Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: F[C:2](F)(F)[C:3]1[CH:8]=[CH:7][C:6]([N:9]=[C:10]=[O:11])=[CH:5][CH:4]=1.[NH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21](=[O:26])[CH:22]([CH3:25])[CH2:23]C)[CH2:17][CH2:16]1.[CH2:27](Cl)Cl>>[CH2:2]([CH:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]([NH:14][CH:15]2[CH2:20][CH2:19][N:18]([C:21](=[O:26])[CH:22]([CH3:25])[CH3:23])[CH2:17][CH2:16]2)=[O:11])[CH2:5][CH2:4]1)[CH3:27]
Reactant: CCC(C)C(=O)N1CCC(N)CC1
Reactant: ClCCl
Reactant: O=C=Nc1ccc(C(F)(F)F)cc1
Product: CCC1CCC(NC(=O)NC2CCN(C(=O)C(C)C)CC2)CC1
Reaction time: 12 h
Yield: 42 %

Procedure:
4-(Trifluoromethyl)phenylisocyanate (100 mg, 0.65 mmol) and 1-(4-aminopiperidin-1-yl)-2-methylbutan-1-one (111 mg, 0.53 mmol) was dissolved in CH2Cl2 (100 mL) and stirred for 12 h. The reaction was quenched by addition of water. The organic layer was isolated and the aqueous layer was extracted with EtOAc for 4 times. The combined organic layer was concentrated under vacuo and was further purified by flash chromatography (EtOAc:Hex/1:1) yielding final product (89 mg, 2.76 mmol, 42%). H-NMR (DMSO-d6) ∂ 0.83 (t, J=8 Hz, 3H), 0.91 (m, 1H), 0.97 (m, 7H), 1.03 (m, 3H), 1.16 (m, 4H), 1.69 (m, 3H), 1.78 (m, 3H), 2.72 (t, J=12 Hz, 1H), 2.85 (m, 1H), 3.10 (t, J=12 Hz, 1H), 3.24 (m, 1H), 3.57 (m, 1H), 3.79 (d, J=13 Hz, 1H), 4.14 (d, J=13 Hz, 1H), 5.56 (d, J=7.5 Hz, 1H), 5.70 (d, J=7.5 Hz, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([NH:12][C:13]([CH2:16][CH3:17])([CH3:15])[CH3:14])=S)[CH:5]=[C:6]([F:8])[CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)Cl.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]=[C:10]=[N:12][C:13]([CH2:16][CH3:17])([CH3:14])[CH3:15])[CH:5]=[C:6]([F:8])[CH:7]=1
Reactant: CCC(C)(C)NC(=S)Nc1cc(F)cc(Cl)c1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)(Cl)Cl
Solvent: ClCCl
Product: CCC(C)(C)N=C=Nc1cc(F)cc(Cl)c1

Procedure:
To a solution of 3.5 g of N-(3-chloro-5-fluorophenyl)-N'-t-pentylthiourea produced in Example A-12 in 20 ml of dichloromethane were added 7.4 g of triphenylphosphine, 4.9 g of carbon tetrachloride and 2.85 g of triethylamine. The mixture was refluxed for 2 hours and evaporated in vacuo. The residue was extracted with petroleum ether and the extract was evaporated in vacuo to give N-(3-chloro-5-fluorophenyl)-N'-t-pentylcarbodiimide as an oil. To a solution of this oil in 20 ml of DMF were added 1.31 g of cyanamide and 2 ml of diisopropylethylamine. The mixture was stirred at 100° C. for 15 hours, cooled to room temperature, poured into ice-water and extracted with ethyl acetate. The extract was evaporated in vacuo. The residue was chromatographed on a silica gel column using chloroform as a solvent and recrystallized from isopropyl alcohol to give 1.0 g of the title compound as colorless needles melting at 130°-131.0° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.ClC(Cl)(O[C:27](=[O:33])OC(Cl)(Cl)Cl)Cl.[F:35][C:36]([F:49])([F:48])[C:37]1[CH:43]=[CH:42][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:40][C:38]=1[NH2:39].C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.C(N(CC)CC)C>[F:35][C:36]([F:48])([F:49])[C:37]1[CH:43]=[CH:42][C:41]([C:44]([F:46])([F:47])[F:45])=[CH:40][C:38]=1[NH:39][C:27]([NH:22][C:19]1[CH:18]=[CH:17][C:16]([O:15][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][CH:7]=2)=[CH:21][CH:20]=1)=[O:33]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Nc1cc(C(F)(F)F)ccc1C(F)(F)F
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=O)Nc4cc(C(F)(F)F)ccc4C(F)(F)F)cc3)c2cc1OC
Yield: 32.2 %

Procedure:
6,7-Dimethoxy-4-(4-aminophenoxy)quinoline (50 mg) was dissolved in toluene (5 ml) with heat, after the addition of triethylamine (1 ml), triphosgene (55 mg) was added, and the admixture was refluxed with heat for 3 minutes. 2,5-Bis(trifluoromethyl)aniline (79 mg) was added to the reaction mixture, and the admixture was refluxed with heat for 20 minutes. After the addition of aqueous sodium hydrogen carbonate, the reaction mixture was extracted 2 times with ethyl acetate, and the organic layer was then washed with brine and dried with anhydrous sodium sulfate. The solvent was removed by reduced-pressure distillation, and the resulting residue was purified by column chromatography on silica gel eluting with chloroform/acetone (10/1) to obtain 30 mg of the title compound (yield: 32%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C:17]([NH2:19])=[O:18])=[CH:4][CH:3]=1.[CH3:20][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:22]=1[N:28]=[C:29]=[O:30]>>[CH3:20][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:22]=1[NH:28][C:29](=[O:30])[NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C:17]([NH2:19])=[O:18])=[CH:6][CH:7]=1
Reactant: Cc1ccc(C)c(N=C=O)c1
Reactant: NC(=O)c1[nH]c2ncccc2c1-c1ccc(N)cc1
Product: Cc1ccc(C)c(NC(=O)Nc2ccc(-c3c(C(N)=O)[nH]c4ncccc34)cc2)c1

Procedure:
75.9 mg of solid white 3-{4-[3-(2,5-dimethylphenyl)ureido]phenyl}-1H-pyrrolo[2,3-b]pyridine-2-carboxamide are prepared as described in Example 7 starting with 3-(4-aminophenyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide and 2,5-dimethylphenyl isocyanate.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][NH:15][CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:6]=1.[F:31][C:32]([F:46])([F:45])[C:33]1[CH:34]=[C:35]([CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:40]=1)[CH2:36]Br.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:36][C:35]2[CH:38]=[C:39]([C:41]([F:43])([F:44])[F:42])[CH:40]=[C:33]([C:32]([F:31])([F:45])[F:46])[CH:34]=2)[CH:6]=1
Reactant: COC(=O)Cc1cccc(OCCCNCC(c2ccccc2)c2ccccc2)c1
Reactant: FC(F)(F)c1cc(CBr)cc(C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)Cc1cccc(OCCCN(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)CC(c2ccccc2)c2ccccc2)c1
Temperature: 45 °C
Reaction time: 18 h
Yield: 75.4 %

Procedure:
To a solution of {3-[3-(2,2-diphenyl-ethylamino)-propoxy]-phenyl}-acetic acid methyl ester (3) (0.50 g, 0.0012 mol) in DMF (10 mL), was added 3,5-bis (trifluoromethyl)-benzyl bromide (0.50 g, 0.0016 mol) and powdered potassium carbonate (1.55 g, 0.011 mol), the reaction mixture was heated and stirred at 45° C. for 18 hours. After cooling, the reaction mixture was diluted with water (30 mL) and extracted with EtOAc (3×25 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4, concentrated to an oil, which was purified by flash chromatography (8:2 Hexanes/EtOAc) to give the desired product as oil 0.57 g in 77% yield. 1H NMR (CDCl3) δ 7.61 (s, 1H), 7.50 (s, 2H), 7.24 (m, 12H), 6.83 (d, 1H), 6.62 (s, 1H), 6.59 (dd 1H), 4.19 (t, 1H), 3.68 (s, 2H), 3.67 (s, 3H), 3.60 (t, 2H), 3.56 (d, 2H), 3.14 (d, 2H), 2.64 (t, 2H), 1.83 (t, 2H); 13C NMR (CDCl3) δ 173.3, 160.3, 144.3, 136.7, 132.8, 130.9, 130.1, 129.9, 129.7, 129.5, 128.0, 125.9, 123.7, 122.9, 122.3, 116.2, 114.5, 114.4, 66.6, 61.1, 59.7, 53.4, 52.1, 51.3, 42.6, 28.1.
Reaction SMILES: [CH2:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH2:4][C@H:3]([C:14]([OH:16])=[O:15])[NH:2]1.[OH-].[K+].[C:19](=[S:21])=[S:20].[C:22]1([CH2:32]Cl)[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][CH:23]=1>C(O)C>[C:22]1([CH2:32][S:20][C:19]([N:2]2[C@@H:3]([C:14]([OH:16])=[O:15])[CH2:4][C:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[NH:12][C:13]=3[CH2:1]2)=[S:21])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][CH:23]=1
Reactant: ClCc1cccc2ccccc12
Reactant: O=C(O)[C@H]1Cc2c([nH]c3ccccc23)CN1
Reactant: S=C=S
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)[C@H]1Cc2c([nH]c3ccccc23)CN1C(=S)SCc1cccc2ccccc12

Procedure:
In the same manner as descsribed in Example 32, (3R)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (3.24 g), KOH (1.75 g), carbon disulfide (0.91 ml), 50% ethanol (70 ml) and 1-naphthylmethyl chloride (3.14 g) are reacted and treated to give the title compound (2.84 g) as pale yellow powder.
Reaction SMILES: [C:1]([N:11]([CH2:20][P:21]([O:25]Cl)([O:23]Cl)=[O:22])[CH2:12][C:13]([O:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[CH2:27]([SH:32])[CH2:28][CH2:29][CH2:30][CH3:31].C(Cl)Cl>C(OCC)C.C(N(CC)CC)C>[C:1]([N:11]([CH2:20][P:21]([O:25][S:32][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])([O:23][S:32][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[O:22])[CH2:12][C:13]([O:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]
Reactant: CCCCOC(=O)CN(CP(=O)(OCl)OCl)C(=O)OCc1ccccc1
Reactant: CCCCCS
Solvent: CCN(CC)CC
Solvent: CCOCC
Solvent: ClCCl
Product: CCCCCSOP(=O)(CN(CC(=O)OCCCC)C(=O)OCc1ccccc1)OSCCCCC
Reaction time: 16 h

Procedure:
Butyl N-carbobenzoxy-N-(dichlorophosphonomethyl)glycinate (13.25 g., 0.34 mole) and pentanethiol (6.96 g., 0.67 mole) were dissolved in 100 ml. of diethyl ether and 50 ml. of methylene chloride. Triethylamine (6.76 g) dissolved in 100 ml. of diethyl ether was then added. The reaction mixture was stirred for 16 hours at ambient temperatures and then filtered. The filtrate was washed with 3% ammonium hydroxide, then with brine, then with 5% hydrochloric acid and then the brine and the ether solution dried over sodium sulfate and then evaporated in vacuo to yield a crude product. The crude product was chromatographed through a silica gel column employing methylene chloride as the eluant. Evaporation of the methylene chloride yielded n-butyl N-carbobenzoxy-N-[di-(n-pentylthio)phosphonomethyl]glycinate as a yellow oil, ND25 =1.5218 and having the following analysis.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:6]=1[S:12][C:13]1[C:18](=[O:19])[O:17][C:16]([C:28]2[CH:41]=[CH:40][C:31]([O:32][CH2:33][CH2:34]OS(C)(=O)=O)=[CH:30][CH:29]=2)([CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:15][C:14]=1[OH:42])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[NH:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1.Cl>CN(C=O)C.O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:6]=1[S:12][C:13]1[C:18](=[O:19])[O:17][C:16]([C:28]2[CH:29]=[CH:30][C:31]([O:32][CH2:33][CH2:34][N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)=[CH:40][CH:41]=2)([CH2:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:15][C:14]=1[OH:42])([CH3:4])([CH3:2])[CH3:3]
Reactant: C1COCCN1
Reactant: Cc1ccc(C(C)(C)C)c(SC2=C(O)CC(CCc3ccccc3)(c3ccc(OCCOS(C)(=O)=O)cc3)OC2=O)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(C(C)(C)C)c(SC2=C(O)CC(CCc3ccccc3)(c3ccc(OCCN4CCOCC4)cc3)OC2=O)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The title compound was prepared by combining methanesulfonic acid 2-{4-[5-(2-tert-butyl-5-methyl-phenylsulfanyl)-4-hydroxy-6-oxo-2-phenethyl-3,6-dihydro-2H-pyran-2-yl]-phenoxy}-ethyl ester (0.07 g, 0.115 mmol) from the previous paragraph, K2CO3 (0.08 g, 0.57 mmol), and morpholine (0.15 mL, 1.72 mmol) in DMF (2 mL). The reaction was stirred overnight at room temperature then combined with H2O and acidified to pH 6.0 with 1N HCl. The product was extracted with EtOAc, dried (MgSO4) and concentrated. Purification by silica gel chromatography, eluting with MeOH:CH2Cl2 :hexane (3:50:50) gave the title compound, m.p. 140°-150° C. 1H NMR (CDCl3) δ 1.48 (s, 9 H), 1.80 (s, 3 H), 2.17-2.29 (m, 3 H), 2.38 (m, 1 H), 2.63 (m, 4 H), 2.84 (m, 2 H), 3.21 (dd, 2 H), 3.74 (m, 4 H), 4.00 (m, 2 H), 6.15 (s, 1 H), 6.78 (m, 2 H), 7.05 (d, 2 H), 7.10-7.22 (m, 5 H), 7.32 (d, 2 H).
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7](Cl)=[O:8])[CH2:2][CH3:3].[NH2:14][C:15]1[S:16][CH:17]=[CH:18][C:19]=1[C:20]([NH2:22])=[O:21].C(N(CC)CC)C>C(#N)C>[CH2:1]([O:4][C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([NH:14][C:15]1[S:16][CH:17]=[CH:18][C:19]=1[C:20]([NH2:22])=[O:21])=[O:8])[CH2:2][CH3:3]
Reactant: NC(=O)c1ccsc1N
Reactant: CCCOc1ccccc1C(=O)Cl
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCCOc1ccccc1C(=O)Nc1sccc1C(N)=O
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A solution of 2-propoxybenzoyl chloride (0.99 g) in acetonitrile (7.5 ml) was added dropwise over 5 minutes to a cooled (0° C.), stirred mixture of 2-aminothiophene-3-carboxamide (0.71 g) and triethylamine (0.51 g) in acetonitrile (7.5 ml). The reaction mixture was stirred for one hour while being allowed to warm to ambient temperature and was then allowed to stand overnight. Acetonitrile was removed under reduced pressure and the residue was washed with water and recrystallised from ethanol-water to afford 2-(2-propoxybenzamido)thiophene-3-carboxamide, 0.91 g, m.p. 176.5°-178.5° C.
Reaction SMILES: [Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1.[F:29][C:30]1[CH:35]=[C:34]([O:36][CH3:37])[C:33]([F:38])=[CH:32][C:31]=1[N:39]1[CH2:44][CH2:43][C:42](=O)[CH2:41][CH2:40]1>O>[F:29][C:30]1[CH:35]=[C:34]([O:36][CH3:37])[C:33]([F:38])=[CH:32][C:31]=1[N:39]1[CH2:44][CH2:43][C:42](=[CH:2][O:3][CH3:4])[CH2:41][CH2:40]1
Reactant: COC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: COc1cc(F)c(N2CCC(=O)CC2)cc1F
Agent: [Cl-]
Solvent: O
Solvent: C1CCOC1
Product: COC=C1CCN(c2cc(F)c(OC)cc2F)CC1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 34.1 %

Procedure:
A reaction vessel was charged with methoxymethyltriphenyl-phosphonium chloride (1.114 g), the atomosphere indide the vessel was substituted with nitrogen, and anhydrous tetrahydrofuran (2 mL) was added, followed by further dropwise addition of 1.57 M n-butyl lithium-in-hexane solution (2 mL) at room temperature and thereafter 10 minutes' stirring at room temperature. To the reaction mixture a mixture of 1-(2,5-difluoro-4-methoxyphenyl)piperidin-4-one (676 mg) and anhydrous tetrahydrofuran (0.5 mL) was added dropwise, followed by 30 minutes' stirring at room temperature. To the reaction mixture water was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated saline solution and dried over anhydrous sodium sulfate. Distilling the solvent off, the crude product as obtained was purified on silica gel column chromatography (eluent, hexane: ethyl acetate=10:1) to provide 1-(2,5-difluoro-4-methoxyphenyl)-4-methoxymethylenepiperidine (257 mg).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:7][C:8]1[S:9][C:10](Cl)=[N:11][N:12]=1>C(O)C>[NH2:7][C:8]1[S:9][C:10]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[N:11][N:12]=1
Reactant: Nc1nnc(Cl)s1
Reactant: C1CCNCC1
Solvent: CCO
Product: Nc1nnc(N2CCCCC2)s1

Procedure:
Piperidine (100 μl) was added to a solution of 2-amino-5-chloro-1,3,4-thiadiazole (50 mg) in ethanol (1 ml) and the mixture heated in a sealed vial at 70° C. for 6 hours The ethanol was evaporated from the cooled reaction under vacuum, the residue diluted with water and the solid product filtered off to give 2-amino-5-piperid-1-yl-1,3,4-thiadiazole.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].[N+](=[CH:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N-]>ClCCl.CCCCCCC.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.[Rh].[Rh]>[CH2:16]([O:15][C:13](=[O:14])[CH2:12][O:6][CH2:5][C:4]1[CH:7]=[CH:8][CH:9]=[C:2]([F:1])[CH:3]=1)[CH3:17]
Reactant: OCc1cccc(F)c1
Reactant: CCOC(=O)C=[N+]=[N-]
Agent: [Rh]
Solvent: CC(=O)O
Solvent: ClCCl
Solvent: CCCCCCC
Product: CCOC(=O)COCc1cccc(F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 98.4 %

Procedure:
To a solution of 3-fluorobenzyl alcohol (1.12 g, 10.0 mmol) in dichloromethane (20 mL) is added rhodium (II) acetate dimer (10 mg) followed by ethyl diazoacetate (0.95 mL, 9.0 mmol). The reaction mixture is stirred at RT for 30 min. The reaction mixture is diluted with heptane, filtered through celite, and the filtrate is evaporated and the residue is vacuum distilled at 150° C. to give 1.88 g of the product 392. 1H NMR (CDCl3) δ 7.30 (m, 1H), 7.12 (m, 2H), 6.99 (dt, 1H), 4.63 (s, 2H), 4.28 (q, 2H), 4.11 (s, 2H), 1.30 (t, 3H); MS: m/z 213 (M++1).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[N:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([O:20][CH3:21])[N:13]=2)[C:3]=1[C:4]([OH:6])=O.S(O)(O)(=O)=O.[NH2:27][N:28]1[CH2:32][CH2:31][O:30][C:29]1=[O:33].C(C1C=C(C(C)C)C=C(C(C)C)C=1S(Cl)(=O)=O)(C)C.CN1C=CN=C1>CN(C)C=O.O.C(N(CC)CC)C>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[N:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([O:20][CH3:21])[N:13]=2)[C:3]=1[C:4]([NH:27][N:28]1[CH2:32][CH2:31][O:30][C:29]1=[O:33])=[O:6]
Reactant: NN1CCOC1=O
Reactant: COc1cc(OC)nc(Oc2cccc(Cl)c2C(=O)O)n1
Agent: CC(C)c1cc(C(C)C)c(S(=O)(=O)Cl)c(C(C)C)c1
Agent: Cn1ccnc1
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COc1cc(OC)nc(Oc2cccc(Cl)c2C(=O)NN2CCOC2=O)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
1.24 Grams of 2-chloro-6-(4,6-dimethoxypyrimidin-2-yl)oxybenzoic acid was dissolved in 20 ml of N,N-dimethylformamide. To the solution were added 1.20 g of 3-amino-2-oxazolidinone sulfate, 0.67 g of triethylamine, 1.82 g of 2,4,6-triisopropylbenzenesulfonyl chloride and 0.98 g of 1-methylimidazole. The resulting solution was stirred at room temperature for 3 hours. The reaction solution was poured into water and extracted with ethyl acetate. The organic layer separated therefrom was washed with water and dried over anhydrous magnesium sulfate. The solvent was removed from the dried layer under reduced pressure to obtain a residue. Purifying the residue with thin layer chromatography (silica gel, chloroform/methanol: 9/1 by volume) gave 0.2 g of 3-{2-chloro-6-(4,6-dimethoxypyrimidin-2-yl)oxybenzoyl}amino-2-oxazolidinone (present compound (172)).
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[CH2:13]([C:15]1[N:16]([C:40]2[CH:45]=[CH:44][C:43]([O:46][CH:47]([CH3:49])[CH3:48])=[CH:42][CH:41]=2)[C:17](=[O:39])[C:18]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]3[C:32]([C:37]#[N:38])=[CH:33][CH:34]=[CH:35][CH:36]=3)=[CH:27][CH:26]=2)=[C:19]([CH2:21][CH2:22][CH3:23])[N:20]=1)[CH3:14]>O>[CH2:13]([C:15]1[N:16]([C:40]2[CH:45]=[CH:44][C:43]([O:46][CH:47]([CH3:49])[CH3:48])=[CH:42][CH:41]=2)[C:17](=[O:39])[C:18]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[C:37]3[NH:3][C:4](=[O:7])[O:5][N:38]=3)=[CH:27][CH:26]=2)=[C:19]([CH2:21][CH2:22][CH3:23])[N:20]=1)[CH3:14]
Reactant: [NH3+]O
Reactant: CCCc1nc(CC)n(-c2ccc(OC(C)C)cc2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: O=C([O-])O
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CCCc1nc(CC)n(-c2ccc(OC(C)C)cc2)c(=O)c1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 63 %

Procedure:
A mixture of hydroxylammonium chloride (1.2 g), sodium hydrogen carbonate (1.7 g) and dimethyl sulfoxide (10 mL) was stirred at 40° C. for 30 min, 4′-{[2-ethyl-1-(4-isopropoxyphenyl)-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (0.51 g) was added, and the mixture was stirred at 90° C. for 24 hr. The mixture was allowed to cool to room temperature, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was dissolved in ethyl acetate. The solution was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was dissolved in tetrahydrofuran (10 mL). N,N′-carbonyldiimidazole (0.25 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.23 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and then with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.36 g, 63%).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[Li]CCCC.[OH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18](=O)[CH3:19])=[CH:14][CH:13]=1.CC1C=CC(S(O)(=O)=O)=CC=1>C1COCC1.C1C=CC=CC=1>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:18]([C:15]1[CH:16]=[CH:17][C:12]([OH:11])=[CH:13][CH:14]=1)=[CH2:19]
Reactant: c1ccsc1
Reactant: CC(=O)c1ccc(O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: c1ccccc1
Product: C=C(c1ccc(O)cc1)c1cccs1
Temperature: -78 °C
Reaction time: 2 h
Yield: 11.5 %

Procedure:
A solution of thiophene (0.60 mL, 7.5 mmol) in THF (15 mL) was cooled to −78° C., BuLi solution (2.5 M in hexanes, 3.0 mL, 7.5 mmol) was added dropwise, after 1 h at −78° C., a solution of 1-(4-hydroxy-phenyl)-ethanone (1.0 g, 7.34 mmol) was added. The slurry mixture was stirred at −78° C. for 2 h, then slowly warmed to rt. The reaction was quenched with saturated aqueous NH4Cl, extracted with ethyl acetate, the extract was washed with brine, dried over MgSO4 and concentrated to give yellow oil residue. To the above oil residue was added benzene (10 mL) and catalytic amount of TsOH. The mixture was heated with Dean-Stark trap for 15 min, then concentrated 4-(1-Thiophen-2-yl-vinyl)-phenol (170 mg, 11.5%) was obtained after flash column chromatography (20%–40% ethyl acetate-hexanes). MS Found: (M+H)+=203.
Reaction SMILES: [C:1]1([S:7](Cl)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:11][NH:12][C:13]([NH:15][NH2:16])=[O:14].C(=O)(O)[O-].[Na+]>C(O)C>[C:1]1([S:7]([NH:11][NH:12][C:13]([NH:15][NH:16][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])=[O:14])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: NNC(=O)NN
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: O=C(NNS(=O)(=O)c1ccccc1)NNS(=O)(=O)c1ccccc1
Reaction time: 0.17 h

Procedure:
175.6 g (1.0 mole) of benzenesulfonyl chloride was added to a stirred mixture of 45 g (0.5 mole) carbohydrazide and 100 g sodium bicarbonate in 1000 ml ethanol in a 3 liter 3 neck flask. The mixture was heated to gentle reflux for six hours. The cooled mixture was filtered and the solid precipitate (containing the desired product along with sodium chloride) was washed with ethanol and dried. Yield: 207 g. This mixture was then suspended in water and stirred for 10 minutes. The insoluble solid was filtered off and washed well with water and dried. Yield: 120.5 g, m.p. 227° C (dec.)
Reaction SMILES: O=P(Cl)(Cl)[Cl:3].[CH2:6]([O:13][C:14]1[C:23]2[C:18](=[C:19]([CH3:26])[C:20]([O:24][CH3:25])=[CH:21][CH:22]=2)[N+:17]([O-])=[CH:16][CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>>[CH2:6]([O:13][C:14]1[C:23]2[C:18](=[C:19]([CH3:26])[C:20]([O:24][CH3:25])=[CH:21][CH:22]=2)[N:17]=[C:16]([Cl:3])[CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: COc1ccc2c(OCc3ccccc3)cc[n+]([O-])c2c1C
Reactant: O=P(Cl)(Cl)Cl
Product: COc1ccc2c(OCc3ccccc3)cc(Cl)nc2c1C
Temperature: 25 °C
Reaction time: 0.58 h
Yield: 90.4 %

Procedure:
POCl3 was added under inert atmosphere at −78° C. to 4-benzyloxy-7-methoxy-8-methylquinoline N-oxide (62, 2.5 g, 8.47 mmol). Then the reaction mixture was allowed to warm up to room temperature, then heated to reflux. After 35 min, the solution was cooled to room temperature and the excess of POCl3 was evaporated under reduced pressure. The residue was partitioned between ice-cooled water and AcOEt, dried (Na2SO4) and evaporated. The residue was triturated in ether, then filtered and successively washed with small portions of methanol and ether to give 2.4 g (90.4%) of the target product 63 as a white powder: m/z=314 (M+H)+.