Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][OH:6].F[C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]=1[C:17]([F:20])([F:19])[F:18].[H-].[Na+].CN(C=O)C>C1COCC1>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][O:6][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]=1[C:17]([F:18])([F:20])[F:19]
Reactant: O=C(O)c1ccc(F)c(C(F)(F)F)c1
Reactant: COCCCO
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: COCCCOc1ccc(C(=O)O)cc1C(F)(F)F
Temperature: 25 °C
Reaction time: 16 h
Yield: 31.9 %

Procedure:
3-Methoxypropan-1-ol (217 mg, 2.40 mmol), 4-fluoro-3-(trifluoromethyl)benzoic acid (500 mg, 2.40 mmol), and NaH (240 mg, 6.0 mmol) were combined in THF (10 mL) and DMF (1 mL) at 0° C. under an atmosphere of nitrogen. The reaction mixture was stirred for 16 h at room temperature. The reaction mixture was partitioned between ethyl acetate and a 1M aqueous solution of hydrochloric acid. The layers were separated and then the organic layer was washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, and evaporated to dryness. The crude material was purified by column chromatography utilizing a gradient of 0-5% methanol in dichloromethane to yield 4-(3-methoxypropoxy)-3-(trifluoromethyl)benzoic acid (213 mg, 32%) as a white solid. ESI-MS m/z calc. 278.1. found 279.3 (M+1)+; Retention time: 1.38 minutes (3 min run). 4-Propoxy-3-(trifluoromethyl)benzoic acid was prepared from 4-fluoro-3-(trifluoromethyl)benzoic acid and 3-fluoro-4-(2-methoxyethoxy)benzoic acid was prepared from 3,4-difluorobenzoic acid using the procedure described above.
Reaction SMILES: CO[C:3]([C:5]1[N:6]=[C:7]([C:23]#[N:24])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=[O:4].[NH2:25][CH2:26][C@H:27]([OH:31])[C:28]([OH:30])=[O:29].C[O-].[Na+].CO>>[C:23]([C:7]1[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:9]=2)[C:14]([OH:15])=[C:5]([C:3]([NH:25][CH2:26][C@H:27]([OH:31])[C:28]([OH:30])=[O:29])=[O:4])[N:6]=1)#[N:24]
Reactant: NC[C@H](O)C(=O)O
Reactant: COC(=O)c1nc(C#N)c2cc(Oc3ccccc3)ccc2c1O
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: N#Cc1nc(C(=O)NC[C@H](O)C(=O)O)c(O)c2ccc(Oc3ccccc3)cc12
Yield: 93.5 %

Procedure:
A mixture of 1-cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (100 mg, 0.31 mmol) and 3-amino-2-(S)-hydroxy-propionic acid (99 mg, 0.94 mmol) (Sigma-Aldrich) in 0.5 M NaOMe/MeOH (1.25 mL, 0.63 mmol) was microwaved at 120° C. for 1 h. Reaction mixture was concentrated and the residue was dissolved in water (70 mL). It was acidified by 1 N HCl to pH=3-4 and then extracted with EtOAc. Organic layer was washed with brine, dried over MgSO4, filtered and concentrated to provide the title compound 113 mg (0.29 mmol) in 93% yield. LC-MS ESI−: 391.98 (M−1)−.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12](=[O:17])[CH2:11][CH2:10]2.[CH3:18][C:19]1[CH:20]=[C:21]([SH:25])[CH:22]=[CH:23][CH:24]=1>>[CH3:18][C:19]1[CH:20]=[C:21]([S:25][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[NH:13][C:12](=[O:17])[CH2:11][CH2:10]3)[CH:22]=[CH:23][CH:24]=1
Reactant: Cc1cccc(S)c1
Reactant: O=C1CCc2cc(OCCCCCl)ccc2N1
Product: Cc1cccc(SCCCCOc2ccc3c(c2)CCC(=O)N3)c1

Procedure:
Prepared analogous to Example 1 from 6-(4-chloro-butoxy)-3,4-dihydro-carbostyril (m.p. 147°-148° C.) and 3-methyl-thiophenol.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])[C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[C:13](F)[CH:12]=2)[CH:8]=[N:7][CH:6]=1)[CH3:2].C([O-])(=[O:23])C.[K+].C1OCCOCCOCCOCCOCCOC1.C(=O)([O-])[O-].[Na+].[Na+]>CC#N>[CH2:1]([O:3][C:4](=[O:20])[C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[C:13]([OH:23])[CH:12]=2)[CH:8]=[N:7][CH:6]=1)[CH3:2]
Reactant: CC(=O)[O-]
Reactant: CCOC(=O)c1cncc(-c2ccc(C#N)c(F)c2)c1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)c1cncc(-c2ccc(C#N)c(O)c2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 5-(4-cyano-3-fluoro-phenyl)-nicotinic acid ethyl ester from Example 1a, potassium acetate (2 equiv.), and 18-crown-6 ether (2 equiv.) in MeCN is heated at reflux in 36 h. The mixture is cooled, aqueous sodium carbonate is added and stirred at room temperature overnight. The mixture was extracted with ether (discarded). The aqueous layer is neutralized with 1N HCl, extracted with EtOAc, dried over MgSO4, and concentrated. Purification by flash column chromatography gives 5-(4-cyano-3-hydroxy-phenyl)-nicotinic acid ethyl ester.
Reaction SMILES: [NH2:1][C:2]1[C:3]([Cl:12])=[C:4]([CH:8]=[C:9]([Cl:11])[CH:10]=1)[C:5]([OH:7])=[O:6].S(=O)(=O)(O)O.[OH-].[Na+].[CH3:20]O>O>[NH2:1][C:2]1[C:3]([Cl:12])=[C:4]([CH:8]=[C:9]([Cl:11])[CH:10]=1)[C:5]([O:7][CH3:20])=[O:6]
Reactant: CO
Reactant: Nc1cc(Cl)cc(C(=O)O)c1Cl
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: COC(=O)c1cc(Cl)cc(N)c1Cl
Reaction time: 3 h
Yield: 79 %

Procedure:
3-amino-2,5-dichlorobenzoic acid (5.00 g, 24.27 mmol) was stirred in methanol (30 ml) at room temperature. Sulfuric Acid (5 ml) was added dropwise. Reaction stirred for 3 hours and was then diluted with water (30 ml) and basified using sodium hydroxide. Mixture was extracted with ethyl acetate×3. Solvent was removed to afford methyl 3-amino-2,5-dichlorobenzoate (4.20 g, 79%) as a solid.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:42])[C@@H:13]([NH:22][C:23]([C:25]2[CH:34]=[C:33]([O:35][C@H:36]([C:38]([OH:40])=O)[CH3:37])[C:32]3[C:27](=[CH:28][C:29]([CH3:41])=[CH:30][CH:31]=3)[N:26]=2)=[O:24])[CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:8][CH2:7]1)=[O:5])[CH3:2].C(Cl)CCl.FC1C(O)=C(F)C(F)=C(F)C=1F.FC(F)(F)C(O)=O.[CH:66]1([NH:71][C:72]([C@@H:74]2[CH2:78][CH2:77][CH2:76][NH:75]2)=[O:73])[CH2:70][CH2:69][CH2:68][CH2:67]1>CN(C=O)C.O>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:42])[C@@H:13]([NH:22][C:23]([C:25]2[CH:34]=[C:33]([O:35][C@@H:36]([CH3:37])[C:38]([N:75]3[CH2:76][CH2:77][CH2:78][C@H:74]3[C:72](=[O:73])[NH:71][CH:66]3[CH2:67][CH2:68][CH2:69][CH2:70]3)=[O:40])[C:32]3[C:27](=[CH:28][C:29]([CH3:41])=[CH:30][CH:31]=3)[N:26]=2)=[O:24])[CH2:14][C:15]([O:17][C:18]([CH3:20])([CH3:21])[CH3:19])=[O:16])[CH2:10][CH2:11]1)=[O:5])[CH3:2]
Reactant: O=C(NC1CCCC1)[C@@H]1CCCN1
Reactant: CCOC(=O)N1CCN(C(=O)[C@H](CC(=O)OC(C)(C)C)NC(=O)c2cc(O[C@@H](C)C(=O)O)c3ccc(C)cc3n2)CC1
Agent: Oc1c(F)c(F)c(F)c(F)c1F
Solvent: O=C(O)C(F)(F)F
Solvent: O
Solvent: ClCCCl
Product: CCOC(=O)N1CCN(C(=O)[C@H](CC(=O)OC(C)(C)C)NC(=O)c2cc(O[C@@H](C)C(=O)N3CCC[C@H]3C(=O)NC3CCCC3)c3ccc(C)cc3n2)CC1
Reaction time: 2 h

Procedure:
To a solution of 146 mg of 4-((S)-3-tert-Butoxycarbonyl-2-{[4-((S)-1-carboxy-ethoxy)-7-methyl-quinoline-2-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester in 1 ml of DMF, 52 mg of EDC, 34 mg of pentafluorophenol and 24 mg of NEM was added and the reaction mixture was stirred for 2 h. Then, 62 mg of (S)-Pyrrolidine-2-carboxylic acid cyclopentylamide trifluoroacetate and 20 mg of NEM in 2 ml of DMF was added. After 1 h the reaction mixture was diluted with water. After filtration through a chem Elut® cartridge by eluting with ethyl acetate the solvents were removed under reduced pressure. The isolated crude product was pure enough for the next reaction step.
Reaction SMILES: C([O:4][C@H:5]1[C@H:10]([O:11]C(=O)C)[C@@H:9]([O:15]C(=O)C)[C@H:8]([C:19]2[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[C:21]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH:36]=[N:37][O:38][CH3:39])=[CH:30][CH:29]=3)[CH:20]=2)[O:7][C@@H:6]1[CH2:40][O:41]C(=O)C)(=O)C.CO.O.O.[OH-].[Li+]>C1COCC1>[CH3:39][O:38][N:37]=[CH:36][CH2:35][O:34][C:31]1[CH:30]=[CH:29][C:28]([CH2:27][C:21]2[CH:20]=[C:19]([C@H:8]3[C@H:9]([OH:15])[C@@H:10]([OH:11])[C@H:5]([OH:4])[C@@H:6]([CH2:40][OH:41])[O:7]3)[CH:24]=[CH:23][C:22]=2[C:25]#[N:26])=[CH:33][CH:32]=1
Reactant: CON=CCOc1ccc(Cc2cc([C@@H]3O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]3OC(C)=O)ccc2C#N)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: CON=CCOc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)ccc2C#N)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.4 %

Procedure:
To a solution of (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-cyano-3-(4-(2-(methoxyimino)ethoxy)benzyl)phenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (60.0 mg, 0.10 mmol), in THF (0.33 mL), methanol (0.5 mL) and water (0.16 mL) was added lithium hydroxide monohydrate (5.37 mg, 0.12 mmol) at 0° C. The reaction was stirred at r.t. for 1 h. After the completion of reaction as confirmed by TLC, volatiles were evaporated in vacuo and the compound was diluted with ethyl acetate (20 mL). The organic layer was washed with water (5 mL), dried over Na2SO4 and concentrated to afford title compound (40 mg, 93%) as a white solid.
Reaction SMILES: [Cl:1][C:2]1[C:3](O)=[N:4][C:5]([C:8]2[S:9][CH:10]=[CH:11][CH:12]=2)=[N:6][CH:7]=1.P(Br)(Br)([Br:16])=O.CN(C)C1C=CC=CC=1>C1(C)C=CC=CC=1>[Br:16][C:3]1[C:2]([Cl:1])=[CH:7][N:6]=[C:5]([C:8]2[S:9][CH:10]=[CH:11][CH:12]=2)[N:4]=1
Reactant: O=P(Br)(Br)Br
Reactant: Oc1nc(-c2cccs2)ncc1Cl
Solvent: Cc1ccccc1
Solvent: CN(C)c1ccccc1
Product: Clc1cnc(-c2cccs2)nc1Br
Temperature: 100 °C
Reaction time: 1 h

Procedure:
A mixture of 5-chloro-2-(thiophen-2-yl)pyrimidin-4-ol (90 mg, 0.42 mmol, 1.0 equiv.), POBr3 (364 mg, 1.27 mmol, 3.0 equiv.) and N,N-dimethylbenzenamine (103 mg, 0.85 mmol, 2.0 equiv.) in toluene (5 mL) was stirred at 100° C. for 1 h, then poured into crashed ice. The mixture was extracted with ethyl acetate. The combined organic layers were washed over saturated NaHCO3, brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to afford 4-bromo-5-chloro-2-(thiophen-2-yl)pyrimidine, which was directly used for the next step. LC-MS (m/z)=275.0 [M+H]+.
Reaction SMILES: [CH3:1][C:2]([CH3:18])([CH:4]1[CH:8]([CH3:9])[O:7][C:6]([C:14]([Cl:17])([F:16])[F:15])([C:10]([Cl:13])([F:12])[F:11])[O:5]1)[OH:3].[O-:19][C:20]#[N:21].[Na+].FC(F)(F)C(O)=O.O>C(Cl)Cl>[C:20]([O:3][C:2]([CH3:1])([CH3:18])[CH:4]1[CH:8]([CH3:9])[O:7][C:6]([C:14]([Cl:17])([F:16])[F:15])([C:10]([Cl:13])([F:11])[F:12])[O:5]1)(=[O:19])[NH2:21]
Reactant: N#C[O-]
Reactant: CC1OC(C(F)(F)Cl)(C(F)(F)Cl)OC1C(C)(C)O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: CC1OC(C(F)(F)Cl)(C(F)(F)Cl)OC1C(C)(C)OC(N)=O
Reaction time: 24 h

Procedure:
A solution of 31.5 grams (0.1 mol) of α,α,5-trimethyl-2,2-bis(chlorodifluoromethyl)-1,3-dioxolane-4-methanol in 180 ml methylene dichloride is treated with 13.0 grams sodium cyanate (0.2 mol) while 22.8 grams of trifluoroacetic acid (0.2 mol) is added dropwise. The reaction is carried out at 25°-35° C. for 24 hours. After the reaction is completed, a small amount of water is added to dissolve salts and the methylene dichloride solution is separated and extracted once more with water. Vacuum stripping yields the product α,α,5-trimethyl-2,2-bis(chlorodifluoromethyl)-1,3-dioxolane-4-methanol carbamate. The product is purified by crystallization from a mixture of benzene and hexane.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]([O:19][C:20](=[O:23])[NH:21][NH2:22])([CH3:18])([CH3:17])[CH3:16]>CCCCCC>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[N:22][NH:21][C:20]([O:19][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: CC(C)(C)OC(=O)NN
Solvent: CCCCCC
Product: CC(C)(C)OC(=O)NN=C1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of 0.15 mole of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (commercially available) and 0.15 mole of tert-butylcarbazate in 250 ml of hexane is stirred for 18 h at RT. The precipitate is filtered off and dried under vacuum. M. p. 172–174° C.
Reaction SMILES: Br[CH2:2][C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][CH2:6]1)=O.[C:19]([NH2:27])(=[S:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CCO>[C:11]([N:8]1[CH2:9][CH2:10][CH:5]([C:3]2[S:26][C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:27][CH:2]=2)[CH2:6][CH2:7]1)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C(CBr)C1CCN(C(=O)c2ccccc2)CC1
Reactant: NC(=S)c1ccccc1
Solvent: CCO
Product: O=C(c1ccccc1)N1CCC(c2cnc(-c3ccccc3)s2)CC1
Temperature: 80 °C
Reaction time: 2 h
Yield: 32.8 %

Procedure:
To 150 mg of 2-bromo-1-(1-benzoyl-4-piperidyl)-1-ethanone in 6 ml of EtOH was added 66 mg of thiobenzamide. The reaction was stirred at 80° C. for 2 hours. The solvent was evaporated under reduced pressure. The residue was purified by flash chromatography with 50% EtOAc in hexane to give 55 mg of the title compound.
Reaction SMILES: S(Cl)(Cl)=O.[CH2:5]([O:7][P:8]([CH:13](O)[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)(=[O:12])[O:9][CH2:10][CH3:11])[CH3:6].C(Cl)[Cl:23].N1C=CC=CC=1>O>[CH2:5]([O:7][P:8]([CH:13]([Cl:23])[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)(=[O:12])[O:9][CH2:10][CH3:11])[CH3:6]
Reactant: CCOP(=O)(OCC)C(O)c1ccc(Cl)cc1
Reactant: ClCCl
Solvent: c1ccncc1
Solvent: O=S(Cl)Cl
Solvent: O
Product: CCOP(=O)(OCC)C(Cl)c1ccc(Cl)cc1
Temperature: 0 °C
Reaction time: 12 h
Yield: 97.5 %

Procedure:
9.2 g (0.0768 mol) of thionyl chloride were added to a mixture of 20.2 g (0.0725 mol) of 4-chloro-α-hydroxybenzylphosphonic acid diethyl ester, 65 g of methylene chloride and 5.8 g (0.0725 mol) of pyridine at 20°-40° C. in the course of about 1 hour, while cooling slightly with water. The reaction mixture was then heated under reflux for 3 hours and subsequently stirred for 12 hours, without further action of heat. The mixture was poured onto about 100 g of ice-water and the organic phase was separated off and dried. After distilling off the solvent, the residue was concentrated under 6 mm Hg and at 45° C. 21 g (97.7% of theory) of 4-chloro-α-chloro-benzylphosphonic acid diethyl ester were obtained as a yellow viscous oil with a purity of 98.6% (gas chromatogram) and a refractive index of nD24 : 1.5250.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH:8]=[CH:7]2.[Br:13]Br>ClCCl>[Br:13][C:7]1[C:6]2[C:11](=[C:2]([CH3:1])[CH:3]=[CH:4][CH:5]=2)[C:10](=[O:12])[NH:9][CH:8]=1
Reactant: Cc1cccc2cc[nH]c(=O)c12
Reactant: BrBr
Solvent: ClCCl
Product: Cc1cccc2c(Br)c[nH]c(=O)c12
Reaction time: 1 h
Yield: 108.1 %

Procedure:
To a solution of 8-methyl-2H-isoquinolin-1-one (1.15 g) in dichloromethane (20 ml) was added dropwise a solution of bromine (1.26 g) in dichloromethane (4 ml) at room temperature. The mixture was stirred at the same temperature for one hour, and the solvent was evaporated under reduced pressure. The residue was crystallized from ether to give 4-bromo-8-methyl-2H-isoquinolin-1-one (1.86 g) as colorless crystals. APCI-Mass m/Z 238/240 (M+H). (2) The above 4-bromo-8-methyl-2H-isoquinolin-1-one was treated in a manner similar to Reference Example 2 to give the target compound as colorless crystals. APCI-Mass m/Z 356/358M+H).
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([Cl:17])=[CH:16][C:11]=3[N:10]=[C:9]2[C:18]([OH:21])([CH3:20])[CH3:19])[CH2:4][CH2:3]1.[Br:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[CH2:28][C@H:27]([CH:32]=O)[CH2:26]2>>[Br:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[CH2:28][C@H:27]([CH2:32][NH:1][C@@H:2]1[CH2:3][CH2:4][C@H:5]([N:8]3[C:12]4[CH:13]=[CH:14][C:15]([Cl:17])=[CH:16][C:11]=4[N:10]=[C:9]3[C:18]([OH:21])([CH3:19])[CH3:20])[CH2:6][CH2:7]1)[CH2:26]2
Reactant: O=C[C@H]1Cc2ccc(Br)cc2C1
Reactant: CC(C)(O)c1nc2cc(Cl)ccc2n1[C@H]1CC[C@@H](N)CC1
Product: CC(C)(O)c1nc2cc(Cl)ccc2n1[C@H]1CC[C@@H](NC[C@H]2Cc3ccc(Br)cc3C2)CC1

Procedure:
This compound was prepared from the hydrochloride salt of cis-2-[1-(4-amino-cyclohexyl)-5-chloro-1H-benzoimidazol-2-yl]-propan-2-ol and (S)-5-bromo-indan-2-carbaldehyde. LC-MS showed a single peak, C26H31BrClN3O (m/e) calcd 515.1339, obsd 516.1 (M+H). 1H-NMR (CD3OD) □ 7.96 (d, 1H), 7.59 (s, 1H), 7.36 (s, 1H), 7.26 (d, 1H), 7.18 (d, 1H), 7.12 (d, 1H), 5.38 (m, 1H), 3.16 (m, 2H), 3.03 (br s, 1H), 2.67-2.83 (m, 7H), 2.07 (m, 2H), 1.72 (br s, 10H).