Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17](O)=[O:18])[CH:15]=3)[N:10]([C:20]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:9]=2)[CH:5]=[CH:4][N:3]=1.Cl.[F:40][C:41]1[CH:54]=[CH:53][CH:52]=[CH:51][C:42]=1[O:43][CH:44]1[CH2:49][CH2:48][CH2:47][CH:46]([NH2:50])[CH2:45]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[F:40][C:41]1[CH:54]=[CH:53][CH:52]=[CH:51][C:42]=1[O:43][CH:44]1[CH2:49][CH2:48][CH2:47][CH:46]([NH:50][C:17]([C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][CH:13]=2)[N:10]([C:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:9]=[C:8]3[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=2)=[O:18])[CH2:45]1
Reactant: NC1CCCC(Oc2ccccc2F)C1
Reactant: Cc1cc(-c2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c3ccc(C(=O)O)cc23)ccn1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(=O)N(C)C
Product: Cc1cc(-c2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c3ccc(C(=O)NC4CCCC(Oc5ccccc5F)C4)cc23)ccn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A reaction mixture of 3-(2-methylpyridin-4-yl)-1-trityl-1H-indazole-5-carboxylic acid (0.15 mmol, 74.3 mg), HCl salt of 3-(2-fluorophenoxy)cyclohexanamine (0.15 mmol, 37 mg), HATU (0.15 mmol, 57 mg) and DIEA in DMA was stirred at room temperature for overnight. The product, N-(3-(2-fluorophenoxy)cyclohexyl)-3-(2-methylpyridin-4-yl)-1-trityl-1H-indazole-5-carboxamide, was obtained after evaporation of solvent.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[C:5]([NH:7][CH:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:6].C([O-])(=O)C.[K+].Br[C:26]1[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=1>CN(C=O)C.C(OCC)(=O)C>[CH2:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:16][CH:8]1[NH:7][C:5](=[O:6])[C:4]1[CH:17]=[CH:18][CH:19]=[C:2]([C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[CH:3]=1
Reactant: Brc1cccnc1
Reactant: O=C(NC1Cc2ccccc2C1)c1cccc(Br)c1
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C(NC1Cc2ccccc2C1)c1cccc(-c2cccnc2)c1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
100 mg of 3-bromo-N-indan-2-yl-benzamide, 88 mg bis-(pinacolato)-dibor, 93 mg potassium acetate and 48 mg PdCl(dppf) were dissolved in 6 ml DMF and stirred at 80° C. for 2 h. The solution was cooled to ambient temperature and 100 mg of 3-bromo-pyridine added. Then, further 24 mg of PdCl(dppf) were added and the mixture stirred at 80° C. for 3.5 h. The mixture was cooled to ambient temperature and diluted with 20 ml ethyl acetate. The crude mixture was washed three times with 5 ml of a saturated aqueous solution of Na2CO3 each and dried over MgSO4. The solvents were removed under reduced pressure and the residue purified by chromatography on silica gel using MTB. Yield 60 mg of a viscous oil. Rf (MTB)=0.2.
Reaction SMILES: [Cl:1][C:2]1[C:7]([OH:8])=[C:6]([N+:9]([O-])=O)[C:5]([C:12]2[C:17]([Cl:18])=[CH:16][C:15]([C:19]([F:22])([F:21])[F:20])=[CH:14][N:13]=2)=[C:4]([F:23])[CH:3]=1>C(O)(=O)C.CO.[Fe]>[NH2:9][C:6]1[C:7]([OH:8])=[C:2]([Cl:1])[CH:3]=[C:4]([F:23])[C:5]=1[C:12]1[C:17]([Cl:18])=[CH:16][C:15]([C:19]([F:22])([F:21])[F:20])=[CH:14][N:13]=1
Reactant: O=[N+]([O-])c1c(O)c(Cl)cc(F)c1-c1ncc(C(F)(F)F)cc1Cl
Agent: [Fe]
Solvent: CC(=O)O
Solvent: CO
Product: Nc1c(O)c(Cl)cc(F)c1-c1ncc(C(F)(F)F)cc1Cl
Yield: 96 %

Procedure:
770 mg (13.7 mmol) of iron powder were added to 1.7 g (4.6 mmol) of 2-(4-chloro-2-fluoro-5-hydroxy-6-nitrophenyl)-3-chloro-5-trifluoromethylpyridine in 9 ml of glacial acetic acid and 18 ml of methanol. The reaction mixture was refluxed for 15 hours with stirring and then concentrated under reduced pressure. The residue was taken up in 100 ml of ethyl acetate. Undissolved components were then filtered off. The filtrate was washed with 20 ml of water, dried over magnesium sulfate and finally concentrated. Yield: 96%; oil.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:9][C:10]2[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=2[C:12](=O)[N:13]=1.[NH:19]([C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1)[NH2:20]>C(O)(=O)C(C)O>[CH:16]1[CH:17]=[CH:18][C:10]([OH:9])=[C:11]([C:12]2[N:13]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[OH:1])[N:19]([C:21]3[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=3)[N:20]=2)[CH:15]=1
Reactant: NNc1ccc(C(=O)O)cc1
Reactant: O=c1nc(-c2ccccc2O)oc2ccccc12
Agent: CC(O)C(=O)O
Product: O=C(O)c1ccc(-n2nc(-c3ccccc3O)nc2-c2ccccc2O)cc1
Temperature: 115 °C
Yield: 48.6 %

Procedure:
A suspension of 0.7 g (2.92 mmol) of 2-(2-hydroxyphenyl)benz[e][1,3]oxazin-4-one and 0.52 g (3.44 mmol) of 4-hydrazinobenzoic acid in 5 ml of lactic acid is heated to its boiling point and maintained at this temperature (115° C.) for 2 hours. After completion of the reaction the mixture is cooled down, causing separation of the crystalline product. 5 ml of ethyl acetate are added. After drying, 0.53 g of raw deferasirox is obtained, i.e. 49% of the theory, with an HPLC content of 94% and a melting temperature of 248 to 260° C.
Reaction SMILES: [C:1]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[CH:8][C:7]([CH2:17][CH2:18][CH:19]=O)=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[C:21]1([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[C:1]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[CH:8][C:7]([CH2:17][CH2:18][CH2:19][N:30]2[CH2:31][CH2:32][N:27]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:28][CH2:29]2)=[N:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: c1ccc(N2CCNCC2)cc1
Reactant: CC(C)(C)n1nc(CCC=O)cc1-c1ccc(Cl)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)n1nc(CCCN2CCN(c3ccccc3)CC2)cc1-c1ccc(Cl)cc1

Procedure:
116 mg (89%) of target compound was obtained by using a method same as in Example 1 by using 3-(1-tert-butyl-5-(4-chlorophenyl)-1H-pyrazol-3-yl)propanal (80 mg, 0.275 mmol), 1-phenylpiperazine (0.041 mL, 0.275 mmol), DIPEA (0.072 mL, 0.413 mmol) and NaBH(OAc)3 (175 mg, 0.825 mmol).
Reaction SMILES: CS[C:3]1[S:4]/[C:5](=[CH:9]\[C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][CH:14]=[CH:13]3)/[C:6](=[O:8])[N:7]=1.Cl.[C:21]1([C@@H:27]2[CH2:29][C@H:28]2[NH2:30])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CCN(C(C)C)C(C)C>>[C:21]1([C@@H:27]2[CH2:29][C@H:28]2[NH:30][C:3]2[S:4]/[C:5](=[CH:9]\[C:10]3[CH:11]=[C:12]4[C:17](=[CH:18][CH:19]=3)[N:16]=[CH:15][CH:14]=[CH:13]4)/[C:6](=[O:8])[N:7]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CSC1=NC(=O)/C(=C/c2ccc3ncccc3c2)S1
Reactant: N[C@@H]1C[C@H]1c1ccccc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Product: O=C1N=C(N[C@@H]2C[C@H]2c2ccccc2)S/C1=C\c1ccc2ncccc2c1

Procedure:
Similar procedure as described in example 1b was used, starting from 2-methylsulfanyl-5-[1-quinolin-6-yl-meth-(Z)-ylidene]-thiazol-4-one, trans-2-phenyl-cyclopropylamine hydrochloride and DIEA to give 2-((1R,2S)-2-phenyl-cyclopropylamino)-5-[1-quinolin-6-yl-meth-(Z)-ylidene]-thiazol-4-one. LC-MS m/e 372 (MH+).
Reaction SMILES: C(O)CCC.[N+:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N:15]=[N:16][C:17]1[CH:22]=[C:21]([C:23](CC)(C)C)[CH:20]=[C:19](C(CC)(C)C)[C:18]=1[OH:33])([O-])=[O:7].[N+](C1C=CC(C)=CC=1N=NC1C=CC=CC=1O)([O-])=O>C(O)CC>[OH:33][C:18]1[CH:19]=[CH:20][C:21]([CH3:23])=[CH:22][C:17]=1[N:16]1[N+:6]([O-:7])=[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]2=[N:15]1
Reactant: CCC(C)(C)c1cc(N=Nc2ccccc2[N+](=O)[O-])c(O)c(C(C)(C)CC)c1
Agent: Cc1ccc([N+](=O)[O-])c(N=Nc2ccccc2O)c1
Solvent: CCCCO
Solvent: CCCO
Product: Cc1ccc(O)c(-n2nc3ccccc3[n+]2[O-])c1
Yield: 87.9 %

Procedure:
The same procedure as in Example 1 was repeated, except that n-butanol 80 g was replaced by n-propanol 80 g, and that 2-nitro-2'-hydroxy-3',5'-di-t-amylazobenzene 25.5 g was replaced by 2-nitro-2'-hydroxy-5-methylazobenzene 17.1 g, thus producing 14.1 g of 2-(2-hydroxy-5-methylphenyl)benzotriazole-N-oxide having a melting point of 138° to 140° C. at the yield of 88%.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]2[OH:14])=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]2=[O:14])=[CH:6][CH:7]=1
Reactant: OC1CCCCC1c1ccc(F)cc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: O=C1CCCCC1c1ccc(F)cc1
Yield: 88.4 %

Procedure:
bi) To a solution of rac-2-(4-fluoro-phenyl)-cyclohexanol (3.8 g, 20 mmol) in DCM (320 mL) was added Dess-Martin periodinane [1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one](10 g, 24 mmol) at room temperature and after 2 h the reaction mixture was washed with sodium hydrogen carbonate (10%, 150 mL). The organic phase was then separated and washed with sodium thiosulfite (10%, 150 mL) and then dried over sodium sulfate, filtered and evaporated. Purification by chromatography through silica gel, eluting with ethyl acetate:hexane (1:4) afforded the title compound (3.4 g, 89%) as white crystals. MS: m/e=192.1 (M).
Reaction SMILES: [C:1]1([N:7]2[CH:11]=[N:10][C:9]([C:12]([OH:14])=O)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][NH:25][C:24]([CH3:29])([CH3:28])[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([C:12]([C:9]2[N:10]=[CH:11][N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:8]=2)=[O:14])[C:24]([CH3:29])([CH3:28])[CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]
Reactant: O=C(O)c1ncn(-c2ccccc2)n1
Reactant: CC1(C)CN(C(=O)OC(C)(C)C)CCN1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCN(C(=O)c2ncn(-c3ccccc3)n2)C(C)(C)C1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 420 mg (2.22 mmol) 1-phenyl-1H-[1,2,4]-triazole-3-carboxylic acid, 500 mg (2.22 mmol) 3,3-dimethyl-piperazine-1-carboxylic acid tert-butyl ester, 750 mg (2.22 mmol) TBTU and 500 μL (2.91 mmol) DIPEA in 5 mL DMF was stirred at RT for 2 h.
Reaction SMILES: Br[C:2]1[CH:14]=[N:13][C:5]2[NH:6][CH2:7][C:8]([CH3:12])([CH3:11])[CH2:9][O:10][C:4]=2[CH:3]=1.[CH3:15][N:16]([CH2:21][C:22]1[O:23][C:24]2[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=2[C:26]=1[CH3:27])[C:17](=[O:20])[CH:18]=[CH2:19].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:11][C:8]1([CH3:12])[CH2:7][NH:6][C:5]2[N:13]=[CH:14][C:2](/[CH:19]=[CH:18]/[C:17]([N:16]([CH3:15])[CH2:21][C:22]3[O:23][C:24]4[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=4[C:26]=3[CH3:27])=[O:20])=[CH:3][C:4]=2[O:10][CH2:9]1
Reactant: C=CC(=O)N(C)Cc1oc2ccccc2c1C
Reactant: CC1(C)CNc2ncc(Br)cc2OC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O
Product: Cc1c(CN(C)C(=O)/C=C/c2cnc3c(c2)OCC(C)(C)CN3)oc2ccccc12
Reaction time: 0.25 h
Yield: 15.2 %

Procedure:
To a solution of 3-bromo-7,7-dimethyl-6,7,8,9-tetrahydro-5-oxa-1,9-diaza-benzocycloheptene (250 mg, 0.972 mmol) in propionitrile (24 mL) and DMF (6 mL) were added N-methyl-N-(3-methyl-benzofuran-2-ylmethyl)acrylamide (290 mg, 1.26 mmol), (i-Pr)2EtN (0.34 mL, 1.94 mmol), Pd(OAc)2 (22 mg, 0.097 mmol) and P(o-tol)3 (59 mg, 0.19 mmol), and the mixture was de-oxygenated with argon for 15 min. The mixture was heated to reflux overnight, allowed to cool and then diluted with water (60 mL). The mixture was extracted with CH2Cl2 (3×50 mL). The combined extracts were washed with water and brine, dried (Na2SO4) and the solvent was removed in vacuo. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 97:4) and then by slow precipitation from CH2Cl2/hexanes gave the title compound (60 mg, 15%) as a pale yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) 7.92 (s, 1H), 7.60-7.55 (m, 2H), 7.50-7.38 (m, 2H), 7.31-6.96 (m, 3H), 6.68-6.65 (m, 1H), 4.96-4.76 (m, 2H), 3.77 (s, 2H), 3.15-2.91 (m, 5H), 2.26 (s, 3H), 0.96 (s, 6H); MS (ESI) m/e 406 (M+H)+.
Reaction SMILES: [CH3:1][N:2]([CH3:15])[C:3]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.[CH3:16][N:17]([CH2:25][CH:26]=O)[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21].C(B)#N.[Na]>CO.C(O)(=O)C.CO.C(Cl)(Cl)Cl>[CH3:1][N:2]([CH3:15])[C:3]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:5][N:6]([CH2:26][CH2:25][N:17]([CH3:16])[C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH2:7][CH2:8]1
Reactant: CN(CC=O)C(=O)OC(C)(C)C
Reactant: CN(C)C1(c2ccccc2)CCNCC1
Agent: BC#N
Agent: [Na]
Solvent: ClC(Cl)Cl
Solvent: CC(=O)O
Solvent: CO
Product: CN(CCN1CCC(c2ccccc2)(N(C)C)CC1)C(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 64.6 %

Procedure:
7 g (1 eq) N,N-dimethyl-4-phenylpiperidin-4-amine were added in portions to a solution of 6.5 g (1.5 eq) tert-butyl methyl(2-oxoethyl)carbamate in 60 ml methanol. This reaction mixture was cooled to 0° C., 3.97 g (2.5 eq) sodium cyanoboron hydride were added in portions and then the mixture was stirred for 10 min at room temperature. The reaction mixture obtained was adjusted to a pH of ˜5 with acetic acid and stirred for 12 h at room temperature. The reaction course was monitored by thin-layer chromatography (20% MeOH/CHCl3). As the conversion was still not complete, 1.5 g sodium cyanoboron hydride and acetic acid were added and the reaction mixture was stirred for a further 30 to 45 min. Once the conversion was complete, the methanol was distilled off, 100 ml saturated NaHCO3 solution were added and the mixture obtained was extracted with chloroform (2×200 ml) and the combined organic phases were dried over Na2SO4. Following removal of the solvent under reduced pressure, the residue was purified by column chromatography (silica gel; 5% MeOH/CHCl3). 8 g (64%) of product were obtained in the form of an oil.
Reaction SMILES: C(O)(=[O:3])C.[Cl:5][C:6]1[CH:24]=[CH:23][C:9]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]=[C:18]([N+]([O-])=O)[CH3:19])=[CH:13][CH:12]=2)=[CH:8][CH:7]=1.O.CO>[Fe].CCCCCC>[Cl:5][C:6]1[CH:24]=[CH:23][C:9]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][C:18](=[O:3])[CH3:19])=[CH:13][CH:12]=2)=[CH:8][CH:7]=1
Reactant: CC(=O)O
Reactant: CC(=Cc1ccc(Oc2ccc(Cl)cc2)cc1)[N+](=O)[O-]
Agent: [Fe]
Solvent: CCCCCC
Solvent: O
Solvent: CO
Product: CC(=O)Cc1ccc(Oc2ccc(Cl)cc2)cc1

Procedure:
A mixture of 4-(4-chlorophenoxy)benzaldehyde (256 g) and butylamine (239 ml) in toluene (1 liter) was heated to reflux and the water formed removed through a Dean & Stark head. After 2 hr the mixture was concentrated in vacuo and the residue dissolved in acetic acid (750 ml) and nitroethane (118.5 ml), heated at 100° for 2 hr, cooled and poured into iced water. The yellow solid was filtered, dried in air and recyrstallised from ethanol (750 ml) to afford 4-(4-chlorophenoxy)phenyl-2-nitropropene (254.7 g), m.p. 69°-71°. Acetic acid (115 ml) was added over 30 min to a well stirred, refluxing mixture of the 4-(4-chlorophenoxy)phenyl-2-nitropropene (28.9 g), iron powder (56 g), water (20 ml) and methanol (150 ml). After 3 hr it was cooled and partitioned between water (500 ml) and dichloromethane (200 ml). The organic phase was filtered, washed with water and satd. aq. sodium bicarbonate, dried over magnesium sulphate and concentrated in vacuo to leave a yellow oil. Trituration with hexane afforded the title compound as fine colourless crystals (14.6 g), m.p. 50°-52°.
Reaction SMILES: C1(C)C=CC(S([O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]=[O:24])=[CH:19][CH:18]=3)=[CH:13][CH:12]=2)(=O)=O)=CC=1.[CH2:26]([CH:32]([CH2:35]O)[CH2:33][OH:34])[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31].S(=O)(=O)(O)O>C1(C)C=CC=CC=1.ClCCl>[CH2:26]([CH:32]1[CH2:35][O:24][CH:23]([C:20]2[CH:19]=[CH:18][C:17]([C:14]3[CH:13]=[CH:12][C:11]([OH:10])=[CH:16][CH:15]=3)=[CH:22][CH:21]=2)[O:34][CH2:33]1)[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]
Reactant: CCCCCCC(CO)CO
Reactant: Cc1ccc(S(=O)(=O)Oc2ccc(-c3ccc(C=O)cc3)cc2)cc1
Agent: O=S(=O)(O)O
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: CCCCCCC1COC(c2ccc(-c3ccc(O)cc3)cc2)OC1
Reaction time: 1.8 h
Yield: 71.2 %

Procedure:
A solution of 2.82 g of 4'-(p-toluenesulphonyloxy)biphenyl-4-carboxaldehyde and 1.54 g of 2-hexyl-1,3-propane-diol in 50 ml of toluene was treated with 3 drops of 10% (vol.) sulphuric acid. The mixture was heated to boiling for 1.5 hours, with about 50 ml of damp toluene being distilled off and 30 ml of fresh toluene being simultaneously added dropwise. Then, 10 drops of triethylamine were added to the reaction mixture. After cooling the mixture was washed with 10 ml of lN sodium hydrogen carbonate solution and three times with 20 ml of water each time, dried over sodium sulphate and concentrated. The resulting crude 5-hexyl-2-[4'-(p-toluenesulphonyloxy)-4-biphenylyl]m-dioxane (4.26 g) was dissolved in 160 ml ethanol. The solution was treated with a solution of 2.64 g of potassium hydroxide in 27 ml of water and heated to boiling for 1.8 hours while stirring. After cooling the reaction mixture was neutralized (to pH 6) with 1.9 ml of glacial acetic acid and concentrated to about 20 ml. The suspension obtained was diluted with 80 ml of dichloromethane and the organic phase was washed twice with 20 ml of water each time, dried over sodium sulphate and concentrated. Chromatography of the residue (2.80 g) on g of silica gel with toluene/acetone (vol. 19:1) gave 1.94 g of 5-hexyl-2-(4'-hydroxy-4-biphenylyl)-m-dioxane.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.[CH2:9]([Sn](CCCC)(CCCC)C=C)[CH2:10]CC>C1(C)C(C)=CC=CC=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>[CH:9]([C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1)=[CH2:10]
Reactant: Nc1ccc(Br)cn1
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1C
Product: C=Cc1ccc(N)nc1
Yield: 45.3 %

Procedure:
4.13 g 5-bromopyridin-2-yl amine, 7.95 g tributyl(vinyl)tin and 1.38 g tetrakis(triphenylphosphine)palladium were heated in 70 mL xylene at 120° C. for 3 hours under nitrogen atmosphere. The solvent was removed, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate), to give 1.3 g of the title compound as pale yellow crystals.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].[CH2:16]([O:18][C:19](=[O:45])[CH:20]([NH:29][C:30]([C:32]1([NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:36][CH2:35][CH2:34][CH2:33]1)=[O:31])[CH2:21][C:22]1[CH:27]=[CH:26][C:25](O)=[CH:24][CH:23]=1)[CH3:17].N1C=CC=CC=1>C(Cl)Cl>[CH2:16]([O:18][C:19](=[O:45])[CH:20]([NH:29][C:30]([C:32]1([NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:36][CH2:35][CH2:34][CH2:33]1)=[O:31])[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:6][S:3]([C:2]([F:15])([F:14])[F:1])(=[O:5])=[O:4])=[CH:24][CH:23]=1)[CH3:17]
Reactant: CCOC(=O)C(Cc1ccc(O)cc1)NC(=O)C1(NC(=O)OC(C)(C)C)CCCC1
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCOC(=O)C(Cc1ccc(OS(=O)(=O)C(F)(F)F)cc1)NC(=O)C1(NC(=O)OC(C)(C)C)CCCC1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
1.2 mL of Trifluoromethanesulfonic anhydride (7.1 mmol) is added slowly dropwise to a solution of 2-[(1-tert-butoxycarbonylamino-cyclopentanecarbonyl)-amino]-3-(4-hydroxy-phenyl)-propionic acid ethyl ester (2.70 g, 6.4 mmol) and 0.7 mL (8.7 mmol) of pyridine in 20 mL of CH2Cl2 at 0° C., and the solution is stirred at 0° C. for 1 hour. The reaction mixture is then partitioned between water and CH2Cl2. The organic phase is separated and washed with saturated aqueous NaHCO3 solution, dried over MgSO4, filtered, and concentrated to yield 2-[(1-tert-butoxycarbonylamino-cyclopentanecarbonyl)-amino]-3-(4-trifluoromethanesulfonyloxy-phenyl)-propionic acid ethyl ester as a tan solid; 1H NMR (250 MHz, CDCl3) δ7.25 (d, 2 H), 7.17 (d, 2 H), 4.80 (q, 1 H), 4.75 (s, 1 H), 4.10 (two quarters, 2 H), 3.12 (ABX m, 2 H), 2.00-2.20 (m, 2 H), 1.60-2.00 (m, 6 H), 1.40 (s, 9 H), 1.18 (t, 3 H).
Reaction SMILES: [CH2:1]([OH:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[C:24](Cl)(=[O:28])[C:25]([Cl:27])=[O:26]>>[C:25]([Cl:27])(=[O:26])[C:24]([O:23][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[O:28]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CCCCCCCCCCCCCCCCCCCCCCO
Product: CCCCCCCCCCCCCCCCCCCCCCOC(=O)C(=O)Cl
Yield: 92.5 %

Procedure:
In this example the product was prepared in two synthetic steps. In the first step docosanol was reacted with 50% molar excess of oxalyl chloride. Upon completion of the reaction the excess oxalyl chloride was stripped from the product at reduced pressure to produce docosyl chlorooxalate having an assay of 91.4% and in a corrected yield of 92.5%. In the second step docosyl chlorooxalate was reacted with 2,5-dimethyl-2,5-dihydroperoxyhexane, in the presence of pyridine, to yield the product:
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([CH:14]([CH3:16])[CH3:15])[C:11]=1[O:12][CH3:13])[CH:7]=O)([CH3:3])[CH3:2].[C:17]1([C:23]2[CH:31]=[C:30]3[C:26]([CH2:27][C:28](=[O:32])[NH:29]3)=[CH:25][CH:24]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH:1]([C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([CH:14]([CH3:16])[CH3:15])[C:11]=1[O:12][CH3:13])[CH:7]=[C:27]1[C:26]2[C:30](=[CH:31][C:23]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:24][CH:25]=2)[NH:29][C:28]1=[O:32])([CH3:3])[CH3:2]
Reactant: COc1c(C(C)C)cc(C=O)cc1C(C)C
Reactant: O=C1Cc2ccc(-c3ccccc3)cc2N1
Product: COc1c(C(C)C)cc(C=C2C(=O)Nc3cc(-c4ccccc4)ccc32)cc1C(C)C

Procedure:
3,5-Diisopropyl-4-methoxybenzaldehyde was condensed with 6-phenyl-2-oxindole to give 0.4 g of 3-(3,5-diisopropyl-4-methoxybenzylidene)-6-phenyl-1,3-dihydroindol-2-one as a yellow-orange solid.
Reaction SMILES: C(OC([N:8]1[CH2:12][C@@H:11]([O:13][CH3:14])[CH2:10][C@H:9]1[CH2:15][O:16][C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][CH:18]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:14][O:13][C@@H:11]1[CH2:12][NH:8][C@H:9]([CH2:15][O:16][C:17]2[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][CH:18]=2)[CH2:10]1
Reactant: COC(=O)c1ccc(OC[C@@H]2C[C@H](OC)CN2C(=O)OC(C)(C)C)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1ccc(OC[C@@H]2C[C@H](OC)CN2)cc1
Reaction time: 14 h
Yield: 99.2 %

Procedure:
To a stirred solution of methyl 4-[(2S,4S)-1tert-butoxycarbonyl-4-methoxy-2-pyrrolidinyl]methoxybenzoate (2.38 g, 3.61 mmol) in CH2Cl2 (46 ml) was added TFA (23 ml) at room temperature. After 14 h stirring, the mixture was concentrated in vacuo. The residue was diluted by the addition of CH2Cl2 and 1 N NaOH, and extracted with CH2Cl2. The combined extracts were washed with brine, dried over Na2SO4, which was concentrated in vacuo. The residue was chromatographed on silica gel [50 g, CHCl3/MeOH (20/1)], to give methyl 4-[(2S,4S)-4-methoxy-2-pyrrolidinyl]methoxybenzoate (950 mg, 99%) as a yellow oil. 1H-NMR (CDCl3) δ2.16 (t, J=5.3 Hz, 1H), 2.72 (s, 1H), 2.95 (d, J=6.8 Hz, 1H), 3.11 (d, J=11.0 Hz, 1H), 3.26 (t, J=1.9 Hz, 3H), 3.52 (br, 1H), 3.84 (d, J=1.7 Hz, 3H), 3.92 (s, 1H), 4.00 (d, J=4.1 Hz, 2H), 6.88 (m, 2H), 7.94 (m, 2H).