Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[N-]1C=CN=C1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH2:28]([C:32]1[C:36]([CH2:37][C:38]2[CH:43]=[CH:42][C:41]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=3[S:50](=[O:53])(=[O:52])[NH2:51])=[CH:40][C:39]=2[F:54])=[C:35]([C:55]#[N:56])[N:34]([C:57]2[CH:62]=[C:61]([C:63](=[O:69])[NH:64][CH2:65][CH2:66][CH2:67][CH3:68])[CH:60]=[CH:59][C:58]=2[C:70]([F:73])([F:72])[F:71])[N:33]=1)[CH2:29][CH2:30][CH3:31].C1CCN2C(=NCCC2)CC1>>[CH2:28]([C:32]1[C:36]([CH2:37][C:38]2[CH:43]=[CH:42][C:41]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=3[S:50](=[O:52])(=[O:53])[NH:51][C:4](=[O:6])[C:3]3[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=3[Cl:1])=[CH:40][C:39]=2[F:54])=[C:35]([C:55]#[N:56])[N:34]([C:57]2[CH:62]=[C:61]([C:63](=[O:69])[NH:64][CH2:65][CH2:66][CH2:67][CH3:68])[CH:60]=[CH:59][C:58]=2[C:70]([F:72])([F:71])[F:73])[N:33]=1)[CH2:29][CH2:30][CH3:31]
Reactant: CCCCNC(=O)c1ccc(C(F)(F)F)c(-n2nc(CCCC)c(Cc3ccc(-c4ccccc4S(N)(=O)=O)cc3F)c2C#N)c1
Reactant: O=C(O)c1ccccc1Cl
Agent: O=C(n1ccnc1)n1ccnc1
Agent: c1c[n-]cn1
Solvent: C1CCC2=NCCCN2CC1
Product: CCCCNC(=O)c1ccc(C(F)(F)F)c(-n2nc(CCCC)c(Cc3ccc(-c4ccccc4S(=O)(=O)NC(=O)c4ccccc4Cl)cc3F)c2C#N)c1

Procedure:
Following the procedure of Example 1, Step H, 2-chlorobenzoic acid is converted to its imidazolide with CDI and subsequently reacted with 3-n-butyl-1-[5-(N-n-butylcarbamoyl)-2-(trifluoromethyl)phenyl]-4-[(3-fluoro-2'-sulfamoylbiphenyl-4-yl)methyl]-1H-pyrazole-5-carbonitrile (from Step L) in the presence of DBU to yield the title compound.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:36])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](OS(C(F)(F)F)(=O)=O)=[C:7]([O:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][C:21]=2[CH2:29][S:30][CH2:31][C:32]([F:35])([F:34])[F:33])[CH:6]=1.[CH3:37][Si:38]([C:41]#[CH:42])([CH3:40])[CH3:39]>C(N(CC)CC)C.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)I>[CH3:1][O:2][C:3](=[O:36])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:42]#[C:41][Si:38]([CH3:40])([CH3:39])[CH3:37])=[C:7]([O:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][C:21]=2[CH2:29][S:30][CH2:31][C:32]([F:35])([F:34])[F:33])[CH:6]=1
Reactant: COC(=O)Cc1ccc(OS(=O)(=O)C(F)(F)F)c(Oc2ccc([N+](=O)[O-])cc2CSCC(F)(F)F)c1
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: I[Cu]I
Solvent: CCN(CC)CC
Product: COC(=O)Cc1ccc(C#C[Si](C)(C)C)c(Oc2ccc([N+](=O)[O-])cc2CSCC(F)(F)F)c1

Procedure:
{3-[4-Nitro-2-(2,2,2-trifluoro-ethylsulfanylmethyl)-phenoxy]-4-trifluoromethanesulfonyloxy-phenyl}-acetic acid methyl ester (0.920 g, 1.63 mmol), (trimethylsilyl)acetylene (0.34 mL, 2.45 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.1155, 0.16 mmol), and copper iodide (0.031 g, 0.16 mmol) were combined in triethylamine (8 mL) and degassed for 5 minutes. The reaction was heated for 8 hours, and then worked-up with CH2Cl2 and H2O. The crude material was purified by silica gel chromatography to give {3-[4-nitro-2-(2,2,2-trifluoro-ethylsulfanylmethyl)-phenoxy]-4-trimethylsilanylethynyl-phenyl}-acetic acid methyl ester.
Reaction SMILES: [C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[OH:12][C:13]1[C:18]2[CH:19]=[CH:20][CH:21]=[C:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:17]=2[O:16][S:15](=O)(=O)[CH:14]=1.Cl>CN(C=O)C>[OH:12][C:13]1[C:18]2[CH:19]=[CH:20][CH:21]=[C:22]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:17]=2[O:16][S:15][C:14]=1[C:8]([NH:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:9]
Reactant: O=S1(=O)C=C(O)c2cccc(-c3ccccc3)c2O1
Reactant: O=C=Nc1ccccc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(Nc1ccccc1)C1=C(O)c2cccc(-c3ccccc3)c2OS1
Yield: 101.3 %

Procedure:
Phenylisocyanate (20.5 mmol) was added to a cooled DMF solution (25 ml) containing 20.5 mmol of NaH and 5.0 g (18.3 mmol) of 4-hydroxy-8-phenyl-1,2-benzoxathiin-2,2-dioxide. The resultant mixture was heated at 75° for 2.5 hours. The mixture was cooled, poured into ice-H2O (100 ml) and acidified with HCl. The resultant precipitate was collected by filtration and gave 6.70 g (93.3%) of the expected product, mp. 175°. The crude product was purified by recrystallization from 2-PrOH/hexane to give the analytical sample, mp. 181°-183°.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:5]2.[F:16][C:17]([F:27])([F:26])[C:18]1[C:23]([CH:24]=O)=[CH:22][N:21]=[CH:20][CH:19]=1.[OH2:28]>CO.[Cl-].[Cl-].[Zn+2]>[OH:28][C:18]([C:17]([F:27])([F:26])[F:16])=[O:11].[CH2:12]([N:6]1[CH2:5][C:4]2[C:8](=[CH:9][CH:10]=[C:2]([NH:1][CH2:24][C:23]3[CH:22]=[N:21][CH:20]=[CH:19][C:18]=3[C:17]([F:27])([F:16])[F:26])[CH:3]=2)[C:7]1=[O:11])[CH2:13][CH2:14][CH3:15]
Reactant: O=Cc1cnccc1C(F)(F)F
Reactant: CCCCN1Cc2cc(N)ccc2C1=O
Reactant: O
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CO
Product: CCCCN1Cc2cc(NCc3cnccc3C(F)(F)F)ccc2C1=O
Product: O=C(O)C(F)(F)F
Yield: 19 %

Procedure:
5-amino-2-butylisoindolin-1-one (35.0 mg, 0.17 mmol), ZnCl2 (14.0 mg, 0.10 mmol) and NaCNBH4 (12.9 mg, 0.21 mmol) were consecutively added to a solution of 4-(trifluoromethyl)nicotinaldehyde (30.0 mg, 0.17 mmol) in MeOH (4 mL). After stirring overnight at room temperature excess water was added. The reaction mixture was extracted with EtOAc, the combined org. layers were washed with water, dried (MgSO4) and the solvent was removed in vacuo. Purification by HPLC provided 2-butyl-5-((4-(trifluoromethyl)pyridin-3-yl)methylamino)isoindolin-1-one TFA (16.0 mg, 19%). ESI-MS [M+H]+=364.2.
Reaction SMILES: [C:1](Cl)(=[O:5])[C:2]([CH3:4])=[CH2:3].[Al+3].[Cl-].[Cl-].[Cl-].[CH2:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13][CH2:12]1.Cl>C(Cl)Cl>[CH3:3][CH:2]1[CH2:4][C:17]2[C:16](=[CH:15][C:14]3[CH2:13][CH2:12][CH2:11][C:19]=3[CH:18]=2)[C:1]1=[O:5]
Reactant: C=C(C)C(=O)Cl
Reactant: c1ccc2c(c1)CCC2
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC1Cc2cc3c(cc2C1=O)CCC3
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
Methacryloyl chloride (50 ml, 0.5 mol) was added to suspension of 133.5 r AlCl3 (1 mol) in 500 ml CH2Cl2 at −78° C., stirred 20 min. Then indane (59 g, 0.5 mol) was added at the same temperature, allowed to warm to room temperature and then was stirred overnight. Next day the mixture obtained was poured carefully into mixture of ice (1000 g) and HCl (200 ml). The organic phase was separated, washed by water, 5% NaHCO3, and dried over MgSO4. Solvent was evaporated and residue was distilled in vacuum given 77.6 of product (83%), b.p. 118-120° C./0.5 torr.
Reaction SMILES: [CH2:1]([C:3]1[C:23]([N+:24]([O-])=O)=[C:6]2[C:7]([O:21][CH3:22])=[CH:8][CH:9]=[C:10]([C:11]3[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=3[O:19][CH3:20])[N:5]2[N:4]=1)[CH3:2].C(O)(=O)C>C(O)C.O.[Zn]>[CH2:1]([C:3]1[C:23]([NH2:24])=[C:6]2[C:7]([O:21][CH3:22])=[CH:8][CH:9]=[C:10]([C:11]3[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=3[O:19][CH3:20])[N:5]2[N:4]=1)[CH3:2]
Reactant: CCc1nn2c(-c3c(C)cc(C)cc3OC)ccc(OC)c2c1[N+](=O)[O-]
Agent: [Zn]
Solvent: O
Solvent: CCO
Solvent: CC(=O)O
Product: CCc1nn2c(-c3c(C)cc(C)cc3OC)ccc(OC)c2c1N
Temperature: 60 °C

Procedure:
2-Ethyl-4-methoxy-7-(2-methoxy-4,6-dimethylphenyl)-3-nitropyrazolo[1,5-a]pyridine (185 mg) was dissolved in a mixture of ethanol (7 mL) and water (7.5 mL), and then acetic acid (0.3 mL) and zinc powder (185 mg) were added and the reaction mixture was heated at 60° C. for 20 minutes. The reaction mixture was filtered with celite, and the obtained filtrate was concentrated under reduced pressure. Water was added, extraction was performed with ethyl acetate, the extract washed with saturated aqueous sodium hydrogencarbonate and brine and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 2-ethyl-4-methoxy-7-(2-methoxy-4,6-dimethylphenyl)pyrazolo[1,5-a]pyridin-3-amine as a crude product.
Reaction SMILES: [Si]([O:8][C@H:9]1[CH2:18][C@H:17]([O:19][C:20](=[O:34])[C:21]([O:24][C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)([CH3:23])[CH3:22])[C@H:16]2[C:11]([CH:12]=[CH:13][C@H:14]([CH3:52])[C@@H:15]2[CH2:35][CH2:36][C@H:37]2[O:42][C:41](=[O:43])[CH2:40][C@H:39]([O:44][Si](C(C)(C)C)(C)C)[CH2:38]2)=[CH:10]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[OH:8][C@H:9]1[CH2:18][C@H:17]([O:19][C:20](=[O:34])[C:21]([O:24][C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)([CH3:22])[CH3:23])[C@H:16]2[C:11]([CH:12]=[CH:13][C@H:14]([CH3:52])[C@@H:15]2[CH2:35][CH2:36][C@H:37]2[O:42][C:41](=[O:43])[CH2:40][C@H:39]([OH:44])[CH2:38]2)=[CH:10]1
Reactant: C[C@H]1C=CC2=C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](OC(=O)C(C)(C)Oc3ccc([N+](=O)[O-])cc3)[C@@H]2[C@H]1CC[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: C[C@H]1C=CC2=C[C@@H](O)C[C@H](OC(=O)C(C)(C)Oc3ccc([N+](=O)[O-])cc3)[C@@H]2[C@H]1CC[C@@H]1C[C@@H](O)CC(=O)O1
Yield: 97.9 %

Procedure:
A procedure similar to that described in Example 2, above, was followed, but using 801 mg of (4R,6R)-6-([1S,2S,6S,8S,8aR]-2-{1,2,6,7,8,8a-hexahydro-6-t-butyldimethylsilyloxy-8-[2-(4-nitrophenoxy)-2-methylpropionyloxy]-2-methyl-1-naphthyl}ethyl)tetrahydro-4-t-butyldimethylsilyloxy-2H-pyran-2-one [prepared as described in Example 184, above] and 14.8 ml of a 1.0 molar solution of tetrabutylammonium fluoride in tetrahydrofuran, to give 548 mg of the title compound as a colorless foam.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][N:14]=[CH:13][N:12]=1)=[O:10].[C:17]([C:21]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1)([CH3:20])([CH3:19])[CH3:18]>>[C:17]([C:21]1[CH:26]=[CH:25][C:24]([S:27]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=2[C:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][N:12]=2)=[O:10])(=[O:29])=[O:28])=[CH:23][CH:22]=1)([CH3:20])([CH3:18])[CH3:19]
Reactant: Nc1ccc(Cl)cc1C(=O)c1ccncn1
Reactant: CC(C)(C)c1ccc(S(=O)(=O)Cl)cc1
Product: CC(C)(C)c1ccc(S(=O)(=O)Nc2ccc(Cl)cc2C(=O)c2ccncn2)cc1

Procedure:
The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using 116 mg of (2-Amino-5-chloro-phenyl)-pyrimidin-4-yl-methanone and 116 mg of 4-tert-butyl-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 1.23 (s, 9H), 7.40 (d, 2H, J=8.4 Hz), 7.51 (dd, 1H, J=8.8 Hz, 2 Hz), 7.71-7.80 (m, 6H), 9.03 (d, 1H, J=4.8 Hz), 9.33 (d, 1.2 Hz), 10.91 (b, 1H). MS: m/z 434.0 (M4+1).
Reaction SMILES: [Cl:1][C:2]([Cl:30])([Cl:29])[CH2:3][O:4][C:5](=[O:28])[C:6]([N:10]1[C@H:13]([S:14]SC2SC3C=CC=CC=3N=2)[C@@H:12]([O:25][CH3:26])[C:11]1=[O:27])=[C:7]([CH3:9])[CH3:8].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CC=CC=1.[C:56](OC(=O)C)(=[O:58])[CH3:57]>C(O)(=O)C>[Cl:30][C:2]([Cl:1])([Cl:29])[CH2:3][O:4][C:5](=[O:28])[C:6]([N:10]1[C@H:13]([S:14][C:56](=[O:58])[CH3:57])[C@@H:12]([O:25][CH3:26])[C:11]1=[O:27])=[C:7]([CH3:8])[CH3:9]
Reactant: CC(=O)OC(C)=O
Reactant: CO[C@H]1C(=O)N(C(C(=O)OCC(Cl)(Cl)Cl)=C(C)C)[C@@H]1SSc1nc2ccccc2s1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC(=O)O
Solvent: c1ccncc1
Product: CO[C@H]1C(=O)N(C(C(=O)OCC(Cl)(Cl)Cl)=C(C)C)[C@@H]1SC(C)=O
Reaction time: 1.25 h

Procedure:
A solution of 3.26 g of 2-[(3S,4R)-4-(benzthiazol-2-yldithio)-3-methoxy-2-oxoazetidin-1-yl]-3-methylcrotonic acid 2,2,2-trichloroethyl ester in 36.3 ml of acetic anhydride and 12.4 ml of acetic acid is cooled to -15° and 1.7 g of triphenylphosphine are added. After stirring under nitrogen at the same temperature for 75 minutes, 24.8 ml of pyridine are added to the mixture. After stirring for a further 3 hours at 0°, the reaction mixture is concentrated by evaporation under reduced pressure and the resulting residue is purified by chromatography over silica gel with toluene and toluene/ethyl acetate (19:1). IR spectrum (in methylene chloride): characteristic absorption bands at 3.40, 5.63, 5.77, 5.80, 6.13, 7.25, 7.35, 8.26, 9.0, 9.52 and 11.90μ.
Reaction SMILES: [C:1]([CH2:3][CH2:4][C:5]1[S:9][C:8]([C:10]2[NH:11][C:12]3[C:17]([CH:18]=2)=[CH:16][CH:15]=[CH:14][C:13]=3[N:19]([CH3:28])[S:20]([C:23]2[S:24][CH:25]=[CH:26][CH:27]=2)(=[O:22])=[O:21])=[N:7][CH:6]=1)#[N:2].C([Sn](=O)CCCC)CCC.C[Si]([N:43]=[N+:44]=[N-:45])(C)C>O1CCCC1>[CH3:28][N:19]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:12]=1[NH:11][C:10]([C:8]1[S:9][C:5]([CH2:4][CH2:3][C:1]3[N:43]=[N:44][NH:45][N:2]=3)=[CH:6][N:7]=1)=[CH:18]2)[S:20]([C:23]1[S:24][CH:25]=[CH:26][CH:27]=1)(=[O:22])=[O:21]
Reactant: CN(c1cccc2cc(-c3ncc(CCC#N)s3)[nH]c12)S(=O)(=O)c1cccs1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: CCCC[Sn](=O)CCCC
Solvent: C1CCOC1
Product: CN(c1cccc2cc(-c3ncc(CCc4nn[nH]n4)s3)[nH]c12)S(=O)(=O)c1cccs1
Yield: 67 %

Procedure:
A mixture of N-{2-[5-(2-cyanoethyl)-1,3-thiazol-2-yl]-1H-indol-7-yl}-N-methylthiophene-2-sulfonamide (0.30 g), dibutyltin oxide (35 mg), trimethylsilylazide (0.74 mL) and tetrahydrofuran (10 mL) was heated under reflux for 3 days. The reaction mixture was concentrated. The residue was subjected to silica gel column chromatography, and the title compound (0.22 g, yield 67%) was obtained as yellow crystals from a fraction eluted with tetrahydrofuran-methanol (9:1, volume ratio). The crystals were recrystallized from ethyl acetate. melting point 211-212° C.
Reaction SMILES: ClC1C=CC(C2C(C3C=CC(Cl)=CC=3)N(C(Cl)=O)C(C3C=CC(C(C)(C)COC)=CC=3OCC)=N2)=CC=1.[N:38]1([C:44](=[O:52])[CH2:45]N2CCNCC2)[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1>>[N:38]1([C:44](=[O:52])[CH3:45])[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1
Reactant: O=C(CN1CCNCC1)N1CCOCC1
Agent: CCOc1cc(C(C)(C)COC)ccc1C1=NC(c2ccc(Cl)cc2)C(c2ccc(Cl)cc2)N1C(=O)Cl
Product: CC(=O)N1CCOCC1
Yield: 337.1 %

Procedure:
4,5-Bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(2-methoxy-1,1-dimethyl-ethyl)-phenyl]-4,5-dihydro-imidazole-1-carbonyl chloride (60 mg, 0.107 mmol) was reacted with 1-morpholin-4-yl-2-piperazin-1-yl-ethanone (34.2 mg, 0.161 mmol, Oakwood Products) using the procedure described in example 25 to give 4,5-bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(2-methoxy-1,1-dimethyl-ethyl)-phenyl]-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-1-morpholin-4-yl-ethanone (70.1 mg) as white solids. The enantiomers were separated by chiral chromatography (Diacel ChiralPak OD, eluting with 40/60 hexane/ethanol). The first peak coming off the column is the desired 2-(4-{(4S,5R)-4,5-bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(2-methoxy-1,1-dimethyl-ethyl)-phenyl]-4,5-dihydro-imidazole-1-carbonyl}-piperazin-1-yl)-1-morpholin-4-yl-ethanone (31.6 mg, white solids). HR-MS (ES, m/z): observed 736.3029, calculated for C39H48Cl2N5O5 [(M+H)+] 736.3027.
Reaction SMILES: [C:1]1([CH:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:8]([N:10]=[C:11]=[O:12])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:19]1([CH2:22][OH:23])[CH2:21][CH2:20]1>>[CH:19]1([CH2:22][O:23][C:11](=[O:12])[NH:10][C:8](=[O:9])[CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:21][CH2:20]1
Reactant: O=C=NC(=O)C(c1ccccc1)c1ccccc1
Reactant: OCC1CC1
Product: O=C(NC(=O)C(c1ccccc1)c1ccccc1)OCC1CC1

Procedure:
The title compound, white solid, m.p.=108° C., MS: m/e=309.4 (M+H+) was prepared in accordance with the general method of example 1 from diphenylacetyl isocyanate and cyclopropyl-methanol.
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11]([CH2:13][OH:14])[C:10]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]3[N:26]=[C:27]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[O:28][C:29]=3[CH3:30])=[CH:19][CH:18]=2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[O-2].[O-2].[Mn+4].O1CCCC1>[CH2:1]([N:8]1[CH:12]=[C:11]([CH:13]=[O:14])[C:10]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]3[N:26]=[C:27]([C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=4)[O:28][C:29]=3[CH3:30])=[CH:19][CH:18]=2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(COc2nn(Cc3ccccc3)cc2CO)cc1
Agent: [Mn+4]
Agent: [O-2]
Solvent: C1CCOC1
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(COc2nn(Cc3ccccc3)cc2C=O)cc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 87.9 %

Procedure:
A mixture of [1-benzyl-3-({4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]benzyl}oxy)-1H-pyrazol-4-yl]methanol (0.40 g), activated manganese dioxide (1.0 g) and tetrahydrofuran (50 mL) was stirred at room temperature for 15 hrs. Manganese dioxide was removed by filtration and the filtrate was concentrated. The obtained crystals were collected by filtration to give 1-benzyl-3-[{4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]benzyl}oxy]-1H-pyrazole-4-carbaldehyde (0.35 g, yield 88%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 133-134° C.
Reaction SMILES: [CH:1]1([C:6]2[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(NCC(C)C)C(C)C.S(Cl)([Cl:25])(=O)=O>C1(C)C=CC=CC=1>[Cl:25][C:10]1[CH:11]=[C:6]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[CH:7]=[CH:8][C:9]=1[OH:12]
Reactant: Oc1ccc(C2CCCC2)cc1
Reactant: O=S(=O)(Cl)Cl
Agent: CC(C)CNCC(C)C
Solvent: Cc1ccccc1
Product: Oc1ccc(C2CCCC2)cc1Cl
Temperature: 25 °C

Procedure:
A solution of 4-cyclopentylphenol (4 g) and diisobutylamine (0.35 mL) in toluene (75 mL) was heated to 70° C. with stirring. Sulfuryl chloride (2.0 mL) was introduced via syringe and the reaction stirred for 2 h at 70° C., then cooled to room temperature. The reaction mixture was concentrated in vacuo and the resulting oil subjected to chromatography on silica gel using hexane/ethyl acetate eluent to afford the title compound (3.5 g). 1H NMR (400 MHz, CDCl3): δ 7.19 (d, 1H, J=2.0 Hz); 7.06 (dd, 1H, J=2.2 Hz, 6.2 Hz); 6.94 (d, 1H, J=8.6 Hz); 5.37 (s, 1H); 2.92 (quint, 1H, J=7.0 Hz); 2.03 (m, 2H); 1.80 (m, 2H); 1.67 (m, 2H); 1.53 (m, 2H). MS: m/e=197(M+).
Reaction SMILES: [Mg].Br[C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:13][CH3:14])[CH:9]=2)[CH:4]=1.[CH3:15][Si:16]([CH3:24])([CH3:23])[O:17][CH:18]([CH3:22])[C:19](Cl)=[O:20]>>[CH3:14][O:13][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[CH:4]=[C:3]([C:19](=[O:20])[CH:18]([O:17][Si:16]([CH3:24])([CH3:23])[CH3:15])[CH3:22])[CH:12]=[CH:11]2
Reactant: COc1ccc2cc(Br)ccc2c1
Reactant: CC(O[Si](C)(C)C)C(=O)Cl
Agent: [Mg]
Product: COc1ccc2cc(C(=O)C(C)O[Si](C)(C)C)ccc2c1

Procedure:
When Z is a group which is convertible to a suitable leaving group, the conversion of Z can take place either before step A or thereafter, but before step B. For example, when the magnesium Grignard of 2-bromo-6-methoxynaphthalene is contacted with (S) 2-trimethylsiloxypropionyl chloride, (S) 1-(6-methoxy-2-naphthyl)-2-trimethylsiloxypropan-1-one is obtained. Regeneration of the hydroxyl group by hydrolysis affords (S) 2-hydroxy-1-(6-methoxy-2-naphthyl)propan-1-one. Further reaction with methanesulfonyl chloride then affords (S) 1-(6-methoxy-2-naphthyl)-2-methanesulfonyloxy propan-1-one, which is processed according to step A. Alternatively, the ketone can first be ketalized according to step A and the regeneration of the hydroxyl group and the formation of the sulfonate ester can occur subsequently but prior to step B.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][NH2:11])[CH:5]=[CH:6][CH:7]=1.C[O:13][C:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21]Br.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:21][C:16]3[C:15](=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:14]2=[O:13])[CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1ccccc1CBr
Reactant: NCCCc1cccc(F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: O=C1c2ccccc2CN1CCCc1cccc(F)c1
Temperature: 100 °C
Reaction time: 16 h
Yield: 72.6 %

Procedure:
A mixture of 3-(3-fluorophenyl)-propylamine (306 mg, 2 mmol), 2-bromomethyl-benzoic acid methyl ester (458 mg, 2 mmol), and K2CO3 (200 mg, 1.45 mmol) in toluene (10 mL) was heated with stirring at 100° C. for 16 h. Workup and silica gel column chromatography using a gradient of hexanes to 50% ethyl acetate in hexanes afforded 2-[3-(3-fluorophenyl)-propyl]-2,3-dihydroisoindol-1-one (391 mg, 73%). GC/MS gave: m/z (rel.int.) 269 (M+, 32), 147 (100), 146 (100), 119 (37), 109 (26) and 91 (45).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[CH:8]2)=[O:4].[Cl:14][C:15]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:16]=1[CH2:17]I>[Ag]=O.O1CCOCC1>[Cl:14][C:15]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:16]=1[CH2:17][C:8]1[C:7]2[C:11](=[CH:12][CH:13]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:6]=2)[NH:10][CH:9]=1
Reactant: COC(=O)c1ccc2[nH]ccc2c1
Reactant: Clc1ccc(CI)c(Cl)c1
Agent: O=[Ag]
Solvent: C1COCCO1
Product: COC(=O)c1ccc2[nH]cc(Cc3ccc(Cl)cc3Cl)c2c1
Yield: 16.4 %

Procedure:
Silver oxide (28.09 g) is added to a dioxane (200 ml) solution of 5-methoxycarbonylindole (17.52 g) and 2,4-dichlorobenzyl iodide (34.49 g), and stirred under reflux for 6.5 hours. The insoluble is removed through filtration, and the filtrate is concentrated under reduced pressure. The resulting oily residue is purified through silica gel column chromatography (eluent: hexane/ethyl acetate=4/1), and recrystallized from hexane/ethyl acetate to obtain 3-(2,4-dichlorobenzyl)-5-methoxycarbonylindole (46) (5.49 g).
Reaction SMILES: C(OC(=O)[NH:7][CH:8]([C:10]1[CH:15]=[CH:14][C:13]([NH:16][S:17]([CH:20]=[CH2:21])(=[O:19])=[O:18])=[C:12]([CH:22]=[CH2:23])[CH:11]=1)[CH3:9])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:20]([S:17]([NH:16][C:13]1[CH:14]=[CH:15][C:10]([CH:8]([NH2:7])[CH3:9])=[CH:11][C:12]=1[CH:22]=[CH2:23])(=[O:18])=[O:19])=[CH2:21]
Reactant: C=Cc1cc(C(C)NC(=O)OC(C)(C)C)ccc1NS(=O)(=O)C=C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: C=Cc1cc(C(C)N)ccc1NS(=O)(=O)C=C
Reaction time: 12 h
Yield: 154.6 %

Procedure:
[1-(4-Ethenesulfonylamino-3-vinyl-phenyl)-ethyl]-carbamic acid tert-butyl ester (20.0 mg, 0.04 mmol) and CF3COOH (5 eq, 0.22 mmol, 17.04 μl) were dissolved in methylene chloride. The reaction mixture was stirred for 12 hrs. A reaction mixture was concentrate to yield [1-(4-Ethenesulfonylamino-3-vinyl-phenyl)-ethylamine (15.6 mg, 76%).
Reaction SMILES: [C:1]1([CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:17]([NH2:20])[CH2:18][CH3:19]>>[C:1]1([CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8]([NH:20][CH2:17][CH2:18][CH3:19])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCCN
Reactant: O=C(Cl)C(c1ccccc1)c1ccccc1
Product: CCCNC(=O)C(c1ccccc1)c1ccccc1

Procedure:
The title compound, light yellow solid, m.p. 90° C. and MS: m/e=254 (M+) was prepared in accordance with the general method of example 1 from diphenylacetyl chloride and propylamine.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].[C:9]1([P:15]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(O)CO>[Ni](Cl)Cl.O>[Br-:1].[C:22]1([P+:15]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[OH:8])[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: Oc1ccccc1Br
Agent: Cl[Ni]Cl
Solvent: OCCO
Solvent: O
Product: Oc1ccccc1[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: [Br-]
Temperature: 160 °C

Procedure:
10.4 g (0.060 mol) of 2-bromophenol, 17.3 g (0.066 mol) of triphenyl phosphine, 0.65 g (5 mmol) of nickel chloride, and 40 ml of ethylene glycol were put into a separable flask (volume, 200 ml) equipped with a condenser and a stirrer, and reacted with stirring under heat at 160° C. The reaction liquid was cooled, 40 ml of pure water was dropwise added thereto, and the deposited crystal was washed with toluene, taken out through filtration, and dried to obtain triphenyl(2-hydroxyphenyl)phosphonium bromide.