-2,3,6,7-tetrahydrofuro[2,3-f]quinoline-7-one (500 mg) was suspended in anhydrous methylene chloride (20 ml). To the suspension, diethylaminosulfur trifluoride (DAST) (372 mg) was added while stirring and cooling at -78° C. Subsequently, the mixture was stirred at room temperature for 30 minutes. After completion of the reaction, methylene chloride was further added thereto, and washed with aqueous sodium bicarbonate solution, and aqueous NaCl solution in this order. After drying, the solvent was distilled off to obtain 487 mg of a crude product. The crude product was purified by silica gel column chromatography (eluent=chloroform:methanol=400:1-20:1), and then by separative thin layer chromatography (developer=chloroform:methanol=10:1) to obtain a purified product, which was subjected to recrystallization using a solvent mixture of chloroform and n-hexane to obtain 163 mg of colorless needles (32%).
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4]2[CH:10]=[C:9]([Cl:11])[C:8]([Cl:12])=[CH:7][C:5]=2[N:6]=1.[OH-].[Na+].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(#N)C>[NH2:1][C:2]1[N:3]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:4]2[CH:10]=[C:9]([Cl:11])[C:8]([Cl:12])=[CH:7][C:5]=2[N:6]=1
Reactant: BrCc1ccccc1
Reactant: Nc1nc2cc(Cl)c(Cl)cc2[nH]1
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Product: Nc1nc2cc(Cl)c(Cl)cc2n1Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 85.1 %

Procedure:
2-Amino-5,6-dichlorobenzimidazole (4) (1 g, 4.95 mmole) was dissolved in acetonitrile (200 ml) and NaOH (198 mg, 4.95 mmole) was added. After stirring for 1 hr at room temperature, benzyl bromide (0.589 ml, 4.95 mmole) was added and the mixture was allowed to stir overnight. The mixture was concentrated under reduced pressure and purified on a silica gel column (3.5×5 cm) using 5% MeOH/CHCl3 to give 1.23 g (85%) of 2-amino-1-benzyl-5,6-dichlorobenzimidazole (182). The compound was then recrystallized from EtOH/H2O to give a white powder. 1H NMR (DMSO-d6): d 5.28 ppm (s, 2H), 6.95 (s, 2H), 7.16 (d, 2H), 7.25 (d, 1H), 7.31 (m, 4H). 13C NMR (DMSO-d6); d 44.74 ppm, 109.15, 115.37, 119.62, 122.66, 125.82, 127.37, 128.55, 134.10, 136.46, 143.13, 156.91. MS (Electron Impact): m/e 291, 200, 158, 91, 65. MP: 245°-246° C. Elemental Analysis: (C14H11Cl2N3'): Calculated: C, 57.55; H, 3.79; N, 14.58. Found: C, 57.66; H, 3.83; N, 13.98. UV Imax nm (e×104): (pH 7) 230 (0.761), 260 (0.324), 302 (0.452); (pH 1) 238 (0.306), 294 (0.383), 299 (0.359); (pH 11) 229 (0.869), 257 (0.316) 301 (0.443).
Reaction SMILES: S(Cl)([Cl:4])(=O)=O.[CH3:6][C:7]1([CH3:14])[O:12][C:11](=[O:13])[CH:10]=[CH:9][O:8]1.O>N1C=CC=CC=1>[Cl:4][C:10]1[C:11](=[O:13])[O:12][C:7]([CH3:14])([CH3:6])[O:8][CH:9]=1
Reactant: CC1(C)OC=CC(=O)O1
Reactant: O=S(=O)(Cl)Cl
Solvent: O
Solvent: c1ccncc1
Product: CC1(C)OC=C(Cl)C(=O)O1
Reaction time: 0.5 h
Yield: 51.2 %

Procedure:
Sulfuryl chloride (2.44 mL, 0.03 mol) was added dropwise to a solution of 2,2-dimethyl-1,3-dioxin-4-one (3.2 g, 0.025 mol) in pyridine (16 mL) under cooling with ice. The mixture was stirred for 30 minutes, while the temperature was maintained, and was further stirred at room temperature for two hours. The reaction mixture was cooled with ice, and water was added to the reaction mixture. The reaction mixture was extracted with dichloromethane, and the formed dichloromethane layer was dried over sodium sulfate anhydrate and concentrated. The concentration residue was purified through silica gel column chromatography (eluent=n-hexane:ethyl acetate=95:5), to thereby yield 2.08 g of the title compound as an oily substance (yield: 51.2%).
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][OH:8].C1COCC1.[C:14](Cl)(=[O:23])[CH:15]=[CH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(N(CC)CC)C>[C:14]([O:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][Br:1])(=[O:23])[CH:15]=[CH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: OCCCCCCBr
Reactant: O=C(Cl)C=Cc1ccccc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(C=Cc1ccccc1)OCCCCCCBr
Yield: 53 %

Procedure:
7 g of 6-bromohexanol was dissolved in a mixed solution of 5 ml of triethylamine as base and 50 ml of THF, and then, cinnamoyl chloride was added dropwise thereto at 0° C. The resultant was filtered to remove the solvent and the residue was purified with a SiO2 column chromatography (EA:n-Hexane=1:5) to obtain 8 g of 6-bromohexyl cinnamate (yield: 53%).
Reaction SMILES: CN(C)[C:3](=[O:5])[CH3:4].FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[F:22][C:23]1[CH:37]=[CH:36][C:26]([O:27][C:28]2[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=2)[CH:31]=[CH2:32])=[CH:25][CH:24]=1.N1C(C)=CC(C)=CC=1C>ClC(Cl)C>[F:22][C:23]1[CH:37]=[CH:36][C:26]([O:27][C:28]2[CH:29]=[C:30]([CH:31]3[CH2:4][C:3](=[O:5])[CH2:32]3)[CH:33]=[CH:34][CH:35]=2)=[CH:25][CH:24]=1
Reactant: C=Cc1cccc(Oc2ccc(F)cc2)c1
Reactant: CC(=O)N(C)C
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: Cc1cc(C)nc(C)c1
Solvent: CC(Cl)Cl
Product: O=C1CC(c2cccc(Oc3ccc(F)cc3)c2)C1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 53.1 %

Procedure:
To a solution of N,N-dimethylacetamide (1.66 g, 19.1 mmol) in dichloroethane (50 mL) at -15° C., was added trifluoromethanesulfonic anhydride (5.39 g, 19.1 mmol) dropwise and the mixture was stirred for 5 min. A mixture of 3-(4-fluorophenoxy)styrene (4.08 g, 19.1 mmol) and collidine (2.31 g, 19.1 mmol) as a solution in dichloroethane (10 mL) was then added dropwise. Upon completion of addition, the cooling bath was withdrawn and the reaction allowed to warm to ambient temperature, then further brought to reflux for 18 hours. Water (20 mL) was then added and the reaction was kept at reflux for an additional 5 hours. It was then cooled to ambient temperature and the layers were separated. The organic phase was washed with 10% aqueous HCl (50 mL) and water (50 mL). It was then dried over MgSO4 and concentrated. The resulting residue was chromatographed (silica gel; hexanes, ether 90:10) to afford 2.60 g (53%) of 3-(3-(4-fluorophenoxy)phenyl)cyclobutanone as a colorless oil.
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[O:14][N:13]=[C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:11]=1.[CH3:22][NH2:23]>CCOCC.O>[C:15]1([C:12]2[N:11]=[C:10]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[C:3]([NH:23][CH3:22])=[O:2])[O:14][N:13]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CN
Reactant: COC(=O)c1ccccc1-c1nc(-c2ccccc2)no1
Solvent: CCOCC
Solvent: O
Product: CNC(=O)c1ccccc1-c1nc(-c2ccccc2)no1
Reaction time: 19 h

Procedure:
A solution of 6.16 g. (0.022 mole) o-(3-phenyl-1,2,4-oxadiazol-5-yl)-benzoic acid methyl ester in 150 milliliters ether is treated with 150 milliliters 40 percent methyl amine in water. The resulting two-phase system is stirred vigorously for 19 hours. The ether is evaporated, and the resulting mixture extracted with methylene chloride. The organic phase is washed with water and then brine, dried over anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The resulting solid is triturated with ether and filtered to give o-(3-phenyl-1,2,4-oxadiazol-5-yl)-N-methyl benzamide, m.p. 145°-146° C.
Reaction SMILES: [C:1](=O)([O-])[O-].[K+].[K+].[CH3:7][C:8]1[CH:16]=[C:15]([C:17]([O-:19])=[O:18])[C:14]([CH3:20])=[CH:13][C:9]=1[C:10]([O-:12])=[O:11].CI>CN(C=O)C>[CH3:1][O:18][C:17]([C:15]1[C:14]([CH3:20])=[CH:13][C:9]([C:10]([OH:12])=[O:11])=[C:8]([CH3:7])[CH:16]=1)=[O:19]
Reactant: Cc1cc(C(=O)[O-])c(C)cc1C(=O)[O-]
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: COC(=O)c1cc(C)c(C(=O)O)cc1C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A 76 mg portion of potassium carbonate was added to a 20 ml DMF solution of 214 mg 2,5-dimethylterephthalate and stirred at room temperature for 30 minutes. 0.068 ml of methyl iodide was added to the reaction solution successively and stirred overnight at room temperature. Successively, work-up and purification were carried out in the standard method to obtain 90 mg of 4-methoxycarbonyl-2,5-dimethylbenzoic acid as colorless solid. EN: 207.
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:33]([OH:35])[CH3:34])[C@@H:3]1[O:5][C@H:4]1[CH2:6][C@@H:7]1[C@@H:12]([OH:13])[C@@H:11]([OH:14])[C@H:10]([CH2:15]/[C:16](/[CH3:32])=[CH:17]/[C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:19])[O:9][CH2:8]1.[O-2:36].[Ca+2:37]>C(OCC(C)C)(=O)C.O>[CH3:1][C@H:2]([C@H:3]1[C@H:4]([CH2:6][C@H:7]2[CH2:8][O:9][C@@H:10]([CH2:15]/[C:16](/[CH3:32])=[CH:17]/[C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([O-:31])=[O:30])=[O:19])[C@H:11]([OH:14])[C@@H:12]2[OH:13])[O:5]1)[C@H:33]([CH3:34])[OH:35].[CH3:1][C@H:2]([C@H:3]1[C@H:4]([CH2:6][C@H:7]2[CH2:8][O:9][C@@H:10]([CH2:15]/[C:16](/[CH3:32])=[CH:17]/[C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([O-:31])=[O:30])=[O:19])[C@H:11]([OH:14])[C@@H:12]2[OH:13])[O:5]1)[C@H:33]([CH3:34])[OH:35].[OH2:36].[OH2:5].[Ca+2:37]
Reactant: C/C(=C\C(=O)OCCCCCCCCC(=O)O)C[C@@H]1OC[C@H](C[C@@H]2O[C@H]2[C@@H](C)[C@H](C)O)[C@@H](O)[C@H]1O
Reactant: [O-2]
Agent: [Ca+2]
Solvent: CC(=O)OCC(C)C
Solvent: O
Product: C/C(=C\C(=O)OCCCCCCCCC(=O)[O-])C[C@@H]1OC[C@H](C[C@@H]2O[C@H]2[C@@H](C)[C@H](C)O)[C@@H](O)[C@H]1O
Temperature: 5 °C
Reaction time: 2 h
Yield: 62 %

Procedure:
Pseudomonic acid was dissolved in isobutyl acetate (130 ml). Calcium oxide (0.29 g) was suspended in water (32 ml) and added to the solution of pseudomonic acid. The mixture was stirred for 2 hours, and the phases were separated. The volume of the aqueous phase was reduced to 15 ml by vacuum distillation. The mixture was cooled to 5° C. After stirring for 2 hours, the crystalline product was filtered and washed with cooled water (5 ml). The product was dried in an air circulated oven at RT. Mupirocin calcium dihydrate (3.3 g, 62%) was obtained.
Reaction SMILES: [C:1]1([N:7]2[C:12]3[N:13]=[CH:14][CH:15]=[CH:16][C:11]=3[CH2:10][NH:9][C:8]2=[O:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C)C=O.[H-].[Na+].[C:25]1(C)[CH:30]=CC(S(OC(C)C)(=O)=O)=C[CH:26]=1>O>[C:1]1([N:7]2[C:12]3[N:13]=[CH:14][CH:15]=[CH:16][C:11]=3[CH2:10][N:9]([CH:25]([CH3:30])[CH3:26])[C:8]2=[O:17])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Cc1ccc(S(=O)(=O)OC(C)C)cc1
Reactant: O=C1NCc2cccnc2N1c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)N1Cc2cccnc2N(c2ccccc2)C1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 256.8 %

Procedure:
To a solution of 4.5 g of 1-phenyl-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine and 50 ml of dry dimethylformamide was added 1.2 g of 50% sodium hydride and the mixture was stirred for 30 minutes at room temperature, and then heated to a temperature of 90° - 100° C. To this was gradually added 1.28 g of isopropyl p-toluenesulfonate and the whole was reacted for 1 hour. After the reaction was complete, the solvent was distilled off from the mixture under reduced pressure. The residue obtained was diluted with water to produce a crude precipitate, which was collected by filtration and then dissolved in ethyl ether. Separation and purification were accomplished by applying the solution on a column of alumina, and the eluate was concentrated to give 4.1 g of 1-phenyl-3-isopropyl-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine as colorless prisms, melting at 164° - 165° C.
Reaction SMILES: [NH2:1][C:2]1[NH:6][N:5]=[C:4]([NH:7][CH2:8][CH2:9][NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:3]=1[C:18]#[N:19].C(O[CH:23](OCC)[N:24]([CH3:26])[CH3:25])C.C1(C)C=CC=CC=1>C(O)C>[C:11]([NH:10][CH2:9][CH2:8][NH:7][C:4]1[C:3]([C:18]#[N:19])=[C:2]([N:1]=[CH:23][N:24]([CH3:26])[CH3:25])[NH:6][N:5]=1)([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12]
Reactant: CC(C)(C)OC(=O)NCCNc1n[nH]c(N)c1C#N
Reactant: CCOC(OCC)N(C)C
Solvent: Cc1ccccc1
Solvent: CCO
Product: CN(C)C=Nc1[nH]nc(NCCNC(=O)OC(C)(C)C)c1C#N
Temperature: 100 °C
Reaction time: 5 h

Procedure:
A mixture of 76.3 9 (286.1 mmol) of 5-amino-3-[2-(Boc-amino)-ethylamino]-4cyano-pyrazole, 54 ml (315.1 mmol) of N,N-dimethylformamide diethyl acetal, 850 ml of toluene and 85 ml of ethanol is stirred at 100° C. for 5 hours. A further 24.5 ml (143 mmol) of N,N-dimethylformamide diethyl acetal are then added to the reaction mixture and stirring is continued for a further 3 hours at 100° C. After cooling to about 10° C., filtration and washing the filter residue with toluene and diethyl ether, 3-[2-(Boc-amino)-ethylamino]-4-cyano-5-(dimethylamino-methyleneamino)-pyrazole is obtained; m.p. 158-160° C.; ESI-MS: (M−H)−=320.