Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:7]2[NH:11][N:10]=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:13][C:14]#[N:15].CN(C)C=O.C(=O)([O-])[O-].[K+].[K+]>O>[C:1]1([C:7]2[N:8]=[N:9][N:10]([CH2:13][C:14]#[N:15])[N:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: c1ccc(-c2nnn[nH]2)cc1
Reactant: N#CCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: N#CCn1nnc(-c2ccccc2)n1

Procedure:
To 146 mg (1 mmol) of 5-phenyltetrazole and 75 mg (1 mmol) of chloroacetonitrile was added three mL of dimethyl formamide. The resulting solution was stirred, then 158 mg (1 mmol) of potassium carbonate was added and the mixture was further stirred at room temperature for 18 hours. Twenty-five mL of water was then added and the mixture was extracted twice with 25 mL of ethyl acetate. Evaporation of the extracts left the crude product, which was purified by silica gel chromatography, leaving an oil that was pure by NMR.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]([O:10]CC)=[O:9])=[CH:6][N:5]=[C:4]([S:13][CH3:14])[N:3]=1.[CH2:15]([NH2:21])[C:16]1[O:20][CH:19]=[CH:18][CH:17]=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>CC(O)C>[O:20]1[CH:19]=[CH:18][CH:17]=[C:16]1[CH2:15][NH:21][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][N:5]=[C:4]([S:13][CH3:14])[N:3]=1
Reactant: NCc1ccco1
Reactant: CCOC(=O)c1cnc(SC)nc1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: CSc1ncc(C(=O)O)c(NCc2ccco2)n1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 89.8 %

Procedure:
To a solution of ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate (1.71 g) in 2-propanol (10 ml) were added furfurylamine (714 mg) and diisopropylethylamine (950 mg), and the mixture was stirred at room temperature for 10 min. The reaction mixture was poured into 2% aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. Ethyl acetate was added to the residue, and the precipitate was collected by filtration. The precipitate was dissolved in ethanol (10 ml), 2 M aqueous sodium hydroxide solution (10 ml) was added and the mixture was stirred at room temperature for 5 hr. The reaction mixture was adjusted to pH 3 with 1 M hydrochloric acid, and the precipitated crystals were collected by filtration to give the object compound (1.75 g) as a powder.
Reaction SMILES: [CH2:1]([C@H:8]([NH:19][C:20](=[O:30])[O:21][C@@H:22]1[C@H:29]2[C@H:25]([O:26][CH2:27][CH2:28]2)[O:24][CH2:23]1)[C@H:9]([OH:18])[CH2:10][NH:11][O:12][CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:31]([C:34]1[CH:35]=[C:36]([S:40](Cl)(=[O:42])=[O:41])[CH:37]=[CH:38][CH:39]=1)([O-:33])=[O:32].C(N(C(C)C)CC)(C)C>O1CCCC1.CN(C1C=CC=CN=1)C>[CH2:1]([C@H:8]([NH:19][C:20](=[O:30])[O:21][C@@H:22]1[C@H:29]2[C@H:25]([O:26][CH2:27][CH2:28]2)[O:24][CH2:23]1)[C@H:9]([OH:18])[CH2:10][N:11]([O:12][CH:13]([CH2:14][CH3:15])[CH2:16][CH3:17])[S:40]([C:36]1[CH:37]=[CH:38][CH:39]=[C:34]([N+:31]([O-:33])=[O:32])[CH:35]=1)(=[O:41])=[O:42])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Cl)c1
Reactant: CCC(CC)ONC[C@@H](O)[C@H](Cc1ccccc1)NC(=O)O[C@H]1CO[C@H]2OCC[C@H]21
Agent: CN(C)c1ccccn1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CCC(CC)ON(C[C@@H](O)[C@H](Cc1ccccc1)NC(=O)O[C@H]1CO[C@H]2OCC[C@H]21)S(=O)(=O)c1cccc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 85.4 %

Procedure:
A mixture of (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[(1-ethylpropoxy)amino]-2-hydroxypropylcarbamate (200 mg, 0.474 mmol), 3-nitrophenylsulphonyl chloride (105 mg, 0.474 mmol), diisoproylethylamine (0.084 mL, 0.474 mmol) and dimethylaminopyridine (˜1 mg) in anhydrous tetrahydrofuran (3 mL) was stirred at ambient temperature over 16 hours under an Argon atmosphere. The reaction was evaporated in vacuo and the residue was partitioned between dichloromethane and aqueous hydrochloric acid (1N). After separating the phases, the aqueous layer was extracted with dichloromethane. The combined organic phases were dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on flash grade silica gel eluting with 1:1 ethyl acetate : hexane. Fractions containing the product were combined, evaporated in vacuo and dried under high vacuum to provide (3R,3aS,6aR)hexahydrofuro [2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-{(1-ethylpropoxy)[(3-nitrophenyl)sulfonyl]amino}-2-hydroxypropylcarbamate (246 mg, 86%). H1-NMR (chloroform-D3): 0.98 (m, 6H), 1.68 (m, 7H), 2.99 (m, 5H), 3.73 (m, 2H), 3.96 (m, 4H), 4.27 (m, 1H), 4.86 (d, 1H), 5.07 (m, 1H), 5.69 (d, 1H), 7.27 (m, 5H), 7.84 (m, 1H), 8.16 (d, 1H), 8.57 (d, 1H), 8.76 (s, 1H). MS (ESI): 630(M+Na).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:31]/[OH:32])/[C:8]([NH:10][C@@H:11]2[C:29](=[O:30])[N:13]3[C:14]([C:26]([O-:28])=[O:27])=[C:15](/[CH:18]=[CH:19]\[C:20]4[CH:21]=[N:22][CH:23]=[N:24][CH:25]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.[Na+].[CH2:34]([CH:36]([CH2:42][CH3:43])[C:37]([O:39][CH2:40]I)=[O:38])[CH3:35].C(OCC)(=O)C>CN(C)C(=O)C>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:31]/[OH:32])/[C:8]([NH:10][C@@H:11]2[C:29](=[O:30])[N:13]3[C:14]([C:26]([O:28][CH2:40][O:39][C:37](=[O:38])[CH:36]([CH2:42][CH3:43])[CH2:34][CH3:35])=[O:27])=[C:15](/[CH:18]=[CH:19]\[C:20]4[CH:25]=[N:24][CH:23]=[N:22][CH:21]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1
Reactant: Nc1nc(/C(=N/O)C(=O)N[C@@H]2C(=O)N3C(C(=O)[O-])=C(/C=C\c4cncnc4)CS[C@H]23)cs1
Reactant: CCC(CC)C(=O)OCI
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(=O)N(C)C
Product: CCC(CC)C(=O)OCOC(=O)C1=C(/C=C\c2cncnc2)CS[C@@H]2[C@H](NC(=O)/C(=N\O)c3csc(N)n3)C(=O)N12

Procedure:
The compound (100 mg) of Example 16 was dissolved in N,N-dimethylacetamide (2 ml), followed by the addition of 2-ethylbutanoyloxymethyl iodide (50 mg). They were reacted for 1 hour. Ethyl acetate (50 ml) was added. The resulting mixture was washed with water, dried over magnesium sulfate, and then concentrated under reduced pressure. Ether was added to the residue and the resulting solid was collected by filtration, whereby the title compound (55 mg) was obtained.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][C@H:11]([CH3:13])[C@H:10]([CH2:14][NH2:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:16](=O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([BH3-])#N.[Na+].[OH-].[Na+]>CO>[CH2:1]([N:8]1[CH2:12][C@H:11]([CH3:13])[C@H:10]([CH2:14][NH:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=Cc1ccccc1
Reactant: C[C@H]1CN(Cc2ccccc2)C[C@H]1CN
Agent: [BH3-]C#N
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: C[C@H]1CN(Cc2ccccc2)C[C@H]1CNCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
cis-1-Benzyl-4-methyl-3-aminomethylpyrrolidine (1000 mg) was dissolved in methanol (10 mL). While this solution was chilled in an ice water bath, benzaldehyde (0.50 mL) was added dropwise and the mixture was stirred at room temperature for 1 hour. Subsequently, sodium cyanoborohydride (184 mg) was added and the mixture was stirred at room temperature for 1.5 hours, followed by addition of a second portion of sodium cyanoborohydride (123 mg) and then further stirring for 5.5 hours. To the resulting mixture, a 2 mol/L aqueous solution of sodium hydroxide (5 mL) was added and the mixture was refluxed for 2 hours. Subsequently, the reaction mixture was concentrated under reduced pressure and the residue was extracted with toluene (2×30 mL). The toluene layers were combined, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane: ethyl acetate=4:1) to give cis-1-benzyl-3-benzylaminomethyl-4-methylpyrrolidine as a pale yellow oil (690 mg).
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[C:12]([C:14]1[C:15]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[N:16][CH:17]=[C:18]([C:20]2[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=2)[CH:19]=1)#[N:13]>C(Cl)(Cl)Cl>[C:12]([C:14]1[C:15]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[N:16][CH:17]=[C:18]([C:20]2[CH:21]=[CH:22][N+:23]([O-:9])=[CH:24][CH:25]=2)[CH:19]=1)#[N:13]
Reactant: N#Cc1cc(-c2ccncc2)cnc1N1CCOCC1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Product: N#Cc1cc(-c2cc[n+]([O-])cc2)cnc1N1CCOCC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
1.1 g M-chloroperbenzoic acid is added at room temperature with stirring to a solution of 1.3 g 3-cyano-2-morpholino-5-(pyrid-4-yl)-pyridine in 20 ml chloroform. The reaction mixture is stirred for 48 hours at room temperature. Subsequently it is extracted with a bicarbonate solution and the chloroform phase is evaporated under vacuum. The residue is treated with water, filtered off with suction, dried at 110° C., and crystallized from a mixture of isopropanol and ethanol. Yield: 1.0 g (73% of the theoretical yield), with a melting point of 233° C.-235° C.
Reaction SMILES: [C:1]1(=[O:10])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][NH:2]1.F[B-](F)(F)F.[CH2:16]([O+](CC)CC)[CH3:17]>C(Cl)(Cl)Cl>[CH2:16]([O:10][C:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][N:2]=1)[CH3:17]
Reactant: O=C1NCc2ccccc21
Reactant: CC[O+](CC)CC
Agent: F[B-](F)(F)F
Solvent: ClC(Cl)Cl
Product: CCOC1=NCc2ccccc21

Procedure:
Scheme VIII shows the synthesis of a benzyl-protected isoindolin-1-one oxime intermediate 27. Isoindolinone 25 is alkylated with triethyloxonium tetrafluoroborate in chloroform to afford the 3-ethoxy-1H-isoindole 26, which is reacted with O-benzylhydroxylamine hydrochloride and sodium carbonate in ethanol, providing intermediate 27. Intermediate 27 can be coupled by Suzuki reaction with intermediates 3 or 6 as in Schemes I and II. Alternatively, intermediate 27 can be converted to the boronate ester intermediate 28 by reaction with bis(pinacolato)diboron in dioxane, using [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)chloride dichloromethane complex. The boronate ester intermediate 28 can be coupled by Suzuki reaction with intermediates 1 or 5 as in Schemes I and II.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH2:11][C:12]#N.[H-].C([Al+]CC(C)C)C(C)C.C[OH:25].O>C1C=CC=CC=1>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH2:11][CH:12]=[O:25]
Reactant: N#CCC1COc2ccccc2O1
Reactant: CO
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: c1ccccc1
Solvent: O
Product: O=CCC1COc2ccccc2O1

Procedure:
The starting material is prepared as follows: To the solution of 20 g of 1,4-benzodioxan-2-yl-acetonitrile in 200 ml of benzene is added dropwise 71 ml of a 1.6 N solution of diisobutyl aluminum hydride in benzene while stirring at 10°. After 6 hours 50 ml of methanol are added, followed by 200 ml of water. The organic layer is separated, dried and evaporated, to yield the 1,4-benzodioxan-2-yl-acetaldehyde.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([OH:16])=O)=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18].[F:21][C:22]([F:33])([F:32])[O:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27][NH2:28]>>[Cl:20][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Cl:1])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([NH:28][CH2:27][C:26]2[CH:29]=[CH:30][CH:31]=[C:24]([O:23][C:22]([F:21])([F:32])[F:33])[CH:25]=2)=[O:16])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18]
Reactant: O=C(O)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1
Reactant: NCc1cccc(OC(F)(F)F)c1
Product: O=C(NCc1cccc(OC(F)(F)F)c1)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1

Procedure:
Prepared according to the procedure described for example 50 from 5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-thiophene-2-carboxylic acid (145 mg, 0.41 mmol) and 3-(trifluoromethoxy)benzylamine (53 mg, 0.39 mmol). The title compound was obtained as a solid (55 mg, 26% yield). 1H NMR (400 MHz, d6-DMSO) δ: 9.45 (1H, m), 8.98 (2H, m), 8.47 (1H, s), 7.48 (2H, m), 7.30 (2H, m), 4.45 (2H, m). MS m/z: 522.09, 524.08 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([S:10]([N:13]1[CH2:18][CH2:17][CH:16]([C:19]2[C:27]3[C:22](=[C:23]([C:39]([NH2:41])=[O:40])[CH:24]=[C:25]([C:28]4[CH:32]=[C:31]([CH2:33][N:34]5[CH2:38][CH2:37][CH2:36][CH2:35]5)[S:30][CH:29]=4)[CH:26]=3)[NH:21][CH:20]=2)[CH2:15][CH2:14]1)(=[O:12])=[O:11])[CH3:9].N1CCCCC1>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([S:10]([N:13]1[CH2:18][CH2:17][CH:16]([C:19]2[C:27]3[C:22](=[C:23]([C:39]([NH2:41])=[O:40])[CH:24]=[C:25]([C:28]4[CH:32]=[C:31]([CH2:33][N:34]5[CH2:35][CH2:36][O:4][CH2:37][CH2:38]5)[S:30][CH:29]=4)[CH:26]=3)[NH:21][CH:20]=2)[CH2:15][CH2:14]1)(=[O:12])=[O:11])[CH3:9]
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4csc(CN5CCCC5)c4)cc23)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: C1CCNCC1
Product: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4csc(CN5CCOCC5)c4)cc23)CC1
Yield: 14.9 %

Procedure:
The title compound was prepared according to the general procedure of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-[5-(1-pyrrolidinylmethyl)-3-thienyl]-1H-indole-7-carboxamide trifluoroacetate, substituting morpholine (70 mg, 0.670 mmol) for piperidine to afford 6.3 mg of the title compound (14.9%).
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9](C3C4C(C=C5C=3C=CC=C5)=CC=CC=4)[CH:10]=[CH:11][C:12]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C(=O)N(Br)C(=O)C1.C1([C:47]2[CH:48]=[C:49]([C:59]3[C:60]4[C:65]([C:66]([Br:73])=C5C=3C=CC=C5)=[CH:64][CH:63]=[CH:62][CH:61]=4)[CH:50]=[CH:51][C:52]=2C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.O>[C:13]1([C:12]2[CH:11]=[C:10]([C:61]3[C:60]4[C:65](=[C:66]([Br:73])[C:48]5[C:49]([CH:59]=4)=[CH:50][CH:51]=[CH:52][CH:47]=5)[CH:64]=[CH:63][CH:62]=3)[CH:9]=[CH:8][C:7]=2[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: c1ccc(-c2ccc(-c3c4ccccc4cc4ccccc34)cc2-c2ccccc2)cc1
Reactant: Brc1c2ccccc2c(-c2ccc(-c3ccccc3)c(-c3ccccc3)c2)c2ccccc12
Agent: O=C1CCC(=O)N1Br
Solvent: O
Solvent: CN(C)C=O
Product: Brc1c2ccccc2cc2c(-c3ccc(-c4ccccc4)c(-c4ccccc4)c3)cccc12
Temperature: 25 °C
Reaction time: 4 h
Yield: 95 %

Procedure:
9-(3,4-Diphenylphenyl)anthracene (3.7 g, 9.1 mmole) was suspended in anhydrous DMF (50 ml). After an anhydrous DMF solution (10 ml) of NBS (1.8 g, 10 mmole, 1.1 eq) was added, the resultant mixture was heated at 55° C. for 5 minutes so that the reaction mixture became a homogeneous solution. The obtained solution was stirred at the room temperature for 4 hours and then left standing for one night. The reaction mixture was diluted with water (50 ml). The formed solid substance was separated by filtration and washed with methanol, and a light yellow solid substance (4.2 g, the yield: 95%) was obtained. The obtained product was identified to be 9-(3,4-diphenylphenyl)-10-bromoanthracene in accordance with 1H-NMR.
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:30]=[CH:31][C:32]=2[O:33][CH3:34])[N:10]([C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-])=O)=[C:20]([C:27]([OH:29])=[O:28])[CH:19]=2)[CH2:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:35](OC(=O)C)(=[O:37])[CH3:36]>CCOC(C)=O.O=[Pt]=O>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:30]=[CH:31][C:32]=2[O:33][CH3:34])[N:10]([C:18]2[CH:23]=[CH:22][C:21]([NH:24][C:35](=[O:37])[CH3:36])=[C:20]([C:27]([OH:29])=[O:28])[CH:19]=2)[CH2:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC(=O)OC(C)=O
Reactant: COc1ccc(N(Cc2cccnc2)c2ccc([N+](=O)[O-])c(C(=O)O)c2)cc1OC1CCCC1
Agent: O=[Pt]=O
Solvent: CCOC(C)=O
Product: COc1ccc(N(Cc2cccnc2)c2ccc(NC(C)=O)c(C(=O)O)c2)cc1OC1CCCC1
Reaction time: 16 h
Yield: 51.3 %

Procedure:
A solution of 3-cyclopentyloxy-4-methoxy-N-(3-carboxy-4-nitrophenyl)-N-(3-pyridylmethyl)aniline (200 mg, 0.43 mmol) in 35 mL of EtOAc and 0.1 mL (1.08 mmol) of acetic anhydride was hydrogenated at atmospheric pressure over 20 mg of PtO2 with stirring for 16 hours. The catalyst was removed by filtration and the solution concentrated. The residue was partitioned between 50 mL of DCM and 100 mL of brine. The organic layer was separated, dried (Na2SO4), and concentrated. The residue was chromatographed over SiO2 using MeOH/DCM (1/20) as eluant to give 105 mg (51% yield) of the target compound.
Reaction SMILES: P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:2].[NH2:15][C:16]1[C:21]2=[C:22]([C:35]#[N:36])[CH:23]=[C:24]([C@@H:25]3[O:31][C@H:30]([CH2:32][OH:33])[C@@H:28]([OH:29])[C@@:26]3([CH3:34])[OH:27])[N:20]2[N:19]=[CH:18][N:17]=1.O>CCO>[NH2:15][C:16]1[C:21]2=[C:22]([C:35](=[S:2])[NH2:36])[CH:23]=[C:24]([C@@H:25]3[O:31][C@H:30]([CH2:32][OH:33])[C@@H:28]([OH:29])[C@@:26]3([CH3:34])[OH:27])[N:20]2[N:19]=[CH:18][N:17]=1
Reactant: C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1c1cc(C#N)c2c(N)ncnn12
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: O
Solvent: CCO
Product: C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1c1cc(C(N)=S)c2c(N)ncnn12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
to anhydrous EtOH (30 μl) was added P2S5 (7.30 mg, 0.02 mmol) and the mixture stirred in a sealed vial for 1 h at RT. To the reaction mixture was added a solution of Compound 14 (51 mg, 0.0033 mmol) in anhydrous EtOH. (30 μl). The mixture was heated in a sealed vial at 120° C. for 3 h and then cooled to RT, whereupon water was added and the mixture extracted with DCM. The aqueous layer was concentrated to dryness and the residue purified by column chromatography silica gel (elution gradient ethyl acetate to 17% methanol in ethyl acetate) to afford Compound 21: ESI-MS m/z 340 ([M+H]+).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]2[CH:8]=[CH:9][NH:10][C:11]=2[CH:12]=[CH:13][CH:14]=1.[CH:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][C:16]=1[CH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.[C:31]([OH:36])(=[O:35])[C:32]([OH:34])=[O:33]>C(OCC)(=O)C>[C:31]([OH:36])(=[O:35])[C:32]([OH:34])=[O:33].[NH:10]1[C:11]2[C:7](=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:28]3[CH2:29][CH2:30][C:25]([OH:33])([C:16]4[CH:17]=[CH:18][C:19]5[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=5)[CH:15]=4)[CH2:26][CH2:27]3)[CH:14]=[CH:13][CH:12]=2)[CH:8]=[CH:9]1
Reactant: c1ccc2cc(C3CCNCC3)ccc2c1
Reactant: ClCCCOc1cccc2[nH]ccc12
Agent: O=C(O)C(=O)O
Solvent: CCOC(C)=O
Product: OC1(c2ccc3ccccc3c2)CCN(CCCOc2cccc3[nH]ccc23)CC1

Procedure:
The title compound was prepared in similar fashion from 1-chloro-3-(1H-indole-4-oxy)propane and 4-(2-naphthyl)piperidine. The resulting free base was dissolved in ethyl acetate, and precipitated with one equivalent of oxalic acid in ethyl acetate in 24% overall yield as a foam. FDHS m/e=400 (H+ of free base).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([CH:11]1[CH2:15][CH2:14][CH:13]([C:16]([OH:18])=O)[CH2:12]1)(=[O:10])=[O:9].CCN(C(C)C)C(C)C.CN(C(O[N:36]1N=[N:43][C:38]2C=CC=N[C:37]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.NCC#N>CN(C=O)C>[C:37]([CH2:38][NH:43][C:16]([CH:13]1[CH2:14][CH2:15][CH:11]([S:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])(=[O:9])=[O:10])[CH2:12]1)=[O:18])#[N:36]
Reactant: O=C(O)C1CCC(S(=O)(=O)c2ccccc2Cl)C1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Agent: N#CCN
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: N#CCNC(=O)C1CCC(S(=O)(=O)c2ccccc2Cl)C1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A solution of 3-(2-chloro-benzenesulfonyl)-cyclopentanecarboxylic acid (0.25 g, 1.0 eq) in DMF (4.0 mL) was treated with DIPEA (0.22 mL, 1.5 eq) and HATU (0.39 g, 1.2 eq). The mixture was stirred at RT for 15 min, then a solution of aminoacetonitrile hydrochloride (0.12 g, 1.5 eq) and DIPEA (0.22 mL, 1.5 eq) in DMF (1 mL) was added. The resulting solution was stirred at RT overnight and then purified by preparative HPLC. The title compound was obtained as a light yellow gum (0.10 g, 37%). MS (ESI): m/z=327.1 [M+H]+.
Reaction SMILES: [CH3:1][C:2]([CH3:7])=[CH:3][C:4](O)=[O:5].CC(C)=CCO.S(Cl)(Cl)=O.[O-][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[Na+]>C1C=CC=CC=1>[CH3:1][C:2]([CH3:7])=[CH:3][CH2:4][O:5][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: CC(C)=CC(=O)O
Reactant: [O-]c1ccccc1
Agent: CC(C)=CCO
Agent: [Na+]
Solvent: c1ccccc1
Solvent: O=S(Cl)Cl
Product: CC(C)=CCOc1ccccc1

Procedure:
3,3-dimethylallylphenyl ether was prepared from 3,3-dimethylacrylic acid by reduction with sodium dihydro-bis (2-methoxyethoxy) aluminate in benzene, chlorination of the resulting 3,3-dimethylallyl alcohol with thionyl chloride and reaction of the product with sodium phenoxide in the presence of a polar solvent.
Reaction SMILES: [H-].[Na+].CN(C)[CH:5]=[O:6].[CH2:8]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]O)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CI>O>[CH2:8]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:6][CH3:5])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CN(C)C=O
Reactant: OCCCCCOCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: O
Product: COCCCCCOCc1ccccc1
Temperature: 25 °C
Yield: 70 %

Procedure:
1.6 g (0.039 mol) of 55% sodium hydride in oil were added to 50 ml of dimethylformamide under stirring at room temperature. 5 ml (0.026 mol) of 5-benzyloxy-1-pentanol and 2.43 ml (0.039 mol) of methyl iodide were then added successively. After a night the excess of sodium hydride was decomposed with water and the solvent evaporated under vacuum. The residue was redissolved with methylene chloride and washed with water. The organic layer was finally dried over anhydrous sodium sulfate and evaporated to give 3.5 g (70% yield) of the title compound.
Reaction SMILES: [CH:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)([CH3:3])[CH3:2].[C:12](OC(=O)C)(=[O:14])[CH3:13].C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>C(O)(=O)C>[CH:1]([N:4]([C:12](=[O:14])[CH3:13])[C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)([CH3:3])[CH3:2]
Reactant: CC(C)Nc1ccc(O)cc1
Reactant: CC(=O)OC(C)=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Product: CC(=O)N(c1ccc(O)cc1)C(C)C
Temperature: 50 °C
Yield: 59.6 %

Procedure:
Ten g (0.066 moles) of N-isopropyl-p-hydroxyaniline was dissolved in 50 ml acetic acid and to this mixture was added 13.5 g (0.132 moles) of acetic anhydride. This reaction was heated to 50° C. for 5 hours, then poured over crushed ice. Sodium carbonate was added until the pH was approximately 8.5, then the solution was extracted with chloroform, dried over anhydrous magnesium sulfate, and evaporated to dryness giving an oil which immediately was placed into 10% sodium hydroxide and warmed to 70° C. for 5 hours. Upon cooling, the mixture was extracted with chloroform, then made acidic with 10% HCl until the pH of the solution was 2-3. The solution was then extracted with chloroform, dried over anhydrous magnesium sulfate, and evaporated to dryness giving 7.6 g (60%) of N-isopropyl-4'-hydroxy-acetanilide as a white solid that was recrystallized from water, m.p. 152°-153° C. I.R. 3300-3200 cm-1 (--OH) and 1660 cm-1 (amide carbonyl). The sodium salt of this compound was prepared by reacting an equal molar quantity thereof with sodium hydroxide in water. The water was evaporated to dryness leaving the sodium salt as a solid which was dried further, m.p. 52°-54° C.