Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][OH:21])=[CH:15][CH:14]=3)=[CH:11][C:10]([C:22]([F:25])([F:24])[F:23])=[N:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:33][S:34](Cl)(=[O:36])=[O:35]>ClCCl>[CH3:33][S:34]([O:21][CH2:20][CH2:19][C:16]1[CH:17]=[CH:18][C:13]([C:12]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[N:9]=[C:10]([C:22]([F:23])([F:25])[F:24])[CH:11]=2)=[CH:14][CH:15]=1)(=[O:36])=[O:35]
Reactant: CS(=O)(=O)Cl
Reactant: OCCc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(Cl)cc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCCc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(Cl)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 2-{4-[1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl}ethanol (2.72 g) and triethylamine (1.55 ml) in dichloromethane (30 ml) was added dropwise methanesulfonyl chloride (0.86 ml) under ice-cooling. The reaction mixture was allowed to warm to room temperature and stirred for 1 hr.
Reaction SMILES: [CH3:1][C:2]1[CH:9]=[C:8](Br)[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH2:11]([B-](F)(F)F)[CH2:12][CH2:13][CH3:14].[K+]>>[CH3:1][C:2]1[CH:9]=[C:8]([CH2:11][CH2:12][CH2:13][CH3:14])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5]
Reactant: Cc1cc(Br)ccc1C=O
Reactant: CCCC[B-](F)(F)F
Agent: [K+]
Product: CCCCc1ccc(C=O)c(C)c1
Yield: 33.8 %

Procedure:
The compound was synthesized as in Example 3.1 using 2-methyl-4-bromobenzaldehyde (113 mg, 0.57 mmol) in place of 5-bromo-2-formylfuran and potassium butyltrifluoroborate (113 mg, 0.69 mmol) in place of hexylboronic acid to give 2-methyl-4-butylbenzaldehyde (34 mg, 35%). Used without further characterization.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:19]12[CH2:26][CH2:25][CH:22]([CH2:23][CH2:24]1)[C@@H:21](O)[CH2:20]2.C1(N=C=NC2CCCCC2)CCCCC1.O.ON1C2C=CC=CC=2N=N1>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:10]([O:12][C@@H:21]1[CH:22]2[CH2:25][CH2:26][N:19]([CH2:24][CH2:23]2)[CH2:20]1)=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@@H](C(=O)O)c1ccccc1
Reactant: O[C@H]1CN2CCC1CC2
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N[C@@H](C(=O)O[C@H]1CN2CCC1CC2)c1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 12.5 %

Procedure:
A mixture of (R)-2-((tert-Butoxycarbonyl)amino)-2-phenylacetic acid (5.0 g, 19.9 mmol), (R) enantiomeric pure form commercially available or obtainable from I-41 with known methods e.g. chiral preparative SFC, (R)-quinuclidin-3-ol (3.8 g, 29.8 mmol), N,N′-Dicyclohexylcarbodiimide (4.72 g, 22.9 mmol) and 1-hydroxybenzotriazole hydrate (3.09 g, 22.9 mmol) in tetrahydrofuran (175 mL) was stirred at room temperature for 18 h. After this time the reaction mixture was filtered through a pad of Celite® and concentrated in vacuo. The residue was partitioned between ethyl acetate (100 mL) and 10% aqueous sodium carbonate solution (50 mL), and the organic fractions were dried over magnesium sulfate, filtered and the solvent was removed in vacuo. Trituration with cold methanol gave the title compound as a white solid (898 mg, 17%) as a single diastereoisomer.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][C:12]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-])=O)=[CH:19][CH:18]=2)[O:14][N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)(=O)C.O.[Zn]>[NH2:23][C:20]1[CH:19]=[CH:18][C:17]([C:15]2[O:14][N:13]=[C:12]([O:11][CH2:10][CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH:16]=2)=[CH:22][CH:21]=1
Reactant: CC(C)(C)OC(=O)NCCOc1cc(-c2ccc([N+](=O)[O-])cc2)on1
Agent: [Zn]
Solvent: O
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)NCCOc1cc(-c2ccc(N)cc2)on1
Reaction time: 2 h
Yield: 89.5 %

Procedure:
3-(2-(N-tert-butoxycarbonylamino)ethoxy)-5-(4-nitrophenyl)isoxazole (0.55 g) was dissolved in a mixture of acetic acid and water (9:1, 5.5 ml), and zinc powder (0.55 g) was added thereto at room temperature, followed by stirring of the resulting mixture at the same temperature for 2 hours. After the reaction, zinc powder was filtered off and the filtrate was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous NaCl solution and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=2/1) to obtain the title compound (0.45 g, 90%) as a colorless powder.
Reaction SMILES: C([Li])CCC.CCCCCC.Br[C:13]1[CH:14]=[C:15]([C:21]2[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=2)[CH:16]=[CH:17][C:18]=1[O:19][CH3:20].C([O:29][B:30](OCC)[O:31]CC)C.[Cl-].[NH4+]>O1CCCC1>[CH3:20][O:19][C:18]1[CH:17]=[CH:16][C:15]([C:21]2[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=2)=[CH:14][C:13]=1[B:30]([OH:31])[OH:29]
Reactant: CCOB(OCC)OCC
Reactant: COc1ccc(-c2ccncc2)cc1Br
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COc1ccc(-c2ccncc2)cc1B(O)O
Temperature: -80 °C
Reaction time: 0.25 h

Procedure:
A solution of n-butyllithium in hexane (1.7 mL of 2.5 M, 4.25 mmol) is added to a stirred solution of 4-(3-bromo-4-methoxyphenyl)pyridine (Example 1 b; 1.06 g, 4 mmol) and triethylborate (0.62 g, 4.2 mmol) in dry tetrahydrofuran (20 mL) at −85° C. under an argon atmosphere. The mixture is stirred for 15 min at −80° C., then treated with a saturated aqueous solution of ammonium chloride (60 mL) and extracted with ethyl acetate (2×80 mL). The combined extracts are dried (Na2SO4), filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by recrystallisation from ethyl acetate-hexane to give 2-methoxy-5-(pyridin4-yl)phenylboronic acid as a beige crystalline solid. m.p. 194-200° C. and having the following physical characteristics:
Reaction SMILES: [C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH2:7].C(OC(=O)C)(=O)C.[Br:16]Br.S([O-])(O)=O.[Na+]>C(O)(=O)C>[Br:16][C:5]1[CH:4]=[CH:3][C:2]([NH2:7])=[C:1]([NH2:8])[CH:6]=1
Reactant: BrBr
Reactant: Nc1ccccc1N
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CC(=O)OC(C)=O
Product: Nc1ccc(Br)cc1N
Temperature: 0 °C
Reaction time: 0.67 h

Procedure:
A mixture of o-phenylenediamine (5 g, 46.2 mmol), acetic acid (40 ml) and acetic anhydride (10.4 g, 102 mmol) was cooled in ice water, to which a solution of bromine (8.9 g, 55.4 mmol) in acetic acid (10 ml) was added and the reaction mixture was stirred for 40 minutes at 50°-55° C. and then the mixture was poured into a solution of sodium hydrogensulfite (1.5 g) in ice water (300 ml).
Reaction SMILES: [S:1]1[CH2:5][CH:4]([C:6]([O-:8])=O)[N:3]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:2]1.CN1CC[O:20][CH2:19]C1.Cl.CO[N:26]([CH3:34])[C:27]([CH:29]1[CH2:33][S:32][CH2:31][NH:30]1)=[O:28].CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:19][O:20][CH2:34][NH:26][C:27]([CH:29]1[CH2:33][S:32][CH2:31][N:30]1[C:6]([CH:4]1[CH2:5][S:1][CH2:2][N:3]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:8])=[O:28]
Reactant: CON(C)C(=O)C1CSCN1
Reactant: CN1CCOCC1
Reactant: CC(C)(C)OC(=O)N1CSCC1C(=O)[O-]
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: COCNC(=O)C1CSCN1C(=O)C1CSCN1C(=O)OC(C)(C)C
Yield: 25.6 %

Procedure:
To a stirred solution of 3,4-thiazolidinedicarboxylic acid, 3-(1,1-dimethylethyl) ester (compound from Example IIIA; 0.81 g, 3.49 mmol) and DMAP (0.43 g, 3.49 mmol) in methylene chloride (20 ml) under argon was added NMM (0.38 ml, 3.49 mmol) followed by N-methoxy-N-methyl-4-thiazolidinecarboxamide, monohydrochloride (compound from Example IIIC; 0.76 g, 3.49 mmol) in methylene chloride (10 ml) and water soluble carbodiimide (0.67 g; 3.49 mmol). After the reaction was complete the reaction was concentrated to about 10 ml and loaded onto a 5×13 cm silica gel column and subjected to flash chromatography, eluting with acetone/ethyl acetate (8:92). Product containing fractions were combined (Rf=0.66) and concentrated to give a white foam (0.35 g). Mass spectral analysis of the product gave MH+=392.1324 [expected mass for C15H60N3O5S2 (MH+)=392.1314].
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[C:8]1[N:9]=[C:10]([CH2:13][CH2:14][CH2:15][CH2:16][NH2:17])[NH:11][CH:12]=1.[CH3:18][O-:19].[Na+].CO>>[CH3:18][O:19][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[C:8]1[N:9]=[C:10]([CH2:13][CH2:14][CH2:15][CH2:16][NH2:17])[NH:11][CH:12]=1
Reactant: C[O-]
Reactant: NCCCCc1nc(-c2cnccc2Cl)c[nH]1
Agent: [Na+]
Solvent: CO
Product: COc1ccncc1-c1c[nH]c(CCCCN)n1
Temperature: 70 °C
Yield: 96 %

Procedure:
To a solution of 4-[4-(4-chloro-3-pyridyl)imidazolyl]butylamine (400 mg, mmoles) was added sodium methoxide, 5.3 M in methanol (10 ml, 53 mmoles). The reaction mixture was heated at 70° C. for 2 hours. Upon cooling the reaction mixture was concentrated to around 4 ml and then was taken up in dichloromethane (125 ml) and was washed with water (20 ml). The aqueous layer was extracted further with dichloromethane (125 ml), the combined organics were dried over MgSO4, filtered, and concentrated yielding 4-[4-(4-methoxy-3-pyridyl)imidazolyl]butylamine (379 mg, 96%). MH+(247)
Reaction SMILES: [NH2:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([N+:10]([O-:12])=[O:11])[C:5]([O:13][CH3:14])=[CH:4][C:3]=1[O:15][CH3:16].C(=O)([O-])[O-].[Ca+2].Cl[C:23]([O:25][CH2:26][CH2:27][Cl:28])=[O:24].Cl>O1CCOCC1.O>[Cl:28][CH2:27][CH2:26][O:25][C:23]([NH:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([N+:10]([O-:12])=[O:11])[C:5]([O:13][CH3:14])=[CH:4][C:3]=1[O:15][CH3:16])=[O:24]
Reactant: O=C(Cl)OCCCl
Reactant: COc1cc(OC)c([N+](=O)[O-])c(OC)c1N
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: O
Solvent: C1COCCO1
Product: COc1cc(OC)c([N+](=O)[O-])c(OC)c1NC(=O)OCCCl
Temperature: 90 °C
Reaction time: 0.5 h

Procedure:
0.26 moles (60 g) of 2-amino-4-nitro-1,3,5-trimethoxybenzene are dissolved in 270 ml of dioxane. 26.3 g of calcium carbonate are added and the temperature is then raised to about 90° C. 0.34 moles (48.6 g) of chloroethyl chloroformate are then added with stirring. When the addition is complete, stirring is continued for additional 30 minutes at 90° C. The reaction mixture is diluted with 600 ml of iced water and is then acidified by adding 25 ml of concentrated hydrochloric acid. The precipitate obtained is filtered off and washed with water. After drying, it melts at 133° C.
Reaction SMILES: [CH3:1][NH2:2].C(O)C.[Br:6][C:7]1[C:8]([CH2:17]Br)=[C:9]([CH:14]=[CH:15][CH:16]=1)[C:10](OC)=[O:11]>C1COCC1>[Br:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:9]2[C:8]=1[CH2:17][N:2]([CH3:1])[C:10]2=[O:11]
Reactant: COC(=O)c1cccc(Br)c1CBr
Reactant: CN
Solvent: C1CCOC1
Solvent: CCO
Product: CN1Cc2c(Br)cccc2C1=O
Reaction time: 2 h

Procedure:
A solution of methylamine in ethanol (10 mL, 80 mmol, 8M solution in ethanol) was added to a solution of Methyl 3-Bromo-2-(bromomethyl)benzoate in THF (30 mL). After stirring for 2 h the reaction mixture was concentrated to dryness and water (30 mL) was added with rapid stirring. The solids produced were isolated by filtration and dried to give the desired product
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([N:12]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[CH2:13][CH2:14][CH3:15])[CH2:9]2)=[CH:4][CH:3]=1.[N:22]1([C:28](Cl)=[O:29])[CH2:27][CH2:26]O[CH2:24][CH2:23]1>ClCCl.CCN(C(C)C)C(C)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([N:12]([CH2:13][CH2:14][CH3:15])[CH:16]3[CH2:17][CH2:18][N:19]([C:28]([N:22]4[CH2:27][CH2:26][CH2:24][CH2:23]4)=[O:29])[CH2:20][CH2:21]3)[CH2:9]2)=[CH:4][CH:3]=1
Reactant: CCCN(C1CCNCC1)C1CCc2ccc(Br)cc2C1
Reactant: O=C(Cl)N1CCOCC1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCCN(C1CCN(C(=O)N2CCCC2)CC1)C1CCc2ccc(Br)cc2C1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of the (7-bromo-1,2,3,4-tetrahydro-naphthalen-2-yl)-piperidin-4-yl-propyl-amine (200 μL of 0.25 M in dichloromethane, 50 μmol) was added 220 μL of 0.25 M solution of morpholine 4-carbonyl chloride in dichloromethane and 30 μL of DIEA. The reaction was stirred at 25° C. for 24 h. Concentrated in vacuo. The final product was isolated by preparative RPHPLC (YMC Combiprep ODS-A column, 10-90% acetonitrile: water (0.1% TFA)) to afford {4-[(7-bromo-1,2,3,4-tetrahydro-naphthalen-2-yl)-propyl-amino]-piperidin-1-yl}-pyrrolidin-1-yl-methanone 34 (4.6 mg), [M+H]+=562.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[CH:26]=[O:27]>O1CCCC1>[CH2:12]([O:11][CH2:10][CH2:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([CH:26]=[O:27])=[CH:3][CH:4]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Brc1ccc(CCCOCc2ccccc2)cc1
Reactant: CN(C)C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: O=Cc1ccc(CCCOCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of benzyl 3-(4-bromophenyl)propyl ether (3.59 g, 11.77 mmol) in tetrahydrofuran (32 mL) at −75° C. under an argon atmosphere was added n-butyllithium (1.6 M in hexane, 8.83 mL). The solution was stirred for 15 min, and N,N-dimethylformamide (1.09 mL, 14.13 mmol) was added dropwise. The reaction was stirred for another 30 min and than warmed to room temperature, quenched with aqueous ammonium chloride solution, extracted with tert-butyl methyl ether and concentrated in vacuo. The crude product was purified on silica gel using a hexane/ethyl acetate gradient, and the appropriate fractions were combined and concentrated.
Reaction SMILES: [C:1]([N:4]([CH3:20])[C:5]1[N:10]=[CH:9][C:8]([NH:11][C:12](=[O:19])OCC(Cl)(Cl)Cl)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[C:21]1([C:27]2[N:28]=[C:29]([N:32]3[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]3)[S:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(N(C(C)C)CC)(C)C.CS(C)=O>O>[C:1]([N:4]([CH3:20])[C:5]1[N:10]=[CH:9][C:8]([NH:11][C:12]([N:35]2[CH2:36][CH2:37][N:32]([C:29]3[S:30][CH:31]=[C:27]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[N:28]=3)[CH2:33][CH2:34]2)=[O:19])=[CH:7][CH:6]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)N(C)c1ccc(NC(=O)OCC(Cl)(Cl)Cl)cn1
Reactant: c1ccc(-c2csc(N3CCNCC3)n2)cc1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: CC(=O)N(C)c1ccc(NC(=O)N2CCN(c3nc(-c4ccccc4)cs3)CC2)cn1
Yield: 44.5 %

Procedure:
A solution of 2,2,2-trichloroethyl {6-[acetyl(methyl)amino]pyridin-3-yl}carbamate (200 mg, 0.587 mmol), 1-(4-phenyl-1,3-thiazol-2-yl)piperazine (144 mg, 0.587 mmol), diisopropylethylamine (0.102 ml, 0.587 mmol) and dimethylsulfoxide (4 ml) was stirred at 70° C. for 12 hours, the reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate and hexane to obtain the desired product (114 mg, 44.5%) as a solid.
Reaction SMILES: O[Li].O.O.C([O:9][C:10]([C:12]1([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22](=[O:40])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][C:28]2([C:33]([O:35]CCCC)=[O:34])[CH2:32][CH2:31][CH2:30][CH2:29]2)[CH2:16][CH2:15][CH2:14][CH2:13]1)=[O:11])CCC>CCO>[C:33]([C:28]1([CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][C:22](=[O:40])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][C:12]2([C:10]([OH:11])=[O:9])[CH2:16][CH2:15][CH2:14][CH2:13]2)[CH2:29][CH2:30][CH2:31][CH2:32]1)([OH:35])=[O:34]
Reactant: CCCCOC(=O)C1(CCCCCC(=O)CCCCCC2(C(=O)OCCCC)CCCC2)CCCC1
Agent: [Li]O
Solvent: CCO
Solvent: O
Product: O=C(CCCCCC1(C(=O)O)CCCC1)CCCCCC1(C(=O)O)CCCC1
Temperature: 25 °C
Yield: 74.2 %

Procedure:
LiOH·H2O (7.83 g, 187 mmol) and H2O (100 mL) were added to a solution of butyl 1-{11-[1-(butoxycarbonyl)cyclopentyl]-6-oxoundecyl}-1-cyclopentanecarboxylate (21.03 g, 90% pure by 1H NMR, 37.3 mmol) in EtOH (300 mL) and the resulting mixture was stirred at reflux temperature for 2 d, allowed to cool to rt and concentrated in vacuo to a smaller volume. H2O (100 mL) was added and the resulting mixture was extracted with Et2O (100 mL), acidified with conc aqueous HCl (25 mL) and extracted with Et2O (3×150 mL). The latter organic layers were combined, dried (Na2SO4; To avoid loss of material, a minimal amount of Na2SO4 was used, with the desiccant becoming a white, oily paste. The organic layer was decanted from the desiccant.) and evaporated in vacuo. The remaining residue was purified by recrystallization from a mixture of iPr2O and heptane to give 1-[11-(1-carboxycyclopentyl)-6-oxoundecyl]-1-cyclopentanecarboxylic acid (12.15 g, 83%) as white granules. mp=78-85° C. 1H NMR (CDCl3): δ=2.37 (t, J=7.4 Hz, 4H), 2.18-2.10 (m, 4H), 1.65-1.45 (m, 20H), 1.29-1.25 (m, 8H). 13C NMR (CDCl3): δ=211.5, 184.8 (2×), 54.0 (2×), 42.4 (2×), 38.9 (2×), 35.9 (4×), 29.2 (2×), 25.5 (2×), 24.9 (4×), 23.5 (2×). Anal. calcd for C23H38O5: C, 70.02; H, 9.71. found: C, 70.37; H, 9.72.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]Cl)=[CH:4][C:3]=1[Cl:10].[NH:11]1[CH2:16][CH2:15][CH:14](NC(=O)OC(C)(C)C)[CH2:13][CH2:12]1.C[N:26](C=O)C>C(N(CC)CC)C>[Cl:10][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:2]=1[Cl:1])[CH2:8][N:11]1[CH2:12][CH2:13][CH2:14][CH2:15][CH:16]1[NH2:26]
Reactant: ClCc1ccc(Cl)c(Cl)c1
Reactant: CN(C)C=O
Reactant: CC(C)(C)OC(=O)NC1CCNCC1
Solvent: CCN(CC)CC
Product: NC1CCCCN1Cc1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
1,2-dichloro-4-(chloromethyl)benzene (390 mg, 1.99 mmol)) was added to a solution of tert-butyl 4-piperidinylcarbamate (400 mg, 2.0 mmol) in DMF (25 ml) and triethylamine (2 ml). The solution was stirred at room temperature for 3 hrs and then concentrated in vacuo. To the solution of the solid in dichloromethane was added (30 ml) trifluoroacetic acid (6 ml) was added and stirred at room temperature for 2 hrs. The solution was diluted with dichloromethane and washed with two portions of water. The combined water washings were treated with 2M NaOH to pH 10 and extracted with ether. The ether was dried (Na2SO4), filtered and evaporated to leave a yellow residue (300 mg, 1.16 mmol).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5](/[C:8](/[CH3:15])=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.[F:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1>>[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:2]2[CH:7]=[CH:6][C:5](/[C:8](/[CH3:15])=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=2)=[CH:19][CH:18]=1
Reactant: OB(O)c1ccc(F)cc1
Reactant: CCOC(=O)/C=C(\C)c1ccc(I)cc1
Product: CCOC(=O)/C=C(\C)c1ccc(-c2ccc(F)cc2)cc1

Procedure:
The colourless solid (E)-ethyl 3-(4′-fluoro-biphenyl-4-yl)-but-2-enoate was prepared from (E)-ethyl 3-(4-iodophenyl)-but-2-enoate (example 91 a) and 4-fluorobenzene boronic acid by a procedure analogous to that described in example 52a.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:16]2[CH2:15][CH2:14][NH:13][CH2:12][C:11]=2[CH:10]=[C:9]1[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1.[CH3:25][S:26](Cl)(=[O:28])=[O:27]>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:16]2[CH2:15][CH2:14][N:13]([S:26]([CH3:25])(=[O:28])=[O:27])[CH2:12][C:11]=2[CH:10]=[C:9]1[C:17]1[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=1
Reactant: COc1ccc(-c2cc3c(n2-c2ccccc2Cl)CCNC3)cc1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Product: COc1ccc(-c2cc3c(n2-c2ccccc2Cl)CCN(S(C)(=O)=O)C3)cc1
Reaction time: 4 h
Yield: 40 %

Procedure:
To an 8-mL vial charged with piperidinomethyl polystyrene (3.57 mmol/g, 99.2 mg, 0.354 mmol) and a solution of 1-(2-chlorophenyl)-2-(4-methoxyphenyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine (Example 2), 40.0 mg, 0.118 mmol) in 4 mL dichloromethane was added methanesulfonyl chloride (18.2 μL, 0.236 mmol). The reaction mixture was mixed by orbital shaking for 4 h. The solid was removed by filtration. The filtrate was evaporated, and the residue was purified by preparative reversed-phase HPLC to give a solid (19.8 mg, 40%): Rf=0.20 (1:2 EtOAc/hexanes).
Reaction SMILES: [F:1][C:2]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][OH:18])([C:7]([F:10])([F:9])[F:8])[C:3]([F:6])([F:5])[F:4].[S:19](=[O:23])(=[O:22])([OH:21])[NH2:20]>CCCCCC>[S:19]([O-:21])([O-:11])(=[O:23])=[O:22].[NH4+:20].[F:1][C:2]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][OH:18])([C:7]([F:9])([F:10])[F:8])[C:3]([F:6])([F:5])[F:4].[NH4+:20]
Reactant: NS(=O)(=O)O
Agent: OCCCCCCOC(F)(C(F)(F)F)C(F)(F)F
Solvent: CCCCCC
Product: O=S(=O)([O-])[O-]
Product: [NH4+]
Reaction time: 1 h

Procedure:
6-Hydroxyhexyl perfluoroisopropyl ether (15.5 g, 0.05 m) and sulfamic acid (5.1 g, 0.05 m) were combined and heated with stirring at 145° for one hour. Hexane (25 ml) was added to the cooled reaction mixture to remove unreacted alcohol. Filtration and vacuum drying gave a brown soft solid product, 6-hydroxyhexyl perfluoroisopropyl ether ammonium sulfate which was designated as Product I (B). IR analysis showed the following major absorption bands: 3200, 2935, 2860, 1430, 1210 cm-1.
Reaction SMILES: [Br:1][C:2]1[C:15]2[S:14][C:13]3[C:8](=[CH:9][CH:10]=[C:11]([O:16][CH3:17])[CH:12]=3)[N:7]([C:18]([O:20][CH:21](Cl)[CH3:22])=[O:19])[C:6]=2[CH:5]=[C:4]([O:24][CH3:25])[C:3]=1[OH:26].[C:27]([OH:30])(=[O:29])[CH3:28]>C(OCC)(=O)C>[C:27]([O:30][CH:21]([O:20][C:18]([N:7]1[C:6]2[CH:5]=[C:4]([O:24][CH3:25])[C:3]([OH:26])=[C:2]([Br:1])[C:15]=2[S:14][C:13]2[C:8]1=[CH:9][CH:10]=[C:11]([O:16][CH3:17])[CH:12]=2)=[O:19])[CH3:22])(=[O:29])[CH3:28]
Reactant: CC(=O)O
Reactant: COc1ccc2c(c1)Sc1c(cc(OC)c(O)c1Br)N2C(=O)OC(C)Cl
Solvent: CCOC(C)=O
Product: COc1ccc2c(c1)Sc1c(cc(OC)c(O)c1Br)N2C(=O)OC(C)OC(C)=O

Procedure:
A mixture of 4-bromo-10-(1-chloroethoxycarbonyl)-2,7-dimethoxy-3-hydroxy-10H-phenothiazine (1 g) and mercuric acetate (1.46 g) in glacial acetic acid (30 ml) was stirred and heated at 85° for 10 minutes. After cooling the mixture was diluted with ethyl acetate, washed with water, aqueous NaHCO3 solution, and brine, dried and evaporated. Flash chromatography on a column of silica gel, eluting with a 1:3 mixture of ethyl acetate and hexane, afforded the pure title product (599 mg) m.p.: 162°-164° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]([OH:15])=O)=[CH:9]2)([O-:3])=[O:2].N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl.[C:39]([S:58][CH2:59][CH2:60][NH2:61])([C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>CN(C)C=O.O.C(N(CC)CC)C>[N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]([NH:61][CH2:60][CH2:59][S:58][C:39]([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)([C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)=[O:15])=[CH:9]2)([O-:3])=[O:2]
Reactant: O=C(O)c1cc2cccc([N+](=O)[O-])c2[nH]1
Reactant: NCCSC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: O=C(NCCSC(c1ccccc1)(c1ccccc1)c1ccccc1)c1cc2cccc([N+](=O)[O-])c2[nH]1
Yield: 95.7 %

Procedure:
A solution of 7-nitro-1H-indole-2-carboxylic acid (4.4 g), 1H-1,2,3-benzotriazol-1-ol (3.8 g), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (4.8 g), 2-(tritylthio)ethylamine hydrochloride (7.4 g) and triethylamine (3.5 mL) in N,N-dimethylformamide (50 mL) was stirred at room temperature for 4 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was crystallized from diethyl ether-hexane to give the title compound (10.1 g, yield 95%) as yellow crystals.