Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1.C(O)C.O.NN.[ClH:31].O1CCOCC1>C(OCC)C.C(OCC)(=O)C>[ClH:31].[NH2:3][CH:12]1[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]1
Reactant: CC(C)(C)OC(=O)N1CCC(N2C(=O)c3ccccc3C2=O)CC1
Agent: Cl
Agent: NN
Solvent: C1COCCO1
Solvent: CCO
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(N)CC1
Yield: 100 %

Procedure:
The compound (837 mg, 2.53 mmol) obtained in step B was added to ethanol (20 ml), hydrazine monohydrate (0.31 ml, 6.4 mmol) was added, and the mixture was heated under reflux for 1 hr. The reaction mixture was cooled, and diethyl ether was added to allow precipitation of a solid. The precipitated solid was filtered, and the obtained solution was concentrated under reduced pressure to give a colorless oil. The oil was dissolved in diethyl ether, 4N hydrochloric acid-dioxane solution (1 ml) was added at room temperature and the mixture was diluted with ethyl acetate to allow precipitation of a solid. This was filtered, washed with ethyl acetate, and dried under reduced pressure to give the title compound (598 mg, yield 100%) as a colorless solid.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:10]2)=[CH:5][CH:4]=1.C(Br)C.[P:23]([O:30]CC)([O:27][CH2:28][CH3:29])[O:24][CH2:25][CH3:26]>>[CH2:25]([O:24][P:23]([CH2:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:10]2)=[CH:5][CH:4]=1)([O:27][CH2:28][CH3:29])=[O:30])[CH3:26]
Reactant: CCOP(OCC)OCC
Reactant: CCOC(=O)c1nn(-c2ccc(CBr)cc2)nc1C
Solvent: CCBr
Product: CCOC(=O)c1nn(-c2ccc(CP(=O)(OCC)OCC)cc2)nc1C
Reaction time: 3 h

Procedure:
155.6 g of 2-(p-bromomethyl-phenyl)-4-methyl-5-carboethoxy-2H-1,2,3-triazole in 430 ml of triethyl phosphite are heated to 150° C. in the course of 21/2 hours and the mixture is kept at this temperature for 3 hours, with stirring, ethyl bromide distilling off. The reaction mixture is evaporated under a waterpump vacuum. The residual dark viscous oil is dissolved in 300 ml of methylene chloride and, after the addition of bleaching earth, the solution is filtered to give a clear filtrate and 300 ml of hexane are added to the filtrate. The resulting mixture is then concentrated to 200 ml and cooled to 0° to 5° C. and the product which has crystallised out is filtered off with suction and dried in vacuo. This gives 56.6 g of 2-(p-diethylphosphonomethyl-phenyl)-4-methyl-5-carboethoxy-2H-1,2,3-triazole of the formula ##STR59##
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([N+:11]([O-])=O)[CH:8]=[CH:7][C:5]=2[N:6]=1>O1CCCC1.[Ni]>[NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([NH2:11])[CH:8]=[CH:7][C:5]=2[N:6]=1
Reactant: Nc1nc2ccc([N+](=O)[O-])cc2s1
Agent: [Ni]
Solvent: C1CCOC1
Product: Nc1ccc2nc(N)sc2c1
Yield: 50 %

Procedure:
To a solution of 2-amino-6-nitrobenzothiazole (10 g, 0.051 mol) in 100 mL of tetrahydrofuran was added 3.0 g Raney-nickel active catalyst. The reaction mixture was hydrogenated until hydrogen consumption ceased. The reaction mixture was filtered through a Celite pad and the solution was concentrated under reduced pressure to produce a brown solid. The solid was recrystallized from toluene, yielding 2,6-diaminobenzothiazole (50% yield, m.p. 202°-203° C.).
Reaction SMILES: C(SC[C@@H:17]([C:19]([OH:21])=[O:20])[NH2:18])/C=C/C1C=C(OC)C(O)=C(OC)C=1.[NH2:22][C@H:23]([C:49]([OH:51])=[O:50])[CH2:24][CH2:25][C:26]([NH:28][C@H:29]([C:46]([OH:48])=O)[CH2:30][S:31][CH2:32]/[CH:33]=[CH:34]/[C:35]1[CH:45]=[C:42]([O:43][CH3:44])[C:40]([OH:41])=[C:37]([O:38][CH3:39])[CH:36]=1)=[O:27]>>[CH2:32]([S:31][CH2:30][C@@H:29]([C:46]([NH:18][CH2:17][C:19]([OH:21])=[O:20])=[O:48])[NH:28][C:26](=[O:27])[CH2:25][CH2:24][C@@H:23]([C:49]([OH:51])=[O:50])[NH2:22])/[CH:33]=[CH:34]/[C:35]1[CH:36]=[C:37]([O:38][CH3:39])[C:40]([OH:41])=[C:42]([O:43][CH3:44])[CH:45]=1
Reactant: COc1cc(/C=C/CSC[C@H](N)C(=O)O)cc(OC)c1O
Reactant: COc1cc(/C=C/CSC[C@H](NC(=O)CC[C@H](N)C(=O)O)C(=O)O)cc(OC)c1O
Product: COc1cc(/C=C/CSC[C@H](NC(=O)CC[C@H](N)C(=O)O)C(=O)NCC(=O)O)cc(OC)c1O

Procedure:
The composition of claim 5, wherein the mixture of S-sinapyl-L-cysteine, N-L-γ-glutamyl-S-sinapyl-L-cysteine, and S-sinapyl glutathione is isolated from pineapple juice.
Reaction SMILES: [CH:1]1([NH:4][C:5]2[N:13]=[C:12]([NH:14]C(=O)C(C)C)[N:11]=[C:10]3[C:6]=2[N:7]=[CH:8][N:9]3[C@@H:20]2[CH2:24][C@H:23]([CH2:25][OH:26])[CH:22]=[CH:21]2)[CH2:3][CH2:2]1.[OH-].[Na+].COC(C)(C)C.[OH:35][S:36]([OH:39])(=[O:38])=[O:37]>C(O)(C)C>[CH2:2]1[CH:1]([NH:4][C:5]2[C:6]3[N:7]=[CH:8][N:9]([C@H:20]4[CH:21]=[CH:22][C@@H:23]([CH2:25][OH:26])[CH2:24]4)[C:10]=3[N:11]=[C:12]([NH2:14])[N:13]=2)[CH2:3]1.[CH2:2]1[CH:1]([NH:4][C:5]2[C:6]3[N:7]=[CH:8][N:9]([C@H:20]4[CH:21]=[CH:22][C@@H:23]([CH2:25][OH:26])[CH2:24]4)[C:10]=3[N:11]=[C:12]([NH2:14])[N:13]=2)[CH2:3]1.[OH:38][S:36]([OH:39])(=[O:37])=[O:35]
Reactant: CC(C)C(=O)Nc1nc(NC2CC2)c2ncn([C@H]3C=C[C@@H](CO)C3)c2n1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: COC(C)(C)C
Product: Nc1nc(NC2CC2)c2ncn([C@H]3C=C[C@@H](CO)C3)c2n1
Temperature: 22.5 °C
Yield: 96.9 %

Procedure:
N-{6-(cyclopropylamino)-9-[(1R,4S)-4-(hydroxymethyl)cyclopent-2-enyl]-9H-purin-2-yl}isobutyramide (6.56 g, 18.40 mmol) was slurried in a mixture of isopropanol (32.8 ml) and 10% solution of NaOH (36.1 ml, 92.0 mmol). The mixture was refluxed for 1 h. The resulting solution was cooled to 20-25° C. and tert-butyl methyl ether (32.8 ml) was added. The layers were separated and H2SO4 96% (0.61 ml, 11.03 mmol) was added dropwise to the organic layer. This mixture was cooled to 0-5° C. and the resulting slurry filtered off. The solid was dried under vacuum at 40° C. Abacavir hemisulfate (5.98 g, 97%) was obtained as a white powder.
Reaction SMILES: [CH2:1]([C:3]([N:12]=[C:13]=[O:14])([CH2:10][CH3:11])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2].[CH3:15][C:16]1[CH:25]=[CH:24][CH:23]=[CH:22][C:17]=1[CH:18]([NH:20][CH3:21])[CH3:19]>>[CH3:15][C:16]1[CH:25]=[CH:24][CH:23]=[CH:22][C:17]=1[CH:18]([N:20]([CH3:21])[C:13]([NH:12][C:3]([CH2:10][CH3:11])([CH2:1][CH3:2])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)=[O:14])[CH3:19]
Reactant: CNC(C)c1ccccc1C
Reactant: CCC(CC)(N=C=O)c1ccccc1
Product: CCC(CC)(NC(=O)N(C)C(C)c1ccccc1C)c1ccccc1
Reaction time: 3 h
Yield: 93.6 %

Procedure:
A mixture consisting of 9.5 g of α,α-diethylbenzylisocyanate and 7.5 g of N-(2-methyl-α-methylbenzyl)-N-methylamine was allowed to stand for 3 hours at room temperature. The white deposit formed was then filtered off. Washing with n-hexane and recrystallization from ethanol gave 15.9 g of the product, mp 93.0°-94.0° C.
Reaction SMILES: [C:1]1([O:11][CH2:12][C:13]([N:15]2[C@H:19]([C:20]([O:22]C)=[O:21])[CH2:18][S:17][CH:16]2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.O.[Li+].[OH-]>O1CCOCC1>[C:1]1([O:11][CH2:12][C:13]([N:15]2[C@H:19]([C:20]([OH:22])=[O:21])[CH2:18][S:17][CH:16]2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)[C@@H]1CSC(c2ccccc2)N1C(=O)COc1cccc2ccccc12
Agent: [Li+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: O=C(O)[C@@H]1CSC(c2ccccc2)N1C(=O)COc1cccc2ccccc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 100.2 %

Procedure:
To a solution of (2RS,4R)-3-((1-naphthyloxy)acetyl)-2-phenylthiazolidine-4-carboxylic acid, methyl ester (2.50 g, 6.14 mmol) in dioxane(15 mL)-water(5.0 mL) at room temperature was added 1.0 N LiOH solution (6.75 mL, 6.75 mmol). After stirring at room temperature for 16 hrs, The mixture was partitioned between EtOAc-5% KHSO4. The organic phase was washed with saturated NaCl solution, dried over anhydrous Na2SO4 and evaporated to give the title compound (2.42 g, 100%) as a viscous oil. TLC(MeOH—CH2Cl2; 1:9) Rf=0.38.
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+].Br[C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[NH:12][C:11]=1[C:19]([O:21][CH2:22][CH3:23])=[O:20].[N+:24]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)([O-:26])=[O:25]>C(O)C.C1(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>[N+:24]([C:27]1[CH:32]=[CH:31][C:30]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][C:11]=2[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:29][CH:28]=1)([O-:26])=[O:25]
Reactant: CCOC(=O)c1[nH]c2ccccc2c1Br
Reactant: O=[N+]([O-])c1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCOC(=O)c1[nH]c2ccccc2c1-c1ccc([N+](=O)[O-])cc1
Yield: 88.1 %

Procedure:
46 ml of a 1M sodium carbonate solution, 2.23 g of lithium chloride and then 1.1 g of tetrakis(triphenylphosphine)palladium are added successively, under argon and with stirring, to a solution of 5 g of ethyl 3-bromo-1H-indole-2-carboxylate and 7.8 g of 4-nitrophenylboronic acid in 110 ml of ethanol and 110 ml of toluene. The solution is refluxed for 2 hours 30 minutes and then concentrated under reduced pressure. The precipitate is filtered off and then recrystallized from ethanol, to give 5.1 g of ethyl 3-(4-nitrophenyl)-1H-indole-2-carboxylate, the characteristics of which are as follows:
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N+:9]([O-])=O.FC(F)(F)C1C=CC=CC=1N=C=O.[CH3:27][S:28]([CH3:30])=O>>[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]=[S:28]([CH3:30])[CH3:27]
Reactant: O=[N+]([O-])c1ccccc1C(F)(F)F
Reactant: CS(C)=O
Agent: O=C=Nc1ccccc1C(F)(F)F
Product: CS(C)=Nc1ccccc1C(F)(F)F

Procedure:
The process of claim 18 in which 2-trifluoromethylnitrobenzene is carbonylated to 2-trifluoromethylphenyl isocyanate, which is reacted with dimethylsulfoxide to obtain N-(2-trifluoromethylphenyl)-S,S-dimethylsulfilimine, rearranged to a 2-(methylthiomethyl)-6-trifluoromethylaniline, and desulfurized to 2-methyl-6-trifluoromethyl aniline.
Reaction SMILES: [C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].[Br:8][C:9]1C=C(O)[CH:12]=[CH:13][CH:14]=1.Cl>N1C=CC=CC=1>[C:5]([O:4][C:1]1[CH:12]=[CH:13][CH:14]=[C:9]([Br:8])[CH:2]=1)(=[O:7])[CH3:6]
Reactant: CC(=O)OC(C)=O
Reactant: Oc1cccc(Br)c1
Agent: Cl
Solvent: c1ccncc1
Product: CC(=O)Oc1cccc(Br)c1
Temperature: 0 °C
Reaction time: 4 h

Procedure:
Acetic anhydride was added dropwise to an ice-cold solution of 3-bromophenol (25.5 g) in pyridine (25 ml) and the solution was then stirred at room temp. for 4 h. 2N Hydrochloric acid (160 ml) was added and the mixture was extracted with ether (×2). The combined organic extracts were washed with water and brine, dried (MgSO4) and concentrated under vacuum to give the title compound as a brown liquid (30.8 g).
Reaction SMILES: [NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.P(Cl)(Cl)(Cl)=O.[C:11]([NH:14][C:15]1[NH:16][C:17](=O)[C:18]2[N:24]=[C:23]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH:22]=[CH:21][C:19]=2[N:20]=1)(=[O:13])[CH3:12].C(N(CC)CC)C>C(#N)C>[C:11]([NH:14][C:15]1[N:16]=[C:17]([C:5]2[N:4]=[CH:3][NH:2][N:1]=2)[C:18]2[N:24]=[C:23]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH:22]=[CH:21][C:19]=2[N:20]=1)(=[O:13])[CH3:12]
Reactant: CC(=O)Nc1nc2ccc(-c3ccc(F)cc3)nc2c(=O)[nH]1
Reactant: c1nc[nH]n1
Solvent: CCN(CC)CC
Solvent: O=P(Cl)(Cl)Cl
Solvent: CC#N
Product: CC(=O)Nc1nc(-c2nc[nH]n2)c2nc(-c3ccc(F)cc3)ccc2n1
Temperature: 50 °C
Reaction time: 24 h
Yield: 72 %

Procedure:
A suspension of 1,2,4-triazole (120 mmol) and phosphorus oxychloride (36 mmol) in dry acetonitrile (150 ml) was added to a stirred suspension of the 2-acetamido-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidin-4(3H)-one of example 1 (12 mmol) and triethylamine (36 mmol) in dry acetonitrile (150 ml). The mixture was stirred at room temperature under nitrogen for 70 hours (or, alternatively, at 50° C. for 24 hours) and the yellow precipitate formed was filtered off, then successively washed with ethanol and ether, and further dried over P2O5 under vacuum. Solvents were evaporated in vacuo, then the crude residue was dissolved in dichloromethane and extracted with a diluted hydrochloric acid solution (HCl 0.01 N). The combined organic layers were dried over anhydrous MgSO4 and evaporated, thus providing the crude title compound in 72% yield, which was characterized by its mass spectrum as follows: MS (m/z): 350 ([M+H]+, 100).
Reaction SMILES: OO.[OH:3][CH:4]([CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH:5]=[CH:6][CH:7]1[C:11](=[CH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH:20]([C:22]([O:24][CH3:25])=[O:23])[CH3:21])[CH:14]=2)[C:10](=[O:26])[CH:9]=[CH:8]1.[OH-].[Na+].[Cl-:34].[NH4+].Cl.C(=O)([O-])O.[Na+]>CO.CC(C)=O>[Cl:34][C:9]1[C:10](=[O:26])[C:11](=[CH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH:20]([C:22]([O:24][CH3:25])=[O:23])[CH3:21])[CH:14]=2)[CH:7]([CH:6]=[CH:5][CH:4]([OH:3])[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH:8]=1
Reactant: CCCCCC(O)C=CC1C=CC(=O)C1=Cc1cccc(OC(C)C(=O)OC)c1
Reactant: [Cl-]
Agent: Cl
Agent: O=C([O-])O
Agent: OO
Solvent: CO
Solvent: CC(C)=O
Product: CCCCCC(O)C=CC1C=C(Cl)C(=O)C1=Cc1cccc(OC(C)C(=O)OC)c1
Yield: 41 %

Procedure:
0.2 ml of 30% aqueous hydrogen peroxide was added to a solution of 100 mg (0.25 mmol) of 4-(3-hydroxy-1-octenyl)-5-[3-(1-methoxycarbonylethyloxy)-phenylmethylidene]-2-cyclopentenone in 2 ml of methanol under ice cooling and stirring, and then 50 microliters of 1N sodium hydroxide was added. The mixture was stirred at 0° C. for 20 minutes. A saturated aqueous solution of ammonium chloride was added, and the mixture was extracted with hexane. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The dried product was filtered and concentrated to give an oily product. The product was dissolved in 3 ml of acetone, and 0.5 ml of concentrated hydrochloric acid was added. The mixture was stirred for 50 minutes. A saturated aqueous solution of sodium hydrogen carbonate was added, and the mixture was extracted with ethylacetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The dried product was filtered, concentrated and subjected to silica gel column chromatography (silica gel, 10 g; eluent, cyclohexane:ethylacetate=4:1) to give 45 mg (yield 41%) of 2-chloro-4-(3-hydroxy-1-octenyl)-5-[3-(1-methoxycarbonylethyloxy)phenylmethylidene]-2-cyclopentenone.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][NH2:11])=[CH:5][CH:4]=1.[C:14](OC(=O)C)(=[O:16])[CH3:15]>>[F:1][C:2]([F:12])([F:13])[C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][NH:11][C:14](=[O:16])[CH3:15])=[CH:7][CH:8]=1
Reactant: CC(=O)OC(C)=O
Reactant: NCCc1ccc(C(F)(F)F)cc1
Product: CC(=O)NCCc1ccc(C(F)(F)F)cc1
Yield: 29 %

Procedure:
In close analogy to the procedure described above, 2-(4-trifluoromethyl-phenyl)-ethylamine is reacted with acetic anhydride to provide the title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C@H:11]([CH3:28])[C@:12]([C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1[F:27])([OH:19])[CH2:13][N:14]1[CH:18]=[N:17][CH:16]=[N:15]1)[N:6]=[CH:5]2.O=[C:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]1.C([BH3-])#N.[Na+]>C(O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[C@@:12]([OH:19])([CH2:13][N:14]1[CH:18]=[N:17][CH:16]=[N:15]1)[C@H:11]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([NH:1][CH:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]3)=[CH:10][CH:9]=2)[CH:5]=[N:6]1)[CH3:28]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: C[C@@H](n1ncc2cc(N)ccc21)[C@](O)(Cn1cncn1)c1ccc(F)cc1F
Agent: [Ti+4]
Agent: CC(C)[O-]
Agent: [BH3-]C#N
Solvent: CCO
Product: C[C@@H](n1ncc2cc(NC3CCN(C(=O)OC(C)(C)C)CC3)ccc21)[C@](O)(Cn1cncn1)c1ccc(F)cc1F
Temperature: 25 °C
Reaction time: 2 h
Yield: 52 %

Procedure:
To a solution of (2R,3R)-3-(5-amino-1H-indazol-1-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (0.419 g, 1.09 mmol) and tert-butyl 4-oxo-1-piperidine carboxylate (0.22 g, 1.09 mmol) in absolute ethanol (2 ml) was added titanium (IV) isopropoxide (0.358 ml, 1.20 mmol), and the solution was stirred at room temperature for 2 hours. The addition of sodium cyanotrihydridoborate (0.137 g, 2.18 mmol) to the solution was followed by stirring at room temperature for 18 hours. The reaction was terminated by adding 10% sodium hydroxide solution (2 ml) before extraction with dichloromethane (20 ml). The organic layer was dried over anhydrous magnesium sulfate and evaporated in a vacuum to concentrate it. The crude product was purified by chromatography on silica gel to give the title compound (Yield 52%).
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[C:5]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:2]=[CH2:3].ClC1C=CC=C(C(OO)=[O:31])C=1>ClCCl>[CH2:16]([O:15][C:5]1[C:6]([CH:10]2[CH2:11][CH2:12][CH2:13][CH2:14]2)=[CH:7][CH:8]=[CH:9][C:4]=1[CH2:1][CH:2]1[CH2:3][O:31]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: C=CCc1cccc(C2CCCC2)c1OCc1ccccc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: c1ccc(COc2c(CC3CO3)cccc2C2CCCC2)cc1
Reaction time: 2.5 h
Yield: 113.3 %

Procedure:
20 g (0.0684 mol) of 1-allyl-2-benzyloxy-3-cyclopentylbenzene are dissolved in 200 ml of dichloromethane. While stirring and cooling in an ice bath, 14 g (0.081 mol) of m-chloroperbenzoic acid are added in portions. The mixture is allowed to reach room temperature and, after 2.5 h, a further 5 g of m-chloroperbenzoic acid are added. The mixture is further stirred at room temperature overnight, and then the precipitated m-chlorobenzoic acid is removed by filtration and the filtrate is concentrated in vacuo. The oily residue is thoroughly stirred with n-pentane and filtered, and the filtrate is washed three times with 2N sodium hydroxide solution and then once with saturated brine. Drying over sodium sulfate is followed by removal of the solvent by distillation in vacuo. 23.9 g of (2-benzyloxy-3-cyclopentylbenzyl)oxirane are obtained as an oil.
Reaction SMILES: C[O:2][CH:3](OC)[C:4]1[O:5][C:6]2[CH:14]=[CH:13][CH:12]=[CH:11][C:7]=2[C:8](=[O:10])[CH:9]=1>Cl>[O:5]1[C:6]2[CH:14]=[CH:13][CH:12]=[CH:11][C:7]=2[C:8](=[O:10])[CH:9]=[C:4]1[CH:3]=[O:2]
Reactant: COC(OC)c1cc(=O)c2ccccc2o1
Agent: Cl
Product: O=Cc1cc(=O)c2ccccc2o1
Yield: 81.6 %

Procedure:
A stirred solution of 2-(dimethoxymethyl)-4H-1-benzopyran- 4-one (1.1 g, 0.005 m) in 5 N hydrochloric acid (20 ml) was heated at 100° for 3 hours. The reaction mixture was cooled and extracted with CHCl3. The extracts were dried over MgSO4 and evaporated under reduced pressure to give a crystalline product. Recrystallization from ethyl acetate gave off-white crystals (710 mg, 81%), m.p. 159°-161°.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[C:14]2[CH2:20][CH2:21]OS(C)(=O)=O.[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>CC#N>[N:27]1([CH2:21][CH2:20][C:14]2[C:13]3[C:17](=[CH:18][CH:19]=[C:11]([O:10][C:2]4[S:1][C:5]5[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=5[N:3]=4)[CH:12]=3)[NH:16][CH:15]=2)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1
Reactant: C1CCNCC1
Reactant: CS(=O)(=O)OCCc1c[nH]c2ccc(Oc3nc4ccccc4s3)cc12
Solvent: CC#N
Product: c1ccc2sc(Oc3ccc4[nH]cc(CCN5CCCCC5)c4c3)nc2c1
Temperature: 80 °C
Yield: 48.1 %

Procedure:
To a solution of methanesulfonic acid 2-[5-(benzothiazol-2-yloxy)-1H-indol-3-yl]-ethyl ester (100 mg, 0.26 mmol) in MeCN (3 mL) was added piperidine (0.03 mL, 0.31 mmol) and the reaction mixture was heated (80° C., 2 h). The reaction mixture was cooled (rt), filtered and purified by basic reverse phase HPLC to provide the title compound as a white solid (47.2 mg, 49%). MS (ESI): mass calcd. for C22H23N3OS, 377.5; m/z found, 378.3 [M+H]+. 1H NMR (500 MHz, CDCl3): 8.08 (s, 1H), 7.77 (d, J=7.6, 1H), 7.65 (d, J=8.0, 1H), 7.59 (d, J=2.3, 1H), 7.43-7.36 (m, 2H), 7.26 (s, 1H), 7.18 (dd, J=8.7, 2.3, 1H), 7.14 (s, 1H), 3.02-2.90 (m, 2H), 2.71-2.63 (m, 2H), 2.51 (s, 4H), 1.63 (dd, J=11.3, 5.6, 4H), 1.47 (s, 2H).
Reaction SMILES: [CH3:1][O:2][CH:3]([C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=1)[C:4](OC)=[O:5].O.[NH2:19][NH2:20]>>[CH3:1][O:2][CH:3]([C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=1)[C:4]([NH:19][NH2:20])=[O:5]
Reactant: COC(=O)C(OC)c1ccc2ccccc2c1
Reactant: NN
Solvent: O
Product: COC(C(=O)NN)c1ccc2ccccc2c1
Yield: 47 %

Procedure:
A stirred solution of methyl 2-methoxy-2-(naphthalen-2-yl)acetate (0.358 g, 1 eq) and hydrazine hydrate (4 mL) was heated to reflux for 1 hour. The reaction mixture was then cooled and the solvents removed under reduced pressure. The crude oil was diluted with EtOAc and washed with H2O and the organic phase dried over Na2SO4, filtered, and the solvents removed under reduced pressure to yield a yellow oil (0.17 g, 47%) that was used without further purification.
Reaction SMILES: Cl.Cl.Cl.[O:4]1[C:12]2[CH:11]=[CH:10][N:9]=[C:8]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[CH2:6][CH2:5]1.[CH:28](O)=[O:29]>>[O:4]1[C:12]2[CH:11]=[CH:10][N:9]=[C:8]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH:27][CH:28]=[O:29])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[CH2:6][CH2:5]1
Reactant: O=CO
Reactant: N[C@H]1CC[C@H](CCN2CCN(c3nccc4c3CCO4)CC2)CC1
Agent: Cl
Product: O=CN[C@H]1CC[C@H](CCN2CCN(c3nccc4c3CCO4)CC2)CC1

Procedure:
The title compound, off-white solid (17 mg, 30%), MS (ISP) m/z=359.4 [(M+H)+], mp 170.5° C., was prepared in accordance with the general method of example 32 from trans-4-{2-[4-(2,3-dihydrofuro[3,2-c]pyridin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexanamine trihydrochloride (intermediate C) (70.4 mg, 0.16 mmol) and formic acid.
Reaction SMILES: [C:1]([O:20][CH2:21][CH3:22])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH2:23](O)[CH2:24][CH2:25]CC>CCOCC>[C:1]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OCC
Reactant: CCCCCO
Solvent: CCOCC
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OCCCCC
Reaction time: 40 h
Yield: 91 %

Procedure:
A mixture containing Catalyst A or B (0.05 g) and ethyl oleate (1.55 g, 5 mmol) and pentanol (10 ml) was refluxed with stirring for 40 h. On cooling ether (30 ml) was added and the catalyst was filtered off. The organic washings were combined and concentrated to give pentyl oleate as an oil (1.6 g, 91% yield).