Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH3:8])[NH:5][C:4]2=[CH:9][C:10]([CH3:12])=[N:11][C:3]=12.[NH2:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C([O-])([O-])=O.[K+].[K+]>O>[CH3:8][C:6]1[NH:5][C:4]2[C:3]([N:11]=[C:10]([CH3:12])[CH:9]=2)=[C:2]([NH:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[N:7]=1
Reactant: Cc1cc2[nH]c(C)nc(Cl)c-2n1
Reactant: NCCN1CCOCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: Cc1cc2[nH]c(C)nc(NCCN3CCOCC3)c-2n1
Yield: 25.1 %

Procedure:
This compound was prepared according to the method described in Example 46(e) by employing 4-chloro-2,6-dimethylpyrrolo[3,2-d]pyrimidine (Example 46(d)) (0.10 g, 0.55 mmol) with 4-(2-aminoethyl)morpholine (Aldrich Chemical Company) (0.388 mL, 2.95 mmol) and K2CO3 (0.36 g, 2.6 mmol) in water (2.5 mL) to give 0.038 g (25%) of the title compound as an off-white solid after recrystallization from EtOAc. Mp: 237-238.5° C. 1H NMR (CDCl3; 500 MHz): δ 2.43 (s, 3), 2.50 (t, 4, J=5.2), 2.58 (s, 3), 2.65 (t, 2, J=5.7), 3.67 (t, 4, J=4.6), 3.70 (q, 2, J=5.4), 5.55 (br s, 1), 6.18 (s, 1), 9.88 (br s, 1). MS m/z: 276 (M+1). Anal. Calcd for C14H21N5O: C, 61.07; H, 7.69; N 25.43. Found: C, 61.19; H, 7.77; N, 25.39.
Reaction SMILES: [CH2:1]([C:8]1[C:12]2[C:13](Cl)=[N:14][CH:15]=[CH:16][C:11]=2[NH:10][C:9]=1[CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22][CH2:21][NH:20]1>>[CH2:1]([C:8]1[C:12]2[C:13]([N:20]3[CH2:21][CH2:22][C:23]4[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:19]3)=[N:14][CH:15]=[CH:16][C:11]=2[NH:10][C:9]=1[CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1[nH]c2ccnc(Cl)c2c1Cc1ccccc1
Reactant: c1ccc2c(c1)CCNC2
Product: Cc1[nH]c2ccnc(N3CCc4ccccc4C3)c2c1Cc1ccccc1
Yield: 89.7 %

Procedure:
In accordance with the same procedures as Example 1, except for using 3-benzyl-4-chloro-2-methyl-1H-pyrrolo[3,2-c]pyridine prepared in Preparation 2 and 1,2,3,4-tetrahydroisoquinoline, the titled compound was obtained as a pale yellow solid. (Yield: 89.7%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][C:12]2=[O:20])=[O:10])=[CH:4][CH:3]=1.[C:21](OC(=O)C)(=[O:23])[CH3:22].Cl>CN(C)C=O.CN(C1C=CN=CC=1)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]([C:21](=[O:23])[CH3:22])[C:12]2=[O:20])=[O:10])=[CH:6][CH:7]=1
Reactant: O=C1Cc2ccccc2N1C(=O)Nc1ccc(F)cc1
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CN(C)C=O
Product: CC(=O)C1C(=O)N(C(=O)Nc2ccc(F)cc2)c2ccccc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 64 %

Procedure:
To a stirred slurry of 811 mg (3.0 mmole) of N-(4-fluorophenyl)-2-oxindole-1-carboxamide in 4 ml of N,N-dimethylformamide was added 806 mg (6.6 mmole) of 4-(N,N-dimethylamino)pyridine. Stirring was continued for a few minutes, and then the slurry was cooled in an ice-bath and a solution of 337 mg (3.3 mmole) of acetic anhydride in 2 ml of N,N-dimethylformamide was added. Stirring was continued for 1 hour, and then the reaction mixture was poured onto a mixture of 60 ml of ice-water and 2.2 ml of 3N hydrochloric acid. The solid which precipitated was recovered by filtration. It was recrystallized from acetonitrile to give 600 mg of the title compound as dark crystals, mp 181°-182° C.
Reaction SMILES: Cl[C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[C:5]([CH3:14])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:21]1([CH2:24][NH:25][CH2:26][CH:27]2[CH2:29][CH2:28]2)[CH2:23][CH2:22]1>CN(C=O)C>[CH:21]1([CH2:24][N:25]([CH2:26][CH:27]2[CH2:29][CH2:28]2)[C:2]2[C:11]([CH:12]=[O:13])=[CH:10][C:9]3[C:4](=[C:5]([CH3:14])[CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH2:23][CH2:22]1
Reactant: Cc1cccc2cc(C=O)c(Cl)nc12
Reactant: C1CC1CNCC1CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cccc2cc(C=O)c(N(CC3CC3)CC3CC3)nc12
Temperature: 25 °C
Yield: 49.2 %

Procedure:
2-Chloro-8-methyl-quinoline-3-carbaldehyde (0.115 g, 0.559 mmol), and potassium carbonate (0.231 g, 1.67 mmol) were put in a 25 mL two necked RB flask. To this, 3 mL of DMF was added followed by dropwise addition of bis-cyclopropylmethyl amine (0.083 g, 0.67 mmol). The reaction mixture was refluxed for 2 h and was cooled to RT. It was then poured on crushed ice (10 mL) and extracted with EtOAc (3×10 mL). The organic layer was washed with brine and dried over sodium sulphate. The solvent was evaporated under vacuum to give a yellow colored oil (0.081 g, 50%).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH3:12])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH2:13]([O:15][C:16](=[O:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]Br)[CH3:14].[H-].[Na+]>CN(C=O)C>[CH2:13]([O:15][C:16](=[O:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][N:11]([CH3:12])[S:8]([C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=1)(=[O:10])=[O:9])[CH3:14]
Reactant: CNS(=O)(=O)c1ccc(C)cc1
Reactant: CCOC(=O)CCCCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)CCCCCCCN(C)S(=O)(=O)c1ccc(C)cc1

Procedure:
4,N-Dimethylbenzenesulphonamide was reacted with ethyl-8-bromooctanoate in DMF under the influence of sodium hydride to obtain 8-[Methyl-(toluene-4-sulfonyl)-amino]-octanoic acid ethyl ester
Reaction SMILES: Cl.[NH2:2][CH:3]1[CH2:7][C:6]([F:9])([F:8])[CH2:5][CH:4]1[NH:10][C:11](=[O:23])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N:18]1[N:22]=[CH:21][CH:20]=[N:19]1.Cl[C:25]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][N:26]=1.CCN(C(C)C)C(C)C>CS(C)=O>[F:8][C:6]1([F:9])[CH2:5][CH:4]([NH:10][C:11](=[O:23])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:18]2[N:19]=[CH:20][CH:21]=[N:22]2)[CH:3]([NH:2][C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][N:26]=2)[CH2:7]1
Reactant: FC(F)(F)c1ccc(Cl)nc1
Reactant: NC1CC(F)(F)CC1NC(=O)c1ccccc1-n1nccn1
Agent: Cl
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NC1CC(F)(F)CC1Nc1ccc(C(F)(F)F)cn1)c1ccccc1-n1nccn1
Temperature: 140 °C

Procedure:
To a solution of N-(2-amino-4,4-difluorocyclopentyl)-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride (Intermediate 42; 120 mg, 0.349 mmol) in dry DMSO (1.2 ml) was added 2-chloro-5-(trifluoromethyl)pyridine (CAS number 52334-81-3; 70 mg, 0.38 mmol) and DIPEA (183 μl, 1.05 mmol). The reaction mixture was heated in a sealed vial at 140° C. for 17 hours then partitioned between ethyl acetate and water. The organics were washed with water, filtered through a hydrophobic frit and concentrated in vacuo. The crude material was purified by column chromatography (basic silica, 0-100% ethyl acetate in petrol) and then was chirally separated using SFC (Waters prep30/MS system using 10% Ethanol, Daicel AD 10 mm id×250 mm long columns at 30 ml/min, 40° C. and 100 bar) to afford the title compound as a single enantiomer.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[OH:9].[CH2:10]([O:12][C:13](=[O:17])[C:14]#[C:15][CH3:16])[CH3:11].N12CCCN=C1CCCCC2>O1CCCC1>[CH2:10]([O:12][C:13](=[O:17])[CH:14]=[C:15]([O:9][C:3]1[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=1[F:1])[CH3:16])[CH3:11]
Reactant: Oc1cc(F)ccc1F
Reactant: CC#CC(=O)OCC
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: CCOC(=O)C=C(C)Oc1cc(F)ccc1F
Temperature: 130 °C
Yield: 62.6 %

Procedure:
A mixture of 2,5-difluoro-phenol (1.15 g, 8.91 mmol) and ethyl-2-butynoate (2.0 g, 17.8 mmol) in tetrahydrofuran (13.7 mL) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (1.33 mL, 8.91 mmol). The reaction was then heated at 130° C. for 2 h. At this time, the reaction was cooled to 25° C. and was concentrated in vacuo. The residue was dissolved in dichloromethane (50 mL) and was washed with a 2N aqueous hydrochloric acid solution (1×100 mL), a 0.5N aqueous sodium hydroxide solution (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL). The organics were then dried over sodium sulfate, filtered and concentrated in vacuo. Purification by Analogix flash chromatography (40 g, 5% ethyl acetate/hexanes) afforded 3-(2,5-difluoro-phenoxy)-but-2-enoic acid ethyl ester (1.35 g, 63%) as a clear oil: HR-ES-MS m/z calculated for C12H12O3F2 [M+H]+ 243.0828, observed 243.0827; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.13 (t, J=7.0 Hz, 3H), 2.43 (s, 3H), 4.02 (q, J=7.0 Hz, 2H), 4.78 (s, 1H), 7.16-7.30 (m, 1H), 7.37 (ddd, J=8.9, 6.2, 3.0 Hz, 1H), 7.51 (td, J=9.7, 5.1 Hz, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][CH:4]=1.[N+:10]([C:13]1[CH:18]=[CH:17][C:16]([CH2:19][C:20](O)=[O:21])=[CH:15][CH:14]=1)([O-:12])=[O:11].Cl.CN(C)CCCN=C=NCC>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:20](=[O:21])[CH2:19][C:16]2[CH:15]=[CH:14][C:13]([N+:10]([O-:12])=[O:11])=[CH:18][CH:17]=2)=[CH:5][CH:4]=1
Reactant: O=C(O)Cc1ccc([N+](=O)[O-])cc1
Reactant: COc1ccc(N)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: c1ccncc1
Product: COc1ccc(NC(=O)Cc2ccc([N+](=O)[O-])cc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 83.8 %

Procedure:
A mixture of p-anisidine (4.92 g, 40 mmol), 4-nitrophenylacetic acid (7.25 g, 40 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (11.5 g, 60 mmol) in pyridine (40 mL) was stirred at room temperature overnight. The solvent was evaporated, and HCl (1M, 50 mL) was added. The resulting product was filtered and washed with water and ether, and recrystallized from ethanol to give N-(4-Methoxyphenyl)-2-(4-nitro-phenyl)-acetamide (9.6 g, 84%).
Reaction SMILES: [F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[O:24][CH2:23][C@@H:19]3[CH2:20][NH:21][CH2:22][C@H:18]3[C@@H:17]2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[CH3:32])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[C:35]1(=O)[CH2:39][CH2:38][C:37](=[O:40])[CH2:36]1>>[F:34][C:2]([F:1])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][CH:16]2[O:24][CH2:23][C@@H:19]3[CH2:20][N:21]([C:35]4[CH2:39][CH2:38][C:37](=[O:40])[CH:36]=4)[CH2:22][C@H:18]3[C@@H:17]2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[CH3:32])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1
Reactant: Cc1cc(F)ccc1[C@@H]1[C@@H](O[C@H](C)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)OC[C@@H]2CNC[C@H]21
Reactant: O=C1CCC(=O)C1
Product: Cc1cc(F)ccc1[C@@H]1C(O[C@H](C)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)OC[C@@H]2CN(C3=CC(=O)CC3)C[C@H]21

Procedure:
The title compound was prepared from (3aS,6R,7R,7aR)-6-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-7-(4-fluoro-2-methylphenyl)octahydropyrano[3,4-c]pyrrole and cyclopentane-1,3-dione according to the procedures used for example 3. MS: (MH)+572.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([NH2:7])[CH2:3][CH2:2]1.[Br:8][C:9]1[CH:17]=[CH:16][C:12]([C:13](O)=[O:14])=[C:11]([CH3:18])[CH:10]=1>>[Br:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([NH:7][CH:4]2[CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)=[O:14])=[C:11]([CH3:18])[CH:10]=1
Reactant: NC1CCOCC1
Reactant: Cc1cc(Br)ccc1C(=O)O
Product: Cc1cc(Br)ccc1C(=O)NC1CCOCC1
Yield: 100 %

Procedure:
The title compound was prepared in substantially the same way as intermediate (iv) by coupling of tetrahydropyran-4-yl amine with 4-bromo-2-methylbenzoic acid to give 0.65 g (100% yield) as a thick oil which solidified on standing.
Reaction SMILES: [CH2:1]([NH:3][CH2:4][CH3:5])[CH3:2].[N+:6]([C:9]1[CH:10]=[C:11]([S:15](Cl)(=[O:17])=[O:16])[CH:12]=[CH:13][CH:14]=1)([O-:8])=[O:7]>N1C=CC=CC=1.C(Cl)Cl>[CH2:1]([N:3]([CH2:4][CH3:5])[S:15]([C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([N+:6]([O-:8])=[O:7])[CH:10]=1)(=[O:16])=[O:17])[CH3:2]
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Cl)c1
Reactant: CCNCC
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCN(CC)S(=O)(=O)c1cccc([N+](=O)[O-])c1
Temperature: 50 °C
Reaction time: 2 h
Yield: 51.2 %

Procedure:
Diethylamine (2.4 g) was dissolved in pyridine (15 ml) and 3-nitrobenzenesulfonyl chloride (6.7 g) was added, followed by stirring at 50° C. for 2 hours. The residue obtained by an evaporation of pyridine under a reduced pressure was dissolved in methylene chloride (150 ml), washed with water, 1N hydrochloric acid, water, and saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. Evaporation of the solvent under a reduced pressure gave N,N-diethyl-3-(nitro)benzenesulfonamide (4.0 g).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].Cl[CH2:16][CH2:17][CH2:18][OH:19]>C(O)C>[OH:19][CH2:18][CH2:17][CH2:16][S:8][C:5]1[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=1
Reactant: Oc1ccc(S)cc1
Reactant: OCCCCl
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCO
Product: OCCCSc1ccc(O)cc1
Reaction time: 8 h

Procedure:
4-Hydroxythiophenol (6.31 g, 50 mmol) was dissolved in ethanol (100 mL) and potassium tert.-butoxide (6.72 g, 60 mmol) was added. The mixture was stirred stirred until a clear, yellow solution was obtained. Then 3-chloro-1-propanol (4.20 mL, 50 mmol) was added with a syringe. The reaction mixture was stirred overnight at room temperature, the potassium chloride precipitate was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (150 mL) and the organic layer was extracted with water (2×100 mL) and brine (100 mL), dried over sodium sulphate and concentrated under reduced pressure. The resulting oil was dissolved in dichloromethane (50 mL) and hexane (100 mL) and left standing open overnight. The solid product was filtered off and dried under high vacuum. Yield: 5.34 g (58%) pale yellow solid.
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@H:8]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17]([I:24])=[N:18][C:19]=3Cl)[O:7][C@@H:6]1[CH2:25][O:26][C:27](=[O:29])[CH3:28])(=[O:3])[CH3:2].[C:30]1([CH:36]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:37][NH2:38])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(N(CC)CC)C>C(#N)C>[C:1]([O:4][C@H:5]1[C@@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@H:8]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17]([I:24])=[N:18][C:19]=3[NH:38][CH2:37][CH:36]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[O:7][C@@H:6]1[CH2:25][O:26][C:27](=[O:29])[CH3:28])(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@H]1O[C@@H](n2cnc3c(Cl)nc(I)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: NCC(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CC(=O)OC[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(I)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 24 h
Yield: 95.3 %

Procedure:
A mixture of (2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-chloro-2-iodo-9H-purin-9-yl)tetrahydro-3-furanyl acetate (J. Med. Chem., 35, 248, (1992)) (15.2g, 28.2 mmol), 2,2-diphenylethylamine (6.1 g, 30.9 mmol), triethylamine (11.4 g, 112.8 mmol) and acetonitrile (200 ml) was stirred at room temperature, under a nitrogen atmosphere, for 24 hours, followed by heating under reflux for 90 minutes. The solvent was removed under reduced pressure and the residue partitioned between dichloromethane (500 ml) and water (200 ml). The organic phase was separated and the solvent removed under reduced pressure to give the title compound as a pale yellow foam (18.8g).
Reaction SMILES: [C:1]1([O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][OH:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:16][S:17](Cl)(=[O:19])=[O:18].C(N(CC)CC)C>C(Cl)Cl>[CH3:16][S:17]([O:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)(=[O:19])=[O:18]
Reactant: CS(=O)(=O)Cl
Reactant: OCCCCCCCOc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCCCCCCOc1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 86.4 %

Procedure:
A solution of 7-(phenyloxy)-1-heptanol (0.21 g, 1.01 mmol) in anhydrous methylene chloride (20 mL), taken in a 50 mL round bottomed flask was cooled to 0° C. using an ice bath. Methanesulfonyl chloride (0.177 g, 1.55 mmol) was added to this followed by a dropwise addition of triethylamine (0.28 mL, 2.11 mmol). The reaction mixture was then stirred at 0° C. for 1 hour and allowed to attain room temperature in 2 hours. It was then quenched with 1N. HCl (10 mL) and diluted with methylene chloride (20 mL). The organic layer was separated and the aqueous layer was extracted with methylene chloride (2×10 mL). The combined organic layer was washed with 1N. HCl (3×10 mL), water (2×10 mL) and brine (2×mL). The organic layer was dried over Na2SO4. Removal of solvent from the dried extract under reduced pressure afforded the product 7-(phenyloxy)-1-heptyl methanesulfonate (0.25 g, 86.5%). The product from the step B was analyzed yielding the following confirmatory data: 1H-NMR (CDCl3) 1.31-1.52 (m, 6H), 1.71-1.84 (m, 4H), 2.98 (s, 3H), 3.94 (t, 2H, J=6.43 Hz), 4.21 (t, 2H, J=6.51 Hz), 6.80-6.94 (m, 3H) and 7.24-7.30 (m, 2H); 13C-NMR (CDCl3) 25.2, 25.7, 28.6, 28.9, 29.0, 37.1, 67.5, 69.9, 114.3, 120.3, 129.2 and 158.9; IR (neat): 1349 cm−1; MS (ES+): 287 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:9]=[C:10]=[O:11])[CH:5]=[C:6]([Cl:8])[CH:7]=1.C([O:14][C:15]([CH:17]1[NH:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18]1)=O)C.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[C:26]([O:25][C:23]([N:19]1[CH2:20][CH2:21][N:22]2[C:10](=[O:11])[N:9]([C:4]3[CH:3]=[C:2]([Cl:1])[CH:7]=[C:6]([Cl:8])[CH:5]=3)[C:15](=[O:14])[CH:17]2[CH2:18]1)=[O:24])([CH3:29])([CH3:28])[CH3:27]
Reactant: O=C=Nc1cc(Cl)cc(Cl)c1
Reactant: CCOC(=O)C1CN(C(=O)OC(C)(C)C)CCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCN2C(=O)N(c3cc(Cl)cc(Cl)c3)C(=O)C2C1
Temperature: 20 °C
Reaction time: 0.5 h
Yield: 136.1 %

Procedure:
3,5-Dichlorophenyl isocyanate (2.85 g, 15.2 mmol) was added portionwise to a mixture of piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (2.61 g, 10.1 mmol, prepared as described in Bioorg. Med. Chem. Lett. 1999, 9, 1121-6) and potassium carbonate (1.68 g, 12.1 mmol) in DCM (30 mL) at 5° C. After 30 min at 5° C., the reaction mixture was stirred at 20° C. for 48 h. The white precipitate was discarded and the filtrate concentrated in vacuo to give an oil (5.5 g) which was chromatographed over silica gel (CH2Cl2), to yield the above compound (2.77 g) as a white solid. Mp=144° C.
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]([OH:13])=[O:12])=[CH:10][C:5]=2[N:4]=[C:3]1[CH3:14].[C:15]1(C)C=CC=CC=1>CO>[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]([O:13][CH3:15])=[O:12])=[CH:10][C:5]=2[N:4]=[C:3]1[CH3:14]
Reactant: Cc1nc2cc(C(=O)O)ccc2n1C
Reactant: Cc1ccccc1
Solvent: CO
Product: COC(=O)c1ccc2c(c1)nc(C)n2C
Reaction time: 1 h

Procedure:
To a suspension of 1,2-Dimethyl-1H-benzo[d]imidazole-5-carboxylic acid (crude, 2.54 g, approx. 9.35 mmol) in MeOH (15.5 ml)/toluene (78 ml) Trimethylsilyldiazomethane (2 M solution in hexane, 7.0 ml, 14 mmol) was added at 0-10° C. The reaction mixture was stirred at it for 1 hour. The reaction mixture was evaporated under reduced pressure. The residue was taken up in DCM, Remaining insoluble solid was filtered off. The filtrate was evaporated again to dryness to afford crude Methyl 1,2-dimethyl-1H-benzo[d]imidazole-5-carboxylate
Reaction SMILES: [OH-].[K+].CS(C)=O.Br.Br.[NH2:9][CH2:10][CH2:11][CH2:12][S:13][C:14](=[NH:16])N.ClC1[N:23]2[CH:24]=[CH:25]N=[C:22]2[CH:21]=[CH:20][CH:19]=1>O>[NH2:9][CH2:10][CH2:11][CH2:12][S:13][C:14]1[N:16]2[CH:25]=[CH:24][N:23]=[C:22]2[CH:21]=[CH:20][CH:19]=1
Reactant: Clc1cccc2nccn12
Reactant: N=C(N)SCCCN
Agent: Br
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: NCCCSc1cccc2nccn12
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 64.2 %

Procedure:
To a mixed solution of 10% potassium hydroxide (69.3 g, 105 mmoles) and dimethylsulfoxide (50 ml) was added S-[3-(amino)propyl]isothiourea.dihydrobromide (8.85 g, 39 mmoles) and the mixture was stirred at room temperature for 1.5 hours. To the reaction solution was added 5-chloroimidazo[1,2-a]pyridine (3.05 g, 20 mmoles), followed by stirring at room temperature for 1.5 hours and additional stirring at 65° C. for 20 hours. Water was added to the reaction solution, which was extracted with chloroform, washed several times with 1N-sodium chloride and dried over anhydrous magnesium sulfate. After the solvent was distilled off to obtain 2.66 g of the desired product (64.3%, pale yellow oily product).
Reaction SMILES: [C:1]1([O:11][CH2:12][CH:13]([OH:16])[CH2:14]Cl)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[C:17]([NH:25][CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)C>[C:1]1([O:11][CH2:12][CH:13]([OH:16])[CH2:14][N:29]2[CH2:30][CH2:31][CH:26]([NH:25][C:17](=[O:24])[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:27][CH2:28]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=C(NC1CCNCC1)c1ccccc1
Reactant: OC(CCl)COc1cccc2ccccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Product: O=C(NC1CCN(CC(O)COc2cccc3ccccc23)CC1)c1ccccc1

Procedure:
3-(α-Naphthoxy)-1-chloropropan-2-ol (1.18 g.) was refluxed for 16 hours in isopropyl alcohol (100 ml.) with 4-benzamidopiperidine (1.032 g.) and anhydrous potassium carbonate (1.037 g.). The mixture was filtered hot, cooled and evaporated to dryness. The gum so obtained gave the title compound as a solid on triturating in ether, m.p. 139°-141° C. (Found: C, 74.1; H, 7.1; N, 6.9. C25H28N2O3 requires C, 74.2; H, 7.0; N, 6.9%).
Reaction SMILES: [H-].[Na+].[Br-].[OH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CS(C)=O.[CH3:34][C:35](=O)[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]>O>[CH3:34][CH:35]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])[CH2:10][CH2:9][CH2:8][CH2:7][CH:6]=[CH:5][OH:4]
Reactant: CCCCCCCCC(C)=O
Reactant: OCCCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCCCCCCCC(C)CCCCC=CO
Temperature: 70 °C
Reaction time: 18 h
Yield: 49.5 %

Procedure:
Into a dried 5L, 3 neck round bottom flask fitted with mechanical stirring, nitrogen inlet, dropping funnel, thermometer and nitrogen outlet is added 80 g of 60% sodium hydride (2.0 mol) in mineral oil. The mineral oil is removed by washing with hexanes. Anhydrous dimethyl sulfoxide (500 ml) is added to the flask and heated to 70° C. until evolution of hydrogen stops. The reaction mixture is cooled to room temperature followed by addition of 1L of anhydrous tetrahydrofuran. (6-hydroxyhexyl) triphenylphosphonium bromide (443.4 g, 1 mol) is slurried with warm anhydrous dimethyl sulfoxide (50° C., 500 ml) and slowly added to the reaction mixture thru the dropping funnel while keeping the reaction at 25-30° C. The reaction is stirred for 30 minutes at room temperature at which time 2-decanone (171.9 g, 1.1 mol) is slowly added thru a dropping funnel. Reaction is slightly exothermic and cooling is needed to maintain 25-30° C. Mixture is stirred for 18 hrs. and then poured into a separatory funnel containing 600 ml of purified water and 300 ml of hexanes. After shaking the oil phase (top) is allowed to separate out and the water phase is removed. The extractions of the oil phase are continued using water until both phases are clear. The organic phase is collected, vacuum distilled and purified by liquid chromatography (90:10 hexanes:ethyl acetate, silica gel stationary phase) to obtain a clear, oily product (119.1 g).