Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[C:2]([O-:5])(C)C.[K+].[CH3:7][C:8]1([CH3:15])[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.C(OC=O)C.[Cl-].[Na+].O>[CH3:7][C:8]1([CH3:15])[CH2:13][CH:12]([CH:2]=[O:5])[C:11](=[O:14])[CH2:10][CH2:9]1
Reactant: CC1(C)CCC(=O)CC1
Reactant: CC(C)(C)[O-]
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Cl-]
Agent: [K+]
Solvent: CCOC=O
Solvent: O
Solvent: C1CCOC1
Product: CC1(C)CCC(=O)C(C=O)C1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 309.4 %

Procedure:
To an ice-cold solution of KOtBu (24.5 g, 109 mmol, 50% solution in tert.-butanol) in THF (700 mL), ethylformate (120 mL, 123 mmol) is slowly added. The mixture is stirred at rt for 30 min before a solution of 4,4-dimethyl-cyclohexanone (50 g, 396 mmol) in ethylformate (50 mL) and THF (70 mL) is added over a period of 20 min. Upon complete addition, stirring is continued at 15-20° C. for 30 min. The orange suspension is poured onto 10% aq. citric acid solution (200 mL) and brine (200 mL) and extracted with EA (2×200 mL). The organic extracts are washed with 0.2 N aq. NaOH and brine, dried over Na2SO4 and evaporated to dryness to give 5,5-dimethyl-2-oxo-cyclohexanecarbaldehyde (52 g) as a yellow oil; LC-MS: tR=0.89 min, [M+1+CH3CN]+=196.15.
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=1.[C:24]([NH:31][CH2:32][CH2:33][NH2:34])([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]>>[C:27]([O:26][C:24](=[O:25])[NH:31][CH2:32][CH2:33][NH:34][C:19]([C:18]1[CH:17]=[N:16][C:15]([O:14][CH2:13][C:3]2[C:4]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)=[N:5][O:6][C:2]=2[CH3:1])=[CH:23][CH:22]=1)=[O:21])([CH3:30])([CH3:28])[CH3:29]
Reactant: CC(C)(C)OC(=O)NCCN
Reactant: Cc1onc(-c2ccccc2)c1COc1ccc(C(=O)O)cn1
Product: Cc1onc(-c2ccccc2)c1COc1ccc(C(=O)NCCNC(=O)OC(C)(C)C)cn1
Yield: 90 %

Procedure:
As described for example 191, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (200 mg, 0.65 mmol) was converted, using N-Boc-ethylenediamine instead of 2-aminoethyl isopropylether, to the title compound (261 mg, 90%) which was obtained as a white solid. MS: m/e=511.5 [M+OAc]−.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.[CH3:19][C:20]([CH3:25])=[CH:21][C:22](Cl)=[O:23].O>C(Cl)(Cl)Cl>[CH3:19][C:20]([CH3:25])=[CH:21][C:22]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:6][CH:7]=1)=[O:23]
Reactant: CC(C)=CC(=O)Cl
Reactant: CCCCCC(C(=O)OCC)c1ccc(N)cc1
Solvent: ClC(Cl)Cl
Solvent: O
Product: CCCCCC(C(=O)OCC)c1ccc(NC(=O)C=C(C)C)cc1
Temperature: 25 °C

Procedure:
10.4 g of (RS)-ethyl 2-(4-aminophenyl)-heptanoate dissolved in 100 ml of chloroform was treated dropwise with 4.64 ml of 3,3-dimethylacryloyl chloride. The mixture was heated to reflux for 6 hours. After cooling to room temperature, 100 ml of water were added. The phases were separated and the aqueous phase was extracted with two portions of 50 ml of chloroform. The combined organic extracts were washed with two portions of 100 ml of saturated aqueous sodium bicarbonate solution and one portion of 100 ml of saturated aqueous sodium chloride solution. The organic phase was dried over MgSO4 and concentrated in vacuo. The product was used without purification. 1H NMR (CDCl3): 7.48 (br. d, J=8.4 Hz, 2H), 7.39 (br. s, 1H), 7.24 (d, J=8.5 Hz, 2H), 5.71 (br. s, 1H), 4.20-4.00 (m, 2H), 3.48 (t, J=7.7 Hz, 1H), 2.21 (br. s, 3H), 2.15-1.95 (m, 1H), 1.87 (s, 3H), 1.80-1.65 (m, 1H), 1.35-1.15 (m, 6H), 1.20 (t, J=7.1 Hz, 3H), 0.85 (t, J=6.7 Hz, 3H).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[N:34]1([CH2:39][CH2:40][OH:41])[CH2:38][CH2:37][CH2:36][CH2:35]1.[CH3:42][O:43][C:44]1[CH:49]=[C:48]([C:50]2[CH:51]=[C:52]3[C:58]([C:59]4[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=4[O:65][CH3:66])=[CH:57][NH:56][C:53]3=[N:54][CH:55]=2)[CH:47]=[CH:46][C:45]=1O>C(Cl)Cl>[CH3:66][O:65][C:60]1[CH:61]=[CH:62][CH:63]=[CH:64][C:59]=1[C:58]1[C:52]2[C:53](=[N:54][CH:55]=[C:50]([C:48]3[CH:47]=[CH:46][C:45]([O:41][CH2:40][CH2:39][N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)=[C:44]([O:43][CH3:42])[CH:49]=3)[CH:51]=2)[NH:56][CH:57]=1
Reactant: COc1cc(-c2cnc3[nH]cc(-c4ccccc4OC)c3c2)ccc1O
Reactant: OCCN1CCCC1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COc1cc(-c2cnc3[nH]cc(-c4ccccc4OC)c3c2)ccc1OCCN1CCCC1
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 15.9 %

Procedure:
To an 8 ml borosilicate reaction vial were added 150 mg (0.350 mmol) of PS-triphenylphosphine (2.33 mmol·g−1; Argonaut Technologies) and anhydrous methylene chloride (5 ml). The vial was fitted with a rubber septum and the suspension was stirred for 5 minutes in an ice-bath (0° C.). Diisopropyl azodicarboxylate (68 μL, 0.35 mmol) was added dropwise, and the mixture was allowed to warm to room temperature over 20 minutes. To the reaction vial was added 2-pyrrolidin-1-yl-ethanol (54 mg, 0.47 mmol) and 2-methoxy-4-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]phenol (60 mg, 0.17 mmol), and the suspension was stirred at room temperature for 8 hours. The yellow reaction mixture was filtered, and the resin was washed three times with DCM and ether, then twice with DCM. The combined filtrate was concentrated to obtain a yellow residue, which was purified by flash chromatography on amine functionalized silica gel (ISCO RediSep® amine column) using a gradient of ethyl acetate in hexanes to afford 12 mg (8%) of 3-(2-methoxy-phenyl)-5-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridine as a light yellow powder. 1H-NMR (d6-DMSO) δ=11.87 (br.s, 1H), 8.51 (d, 1H), 8.18 (s, 1H), 8.11 (d, 1H), 7.70 (d, 1H), 7.57 (dd, 1H), 7.27 (m, 1H), 7.24 (d, 1H), 7.17 (dd, 1H), 7.12 (dd, 1H), 7.06 (s, 1H), 7.04 (m, 1H), 4.08 (t, 2H), 3.85 (s, 3H), 3.83 (s, 3H), 2.82 (t, 2H), 2.55 (m, 4H), 1.69 (m, 4H); MS m/z: 444 [MH]+.
Reaction SMILES: [N:1]1([C:7]([C@H:9]2[CH2:14][CH2:13][C@H:12]([C:15]([O:17]C)=[O:16])[CH2:11][CH2:10]2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[OH-].[Na+]>CO>[N:1]1([C:7]([C@H:9]2[CH2:10][CH2:11][C@H:12]([C:15]([OH:17])=[O:16])[CH2:13][CH2:14]2)=[O:8])[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1
Reactant: COC(=O)[C@H]1CC[C@H](C(=O)N2CCOCC2)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)[C@H]1CC[C@H](C(=O)N2CCOCC2)CC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Methyl trans-4-(morpholin-4-ylcarbonyl)cyclohexanecarboxylate (860 mg) obtained in Reference Example 82(1) is dissolved in methanol (40 ml), and thereto is added 4 N aqueous sodium hydroxide solution (1.68 ml). The mixture is then stirred at room temperature for 18 hours. The reaction solution is concentrated under reduced pressure. The residue is diluted with ice-water, neutralized with 10% hydrochloric acid and extracted with chloroform. The organic layer is dried over sodium sulfate and the solvent is concentrated under reduced pressure to give title compound (638 mg).
Reaction SMILES: [CH3:1][N:2]([CH3:28])[S:3]([C:6]1[CH:7]=[C:8]([CH:12]2[C:21]([CH3:23])([CH3:22])[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:24]([O:26]C)=[O:25])[CH:18]=3)[NH:13]2)[CH:9]=[CH:10][CH:11]=1)(=[O:5])=[O:4].[OH-].[Na+]>CO.O1CCCC1>[CH3:28][N:2]([CH3:1])[S:3]([C:6]1[CH:7]=[C:8]([CH:12]2[C:21]([CH3:23])([CH3:22])[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:24]([OH:26])=[O:25])[CH:18]=3)[NH:13]2)[CH:9]=[CH:10][CH:11]=1)(=[O:5])=[O:4]
Reactant: COC(=O)c1ccc2c(c1)CC(C)(C)C(c1cccc(S(=O)(=O)N(C)C)c1)N2
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: CN(C)S(=O)(=O)c1cccc(C2Nc3ccc(C(=O)O)cc3CC2(C)C)c1
Yield: 20.2 %

Procedure:
To a stirred solution of methyl 2-(3-(N,N-dimethylsulfamoyl)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate (149 mg, 0.37 mmol) in methanol/tetrahydrofuran (5 mL/5 mL) was added 1N sodium hydroxide (5.6 mL). The resultant mixture was heated to reflux for 2.5 h. Organic solvent was removed and the residue was dissolved in water. The aqueous layer was acidified to pH=4. The precipitates were filtered, and dissolved in tetrahydrofuran, dried over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was removed, and after evaporation, the residue was treated with ethyl acetate to afford 29 mg of 2-(3-(N,N-dimethylsulfamoyl)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylic acid. (Yield: 20%). MS (ESI+APCI) M+1=389.1.
Reaction SMILES: [CH2:1]([C@H:3]([NH:10][C:11]([C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[C:15]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:14]=1[O:29][CH2:30][CH2:31][N:32]1C(=O)C2=CC=CC=C2C1=O)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2].O.NN>CCO>[CH2:1]([C@H:3]([NH:10][C:11]([C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[C:15]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:14]=1[O:29][CH2:30][CH2:31][NH2:32])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2]
Reactant: CC[C@H](NC(=O)c1c(OCCN2C(=O)c3ccccc3C2=O)c(-c2ccccc2)nc2ccccc12)c1ccccc1
Agent: NN
Solvent: O
Solvent: CCO
Product: CC[C@H](NC(=O)c1c(OCCN)c(-c2ccccc2)nc2ccccc12)c1ccccc1
Yield: 72.3 %

Procedure:
2.2 g (3.9 mmol) of (S)-N-(α-ethylbenzyl)-2-phenyl-3-(2-phthalimidoethoxy) quinoline-4-carboxamide (compound of Description 3) were dissolved in 150 ml of 96% EtOH; the solution was heated to reflux; 0.38 ml (7.8 mmol) of hydrazine hydrate were added and the reaction mixture refluxed for 4 hours. Additional 0.4 ml (8.2 mmol), 0.2 ml (4.1 mmol), 0.2 ml (4.1 mmol), 0.4 ml (8.2 mmol), 0.4 ml (8.2 mmol) of hydrazine hydrate were added every 12 hours while refluxing the reaction mixture. Then it was evaporated in-vacuo to dryness and 20 ml of H2O were added; it was cooled with an ice bath and 10 ml of conc. HCl were added. The reaction mixture was refluxed for 1 hour and then, after cooling, the phthalhydrazide was filtered off. The resulting aqueous filtrate was washed with EtOAc, basified with 2N NaOH and extracted with EtOAc. The organic layer was washed with sat. sol. NaCl, dried over Na2SO4 and evaporated in-vacuo to dryness. The residue was purified by flash column chromatography on 230-400 mesh silica gel, eluting with a mixture of EtOAc/MeOH 96:4 containing 1.2% NH4Oh (28%) to yield 1.2 g of the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:9][C:8](Br)=[N:7][CH:6]=1)=[O:4].Br[Zn][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C:5]1[S:9][C:8]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[N:7][CH:6]=1)=[O:4]
Reactant: Br[Zn]c1ccccn1
Reactant: COC(=O)c1cnc(Br)s1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)c1cnc(-c2ccccn2)s1

Procedure:
To a suspension of 2-bromo-1,3-thiazole-5-carboxylic acid methyl ester (0.5 g, 2.25 mmol) and Pd(PPh3)4 (0.13 g, 0.11 mmol) in THF (12.5 ml) was added bromo-(pyridine-2-yl)-zinc (6.75 ml, 0.5M THF solution) under inert gas atmosphere. The reaction mixture was irradiated under microwave conditions at 120° C. for 10 min. The solvent was removed and the product was obtained after purification by silica gel chromatography using a heptane/ethyl acetate gradient as yellow crystals (0.34 g, 68%) MS: M=221.2 (M+H)+
Reaction SMILES: [C:1]1([C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([NH2:16])[CH:10]=2)[CH:6]=[CH:5][C:4]([NH2:7])=[C:3]([NH2:8])[CH:2]=1.[CH3:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=1>>[CH3:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([C:23]2[NH:16][C:11]3[CH:10]=[C:9]([C:1]4[CH:2]=[C:3]([NH2:8])[C:4]([NH2:7])=[CH:5][CH:6]=4)[CH:14]=[CH:13][C:12]=3[N:15]=2)=[CH:21][CH:20]=1
Reactant: COc1ccc(C=O)cc1
Reactant: Nc1ccc(-c2ccc(N)c(N)c2)cc1N
Product: COc1ccc(-c2nc3ccc(-c4ccc(N)c(N)c4)cc3[nH]2)cc1
Temperature: 180 °C

Procedure:
Prepared by Method 2, using a 1:1 ratio of biphenyl-3,3′,4,4′-tetraamine to 4-methoxybenzaldehyde, and heating to 180° C. for 10 min.
Reaction SMILES: C(OC([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1B(O)O)=O)(C)(C)C.Cl[C:19]1[C:20]([C:31]#[N:32])=[N:21][CH:22]=[C:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.CO>[C:25]1([C:23]2[CH:22]=[N:21][C:20]3[C:19]([CH:24]=2)=[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]2=[N:8][C:31]=3[NH2:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: N#Cc1ncc(-c2ccccc2)cc1Cl
Reactant: CC(C)(C)OC(=O)Nc1ccccc1B(O)O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: CO
Product: Nc1nc2ccccc2c2cc(-c3ccccc3)cnc12
Temperature: 25 °C

Procedure:
A solution of 2-(tert-butoxycarbonylamino)phenylboronic acid (1.0 eq.) and 3-chloro-5-phenylpicolinonitrile (from step 1) (1.0 eq.), tetrakis(triphenyl-phosphine)palladium (5 mol %), and 2N aqueous sodium carbonate solution (2.0 eq.) in toluene/ethanol (2:1, 0.03 M) was stirred at 100° C. overnight. After cooling to ambient temperature, the reaction content was diluted with methanol. The insoluble solids were filtered off, and the filtrate was concentrated en vacuo to obtain a crude residue. The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-80% ethyl acetate in hexane to give 2-phenylbenzo[f][1,7]naphthyridin-5-amine as a white solid. 1H NMR (dmso-d6): δ 9.13 (d, 1H), 9.03 (d, 1H), 8.56 (d, 1H), 7.98 (d, 2H), 7.43-7.56 (m, 5H), 7.27 (m, 1H), 7.13 (bs, 2H). LRMS [M+H]=272.2.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH2:12][CH2:11][N:10]([CH2:13][C:14](O)=[O:15])[C:9]2=[O:17])=[CH:4][CH:3]=1.FC1C=CC(C2(C3C=CC(F)=CC=3)CCCN(CC(O)=O)C2=O)=CC=1.[F:50][C:51]([F:63])([F:62])[C:52]1[CH:61]=[C:60]2[C:55]([CH2:56][CH2:57][NH:58][CH2:59]2)=[CH:54][CH:53]=1.C1(C2(C3C=CC=CC=3)CCNC2)C=CC=CC=1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)[CH2:12][CH2:11][N:10]([CH2:13][C:14](=[O:15])[N:58]3[CH2:57][CH2:56][C:55]4[C:60](=[CH:61][C:52]([C:51]([F:50])([F:63])[F:62])=[CH:53][CH:54]=4)[CH2:59]3)[C:9]2=[O:17])=[CH:6][CH:7]=1
Reactant: O=C(O)CN1CCC(c2ccc(F)cc2)(c2ccc(F)cc2)C1=O
Reactant: FC(F)(F)c1ccc2c(c1)CNCC2
Agent: O=C(O)CN1CCCC(c2ccc(F)cc2)(c2ccc(F)cc2)C1=O
Agent: c1ccc(C2(c3ccccc3)CCNC2)cc1
Product: O=C(CN1CCC(c2ccc(F)cc2)(c2ccc(F)cc2)C1=O)N1CCc2ccc(C(F)(F)F)cc2C1

Procedure:
The title compound was prepared using the procedure described in Example 172 substituting 2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid from Example 58D for 2-(3,3-bis(4-fluorophenyl)-2-oxopiperidin-1-yl)acetic acid and 7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline for 3,3-diphenylpyrrolidine. 1H NMR (300 MHz, CDCl3) δ ppm 7.51-7.35 (m, 2H), 7.36-7.21 (m, 5H), 6.98 (td, J=5.3, 8.6, 4H), 4.70 (d, J=35.4, 2H), 4.27 (s, 2H), 3.83 (t, J=6.0, 1H), 3.68 (t, J=5.9, 1H), 3.53 (t, J=6.5, 2H), 2.88 (dd, J=8.0, 13.3, 2H), 2.81-2.73 (m, 2H); MS (DCI) m/z 515.1 (M+H)+.
Reaction SMILES: [C:1]([C:9]1[CH:17]=[CH:16][C:12]([C:13](Cl)=[O:14])=[CH:11][CH:10]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([OH:31])=[O:30].[OH-].[Na+].Cl>C(Cl)(Cl)Cl.O>[C:1]([C:9]1[CH:17]=[CH:16][C:12]([C:13]([NH:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:14])=[CH:11][CH:10]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccc(C(=O)c2ccccc2)cc1
Reactant: NCCCCCCCCCCC(=O)O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClC(Cl)Cl
Product: O=C(O)CCCCCCCCCCNC(=O)c1ccc(C(=O)c2ccccc2)cc1
Reaction time: 1 h
Yield: 81.8 %

Procedure:
Compound I (50 g, 0.204 mol), prepared according to the general method described in Example 1, was dissolved in 2500 ml of chloroform, followed by the addition of a solution of 43.1 g (0.214 mol) of 11-aminoundecanoic acid and 60.0 g (1.5 mol) of sodium hydroxide in 1500 ml of water. The mixture was stirred vigorously for one hour in a 5 liter Morton flask to insure thorough mixing of the two layers. The mixture was acidified with 250 ml of concentrated hydrochloric acid and stirred an additional 30 minutes. The organic layer was separated and the aqueous was extracted with 3×500 ml of chloroform. The combined organic extracts were dried over sodium sulfate, filtered, and evaporated to give a solid. The product was recrystallized from toluene to give 68.37 g (82%) of 11-(4-benzoylbenzamido)undecanoic acid with a melting point of 107-109° C. Analysis on an NMR spectrometer was consistent with the desired product: 1H NMR (CDCI3) aromatic protons 7.20-7.80 (m, 9H), amide NH 6.30 (broad t, 1H), methylene adjacent to amide N 3.35 (m, 2H), methylene adjacent to carbonyl 2.25 (t, 2H), and remaining methylenes 1.00-1.80 (m, 16H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[C:12]3[CH:13]=[C:14]([C:17]#[C:18][C:19]4([OH:32])[CH2:22][CH:21]([C:23](C)(C)[O:24][SiH2]C(C)(C)C)[CH2:20]4)[CH:15]=[CH:16][C:11]=3[N:10]=[C:9]2[CH3:33])[N:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[C:12]3[CH:13]=[C:14]([C:17]#[C:18][C:19]4([OH:32])[CH2:22][CH:21]([CH2:23][OH:24])[CH2:20]4)[CH:15]=[CH:16][C:11]=3[N:10]=[C:9]2[CH3:33])[N:3]=1
Reactant: Cc1nc2ccc(C#CC3(O)CC(C(C)(C)O[SiH2]C(C)(C)C)C3)cc2n1-c1ncnc(N)n1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Cc1nc2ccc(C#CC3(O)CC(CO)C3)cc2n1-c1ncnc(N)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 85.6 %

Procedure:
In a solution of 1-[3-(4-amino-[1,3,5]triazin-2-yl)-2-methyl-3H-benzoimidazol-5-ylethynyl]-3-(tert-butyl-dimethyl-silanyloxymethyl)-cyclobutanol (55 mg, 0.1 mmol) in tetrahydrofuran (20 ml) was added tetrabutylammonium fluoride (70 mg, 0.3 mmol). Then the solution stirred overnight at room temperature. The reaction mixture was washed with water and purified by column to afford title compound (30 mg, 86%): 1H NMR (400 MHz, MeOD) delta 2.05-2.10 (m, 2H), 2.36-2.38 (m, 1H), 2.57-2.62 (m, 2H), 3.59 (d, J=6.4 Hz, 2H), 7.40 (dd, J=1.6, 8.0 Hz, 1H), 7.55 (dd, J=0.4, 8.4 Hz, 1H), 8.56 (dd, J=0.4, 1.6 Hz, 1H), 8.59 (s, 1H). LCMS: m/z=+351.1 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@H:6]1[O:8][C@@H:7]1[C:9]([OH:11])=O)=[O:5])[CH3:2].[C:12]1([CH:18]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:19][CH2:20][C@@H:21]([NH2:26])[CH2:22][CH:23]([CH3:25])[CH3:24])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[C:12]1([CH:18]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:19][CH2:20][C@@H:21]([NH:26][C:9]([C@H:7]2[O:8][C@@H:6]2[C:4]([O:3][CH2:1][CH3:2])=[O:5])=[O:11])[CH2:22][CH:23]([CH3:25])[CH3:24])[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CC(C)C[C@H](N)COC(c1ccccc1)c1ccccc1
Reactant: CCOC(=O)[C@H]1O[C@@H]1C(=O)O
Product: CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@H](COC(c1ccccc1)c1ccccc1)CC(C)C

Procedure:
The procedures of Example 1a were repeated employing (2S,3S)-3-ethoxycarbonyloxirane-2-carboxylic acid and 1-(S)-(diphenylmethoxy)methyl-3-methylbutylamine (its preparation is described in the after-mentioned Reference Example 3), to prepare the titled compound
Reaction SMILES: N1C=CC=CC=1.[ClH:7].[CH3:8][N:9]([N:11]=[CH:12][NH:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=1)[CH3:10].Cl.[C:24]([C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[C:33]([CH2:37][C:38](=[O:40])[NH2:39])=[C:32](O)[CH:31]=[CH:30]2)(=[NH:26])[NH2:25].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.C(C(C)=O)C.O.C(O)=O>[ClH:7].[ClH:7].[CH3:10][N:9]([N:11]=[CH:12][NH:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([O:20][C:32]2[CH:31]=[CH:30][C:29]3[C:34](=[CH:35][CH:36]=[C:27]([C:24](=[NH:25])[NH2:26])[CH:28]=3)[C:33]=2[CH2:37][C:38](=[O:40])[NH2:39])=[O:19])=[CH:16][CH:15]=1)[CH3:8]
Reactant: CN(C)N=CNc1ccc(C(=O)O)cc1
Reactant: N=C(N)c1ccc2c(CC(N)=O)c(O)ccc2c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: O=CO
Solvent: c1ccncc1
Solvent: O
Product: CN(C)N=CNc1ccc(C(=O)Oc2ccc3cc(C(=N)N)ccc3c2CC(N)=O)cc1
Reaction time: 2 h
Yield: 64.7 %

Procedure:
40 Milliliters of 20% hydrous pyridine was added to 1.44 g of 4-dimethylaminoiminomethylaminobenzoic acid.hydrochloride, 1.5 g of 6-amidino-1-carbamoylmethyl-2-naphthol.hydrochloride, 1.33 g of DCC and 65.5 mg of DMAP, followed by stirring for 2 hours under cooling with ice and then 72 hours at room temperature. Then, the precipitate was filtered and the filtrate was concentrated under reduced pressure. To the residue was added 25 ml of DMF, and the resulting solution was added dropwise to a mixed liquid of 200 ml of ether and 100 ml of acetone, followed by stirring for 2 hours under cooling with ice. Then, the precipitate was collected by filtration to obtain a crude product. Then, the product was subjected to silica gel column chromatography using methyl ethyl ketone-water-formic acid (80:15:5) as an eluent, and the desired fractions were collected and the solvent was distilled off under reduced pressure. To the residue were added 15 ml of methanol and 2.8 ml of concentrated hydrochloric acid, and the resultant solution was added dropwise to 150 ml of acetone, followed by stirring for 2 hours under cooling with ice. Then, the precipitate was collected by filtration, and to the collected precipitate were added 10 ml of methanol and 5 ml of ethanol, followed by stirring for 2 hours under cooling with ice. The precipitate was collected by filtration and washed with a small amount of acetone to obtain 966 mg of the desired product.
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].N#N.[CH2:7]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][Si:23]([CH2:26][CH2:27][CH2:28][CH3:29])([CH3:25])[CH3:24])[CH:8]1[O:10][CH2:9]1>C(O)C>[OH:2][CH2:1][CH2:3][NH:4][CH2:9][CH:8]([OH:10])[CH2:7][O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][Si:23]([CH2:26][CH2:27][CH2:28][CH3:29])([CH3:25])[CH3:24]
Reactant: CCCC[Si](C)(C)CCCCCCCCCCCOCC1CO1
Reactant: NCCO
Agent: N#N
Solvent: CCO
Product: CCCC[Si](C)(C)CCCCCCCCCCCOCC(O)CNCCO
Temperature: 80 °C
Yield: 73.3 %

Procedure:
A 100-ml two-necked flask equipped with a stirrer, dropping funnel and N2 inlet tube was charged with 4.58 g (75 mmol) of ethanolamine and 9.2 g of ethanol. The contents were heated to 80° C. with stirring in an N2 atmosphere, and an ethanol solution of 1.71 g (5 mmol) of 11-(butyldimethylsilyl)undecyl glycidyl ether was added dropwise to the contents over 1 hour. The resultant mixture was stirred further for 1 hour at 80° C. After completion of the reaction, ethanol and excess ethanolamine were distilled off under reduced pressure, and the resultant residue was purified by column chromatography on silica gel, thereby obtaining 1.48 g (yield: 73%) of the title compound (Ia-18).
Reaction SMILES: [OH:1][CH:2]1[NH:6][C:5](=[O:7])[CH2:4][CH2:3]1.[CH3:8][CH:9](O)[CH2:10][CH2:11][CH3:12]>>[CH3:8][CH:9]([O:1][CH:2]1[NH:6][C:5](=[O:7])[CH2:4][CH2:3]1)[CH2:10][CH2:11][CH3:12]
Reactant: CCCC(C)O
Reactant: O=C1CCC(O)N1
Product: CCCC(C)OC1CCC(=O)N1

Procedure:
5.5 g of 5-hydroxy-pyrrolidin-2-one, 30 cm3 of 2-pentanol and 2.75 g of Amberlite-15 resin are agitated for 5 hours at ambient temperature. After filtering, the excess pentanol is distilled off under 1 mm Hg at 40° C. The residue is chromatograp:hed on silica, (eluent: ethyl acetate), and 3.7 g of the expected product is obtained.