Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]1[O:16][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].[NH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][NH2:24]>C(O)(C)C>[CH2:23]([NH:24][CH2:1][CH:2]([OH:16])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][NH:17][CH2:1][CH:2]([OH:16])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: NCCCCCCN
Reactant: CCCCCCCCCCCCCC1CO1
Solvent: CC(C)O
Product: CCCCCCCCCCCCCC(O)CNCCCCCCNCC(O)CCCCCCCCCCCCC

Procedure:
In a manner similar to that of Example 1, condensation of 1-pentadecene oxide (81.7 g.) and hexamethylenediamine (21 g.) and recrystallization of the resulting product (74.3 g.) from isopropyl alcohol gave N,N'-(1,6-hexylene)-bis[2-hydroxypentadecylamine] (I: R= CH3 (CH2)12, R' = H, X = (CH2)6, Z= H) (m.p. 117.4°-124.0° C.).
Reaction SMILES: [N+](C1C=CC=CC=1O)([O-])=O.[CH3:11][O:12][C:13]1[CH:25]=[CH:24][C:16]([C:17]([CH2:19][CH2:20][C:21]([OH:23])=O)=[O:18])=[CH:15][C:14]=1[F:26].CC(C)N=C=NC(C)C.[N:36]1[CH:41]=[CH:40][C:39]([N:42]2[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)=[CH:38][CH:37]=1>ClCC(Cl)C.CN(C=O)C.C(N(CC)CC)C>[F:26][C:14]1[CH:15]=[C:16]([C:17](=[O:18])[CH2:19][CH2:20][C:21]([N:45]2[CH2:46][CH2:47][N:42]([C:39]3[CH:40]=[CH:41][N:36]=[CH:37][CH:38]=3)[CH2:43][CH2:44]2)=[O:23])[CH:24]=[CH:25][C:13]=1[O:12][CH3:11]
Reactant: c1cc(N2CCNCC2)ccn1
Reactant: COc1ccc(C(=O)CCC(=O)O)cc1F
Agent: CC(C)N=C=NC(C)C
Agent: O=[N+]([O-])c1ccccc1O
Solvent: CC(Cl)CCl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1ccc(C(=O)CCC(=O)N2CCN(c3ccncc3)CC2)cc1F
Temperature: 25 °C
Reaction time: 13 h
Yield: 718.3 %

Procedure:
To the polymeric nitrophenol (1.5 g, approx. 1 mmol) was added a solution of 3-(4-methoxy-3-fluorobenzoyl)propionic acid (1.66 g, 7.34 mmol) in a mixture of 1,2-dichloropropane (15 ml) and DMF (6 ml), followed by the addition of DIC (0.78 ml, 5.01 mmol). The mixture was shaken at room temperature for 13 hours, filtered, and the polymer was extensively washed with DCM, DMF, and 1,2-dichloropropane. To the polymer was added 1,2-dichloropropane (5 ml), a solution of 1-(4-pyridyl)piperazine (116 mg, 0.71 mmol) in 1,2-dichloropropane (10 ml), and triethylamine (0.2 ml). The resulting mixture was shaken at room temperature for 21 hours, filtered, and the polymer was carefully washed with DCM and methanol. The combined filtrates were concentrated to yield the crude product as an oil (0.38 g). Crystallization from acetonitrile (2 ml) at −20° C. yielded 0.19 g (5.1 mmol, 72%) of the title compound as almost colourless solid.
Reaction SMILES: [C:1]12[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=1)[NH:6]C(=O)[O:4][C:2]2=O.CC(N(C)C)=O.[CH2:19]([NH2:37])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36].C(=O)=O>O.CN(C)C=O>[CH2:19]([NH:37][C:2](=[O:4])[C:1]1[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=1)[NH2:6])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36]
Reactant: O=c1[nH]c2ccccc2c(=O)o1
Reactant: CCCCCCCCCCCCCCCCCCN
Agent: O=C=O
Solvent: CC(=O)N(C)C
Solvent: O
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCCCCNC(=O)c1ccccc1N

Procedure:
80.8 parts of isatoic anhydride are introduced into 125 parts of dimethylacetamide, and a solution of 134.7 parts of stearylamine in 50 parts of dimethylformamide is added dropwise. When the evolution of CO2 has ended (3 hours) the resulting clear solution is stirred into 2 liters of H2O and the resulting precipitate is recrystallised from ethanol, using active charcoal. Anthranilic acid stearylamide of melting point 89°-90° C. is obtained.
Reaction SMILES: [CH2:1]([N:4]([CH2:54][CH2:55][CH3:56])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:19]([CH2:20]/[CH:21]=[CH:22]/[CH2:23][N:24]3[C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[N:26]=[C:25]3[C:33]3[CH:49]=[CH:48][C:36]([O:37][CH2:38][CH2:39][CH2:40][N:41]([CH2:45][CH2:46][CH3:47])[CH2:42][CH2:43][CH3:44])=[CH:35][CH:34]=3)[C:18]3[CH:50]=[CH:51][CH:52]=[CH:53][C:17]=3[N:16]=2)=[CH:11][CH:10]=1)[CH2:2][CH3:3]>CO.[Pd]>[NH3:4].[CH2:54]([N:4]([CH2:1][CH2:2][CH3:3])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:19]([CH2:20][CH2:21][CH2:22][CH2:23][N:24]3[C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[N:26]=[C:25]3[C:33]3[CH:34]=[CH:35][C:36]([O:37][CH2:38][CH2:39][CH2:40][N:41]([CH2:42][CH2:43][CH3:44])[CH2:45][CH2:46][CH3:47])=[CH:48][CH:49]=3)[C:18]3[CH:50]=[CH:51][CH:52]=[CH:53][C:17]=3[N:16]=2)=[CH:11][CH:10]=1)[CH2:55][CH3:56]
Reactant: CCCN(CCC)CCCOc1ccc(-c2nc3ccccc3n2C/C=C/Cn2c(-c3ccc(OCCCN(CCC)CCC)cc3)nc3ccccc32)cc1
Agent: [Pd]
Solvent: CO
Product: CCCN(CCC)CCCOc1ccc(-c2nc3ccccc3n2CCCCn2c(-c3ccc(OCCCN(CCC)CCC)cc3)nc3ccccc32)cc1
Product: N
Yield: 97.7 %

Procedure:
E-(3-{4-[1-(4-{2-[4-(3-Dipropylaminopropoxy)phenyl]benzoimidazol-1-yl}but-2-enyl)-1H-benzoimidazol-2-yl]phenoxy}propyl)dipropylamine (Example 2) (100 mg) is hydrogenated at 50 pounds per square inch (psi) in methanol (20 mL) with 20% palladium on carbon (10 mg) for 6 hours. The mixture is filtered and evaporated to leave a yellow solid. The solid is purified by MPLC on silica gel eluting with 200:8:1 dichloromethane:ethanol:0.880 aqueous ammonia to give 49 mg of the title compound as a white solid; mp 141°-143° C.
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C@H:3]1[F:15].[Cl:16][C:17]1[N:18]=[C:19]([C:24](O)=[O:25])[NH:20][C:21]=1[CH2:22][CH3:23].O.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl.C(N(CC)CC)C>>[Cl:16][C:17]1[N:18]=[C:19]([C:24]([NH:1][C@@H:2]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])[CH2:4][C@H:3]2[F:15])=[O:25])[NH:20][C:21]=1[CH2:22][CH3:23]
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](N)[C@H](F)C1
Reactant: CCc1[nH]c(C(=O)O)nc1Cl
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: O
Product: CCc1[nH]c(C(=O)N[C@@H]2CCN(C(=O)OC(C)(C)C)C[C@H]2F)nc1Cl
Yield: 72.1 %

Procedure:
The same operation as in Example (196d) was performed using tert-butyl trans(±)-4-amino-3-fluoropiperidine-1-carboxylate obtained in Example (197a) (30.0 mg, 0.137 mmol), 4-chloro-5-ethyl-1H-imidazole-2-carboxylic acid obtained in Example (1d) (28.8 mg, 0.165 mmol), 1-hydroxybenzotriazole hydrate (27.9 mg, 0.206 mmol), WSC hydrochloride (39.5 mg, 0.206 mmol) and triethylamine (28.7 μL, 0.206 mmol), to obtain 37.0 mg of the title compound (72%) as a pale yellow foamy substance.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[C:21]([NH:23][S:24]([CH3:27])(=[O:26])=[O:25])[CH:20]=[CH:19][C:3]=1[C:4]([CH:6]([C:14]([CH:16]1[CH2:18][CH2:17]1)=[O:15])C(OC(C)(C)C)=O)=[O:5].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:22]=[C:21]([NH:23][S:24]([CH3:27])(=[O:25])=[O:26])[CH:20]=[CH:19][C:3]=1[C:4](=[O:5])[CH2:6][C:14]([CH:16]1[CH2:17][CH2:18]1)=[O:15]
Reactant: CC(C)(C)OC(=O)C(C(=O)c1ccc(NS(C)(=O)=O)cc1Cl)C(=O)C1CC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CS(=O)(=O)Nc1ccc(C(=O)CC(=O)C2CC2)c(Cl)c1
Yield: 97.5 %

Procedure:
t-Butyl 2-[2-chloro-4-(methylsulphonylamino)benzoyl]-3-cyclopropyl-3-oxopropionate (2 g) was dissolved in toluene and p-toluenesulphonic acid (0.2 g) was added. The mixture was stirred and heated at reflux for 0.5 hours. It was cooled, washed with water, dried (magnesium sulphate) and filtered. The filtrate was evaporated to dryness to give 1-[2-chloro-4-(methylsulphonylamino)phenyl]-3-cyclopropylpropan-1,3-dione (1.48 g) as a white solid, m.p. 119.9-121.6° C.
Reaction SMILES: [CH3:1][C:2]1([CH2:36][OH:37])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14]CC3C=CC=CC=3)=[CH:10][CH:9]=2)=[C:4]([C:22]2[CH:27]=[CH:26][C:25]([O:28]CC3C=CC=CC=3)=[CH:24][CH:23]=2)[CH2:3]1>C(Cl)Cl.C(OCC)(=O)C.O.Cl[Ti](Cl)(Cl)Cl>[CH3:1][C:2]1([CH2:36][OH:37])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[C:4]([C:22]2[CH:23]=[CH:24][C:25]([OH:28])=[CH:26][CH:27]=2)[CH2:3]1
Reactant: CC1(CO)CCC(c2ccc(OCc3ccccc3)cc2)=C(c2ccc(OCc3ccccc3)cc2)C1
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: O
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC1(CO)CCC(c2ccc(O)cc2)=C(c2ccc(O)cc2)C1
Temperature: -10 °C
Reaction time: 3 h

Procedure:
To a solution of (1-methyl-3,4-di(4-benzyloxy-phenyl)-cyclohex-3-enyl)-methanol (150 mg, 0.306 mmol) in DCM (5.0 mL) at −10° C. was added TiCl4 (0.102 mL, 3.0 eq.) and the reaction mixture stirred at −10° C. for 3 h. The reaction mixture was then diluted with ethyl acetate (20 mL and H2O (10 mL). The organic layer was separated, dried over MgSO4, and purified by SiO2 (50˜100% ethyl acetate/hexane) to yield a lower TLC spot of (1-methyl-3,4-di(4-hydroxy-phenyl)-cyclohex-3-enyl)-methanol.
Reaction SMILES: [CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:53])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([OH:50])[CH:46]([O:51][CH3:52])[CH2:45]2)[CH:7]([CH3:54])[CH:6]([OH:55])[CH2:5][C:4]1=[O:56])[CH3:2].N1[C:62]([CH3:63])=[CH:61]C=CC=1C.FC(F)(F)S(O[Si:71]([CH:78]([CH3:80])[CH3:79])([CH:75]([CH3:77])[CH3:76])[CH:72]([CH3:74])[CH3:73])(=O)=O>C(Cl)Cl>[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:53])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([O:50][Si:71]([CH:78]([CH3:80])[CH3:79])([CH:75]([CH3:77])[CH3:76])[CH:72]([CH3:74])[CH3:73])[CH:46]([O:51][CH3:52])[CH2:45]2)[CH:7]([CH3:54])[CH:6]([O:55][Si:71]([CH:62]([CH3:61])[CH3:63])([CH:75]([CH3:77])[CH3:76])[CH:72]([CH3:74])[CH3:73])[CH2:5][C:4]1=[O:56])[CH3:2]
Reactant: CC(C)[Si](OS(=O)(=O)C(F)(F)F)(C(C)C)C(C)C
Reactant: Cc1cccc(C)n1
Reactant: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(O)C(OC)C3)C(C)C(O)CC1=O)C(C)CC2OC
Solvent: ClCCl
Product: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(O[Si](C(C)C)(C(C)C)C(C)C)C(OC)C3)C(C)C(O[Si](C(C)C)(C(C)C)C(C)C)CC1=O)C(C)CC2OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 89.6 %

Procedure:
To a cooled solution (0° C.) of 17-ethyl-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25 -dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (120 mg) in dry methylene chloride (15 ml) was added 2,6-lutidine (64.3 mg) followed by triisopropylsilyl trifluoromethanesulfonate (184 mg). Reaction temperature was raised to r.t. and stirred overnight under nitrogen atmosphere. The reaction was quenched with 10 ml of water and extracted with ethyl acetate. Organic layer was washed (water, sat'd NaHCO3, sat'd NaCl) and dried (anhydrous MgSO4). Removal of solvent followed by chromatography on silica gel (70% hexane/ethyl acetate) gave 150 mg of product. MASS: (FAB) 1110 (M+ +Li).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:7]=[C:6]([C@H:8]([CH2:17][CH2:18][CH2:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[O:5][N:4]=1.[CH:26]1([C:29](Cl)=[O:30])[CH2:28][CH2:27]1>>[CH:20]1([CH2:19][CH2:18][CH2:17][C@@H:8]([C:6]2[O:5][N:4]=[C:3]([CH2:2][NH:1][C:29]([CH:26]3[CH2:28][CH2:27]3)=[O:30])[N:7]=2)[CH2:9][C:10]([O:12][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:11])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1
Reactant: CC(C)(C)OC(=O)C[C@@H](CCCC1CCCCC1)c1nc(CN)no1
Reactant: O=C(Cl)C1CC1
Product: CC(C)(C)OC(=O)C[C@@H](CCCC1CCCCC1)c1nc(CNC(=O)C2CC2)no1
Yield: 107.5 %

Procedure:
Method as for preparation 50 using tert-butyl(3R)-3-[3-(aminomethyl)-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoate (preparation 18) (204 mg, 0.57 mmol) and cyclopropane carboxylic acid chloride (62 μl, 0.68 mmol) as starting materials to afford the title compound as a colourless oil (257 mg).
Reaction SMILES: [CH:1]([O:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:22][C:23]1[O:27][C:26]([C:28]([O:30][CH3:31])=[O:29])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+].C(#N)C>C(OCC)(=O)C.O>[CH:1]([O:14][CH:15]1[CH2:20][CH2:19][N:18]([CH2:22][C:23]2[O:27][C:26]([C:28]([O:30][CH3:31])=[O:29])=[CH:25][CH:24]=2)[CH2:17][CH2:16]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1ccc(CCl)o1
Reactant: c1ccc(C(OC2CCNCC2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC#N
Product: COC(=O)c1ccc(CN2CCC(OC(c3ccccc3)c3ccccc3)CC2)o1
Reaction time: 18 h
Yield: 78.1 %

Procedure:
A mixture of 401 mg of 4-benzhydryloxypiperidine synthesized in Production Example 1, 288 mg of methyl 5-chloromethylfuran-2-carboxylate, 352 mg of potassium carbonate, and 3.5 mL of acetonitrile was stirred for 18 hours. The reaction solution was diluted with ethyl acetate and then thrown into water, and the organic layer was collected by separation. The organic layer was washed with a saturated saline solution and then dried over magnesium sulfate. The solvent was distilled off. The resulting product was subjected to a silica gel column chromatography (chloroform/acetone (volume ratio)=20:1 to 10:1) to give the title compound (475 mg).
Reaction SMILES: [C:1](=[N:4][O:5][CH:6]([CH3:10])[C:7]([OH:9])=[O:8])([CH3:3])[CH3:2].[CH3:11][CH2:12][O-].[Na+].CC(=NO)C.BrC(C)C(OCC)=O>>[C:1](=[N:4][O:5][CH:6]([CH3:10])[C:7]([O:9][CH2:11][CH3:12])=[O:8])([CH3:3])[CH3:2]
Reactant: CC(C)=NOC(C)C(=O)O
Reactant: CC[O-]
Agent: CC(C)=NO
Agent: CCOC(=O)C(C)Br
Agent: [Na+]
Product: CCOC(=O)C(C)ON=C(C)C
Temperature: 0 °C
Reaction time: 18 h
Yield: 83 %

Procedure:
The synthesis of (±)-α-(isopropylideneaminooxy)propionic acid (2) was adapted from Melvin, S et al., Organic Syntheses, 1973, Coll. Vol. 5, 1029-37. Briefly, to a freshly prepared 1M NaOEt solution (35 g in 1 L) was added acetone oxime (110 g, 1.505 mol) and cooled to 0° C. Ethyl α-bromopropionate (175 mL, 1.347 mol) was added at a rate that such that the temperature of the reaction mixture did not rise above 20° C. After 18 hr at rt, the mixture was filtered and the filtrate was concentrated to approximately 500 mL. Water (500 mL) was added and the mixture was extracted with 1:1 benzene:Et2O (3×150 mL). The combined extracts were washed with water (500 mL), dried over Na2SO4 and the solvent was removed and the oily residue was distilled to afford 197 g of ethyl α-(isopropylideneaminooxy)propionate as a clear oil (83%) 1H NMR (CDCl3): δ 4.5 (q, 1H, J=6.9 Hz, CH), 4.1 (m, 2H, J=7.2 Hz, O—CH2-Me), 1.84 (s, 3H, CH3), 1.61 (s, 3H, CH3), 1.22 (d, 3H, J=6.9 Hz, CH—CH3), 1.17 (t, 3H, J=7.2 Hz, —CH3); B.P. 62-64° C. (4 mm).
Reaction SMILES: [NH:1]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@H:2]([C:22]([OH:24])=[O:23])[CH2:3][NH:4]C(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O.[CH2:32]([N-:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43].C(NCC)C>ClCCl>[NH:1]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@H:2]([C:22]([OH:24])=[O:23])[CH2:3][NH2:4].[CH2:32]([N-:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]
Reactant: CC(C)(C)OC(=O)N[C@@H](CNC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Agent: CCCCCCCCCCCCCC[N-]CCCCCCCCCCCC
Solvent: CCNCC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@@H](CN)C(=O)O
Reaction time: 4.5 h
Yield: 87.1 %

Procedure:
607 mg Boc-Dap(Fmoc)-N-lauryl-N-myristyl amide were dissolved in 8 ml anhydrous dichloromethane in a 50 ml round-bottom flask (FIG. 6). 3 ml diethylamine were added and the reaction steered at room temperature for 4.5 hours. The volatile constituents were removed using a rotary evaporator and the residue was purified by chromatography using 40 g silica gel 60 (Merck) with hexane/ethylacetate 5:1. The product was eluted by a step gradient consisting of ethylacetate, dichloromethane and dichloromethane/methanol 3:1. 372 mg (0.655 mmol) Boc-Dap-N-lauryl-N-myristyl amide were obtained as yellowish, viscous oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6](Cl)=[C:7]3[N:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:8]3=[N:9][C:10]=2[CH:11]=1.[CH2:19]([N:21]([CH2:27][CH3:28])[CH2:22][CH2:23][CH2:24][CH2:25][NH2:26])[CH3:20].C1(O)C=CC=CC=1.[ClH:36]>CC(C)=O.C(O)C>[ClH:1].[ClH:36].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]([NH:26][CH2:25][CH2:24][CH2:23][CH2:22][N:21]([CH2:27][CH3:28])[CH2:19][CH3:20])=[C:7]3[N:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:8]3=[N:9][C:10]=2[CH:11]=1
Reactant: COc1ccc2nc3cc(Cl)ccc3c(Cl)c2n1
Reactant: CCN(CC)CCCCN
Agent: Cl
Solvent: CCO
Solvent: Oc1ccccc1
Solvent: CC(C)=O
Product: CCN(CC)CCCCNc1c2ccc(Cl)cc2nc2ccc(OC)nc12

Procedure:
A mixture of 2.8 g. of 7,10-dichloro-2-methoxypyrido[3,2-b]quinoline, 1.5 g. of 4-diethylaminobutylamine and 6.5 g. of phenol is heated at 100° C. for 3 hours. The reaction is cooled, 20 ml. of ethanol is added and this mixture is poured into a mixture of 200 ml. of acetone and 2.5 ml. of concentrated hydrochloric acid. The yellow solic is collected, air-dried and recrystallized from ethanol, giving the desired product, mp. 246°-274° C. (dec.).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:18]=[CH:17][C:8]([C:9]([CH:11]([CH3:16])[CH2:12][C:13]([OH:15])=[O:14])=[O:10])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[H-].[Na+].Br[CH2:22][CH2:23][CH2:24][N:25]1[C:29](=[O:30])[C:28]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:27]2[C:26]1=[O:35].O>CS(C)=O>[C:26]1(=[O:35])[N:25]([CH2:24][CH2:23][CH2:22][N:4]([C:5]2[CH:18]=[CH:17][C:8]([C:9]([CH:11]([CH3:16])[CH2:12][C:13]([OH:15])=[O:14])=[O:10])=[CH:7][CH:6]=2)[C:1](=[O:3])[CH3:2])[C:29](=[O:30])[C:28]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:27]12
Reactant: CC(=O)Nc1ccc(C(=O)C(C)CC(=O)O)cc1
Reactant: O=C1c2ccccc2C(=O)N1CCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CC(=O)N(CCCN1C(=O)c2ccccc2C1=O)c1ccc(C(=O)C(C)CC(=O)O)cc1
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
30.0 g (120 mmol) of 3-(4-acetamidobenzoyl)-butyric acid are added to a suspension of 7.6 g (253 mmol) of sodium hydride (80%) in 150 ml of dimethyl sulphoxide and the mixture is stirred for 30 minutes at 60° C. After the addition of 33.2 g (120 mmol) of N-(3-bromopropyl)-phthalimide, stirring is continued at 80° C. for 6 hours. After cooling, the reaction mixture is poured out on 200 ml of iced water and extracted with 3×100 ml of dichloromethane. The extracts are discarded. The aqueous phase is then adjusted to pH 6.5 with 2N hydrochloric acid and again extracted with 3×100 ml of dichloromethane. The combined organic phases are dried and concentrated by evaporation under vacuum. The oil obtained as residue crystallizes when triturated with 20 ml of ethanol.
Reaction SMILES: [CH3:1][C:2]1[C:11]2[C:6](=[C:7]([CH3:13])[C:8]([OH:12])=[CH:9][CH:10]=2)[O:5][C:4](=[O:14])[CH:3]=1.CI.[C:17](=O)([O-])[O-].[K+].[K+]>CC(C)=O.[OH-].[Na+]>[CH3:1][C:2]1[C:11]2[C:6](=[C:7]([CH3:13])[C:8]([O:12][CH3:17])=[CH:9][CH:10]=2)[O:5][C:4](=[O:14])[CH:3]=1
Reactant: O=C([O-])[O-]
Reactant: Cc1cc(=O)oc2c(C)c(O)ccc12
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: CI
Solvent: CC(C)=O
Product: COc1ccc2c(C)cc(=O)oc2c1C
Yield: 66 %

Procedure:
A solution of 4,8-dimethyl-7-hydroxycoumarin (0.190 g, 1.00 mmol) and methyl iodide (0.180 g, 1.30 mmol) in 50 ml of dry acetone was heated at reflux in the presence of 0.5 g of potassium carbonate for 14 hours. The solution was then cooled and filtered. The filtrate was evaporated under reduced pressure to yield a beige solid. The beige solid was taken up in 20% sodium hydroxide (aqueous) and collected by vacuum filtration. The crude product was recrystallized from methanol to yield shiny white crystals, m.p. 162°-164° C., 135 mg, 66% yield. 1H-NMR: 2.27 (s, 3H, C8 --CH3), 2.4 (d, 3H, C4 --CH3, J=1.2 Hz), 3.9 (s, 3H, OCH3), 6.1 (q, 1H, C3 --H, J=1.2 Hz), 6.8-6.9 (d, 1H, C6 --H, J=8.8 Hz), 7.4- 7.5 (d, 1H, C5 --H, J=8.8 Hz).
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][C:7]=2[C:16]2[C:17]3[N:24]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:23]([CH3:33])=[C:22]([C:34](O)=[O:35])[C:18]=3[N:19]=[CH:20][N:21]=2)[CH2:3][CH2:2]1.[NH2:37][C@@H:38]1[CH2:43][CH2:42][C@H:41]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[CH2:40][CH2:39]1>>[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([C:12]([F:13])([F:15])[F:14])=[CH:8][C:7]=2[C:16]2[C:17]3[N:24]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:23]([CH3:33])=[C:22]([C:34]([NH:37][C@@H:38]4[CH2:43][CH2:42][C@H:41]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:49])([CH3:48])[CH3:50])[CH2:40][CH2:39]4)=[O:35])[C:18]=3[N:19]=[CH:20][N:21]=2)[CH2:2][CH2:3]1
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@@H](N)CC1
Reactant: Cc1c(C(=O)O)c2ncnc(-c3cc(C(F)(F)F)ccc3OCC3CC3)c2n1COCC[Si](C)(C)C
Product: Cc1c(C(=O)N[C@H]2CC[C@@H](NC(=O)OC(C)(C)C)CC2)c2ncnc(-c3cc(C(F)(F)F)ccc3OCC3CC3)c2n1COCC[Si](C)(C)C

Procedure:
Starting from 4-[2-(cyclopropylmethoxy)-5-(trifluoromethyl)phenyl]-6-methyl-5-{[2-(trimethylsilyl)ethoxy]methyl}-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid (example D.c8) and commercially available tert-butyl cis-(4-amino-cyclohexyl)-carbamate the title compound is obtained as colorless foam.
Reaction SMILES: [CH2:1]([N:8]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[C:9](=[O:20])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([O:18][CH3:19])[CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:27][O:28][C:29](=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[CH2:36]Br.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:1]([N:8]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[C:9](=[O:20])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:36][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[C:29]([O:28][CH3:27])=[O:38])=[C:13]([O:18][CH3:19])[CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCCCCN(Cc1ccccc1)C(=O)Cc1ccc(O)c(OC)c1
Reactant: COC(=O)c1ccccc1CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCCCCCN(Cc1ccccc1)C(=O)Cc1ccc(OCc2ccccc2C(=O)OC)c(OC)c1
Yield: 85.8 %

Procedure:
N-Benzyl-N-hexyl-2-(4-hydroxy-3-methoxyphenyl)acetamide (84 mg, 0.236 mmol), 2-bromomethylbenzoic acid methyl ester (57 mg, 0.248 mmol) and potassium carbonate anhydrous (49 mg, 0.355 mmol) were mixed in acetonitrile (5 ml). The mixture was heated to reflux overnight and then evaporated to dry. Ethyl acetate and water were added and the two phases were separated. The organic phase was washed with brine and dried (magnesium sulphate) and evaporated. Chromatography of the residue on a column (ISOLUTE® SI, 2 g/6 ml) using DCM, MeOH/DCM (0.5:99.5) as eluant gave 102 mg the desired product yield 86%.