Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.[OH:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1>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.C(#N)C>[C:11]1([C:9]2[N:10]=[C:5]3[CH:4]=[CH:3][C:2]([C:22]4[CH:23]=[CH:24][C:19]([CH2:18][OH:17])=[CH:20][CH:21]=4)=[CH:7][N:6]3[CH:8]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Brc1ccc2nc(-c3ccccc3)cn2c1
Reactant: OCc1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Product: OCc1ccc(-c2ccc3nc(-c4ccccc4)cn3c2)cc1
Yield: 31.5 %

Procedure:
150 mg of 6-bromo-2-phenylimidazo[1,2-a]pyridine, 125 mg of 4-(hydroxymethyl)phenylboronic acid, 19 mg of tetrakis(triphenylphosphine)palladium and 2 ml of acetonitrile are placed in a microwave tube. Under a stream of nitrogen, 2 ml of nitrogen-degassed toluene and then 2 ml of a 2M solution of sodium carbonate are added thereto. The tube is placed in a microwave device and irradiated at 150° C. for 15 min. The organic phase is recovered, dried and then concentrated under reduced pressure. The residue is taken up with diisopropyl ether and the precipitate is recovered by filtration, washed and dried. It is purified by recrystallization from n-butanol. 52 mg of compound are obtained. Mp=238-240° C. 1H NMR (DMSO-d6, δ in ppm): 4.54 (d, J=5.5 Hz, 2H); 5.2 (t, J=5.6 Hz, 1H); from 7.24 to 7.73 (m, 9H); 7.96 (m, 2H); 8.36 (s, 1H); 8.84 (t, J=1.3 Hz, 1H). M+H=301.
Reaction SMILES: [CH:1]1([N:7]2[C:12]([OH:13])=[C:11]([C:14]([NH:16][CH2:17][C:18]([O:20]CC)=[O:19])=[O:15])[C:10](=[O:23])[NH:9][C:8]2=[O:24])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[F:31][C:32]1[C:39]([F:40])=[CH:38][CH:37]=[CH:36][C:33]=1[CH2:34]Br.Cl>CC(N(C)C)=O>[CH:1]1([N:7]2[C:12]([OH:13])=[C:11]([C:14]([NH:16][CH2:17][C:18]([OH:20])=[O:19])=[O:15])[C:10](=[O:23])[N:9]([CH2:34][C:33]3[CH:36]=[CH:37][CH:38]=[C:39]([F:40])[C:32]=3[F:31])[C:8]2=[O:24])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CCOC(=O)CNC(=O)c1c(O)n(C2CCCCC2)c(=O)[nH]c1=O
Reactant: Fc1cccc(CBr)c1F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: O=C(O)CNC(=O)c1c(O)n(C2CCCCC2)c(=O)n(Cc2cccc(F)c2F)c1=O
Reaction time: 8 h
Yield: 32 %

Procedure:
A mixture of ethyl N-[(1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycinate (340 mg, 1.0 mmoles), pulv. potassium carbonate (750 mg, 5.35 mmoles) and 2,3-difluorobenzyl bromide (255 uL, 2.0 mmoles) in dimethylacetamide (5 mL) was vigorously stirred at 100° C. for 3 hours. The mixture was poured into 1 molar hydrochloric acid and extracted with ethyl acetate (×2). The combined organic solutions were washed with 1 molar hydrochloric acid and evaporated. The residue was purified by flash chromatography (10-50% ethyl acetate in hexane), the required fractions evaporated, dissolved in ethanol (5 mL) and 1 molar sodium hydroxide solution (3.0 mL) added. The mixture was stirred overnight, acidified and extracted with ethyl acetate (×2), the combined extracts washed with 1 molar hydrochloric acid, dried and evaporated. Recrystallization from ethanol-water gave the title compound (140 mg, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.10 (br. s., 1 H), 10.11 (br. s., 1 H), 7.25-7.43 (m, 1 H), 7.08-7.23 (m, 1 H), 7.03 (t, J=7.07 Hz, 1 H), 5.08 (s, 2 H), 4.55-4.73 (m, 1 H), 4.13 (d, J=5.81 Hz, 2 H), 2.12-2.35 (m, 2 H), 1.78 (d, J=12.63 Hz, 2 H), 1.63 (s, 3 H), 1.20-1.38 (m, 2 H), 1.02-1.18 (m, 1 H)
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([N:11]2[CH2:15][CH:14]([CH3:16])[C:13]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)=[N:12]2)=[O:10])=[CH:4][CH:3]=1.C(NC(C)C)(C)C.C([Li])CCC.Cl[C:37]([O:39][CH3:40])=[O:38]>O1CCCC1.CCCCCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([N:11]2[CH2:15][C:14]([C:37]([O:39][CH3:40])=[O:38])([CH3:16])[C:13]([C:17]3[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=3)=[N:12]2)=[O:10])=[CH:6][CH:7]=1
Reactant: COC(=O)Cl
Reactant: CC1CN(C(=O)Nc2ccc(Cl)cc2)N=C1c1ccc(Cl)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: CC(C)NC(C)C
Product: COC(=O)C1(C)CN(C(=O)Nc2ccc(Cl)cc2)N=C1c1ccc(Cl)cc1
Temperature: -20 °C
Reaction time: 0.33 h

Procedure:
To 3.4 g of N,3-bis-(4-chlorophenyl)-4-methyl-4,5-dihydro-1H-pyrazole-1-carboxamide and 1.1 g of diisopropylamine dissolved in 20 ml of tetrahydrofuran and cooled in an acetone bath maintained at -20° C., was added 8.0 ml of a 2.7 molar solution of butyllithium in hexane. The resulting solution was stirred for 20 minutes and then cooled to -70° C. To this solution was added 0.9 ml of methyl chloroformate. The reaction was allowed to stir for 10 minutes and then allowed to warm to room temperature over 10 minutes. The reaction was quenched with 1.0 ml of acetic acid and the reaction mixture was partitioned between diethyl ether and water and the organic layer was dried over anhydrous magnesium sulfate. The resulting solution was filtered evaporated in vacuo to give 2.9 g of N,3-bis-(4-chlorophenyl)-4-carbomethoxy-4-methyl-4,5-dihydro-1H-pyrazole-1-carboxamide. NMR and IR data were consistent with the structure.
Reaction SMILES: C[O:2][C:3](=[O:53])[C@H:4]([OH:52])[CH2:5][NH:6][C:7](=[O:51])[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][N:15]([C:39]2[CH:44]=[CH:43][C:42]([CH:45]3[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]3)=[CH:41][CH:40]=2)[C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[C:21]([CH2:30][O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH:20]=2)=[O:17])=[CH:10][CH:9]=1.[OH-].[Na+]>C(O)C>[Si:32]([O:31][CH2:30][C:21]1[CH:20]=[C:19]([NH:18][C:16](=[O:17])[N:15]([CH2:14][C:11]2[CH:10]=[CH:9][C:8]([C:7]([NH:6][CH2:5][C@@H:4]([OH:52])[C:3]([OH:53])=[O:2])=[O:51])=[CH:13][CH:12]=2)[C:39]2[CH:44]=[CH:43][C:42]([CH:45]3[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]3)=[CH:41][CH:40]=2)[CH:24]=[CH:23][C:22]=1[O:25][C:26]([F:28])([F:27])[F:29])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33]
Reactant: COC(=O)[C@H](O)CNC(=O)c1ccc(CN(C(=O)Nc2ccc(OC(F)(F)F)c(CO[Si](C)(C)C(C)(C)C)c2)c2ccc(C3CCCCC3)cc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CC(C)(C)[Si](C)(C)OCc1cc(NC(=O)N(Cc2ccc(C(=O)NC[C@@H](O)C(=O)O)cc2)c2ccc(C3CCCCC3)cc2)ccc1OC(F)(F)F
Reaction time: 2 h
Yield: 71.4 %

Procedure:
(R)-3-{4-[3-[3-(tert-butyldimethylsilanyloxymethyl)-4-trifluoromethoxyphenyl]-1-(4-cyclohexyl-phenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid methyl ester (24 mg, 0.032 mmol) was dissolved in ethanol (1 mL) and sodium hydroxide (0.05 mL, 019 mmol) was added. The reaction mixture was stirred for 2 hours and concentrated to remove the ethanol. The residue was diluted with water (10 mL), acidified with hydrochloric acid (4 N, 0.3 mL) and extracted with ethyl acetate (2×10 mL). The combined organic phases were washed with water (3×10 mL) and dried with magnesium sulphate and concentrated in vacuo to give 17 mg of (R)-3-{4-[3-[3-(tert-butyldimethylsilanyloxymethyl)-4-trifluoromethoxyphenyl]-1-(4-cyclohexylphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][C:9]=1[NH:19][C:20](=[O:39])[CH2:21][C:22]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]2[CH:35]=[CH:34][N:33]=[C:32]([CH:36]3[CH2:38][CH2:37]3)[CH:31]=2)[CH:25]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:36]1([C:32]2[CH:31]=[C:30]([C:26]3[CH:25]=[C:24]([C:22]4[CH2:21][C:20](=[O:39])[NH:19][C:9]5[CH:10]=[C:11]([C:15]([F:18])([F:17])[F:16])[C:12]([CH3:14])=[CH:13][C:8]=5[N:7]=4)[CH:29]=[CH:28][CH:27]=3)[CH:35]=[CH:34][N:33]=2)[CH2:37][CH2:38]1
Reactant: Cc1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-c3ccnc(C4CC4)c3)c2)cc1C(F)(F)F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc2c(cc1C(F)(F)F)NC(=O)CC(c1cccc(-c3ccnc(C4CC4)c3)c1)=N2

Procedure:
The title compound was prepared from (2-{3-[3-(2-cyclopropyl-pyridin-4-yl)-phenyl]-3-oxo-propionylamino}-5-methyl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M267) (286 mg, 0.52 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (198 mg, 87%).
Reaction SMILES: [F:1][C:2]([F:8])([F:7])[S:3]([O-:6])(=[O:5])=[O:4].CO[C:11]1[C:12](OC)=CC2[Te]C(C)=[N+](CC#C)C=2[CH:23]=1.[CH3:26][C:27]1[Te:28][C:29]2[CH:35]=[C:34]([CH3:36])[C:33]([CH3:37])=[CH:32][C:30]=2[N:31]=1>>[F:1][C:2]([F:8])([F:7])[S:3]([O-:6])(=[O:5])=[O:4].[CH3:26][C:27]1[Te:28][C:29]2[CH:35]=[C:34]([CH3:36])[C:33]([CH3:37])=[CH:32][C:30]=2[N+:31]=1[CH2:12][C:11]#[CH:23]
Reactant: Cc1nc2cc(C)c(C)cc2[te]1
Reactant: C#CC[n+]1c(C)[te]c2cc(OC)c(OC)cc21
Agent: O=S(=O)([O-])C(F)(F)F
Product: C#CC[n+]1c(C)[te]c2cc(C)c(C)cc21

Procedure:
This compound was prepared in the same way and on the same molar scale as the compound of Example 46, except that 2,5,6-trimethylbenzotellurazole (Example 22) was used in place of 5,6-dimethoxy-2-methylbenzotellurazole. Yield 1.10 g (72% of theory) cream colored powder, m.p. 189°-192° C. dec. The infrared, nuclear magnetic resonance, and mass spectra were in agreement with that expected for the structural formula.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:12]=[CH:13][CH:14]=1)[NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1.[N+:15]([O-])([OH:17])=[O:16]>>[CH3:1][C:2]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[C:4]([CH:3]=1)[NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1
Reactant: Cc1cccc(Nc2ccccn2)c1
Reactant: O=[N+]([O-])O
Product: Cc1ccc([N+](=O)[O-])c(Nc2ccccn2)c1
Temperature: 25 °C
Reaction time: 40 h
Yield: 18 %

Procedure:
Nitric acid (100 ml) and 3-methyl-N-(2-pyridyl)aniline (Hirota, M.; Kobayashi, K. Bull Chem. Soc. Jpn. 1981, 54, 1583) (16.8 g, 91.2 mmol) was mixed with ice cooling, the ice bath was removed and the reaction mixture was stirred for 40 h at room temperature. The reaction mixture was poured into saturated aqueous sodium bicarbonate solution (200 ml), the aqueous mixture was basified with the addition of potassium carbonate and the resulting basic solution was extracted with ethyl acetate (500 ml). The organic extracts were washed with water (50 ml) and brine (50 ml), dried (magnesium sulfate) and concentrated to dryness. The residue was purified by column chromatography (silica gel, 350 g; n-hexane/ethyl acetate (9/1)) to give 3.85 g (18%) of the titled compound as yellow solids. 1H-NMR (CDCl3) δ: 10.21 (1H, br.s), 8.54 (1H, s), 8.38-8.32 (1H, m), 8.13 (1H, d J=8.8 Hz), 7.68-7.60 (1H, m), 6.98-6.92 (2H, m), 6.80-6.70 (1H, m), 2,42 (3H, s).
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]([CH2:28][CH2:29][OH:30])[C:5]([C:7]1[CH:8]=[N:9][N:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][C@H:23]3[CH3:27])=[CH:14][CH:13]=2)[CH:11]=1)=[O:6].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)(Cl)Cl.O>[OH:1][CH:2]1[O:30][CH2:29][CH2:28][N:4]([C:5]([C:7]2[CH:8]=[N:9][N:10]([C:12]3[CH:13]=[CH:14][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]4[CH2:26][CH2:25][CH2:24][C@H:23]4[CH3:27])=[CH:16][CH:17]=3)[CH:11]=2)=[O:6])[CH2:3]1
Reactant: C[C@@H]1CCCN1CCCOc1ccc(-n2cc(C(=O)N(CCO)CCO)cn2)cc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: O
Solvent: ClC(Cl)Cl
Product: C[C@@H]1CCCN1CCCOc1ccc(-n2cc(C(=O)N3CCOC(O)C3)cn2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 2.2 %

Procedure:
To a solution of 1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carboxylic acid bis-(2-hydroxyethyl)-amide obtained in Example 20 (1.0 g) in chloroform (8 mL), Dess-Martin reagent (1.1 g) was added and stirred at room temperature for 16 hours. The reaction mixture was diluted with water and extracted with chloroform. The organic layer was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting solvent: chloroform:methanol=4:1) and further purified by preparative TLC (1 mm thickness, developing solvent: chloroform:methanol=9:1) to give the titled compound (0.022 g) as a colorless amorphous substance.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([S:11]([C:14]3[CH:15]=[CH:16][C:17]([CH3:21])=[C:18]([NH2:20])[CH:19]=3)(=[O:13])=[O:12])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[CH3:22][N:23]1[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]1.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[CH3:21][C:17]1[CH:16]=[CH:15][C:14]([S:11]([C:6]2[C:5]3[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=3)[NH:8][CH:7]=2)(=[O:13])=[O:12])=[CH:19][C:18]=1[NH:20][CH:26]1[CH2:27][CH2:28][N:23]([CH3:22])[CH2:24][CH2:25]1
Reactant: CN1CCC(=O)CC1
Reactant: Cc1ccc(S(=O)(=O)c2c[nH]c3cc(Cl)ccc23)cc1N
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: Cc1ccc(S(=O)(=O)c2c[nH]c3cc(Cl)ccc23)cc1NC1CCN(C)CC1
Temperature: 30 °C
Reaction time: 4 h
Yield: 39.7 %

Procedure:
5-(6-Chloro-1H-indole-3-yl sulfonyl)-2-methyl phenyl amine [obtained from preparation 1, Step (v)](600 mg, 1.87 mmol) was added to a 100 mL three necked round bottomed flask, followed by the addition of 1-methyl-4-piperidone (423 mg, 3.74 mmol), sodium sulfate (2.6 grams, 18.7 mmol) and acetic acid (12 mL). The reaction mass was stirred for 4 hours at room temperature (30° C.). Then sodium tri acetoxy borohydride (1.18 grams, 5.61 mmol) was added to the reaction mass at 20-25° C. in 5 minutes. This reaction mixture was further stirred over night at room temperature. The reaction mixture was then quenched into 100 mL water, basified to pH 9 with 50% aqueous sodium hydroxide solution under cooling (10° C.) and extracted the product with ethylacetate (4×50 mL). The combined organic layer was washed with saturated brine solution (2×50 mL), dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to obtain oily mass. The technical product was further purified by column chromatography using ethylacetate and methanol as an eluents to obtain 0.31 grams of the title product.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]([S:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:9][CH:10]=1)[C:5](O)=[O:6].Cl>O1CCCC1.C1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:8]([S:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:9][CH:10]=1)[CH2:5][OH:6]
Reactant: O=C(O)c1cc(F)ccc1Sc1ccccc1
Agent: Cl
Solvent: C1CCOC1
Solvent: c1ccccc1
Product: OCc1cc(F)ccc1Sc1ccccc1
Temperature: 20 °C

Procedure:
144 g of 3-fluoro-6-(phenylthio)-benzoic acid in 1000 ml of tetrahydrofuran is treated dropwise under a nitrogen atmosphere and under reflux with a 70% sodium-dihydro-bis(2-methoxyethoxy)-aluminate solution in benzene. The mixture is held under reflux for a further 2 hours. After the addition of 400 ml of benzene, the mixture is cooled to 20° C, acidified with 435 ml of 3-N hydrochloric acid and subsequently treated with 600 ml of concentrated hydrochloric acid. The organic phase is washed with water, dried over sodium sulphate and evaporated. There is obtained 3-fluoro-6-(phenylthio)-benzyl alcohol as a thick oil.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([CH:6]([N:8]([OH:12])[C:9]([NH2:11])=[O:10])[CH3:7])=[CH:2]1.[CH3:13][C@H:14]([C:27](O)=[O:28])[C:15]1[CH:16]=[CH:17][C:18]2[CH:19]=[C:20]([O:25][CH3:26])[CH:21]=[CH:22][C:23]=2[CH:24]=1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[CH3:26][O:25][C:20]1[CH:19]=[C:18]2[C:23](=[CH:22][CH:21]=1)[CH:24]=[C:15]([C@H:14]([CH3:13])[C:27]([O:12][N:8]([CH:6]([C:3]1[CH:4]=[CH:5][O:1][CH:2]=1)[CH3:7])[C:9]([NH2:11])=[O:10])=[O:28])[CH:16]=[CH:17]2
Reactant: CC(c1ccoc1)N(O)C(N)=O
Reactant: COc1ccc2cc([C@H](C)C(=O)O)ccc2c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Product: COc1ccc2cc([C@H](C)C(=O)ON(C(N)=O)C(C)c3ccoc3)ccc2c1
Reaction time: 18 h
Yield: 68.3 %

Procedure:
To a solution of N-1-(fur-3-yl)ethyl-N-hydroxyurea (1.00 g, 5.9 mmol), prepared as described in U.S. Pat. No. 5,112,848, in CH2Cl2 (25 mL) was added naproxen (135 g, 5.9 mmol) followed by dicyclohexylcarbodiimide (1.34 g, 6.49 mmol), and a crystal of 4-N,N-dimethylaminopyridine. The reaction was stirred for 18 hours. The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel (ether), followed by crystallization in ethyl acetate/hexanes to give N-[(S)-2-(6-methoxynaphth-2-yl)propionyloxy]-N-[1-(fur-3-yl)ethyl]urea (1.54 g). m.p. 128.5°-134° C. 1H NMR (300 MHz, DMSO-d6, mixture of diastereomers) δ 0.72 and 1.12 (bm, 3H), 1.48 (bm, 3H), 3.87 (s, 3H), 4.13 (bm, 1H), 5.14 (bm, 1H), 6.79 and 6.94 (bs, 2H), 7.16 (m, 2H), 7.29-7.46 (m, 3H), 7.69-7.86 (m, 3H). MS (DCI/NH3) m/e 383 (M+H)+. Analysis calc'd for C21H22N2O5 : C, 65.95; H, 5.80; N, 7.33. Found: C, 65.39; H; 5.80; N, 7.26.
Reaction SMILES: [CH2:1]([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@H:10]1[CH2:11][CH2:12][C@H:13]2[C:18]([OH:20])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:21]([NH:25][NH2:26])(=[O:24])[CH2:22][CH3:23].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl>[CH2:1]([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@H:10]1[CH2:11][CH2:12][C@H:13]2[C:18]([NH:26][NH:25][C:21](=[O:24])[CH2:22][CH3:23])=[O:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCC(=O)NN
Reactant: O=C(O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: CCC(=O)NNC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.9 %

Procedure:
To a mixture of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.250 g, 0.905 mmol) in DCM (15.0 mL) were added propanehydrazide 202 (0.120 g, 1.358 mmol), 1-hydroxybenzotriazole (0.186 g, 1.358 mmol) and 1-ethyl-(3-dimethylamino propyl) carbodiimide hydrochloride (0.260 g, 1.358 mmol) sequentially at room temperature. The mixture was stirred at room temperature overnight, diluted with DCM and concentrated to provide a residue which was subjected to chromatography to give 203 (0.31 g, 99%) as a white foam.
Reaction SMILES: Cl[CH2:2][C@H:3]([CH3:15])[CH2:4][O:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=1[F:14].[CH3:16][CH:17]([CH3:33])[C:18]([NH:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH:22]=1)=[O:19]>>[CH3:16][CH:17]([CH3:33])[C:18]([NH:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]2[CH2:32][CH2:31][N:30]([CH2:2][C@H:3]([CH3:15])[CH2:4][O:5][C:6]3[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=3[F:14])[CH2:29][CH2:28]2)[CH:22]=1)=[O:19]
Reactant: CC(C)C(=O)Nc1cccc(C2CCNCC2)c1
Reactant: C[C@@H](CCl)COc1cc(F)c(F)cc1F
Product: CC(C)C(=O)Nc1cccc(C2CCN(C[C@H](C)COc3cc(F)c(F)cc3F)CC2)c1

Procedure:
Prepared by Procedure G and Scheme B1 using 1-{[(2R)-3-chloro-2-methylpropyl]oxy}-2,4,5-trifluorobenzene and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 449.2 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][N:6]=[C:5]2[Cl:13].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][C:28]=2[CH2:37][NH2:38])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>CC(N(C)C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:34])([F:35])[F:36])=[CH:29][C:28]=2[CH2:37][NH:38][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[C:8](=[O:12])[NH:7][N:6]=[C:5]3[Cl:13])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]
Reactant: O=c1[nH]nc(Cl)c2cc(Br)ccc12
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(C(F)(F)F)cc2CN)CC1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CC(=O)N(C)C
Product: CC(C)(C)OC(=O)N1CCN(c2ccc(C(F)(F)F)cc2CNc2ccc3c(=O)[nH]nc(Cl)c3c2)CC1
Temperature: 90 °C
Yield: 7.3 %

Procedure:
A mixture of 6-bromo-4-chloro-2H-phthalazin-1-one (183 mg, 0.70 mmol), 4-(2-aminomethyl-4-trifluoromethyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (230 mg, 0.64 mmol), Pd2(dba)3 (59 mg, 0.064 mmol), BINAP (120 mg, 0.19 mmol) and NaOt-Bu (180 mg, 1.92 mmol) in DMA (10 mL) was purged with nitrogen for 10 min. The mixture was heated at 90° C. for 5 h. The mixture was allowed to cool and diluted with ethyl acetate (30 mL) and washed with ammonium chloride (25 mL). The organic layer was dried and concentrated. Chromatography on silica yielded the title compound (25 mg) m/z (M+H)=538.90.
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:7]([O:11][CH3:12])(=[O:10])[CH:8]=[CH2:9].C(O)(=O)C>C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Pd+2].[Pd].[Cu]>[C:7]([O:11][CH3:12])(=[O:10])[CH:8]=[CH:9][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=CC(=O)OC
Reactant: c1ccccc1
Agent: [Cu]
Agent: [Pd+2]
Agent: [Pd]
Solvent: CC(=O)O
Product: COC(=O)C=Cc1ccccc1
Temperature: 120 °C
Yield: 70 %

Procedure:
As a further illustration of the ability of a catalyst which is maintained in a soluble, non-solid, oxidized stated to convert the reactants into a relatively high yield of the desired product, a mixture comprising 0.5 mole of benzene, 0.10 mole of methyl acrylate, 0.50 mole of glacial acetic acid, 0.002 mole of palladium (II) acetylacetonate and 0.002 mole of cupric acetate monohydrate was charged to a 300 cc. stirred, stainless steel autoclave. The autoclave was sealed and air was pressed in until an initial operating pressure of 1100 pounds per square inch gauge was reached. The autoclave was stirred, heated to a temperature of 120°C. and maintained at the aforementioned operating temperature and pressure for a period of 6 hours. During this time the bulk of the palladium and copper salt remained dissolved in the reaction medium. During the 6-hour reaction time, liquid samples were periodically withdrawn and analyzed by means of gas chromatography. At the end of the 6-hour period, an 86% conversion of the methyl acrylate and a 70% yield of methyl cinnamate, the desired product, based on the methyl acrylate charged, were noted.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:18]3[C:23]([CH:24]=[C:25]4[C:30]=2[CH:29]=[CH:28][CH:27]=[CH:26]4)=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:13][CH:12]=1.[Br:31]N1C(=O)CCC1=O.O>CN(C)C=O>[Br:31][C:24]1[C:25]2[C:30]([C:17]([C:14]3[CH:15]=[CH:16][C:11]([C:2]4[CH:3]=[CH:4][C:5]5[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=5)[CH:1]=4)=[CH:12][CH:13]=3)=[C:18]3[C:23]=1[CH:22]=[CH:21][CH:20]=[CH:19]3)=[CH:29][CH:28]=[CH:27][CH:26]=2
Reactant: O=C1CCC(=O)N1Br
Reactant: c1ccc2cc(-c3ccc(-c4c5ccccc5cc5ccccc45)cc3)ccc2c1
Solvent: O
Solvent: CN(C)C=O
Product: Brc1c2ccccc2c(-c2ccc(-c3ccc4ccccc4c3)cc2)c2ccccc12
Temperature: 25 °C
Reaction time: 7 h
Yield: 99 %

Procedure:
9-(4-Naphthalene-2-yl-phenyl)anthracene 13.25 g was dispersed in DMF (dimethylformamide) 100 ml, and a DMF solution (100 ml) of NBS (N-bromosuccinimide) 7.44 g was dropwise added thereto at room temperature. The solution was stirred at room temperature for 7 hours and then left standing for a nigh. Water 200 ml was added thereto, and the deposited crystal was filtered, sufficiently washed with ethanol and dried, whereby targeted (9-bromo-10-(4-naphthalene-2-yl-phenyl)anthracene 15.84 g was obtained (yield: 99%).