Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[O:3][CH:4]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]=1[CH2:7][OH:8].C(N(CC)CC)C.[C:22](Cl)(=[O:34])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]>O1CCCC1>[C:22]([O:8][CH2:7][C:6]1[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:4][O:3][C:2]=1[CH3:1])(=[O:34])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]
Reactant: Cc1occ(-c2ccccc2)c1CO
Reactant: CCCCCCCCCCCC(=O)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCCCCCCCCCCC(=O)OCc1c(-c2ccccc2)coc1C
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a stirred solution of 2-methyl-4-phenyl-3-furanmethanol (48 mg, 0.26 mmol) and triethylamine (39 mg. 0.38 mmol) in tetrahydrofuran (3 ml) at 0 degrees under argon was added lauroyl chloride (73 mg. 0.33 mmol). This solution was warmed gradually to room temperature and stirred for 41/2 hours. The organics were extracted into ethyl ether and washed with a 5% aqueous sodium bicarbonate solution, H2O and brine. Evaporation of the dried (magnesium sulfate) extracts gave an oil which was purified by flash chromatography on silica using 3% ether/hexanes to give the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH:14]=[CH:13][N:12]3[N:15]=[CH:16][C:17]([CH:18]=O)=[C:11]3[N:10]=2)=[CH:4][CH:3]=1.[S:20]1[CH2:24][C:23](=[O:25])[NH:22][C:21]1=[O:26].N1CCCCC1>CCO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][N:12]3[N:15]=[CH:16][C:17]([CH:18]=[C:24]4[S:20][C:21](=[O:26])[NH:22][C:23]4=[O:25])=[C:11]3[N:10]=2)=[CH:6][CH:7]=1
Reactant: O=Cc1cnn2ccc(Nc3ccc(Cl)cc3)nc12
Reactant: O=C1CSC(=O)N1
Solvent: C1CCNCC1
Solvent: CCO
Product: O=C1NC(=O)C(=Cc2cnn3ccc(Nc4ccc(Cl)cc4)nc23)S1
Temperature: 70 °C

Procedure:
To 5-(4-chlorophenylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde (117 mg, 0.430 mmol) in EtOH was added thiazolidine-2,4-dione (50 mg, 0.430 mmol) and piperidine (43 μl, 0.430 mmol). The mixture was heated at 70° C. and the product formed quickly. The solid formed was isolated by filtration and air dried to yield 5-((5-(4-chlorophenylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)thiazolidine-2,4-dione. LCMS (M+1=372)
Reaction SMILES: COC(C1CC(=O)[N:7](C2C=CC(O)=CC=2)[CH2:6]1)=O.FC1C=C(F)C=C(F)C=1CBr.C[O:30][C:31]([CH:33]1[CH2:37][C:36](=[O:38])[N:35]([C:39]2[CH:44]=[CH:43][C:42]([O:45][CH2:46][C:47]3[CH:52]=[C:51]([F:53])[C:50]([F:54])=[C:49]([F:55])[CH:48]=3)=[CH:41][CH:40]=2)[CH2:34]1)=O>C(O)C>[CH3:6][NH2:7].[CH3:6][NH:7][C:31]([CH:33]1[CH2:37][C:36](=[O:38])[N:35]([C:39]2[CH:44]=[CH:43][C:42]([O:45][CH2:46][C:47]3[CH:52]=[C:51]([F:53])[C:50]([F:54])=[C:49]([F:55])[CH:48]=3)=[CH:41][CH:40]=2)[CH2:34]1)=[O:30]
Reactant: COC(=O)C1CC(=O)N(c2ccc(O)cc2)C1
Reactant: COC(=O)C1CC(=O)N(c2ccc(OCc3cc(F)c(F)c(F)c3)cc2)C1
Agent: Fc1cc(F)c(CBr)c(F)c1
Solvent: CCO
Product: CN
Product: CNC(=O)C1CC(=O)N(c2ccc(OCc3cc(F)c(F)c(F)c3)cc2)C1

Procedure:
The title compound is prepared by alkylation of the (RS)-1-(4-hydroxyphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester with 2,4,6-trifluorobenzyl bromide giving the (RS)-5-oxo-1-[4-(3,4,5-trifluoro-benzyloxy)-phenyl]-pyrrolidine-3-carboxylic acid methyl ester as a white solid (99% of theory) which, thereupon, by treatment with methylamine in ethanol at 50° C. yields the (RS)-5-oxo-1-[4-(3,4,5-trifluoro-benzyloxy)-phenyl]-pyrrolidine-3-carboxylic acid methylamide. Yield: 99% of theory as a white solid; MS: m/e=379 (M+H)+.
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[CH:9][C:10]3[O:14][C:13]([CH2:15][OH:16])=[N:12][C:11]=3[CH:17]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:18](N1C=CN=C1)(N1C=CN=C1)=[O:19].CC1C=CC(S(O)(=O)=O)=CC=1.[CH2:41]([O:44][C:45](=[O:55])[C@@H:46]([CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[NH2:47])[CH:42]=[CH2:43].C(N(CC)CC)C>C(Cl)Cl>[CH2:41]([O:44][C:45](=[O:55])[C@H:46]([NH:47][C:18]([O:16][CH2:15][C:13]1[O:14][C:10]2[CH:9]=[CH:8][C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:17][C:11]=2[N:12]=1)=[O:19])[CH2:48][C:49]1[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=1)[CH:42]=[CH2:43]
Reactant: OCc1nc2cc(-c3ccccc3)ccc2o1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: C=CCOC(=O)[C@H](N)Cc1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CCOC(=O)[C@@H](Cc1ccccc1)NC(=O)OCc1nc2cc(-c3ccccc3)ccc2o1
Reaction time: 8 h
Yield: 80.3 %

Procedure:
(5-Phenyl-benzoxazole-2-yl)methanol 51 (437 mg, 1.94mmol) and carbonyidiimidazole (393 mg, 2.43 mmol) in 7 ml of dry CH2Cl2 were stirred at room temperature for 3 hrs. The tosic acid salt of (R)-phenylalanine allyl ester(767 mg, 1.94 mmol) was added followed by 0.42 ml of triethylamine (301 mg, 2.98 mmol). The mixture was stirred overnight. The mixture was diluted and washed with 1M HCl solution then with brine. After drying, the organic phase was filtered and concentrated. The crude product was chromatographed to give about 711 mg of (R)-3-phenyl-2-(5-phenyl-benzoxazol-2-ylmethoxycarbonylamino) propionic acid allyl ester 52.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][CH:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:6][CH2:5]1.[O:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1.[C:25](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C=O.C(=O)(O)[O-].[Na+]>ClC(Cl)C>[CH3:25][N:1]([CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][CH:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:14])([CH3:16])[CH3:15])[CH2:6][CH2:5]1)[CH:21]1[CH2:22][CH2:23][O:18][CH2:19][CH2:20]1
Reactant: CC(C)(C)OC(=O)NC1CCN(CCN)CC1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: O=C1CCOCC1
Agent: C=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(Cl)Cl
Product: CN(CCN1CCC(NC(=O)OC(C)(C)C)CC1)C1CCOCC1
Reaction time: 2.5 h
Yield: 100.9 %

Procedure:
Into a solution of tert-butyl 1-(2-aminoethyl)-4-piperidinylcarbamate (2.4 g) and tetrahydro-4H-pyran-4-one (0.79 g) in dichloroethane (35 ml) was added at room temperature sodium triacetoxyborohydride (2.19 g), and the resulting mixture was stirred for 2.5 hours. To the reaction mixture were added 37% formalin (0.65 g) and sodium triacetoxyborohydride (2.19 g), and the resulting mixture was stirred for 64 hours. The reaction mixture was mixed with an aqueous solution of sodium bicarbonate and was extracted with chloroform. The organic layer was washed with an aqueous saturated solution of sodium chloride and was dried with magnesium sulfate. The resulting organic layer was concentrated under reduced pressure to obtain tert-butyl 1-[2-[N-methyl-N-(tetrahydropyran-4-yl)amino]ethyl]-4-piperidinylcarbamate (2.72 g) as a yellow oil.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](S(C)=O)[C:5]([C:11]#[N:12])=[C:4]([C:13]2[O:14][C:15]([CH3:18])=[CH:16][CH:17]=2)[N:3]=1.Cl.[NH2:20][CH2:21][C:22]1[C:27]([Cl:28])=[CH:26][C:25]([C:29]([F:32])([F:31])[F:30])=[CH:24][N:23]=1.C1CCN2C(=NCCC2)CC1>COCCOC>[NH2:1][C:2]1[N:7]=[C:6]([NH:20][CH2:21][C:22]2[C:27]([Cl:28])=[CH:26][C:25]([C:29]([F:32])([F:31])[F:30])=[CH:24][N:23]=2)[C:5]([C:11]#[N:12])=[C:4]([C:13]2[O:14][C:15]([CH3:18])=[CH:16][CH:17]=2)[N:3]=1
Reactant: NCc1ncc(C(F)(F)F)cc1Cl
Reactant: Cc1ccc(-c2nc(N)nc(S(C)=O)c2C#N)o1
Agent: Cl
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: Cc1ccc(-c2nc(N)nc(NCc3ncc(C(F)(F)F)cc3Cl)c2C#N)o1

Procedure:
From 2-amino-4-methanesulfinyl-6-(5-methyl-furan-2-yl)-pyrimidine-5-carbonitrile, 2-aminomethyl-3-chloro-5-(trifluoromethyl)pyridine hydrochloride and DBU in DME. ES-MS m/e (%): 411 (M{37Cl}+H+, 45), 409 (M{35Cl}+H+, 100).
Reaction SMILES: [Cl:1][C:2]1[C:7]([O:8][C:9]2[N:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([C:25](O)=[O:26])=[CH:17]1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C>[Cl:1][C:2]1[C:7]([O:8][C:9]2[N:14]=[CH:13][C:12]([NH:15][C:25]([C:18]3[C:19]4[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=4)[NH:16][CH:17]=3)=[O:26])=[CH:11][CH:10]=2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: Nc1ccc(Oc2cccnc2Cl)nc1
Reactant: O=C(O)c1c[nH]c2ccccc12
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CN(C)C=O
Product: O=C(Nc1ccc(Oc2cccnc2Cl)nc1)c1c[nH]c2ccccc12
Temperature: 70 °C
Reaction time: 8 h
Yield: 60.9 %

Procedure:
The 6-(2-chloropyridine-3-yloxy)-pyridine-3-amine (200 mg, 0.9 mmol) and indole-3-carboxylic acid (150 mg, 0.9 mmol) were dissolved in DMF (5 ml), DCC (200 mg, 0.99 mmol) was added to the solution, and then the mixture was stirred at 70° C. for 8 hours. After the reaction was completed, the product was washed and filtered to yield a target compound as a white solid (200 mg, 61%) by chromatography (methanol:dichloromethane=1:30).
Reaction SMILES: [CH:1]1[CH2:5][CH:4]=[CH:3][CH:2]=1.CCCCCC.C([Li])CCC.[Cl:17][C:18]1[CH:32]=[CH:31][C:21]([C:22]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)=O)=[CH:20][CH:19]=1>O1CCCC1>[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([C:22]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)=[C:2]2[CH:1]=[CH:5][CH:4]=[CH:3]2)=[CH:31][CH:32]=1
Reactant: C1=CCC=C1
Reactant: O=C(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: Clc1ccc(C(=C2C=CC=C2)c2ccc(Cl)cc2)cc1
Temperature: 0 °C

Procedure:
A reaction vessel equipped with a dropping funnel was charged with 40 ml of dehydrated tetrahydrofuran and 2.15 ml (25.9 mmol) of cyclopentadiene under a nitrogen atmosphere. Then, 18.0 mL (28.5 mmol) of a 1.58 mol/L hexane solution of n-butyllithium was slowly added dropwise while cooling this solution to 0° C., and the mixture was stirred. Subsequently, the dropping funnel was charged with a solution prepared by dissolving 5.00 g (19.9 mmol) of 4,4′-dichlorobenzophenone in 30 ml of dehydrated tetrahydrofuran was placed in. The solution was slowly added dropwise while cooling to −0° C. Thereafter, the mixture was left to stand and the temperature thereof was returned to room temperature. The mixture was then stirred for one day. This reaction solution was subjected to extraction with diethyl ether. The organic layer was washed with 1 N hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated brine. The organic phase collected by separation was dried over anhydrous magnesium sulfate. Subsequently, magnesium sulfate was separated by filtration, and the filtrate was subjected to distillation under reduced pressure with use of a rotary evaporator to remove the solvent. The residue was purified by using a silica gel column to obtain a target product (yield 3.37 g (57%)). The target product was identified by 1H-NMR.
Reaction SMILES: [C:1]1(=[O:10])[O:9][C:6]([CH3:8])([CH3:7])[O:5][C:3](=[O:4])[CH2:2]1.C(N(CC)CC)C.[F:18][C:19]([F:30])([F:29])[C:20]1[CH:25]=[CH:24][C:23]([N:26]=[C:27]=[O:28])=[CH:22][CH:21]=1.Cl>CS(C)=O.O>[CH3:7][C:6]1([CH3:8])[O:9][C:1](=[O:10])[C:2]([C:27](=[O:28])[NH:26][C:23]2[CH:24]=[CH:25][C:20]([C:19]([F:18])([F:30])[F:29])=[CH:21][CH:22]=2)=[C:3]([OH:4])[O:5]1
Reactant: CC1(C)OC(=O)CC(=O)O1
Reactant: O=C=Nc1ccc(C(F)(F)F)cc1
Agent: Cl
Solvent: CS(C)=O
Solvent: O
Solvent: CCN(CC)CC
Product: CC1(C)OC(=O)C(C(=O)Nc2ccc(C(F)(F)F)cc2)=C(O)O1

Procedure:
To a solution of 14.4 g of isopropylidene malonate in 150 ml of dimethyl sulphoxide were added dropwise, at room temperature, 10.1 g of triethylamine and thereafter, at 20° to 30° C., 18.7 g of 4-trifluoromethylphenylisocyanate. The mixture was reacted for 12 to 15 hours at room temperature and the resultant solution was poured into a solution of 15 ml of concentrated hydrochloric acid in 350 ml of water. The precipitate which formed was collected with suction. Recrystallisation from 130 ml of acetone yielded the product of the formula ##STR5## with a melting point of 206°-208° C.
Reaction SMILES: N1C=CC=C([O:7][C:8]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]([OH:18])=O)[CH2:12][CH2:11]2)=[O:9])C=1.O[N:20]1[C:24]2C=[CH:26][CH:27]=[CH:28][C:23]=2N=N1.[CH:29]1[CH:34]=[CH:33][C:32]([C:35]([NH:37][NH2:38])=[O:36])=[CH:31][CH:30]=1.C(N=C=NCCCN(C)C)C>O.C(Cl)(Cl)Cl.C(Cl)Cl>[N:20]1[CH:26]=[CH:27][CH:28]=[C:23]([CH:15]2[CH2:14][CH:13]([C:16]([NH:38][NH:37][C:35](=[O:36])[C:32]3[CH:33]=[CH:34][CH:29]=[CH:30][CH:31]=3)=[O:18])[CH2:12][CH2:11][N:10]2[C:8]([OH:7])=[O:9])[CH:24]=1
Reactant: NNC(=O)c1ccccc1
Reactant: O=C(O)C1CCN(C(=O)Oc2cccnc2)CC1
Reactant: On1nnc2ccccc21
Agent: CCN=C=NCCCN(C)C
Solvent: O
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: O=C(NNC(=O)C1CCN(C(=O)O)C(c2cccnc2)C1)c1ccccc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 55.3 %

Procedure:
To a mixture of 1-[(pyridin-3 yloxy)carbonyl]piperidine-4-carboxylic acid (1.5 g) and DCM (15 mL) were added 1-hydroxybenzotriazole (HOBt) (0.85 g), benzohydrazine (0.86 g), and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (WSC) hydrochloride (1.21 g), followed by stirring at room temperature for about 15 hours. To the reaction liquid were added chloroform and water, and the organic phase was separated. The organic phase was washed with water and saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol=100/0 to 90/10). To the purified product were added diisopropyl ether and methanol, and the resulting solid was collected by filtration and dried under reduced pressure to obtain pyridin-3-yl 4-[(2-benzoylhydrazino)carbonyl]piperidine-1-carboxylic acid (1.22 g).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][I:7].[C:8]1([P:14]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C(#N)C>[I-:7].[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][P+:14]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: COCCCCI
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Product: COCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: [I-]
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
10.70 g of 4-methoxybutyl iodide are taken up in 80 ml of acetonitrile. 14.43 g of triphenylphosphine are added and the reaction solution is heated to reflux for 16 hours. The reaction solution is concentrated by evaporation and the residue is admixed with diethyl ether. The suspension is stirred at room temperature for 30 minutes and the precipitated solid is filtered off and dried. The title compound is used for the next stage without further purification.
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:30])[NH:17][C:18]2[S:26][C:21]3[CH2:22][NH:23][CH2:24][CH2:25][C:20]=3[C:19]=2[C:27]([NH2:29])=[O:28])=[CH:11][CH:10]=1.[C:31]([NH2:35])(=[O:34])[CH:32]=[CH2:33].C(N(C(C)C)CC)(C)C>CN(C)C=O>[NH2:35][C:31](=[O:34])[CH2:32][CH2:33][N:23]1[CH2:24][CH2:25][C:20]2[C:19]([C:27]([NH2:29])=[O:28])=[C:18]([NH:17][C:16]([NH:15][C:12]3[CH:11]=[CH:10][C:9]([Cl:8])=[CH:14][CH:13]=3)=[O:30])[S:26][C:21]=2[CH2:22]1
Reactant: NC(=O)c1c(NC(=O)Nc2ccc(Cl)cc2)sc2c1CCNC2
Reactant: C=CC(N)=O
Solvent: CN(C)C=O
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: NC(=O)CCN1CCc2c(sc(NC(=O)Nc3ccc(Cl)cc3)c2C(N)=O)C1
Temperature: 25 °C
Yield: 99 %

Procedure:
A solution of compound A4 (200 mg, 0.431 mmol), acrylamide (156 mg, 2.19 mmol), and diisopropylethylamine (0.400 mL, 2.25 mmol) in N,N-dimethylformamide (2.5 mL) was heated at 50° C. for 8 h. After this time, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel eluting with 0% to 10% methanol/methylene chloride to afford compound D1 as a yellow solid (180 mg, 99%): 1H NMR (300 MHz, DMSO-d6) δ 10.95 (s, 1H), 10.19 (s, 1H), 7.59-7.29 (m, 6H), 6.90-6.73 (m, 2H), 3.48 (s, 2H), 2.83-2.65 (m, 6H), 2.33-2.25 (m, 2H). MS (M+H) 422.
Reaction SMILES: C1CCC(N=C=NC2CCCCC2)CC1.[C:16]([OH:33])(=[O:32])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31].[CH2:34]([O:41][CH2:42][C@H:43](O)[CH2:44][O:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53]/[CH:54]=[CH:55]\[CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH3:63])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(Cl)(Cl)Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:34]([O:41][CH2:42][C@H:43]([O:32][C:16](=[O:33])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH2:44][O:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53]/[CH:54]=[CH:55]\[CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH3:63])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: CCCCCCCCCCCCCCCC(=O)O
Reactant: CCCCCCCC/C=C\CCCCCCCCOC[C@@H](O)COCc1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: CCCCCCCC/C=C\CCCCCCCCOC[C@H](COCc1ccccc1)OC(=O)CCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A 4 mL solution of DCC (111 mg, 0.54 mmol), DMAP (3 mg, 0.02 mmol) and palmitic acid (86 mg, 0.34 mmol) in CH2Cl2 was cooled to 0° C. A solution of 3-O-benzyl-1-O-oleyl-sn-glycerol (100 mg, 0.228 mmol) in CH2Cl2 (2 mL) was added to it in a drop-wise manner and stirred for 12 h at rt. The mixture was filtered over Celite, washed with saturated aqueous sodium bicarbonate solution and brine, dried on anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography using silica gel (hexane:EtOAc=15:1, Rf=0.35) to get the product (154 mg, quantitative) as colorless oil. [α]D28+5° (c=2.0, CHCl3); IR (CHCl3) cm−1 2924, 2854, 1742, 1651, 1460, 1369, 1241, 1164, 1109, 1028, 733, 698 cm−1; 1H NMR (600 MHz, CDCl3) δ 0.88 (t, J=7.2 Hz, 6H, CH3), 1.22-1.38 (m, 44H, CH2), 1.52 (dt, J=7.2, 14.4 Hz, 4H, CH2), 1.94 (dd, J=6.6, 12.6 Hz, 4H, CH2), 2.20 (t, J=7.8 Hz, 2H, CH2), 2.24 (t, J=7.8 Hz, 2H, CH2), 3.51 (ddd, J=5.0, 10.2, 15.6 Hz, 2H, CH2OBn), 4.11 (dd, J=5.4, 12.0 Hz, 1H, CH2OAcyl), 4.27 (dd, J=3.6, 12.0 Hz, 1H, CH2OAcyl), 4.44, 4.48 (AB q, J=12.0 Hz, 2H, PhCH2), 4.06 (dt, J=4.2, 9.0 Hz, 1H, CH), 5.35 (ddd, J=6.0, 11.4, 15.6 Hz, 2H, CH═CH 7.20-7.32 (m, 5H, ArH); 13C NMR (150 MHz, CDCl3) δ 14.1, 22.65, 22.66, 24.8, 24.9, 27.1, 27.2, 29.06, 29.09, 29.16, 29.27, 29.29, 29.33, 29.46, 29.50, 29.61, 29.63, 29.67, 29.74, 31.88, 31.90, 34.1, 34.3, 62.6, 68.2, 70.0, 73.3, 127.6, 127.7, 128.4, 129.7, 130.0, 137.7, 173.0, 173.3; EMSI calc'd for C44H76NaO5 [M+Na]+ 707.56. found: 707.50.
Reaction SMILES: [CH3:1][CH:2]([CH:6]([CH3:10])[C:7]([OH:9])=O)[C:3]([OH:5])=[O:4].[ClH:11].Cl.[NH2:13][CH2:14][C:15]1[O:19][C:18]([C:20]([O:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]=2C(=N)N)=[O:21])=[CH:17][CH:16]=1.C1CCC([N:42]=[C:43]=[N:44]C2CCCCC2)CC1>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[ClH:11].[C:3]([CH:2]([CH3:1])[CH:6]([CH3:10])[C:7]([NH:13][CH2:14][C:15]1[O:19][C:18]([C:20]([O:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[C:28]([C:43](=[NH:42])[NH2:44])[CH:29]=3)[CH:24]=2)=[O:21])=[CH:17][CH:16]=1)=[O:9])([OH:5])=[O:4]
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: N=C(N)c1c(OC(=O)c2ccc(CN)o2)ccc2ccccc12
Reactant: CC(C(=O)O)C(C)C(=O)O
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: c1ccncc1
Product: CC(C(=O)O)C(C)C(=O)NCc1ccc(C(=O)Oc2ccc3cc(C(=N)N)ccc3c2)o1
Reaction time: 0.17 h

Procedure:
To 2.3 g of 2,3-dimethylsuccinic acid, 2.0 g of -amidino-2-naphthyl 5-aminomethylfuran-2-carboxylate dihydrochloride and 66 mg of DMAP was added 25 ml of pyridine, and the mixture was stirred while cooling with ice. After 10 minutes, 2.16 g of DCC was added and the mixture was stirred for 1 hour at 4°-8° C. and then for 2 hours at 16°-17° C. The precipitate was filtered off, the filtrate was added in small portions into 150 ml of ether and the mixture was stirred for 1 hour at room temperature. The precipitate was collected by filtration, then 60 ml of acetone was added thereto and the mixture was stirred for 3 hours. The precipitate was collected by filtration to obtain 1.3 g of the intended product.
Reaction SMILES: [NH2:1][C:2]1[C:3]([N:19]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:4][C:5]([CH3:18])=[C:6]([CH3:17])[C:7]=1[NH:8][CH2:9][C:10]1([OH:16])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.[CH2:34]([O:36][CH2:37][C:38](Cl)=O)[CH3:35]>>[CH2:20]([N:19]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:3]1[C:2]2[N:1]=[C:35]([CH2:34][O:36][CH2:37][CH3:38])[N:8]([CH2:9][C:10]3([OH:16])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)[C:7]=2[C:6]([CH3:17])=[C:5]([CH3:18])[N:4]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CCOCC(=O)Cl
Reactant: Cc1nc(N(Cc2ccccc2)Cc2ccccc2)c(N)c(NCC2(O)CCCCC2)c1C
Product: CCOCc1nc2c(N(Cc3ccccc3)Cc3ccccc3)nc(C)c(C)c2n1CC1(O)CCCCC1

Procedure:
1-[(3-Amino-2-dibenzylamino-5,6-dimethylpyridin-4-ylamino)methyl]cyclohexanol (0.94 g, 2.1 mmol, prepared as described in Parts A through C of Example 59 was reacted with ethoxyacetyl chloride (0.31 g, 2.52 mmol) according to the general method of Part A of Example 58. The resulting amide was cyclized according to the general method of Part A of Example 58 to provide 0.67 g of 1-[(4-dibenzylamino-2-ethoxymethyl-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]cyclohexanol as a white solid.
Reaction SMILES: [CH3:1][N:2]([CH3:35])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:34])/[C:14](/[C:24]2[CH:29]=[CH:28][C:27]([O:30]COC)=[CH:26][CH:25]=2)=[C:15](/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)\[CH2:16][CH3:17])=[CH:8][CH:7]=1.Cl.C([O-])(O)=O.[Na+]>CO.CCOC(C)=O.O>[CH3:35][N:2]([CH3:1])[CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([NH:12][C:13](=[O:34])/[C:14](/[C:24]2[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=2)=[C:15](/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)\[CH2:16][CH3:17])=[CH:10][CH:11]=1
Reactant: CC/C(=C(\C(=O)Nc1ccc(OCCN(C)C)cc1)c1ccc(OCOC)cc1)c1ccccc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: O
Product: CC/C(=C(\C(=O)Nc1ccc(OCCN(C)C)cc1)c1ccc(O)cc1)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 91 %

Procedure:
Method A; To a suspension of 4 (1.39 g, 2.93 mmol) in MeOH (4 ml) was added a solution of 3N HCl in AcOEt (10 ml) under ice cooling, and the mixture was stirred at room temperature for 2 h. A solution of NaHCO3 (2.8 g) in H2O was poured into the reaction mixture under ice cooling, and the whole was extracted with AcOEt and a little MeOH. The organic layer was washed with brine, dried over Na2SO4, and then concentrated. The residual solid was triturated with Et2O to give 5 (91%). 5: colorless powder; 1H-NMR (CD3OD) δ 0.97 (3H, t, J=7.4 Hz), 2.38 (6H, s), 2.65 (2H, q, J=7.4 Hz), 2.82 (2H, t, J=5.4 Hz), 4.11 (2H, t, J=5.74 Hz), 6.50 (2H, d, J=8.8 Hz), 6.92 (2H, d, J=8.8 Hz), 6.94 (2H, d, J=9.2 Hz) 7.11-7.25 (5H, m), 7.53 (2H, d, J=9.1 Hz). 13C-NMR (CD3OD) δ 13.21, 30.40, 45.76, 59.09, 66.74, 115.69, 115.75, 123.42, 127.91, 129.10, 129.31, 130.42, 131 0.78,