Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][C:4](=[O:32])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C@@H:11]1[C@@H:15]([CH:16]=[CH:17][C:18]23[O:31][CH2:30][CH2:29][O:28][C:19]2([O:24][CH2:25][CH2:26][O:27]3)[CH2:20][CH2:21][CH2:22][CH3:23])[CH2:14][CH2:13][CH2:12]1)C.O1CCOCC1.[OH-].[Na+]>O>[CH2:26]1[CH2:25][O:24][C:19]2([O:28][CH2:29][CH2:30][O:31][C:18]2([CH:17]=[CH:16][C@@H:15]2[C@@H:11]([CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][C:4]([OH:32])=[O:3])[CH2:12][CH2:13][CH2:14]2)[O:27]1)[CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCC12OCCOC1(C=C[C@H]1CCC[C@@H]1CCCCCCC(=O)OCC)OCCO2
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: CCCCC12OCCOC1(C=C[C@H]1CCC[C@@H]1CCCCCCC(=O)O)OCCO2

Procedure:
A mixture of 0.9 g of 9,9;15,15-bis-(ethylenedioxy)-13-prostenoic acid ethyl ester, 60 ml of dioxan, 40 ml of H2O and 0.08 g of NaOH is boiled for 2 hours. The solvent is distilled. After recrystallization of the residue from methanol, the sodium salt of 9,9;15,15-bis-(ethylenedioxy)-13-prostenoic acid is obtained.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([C@H:12]([CH:17](C)C)[C:13]([O:15][CH3:16])=[O:14])[C:8]2=[O:11])=[CH:4][CH:3]=1.Cl.[CH3:21]OC(=O)C(C)(C)N>>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([C:12]([CH3:17])([CH3:21])[C:13]([O:15][CH3:16])=[O:14])[C:8]2=[O:11])=[CH:4][CH:3]=1
Reactant: COC(=O)[C@@H](C(C)C)N1Cc2ccc(Br)cc2C1=O
Reactant: COC(=O)C(C)(C)N
Agent: Cl
Product: COC(=O)C(C)(C)N1Cc2ccc(Br)cc2C1=O

Procedure:
The compound of example 338 was prepared analogous to compound of example 329 by reaction of the compound of example 328 and 2,2-dimethyl glycine methyl ester hydrochloride.
Reaction SMILES: [NH:1]([C:5]1[C:6]([NH:15][C:16](=[O:33])[CH:17]([S:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)C(C)=O.Cl>C(O)(C)C>[NH2:1][C:5]1[C:6]([NH:15][C:16](=[O:33])[CH:17]([S:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2
Reactant: CCCCCCCCC(SCCCCCC)C(=O)Nc1c(NC(C)=O)ccc2ncccc12
Agent: Cl
Solvent: CC(C)O
Product: CCCCCCCCC(SCCCCCC)C(=O)Nc1c(N)ccc2ncccc12

Procedure:
N-(6-Acetaminoquinolin-5-yl)-2-(hexylthio)decanoic amide, prepared as described in Example 151, was treated with aqueous hydrochloric acid and isopropanol to give the title compound. Mass spectrum m/e: 428.3 (M+-1).
Reaction SMILES: [C:1]([O:5][C:6](=[O:43])[N:7]([C:19]1[CH:20]=[CH:21][C:22]2[N:27]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30](Cl)[CH:29]=3)[C:26](=[O:35])[C:25]([CH3:41])([CH2:36][CH:37]=[C:38]([CH3:40])[CH3:39])[O:24][C:23]=2[N:42]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=1[O:17][CH3:18])([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C:1]([O:5][C:6](=[O:43])[N:7]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=1[O:17][CH3:18])[C:19]1[CH:20]=[CH:21][C:22]2[N:27]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:26](=[O:35])[C:25]([CH3:41])([CH2:36][CH2:37][CH:38]([CH3:39])[CH3:40])[O:24][C:23]=2[N:42]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: COc1ccc(CN(C(=O)OC(C)(C)C)c2ccc3c(n2)OC(C)(CC=C(C)C)C(=O)N3c2cccc(Cl)c2)c(OC)c1
Agent: [Pd]
Solvent: CO
Product: COc1ccc(CN(C(=O)OC(C)(C)C)c2ccc3c(n2)OC(C)(CCC(C)C)C(=O)N3c2ccccc2)c(OC)c1
Yield: 35.3 %

Procedure:
[1-(3-Chloro-phenyl)-3-methyl-3-(3-methyl-but-2-enyl)-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl]-(2,4-dimethoxy-benzyl)-carbamic acid tert-butyl ester (Intermediate A3) (360 mg, 0.59 mmol) was dissolved in MeOH (20 mL) and stirred at ambient temperature for 16 hours in the presence of Pd/C (10%, 63 mg) under H2. The resulting suspension was filtered through Celite and the solvent was removed in vacuo to give (2,4-dimethoxy-benzyl)-[3-methyl-3-(3-methyl-butyl)-2-oxo-1-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl]-carbamic acid tert-butyl ester as a pale yellow solid (120 mg). MS: [M+H]+=576.
Reaction SMILES: NC1S[C:4](S)=[N:5]N=1.COC1C=CN=C(CS([C:19]2[NH:23][C:22]3[CH:24]=[C:25]4[C:29](=[CH:30][C:21]=3[N:20]=2)[C:28]([CH3:32])([CH3:31])[C:27](=[O:33])[C:26]4([CH3:35])[CH3:34])=O)C=1C.[ClH:37]>>[ClH:37].[Cl-:37].[CH3:31][C:28]1([CH3:32])[C:29]2[C:25](=[CH:24][C:22]3[NH:23][C:19]([N+:5]4[CH:4]=[CH:24][CH:22]=[CH:21][CH:30]=4)=[N:20][C:21]=3[CH:30]=2)[C:26]([CH3:35])([CH3:34])[C:27]1=[O:33]
Reactant: Nc1nnc(S)s1
Reactant: COc1ccnc(CS(=O)c2nc3cc4c(cc3[nH]2)C(C)(C)C(=O)C4(C)C)c1C
Agent: Cl
Product: CC1(C)C(=O)C(C)(C)c2cc3[nH]c(-[n+]4ccccc4)nc3cc21
Product: [Cl-]
Temperature: 25 °C

Procedure:
1.1 g of 2-amino-5-mercapto-1,3,4-thiadiazole are dissolved in 15 ml of about 6N methanolic hydrochloric acid. The solution is treated with 3 g of 5,7-dihydro-2-[[(4-methoxy-3 -methyl-2-pyridyl)methyl]sulphinyl]-5,5,7,7 -tetramethylindeno[5,6-d]imidazol-6(1H )-one. stirred at room temperature and then concentrated by means of a water-jet pump until crystallization is complete. The 2-[[5-amino-1,3,4-thiadiazol-2 -yl)dithio]methyl]-1-(1,5,6,7 -tetrahydro-5,5,7,7-tetramethyl-6 -oxoindeno[5,6-d]imidazol-2-yl)pyridinium chloride hydrochloride obtained is filtered off and washed with cold methanol; it exhibits a melting point of 161° (decomposition).
Reaction SMILES: [C:1]([CH2:4][N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C@H:7]([NH:16][C:17]([C:19]2([CH2:24][CH:25]([CH2:29][C:30]([NH:32][CH2:33][CH2:34][CH2:35][OH:36])=[O:31])[C:26]([OH:28])=[O:27])[CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:18])[C:6]1=[O:37])([OH:3])=[O:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:44](Br)[CH3:45]>CN(C)C=O.O.ClCCl>[CH2:44]([O:2][C:1](=[O:3])[CH2:4][N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C@H:7]([NH:16][C:17]([C:19]2([CH2:24][CH:25]([CH2:29][C:30]([NH:32][CH2:33][CH2:34][CH2:35][OH:36])=[O:31])[C:26]([OH:28])=[O:27])[CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:18])[C:6]1=[O:37])[CH3:45]
Reactant: CCBr
Reactant: O=C(O)CN1C(=O)[C@@H](NC(=O)C2(CC(CC(=O)NCCCO)C(=O)O)CCCC2)CCc2ccccc21
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: ClCCl
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CN1C(=O)[C@@H](NC(=O)C2(CC(CC(=O)NCCCO)C(=O)O)CCCC2)CCc2ccccc21
Yield: 28576.1 %

Procedure:
800 mg of the 2-{[1-({[(3S)-1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-[(3-hydroxypropyl)amino]-4-oxobutyric acid (isomer mixture) obtained above according to Example 9 was dissolved in 15 ml dimethyl formamide (=DMF). 302.5 mg Cs2CO3 and 169 mg ethyl bromide were added to this receiving solution at room temperature with stirring. After stirring overnight, it was diluted with 42 ml water and 21 ml dichloromethane and the aqueous phase was extracted with dichloromethane. The solvent was largely evaporated at reduced pressure and the remaining residue was chromatographed (stationary phase: silica gel, mobile phase: EA (100%) to EE/MeOH 7:3 (v/v)). Drying the product fractions in an oil pump vacuum (5×10−2 mbar) yielded 241 g of the title compound as foam resin, MS: [M+H]+: 546; m/z: 453, 425, 379; 1H-NMR (CDCl3): 7.34-7.1, m, [4]; 4.82, 4.77, 4.34, 4.29, AB-Q-. [2]; 3.62, m, [2]; 3.37, m, [3].
Reaction SMILES: Cl[CH:2]([CH:8]=O)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH3:10][O:11][CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([NH2:21])[CH:16]=1>CCO>[CH3:10][O:11][CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][N:18]2[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[CH:8][N:21]=[C:17]2[CH:16]=1
Reactant: CCOC(=O)C(Cl)C=O
Reactant: COCCOc1ccnc(N)c1
Solvent: CCO
Product: CCOC(=O)c1cnc2cc(OCCOC)ccn12
Yield: 57 %

Procedure:
Ethyl 2-chloro-3-oxopropanoate (5.1 g, 33.9 mmol, Heterocycles 1991, pg. 699) and 4-(2-methoxyethoxy)pyridin-2-amine (5.70 g, 33.9 mmol) was dissolved in EtOH (50 mL) and heated to reflux overnight. The crude reaction mixture was concentrated and purified by flash column chromatography (EtOAc/MeOH 10:0 to 10:1) provided the desired product (57%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@H:13]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C@@H:12]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@H:11]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C@@H:10]([CH2:38][O:39][CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[O:9]2)=[CH:4][C:3]=1[CH2:47][C:48]#N.[OH-:50].[Na+].Cl.[OH2:53]>CCO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@H:13]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C@@H:12]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@H:11]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C@@H:10]([CH2:38][O:39][CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[O:9]2)=[CH:4][C:3]=1[CH2:47][C:48]([OH:53])=[O:50]
Reactant: N#CCc1cc([C@@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)ccc1Cl
Reactant: [OH-]
Reactant: O
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: O=C(O)Cc1cc([C@@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)ccc1Cl
Temperature: 25 °C
Yield: 98 %

Procedure:
To a solution of cyanide β-39 (53 g, 79 mmol) in EtOH (300 mL) was added aq. NaOH solution (8.0 N, 300 mL, 2.4 mol). The reaction mixture was refluxed overnight. After cooling to room temperature, hydrochloric acid (3.0N) was added to neutralize the reaction mixture. The mixture was diluted with water and extracted with EtOAc. The organic layer was washed with water and brine prior to drying over anhydrous MgSO4. Filtration and concentration under reduced pressure yielded the titled compound 55 (54 g, 98%) as a white solid.
Reaction SMILES: [CH3:1][N:2]([CH:4]([CH:7]1[CH2:16][CH2:15][C:10]2([O:14][CH2:13][CH2:12][O:11]2)[CH2:9][CH2:8]1)[C:5]#N)[CH3:3].C1COCC1.[F:22][C:23]1[CH:28]=[CH:27]C([Mg]Br)=[CH:25][CH:24]=1.[Cl-].[NH4+]>C(OCC)C.O>[O:14]1[C:10]2([CH2:15][CH2:16][CH:7]([CH:4]([N:2]([CH3:3])[CH3:1])[C:5]3[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=3)[CH2:8][CH2:9]2)[O:11][CH2:12][CH2:13]1
Reactant: Fc1ccc([Mg]Br)cc1
Reactant: CN(C)C(C#N)C1CCC2(CC1)OCCO2
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: O
Product: CN(C)C(c1ccc(F)cc1)C1CCC2(CC1)OCCO2
Reaction time: 20 h

Procedure:
A solution of the aminonitrile 3 (19.89 g, 88 mmol) in abs. THF (160 ml) was added dropwise, under argon and while cooling with ice, to a 1M solution of 4-fluorophenylmagnesium bromide in THF (220 ml, 220 mmol), and stirring was carried out for 20 h at RT. For working up the reaction mixture, saturated ammonium chloride solution (100 ml) and water (100 ml) were added, while cooling with ice, and extraction with diethyl ether (3×100 ml) was carried out. The organic phase was washed with water and saturated sodium chloride solution, dried (Na2SO4) and concentrated.
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([CH:20]=[CH:21][CH:22]=1)[O:11][C:12]1[C:17]([CH:18]=O)=[CH:16][CH:15]=[CH:14][N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(CSC)=[O:25].C1[CH2:33][O:32][CH2:31]C1>CO.O.Cl>[O:1]([C:8]1[CH:9]=[C:10]([CH:20]=[CH:21][CH:22]=1)[O:11][C:12]1[C:17]([CH2:18][C:31]([O:32][CH3:33])=[O:25])=[CH:16][CH:15]=[CH:14][N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=Cc1cccnc1Oc1cccc(Oc2ccccc2)c1
Reactant: CSCS(C)=O
Reactant: C1CCOC1
Agent: Cl
Solvent: O
Solvent: CO
Product: COC(=O)Cc1cccnc1Oc1cccc(Oc2ccccc2)c1
Reaction time: 8 h

Procedure:
To a stirred solution of the aldehyde (3.03 g, 0.01 mol) and methyl methylsulphinylmethyl sulphide (1.29 g, 0.01 mol) in dry THF (8 ml) at room temperature was added dropwise a solution of Triton B (2.5 ml, 40% in methanol). The resultant solution was heated to reflux for 1 hour, cooled and then diluted with water. Extraction with dichloromethane followed by drying and evaporation yielded a yellow oil which was dissolved in methanolic hydrogen chloride (100 ml) and allowed to stand overnight. The methanol was evaporated and the residue treated with saturated sodium bicarbonate solution and then extracted with dichloromethane. The combined organic extracts were dried, filtered and evaporated. The residue was chromatographed on silica gel (eluent hexane-ether, 1:1) to afford methyl 2-(3-phenoxyphenoxy)pyrid-3-ylacetate (1.35 g) as a pale yellow oil;
Reaction SMILES: [CH2:1]1[CH:10]2[N:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[CH:4](C(Cl)=O)[CH2:3][CH2:2]1.NC1C=CC=C(C(O)=O)C=1O.C1C2N(CCCC2)C([C:35]2[O:36][C:37]3[C:43]([C:44]([NH2:46])=[O:45])=[CH:42][CH:41]=[CH:40][C:38]=3[N:39]=2)CC1>>[CH:9]1([C:35]2[O:36][C:37]3[C:43]([C:44]([NH2:46])=[O:45])=[CH:42][CH:41]=[CH:40][C:38]=3[N:39]=2)[CH:10]2[N:5]([CH2:4][CH2:3][CH2:2][CH2:1]2)[CH2:6][CH2:7][CH2:8]1
Reactant: O=C(Cl)C1CCCC2CCCCN21
Reactant: NC(=O)c1cccc2nc(C3CCCC4CCCCN43)oc12
Agent: Nc1cccc(C(=O)O)c1O
Product: NC(=O)c1cccc2nc(C3CCCN4CCCCC34)oc12

Procedure:
Following the experimental procedure as described in Examples 2A to 2B, and substituting benzyl 4-methylbenzoylchlordie with octahydro-1H-quinolizine-4-carbonyl chloride, and replacing 3-hydroxyanthranilic with 3-aminosalicylic acid, the title compound 2-(octahydro-1H-quinolizin-4-yl)benzo[d]oxazole-7-carboxamide is made
Reaction SMILES: [CH2:1]([OH:6])[CH:2]([OH:5])[CH2:3][OH:4].[CH2:7]([OH:12])[CH:8]([OH:11])[CH2:9][OH:10].[CH2:13]([OH:18])[CH:14]([OH:17])[CH2:15][OH:16].[CH2:19]([OH:24])[CH:20]([OH:23])[CH2:21][OH:22].[C:25](O)(=O)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32].CCN=C=NCCCN(C)C.Cl>C1COCC1>[CH2:25]([CH:2]([CH2:1][CH2:7][CH2:8][CH3:9])[C:3]([OH:4])=[O:16])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32].[OH:24][CH2:19][CH:20]([CH2:21][OH:22])[OH:23].[OH:18][CH2:13][CH:14]([CH2:15][OH:16])[OH:17].[OH:12][CH2:7][CH:8]([CH2:9][OH:10])[OH:11].[OH:6][CH2:1][CH:2]([CH2:3][OH:4])[OH:5]
Reactant: CCCCCCCC(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: C1CCOC1
Solvent: OCC(O)CO
Product: CCCCCCCCC(CCCC)C(=O)O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Into a 250 mL vessel, tetraglycerol (5.0 g, 15.91 mmol) was added and dissolved into anhydrous THF (50 mL). Octanoic acid (15.12 mL, 95.44 mmol) was also dissolved into the reaction mixture which was stirred magnetically at room temperature for one hour to fully dissolve the reagents. N,N-dimethylaminopyridine (0.194 g, 1.59 mmol) was dissolved in the solution. When the catalyst was fully dissolved, EDC HCl (18.32 g, 95.6 mmol) was added into the vessel and was sealed to keep the reaction dry. The reaction proceeded overnight at 55° C. The solution was stripped of THF via rotoevaporation and redissolved into chloroform. The organic layer was washed 2× with sodium bicarbonate buffer and 2× with deionized water to remove unreacted starting materials. The chloroform was removed to yield a clear viscous liquid. NMR analysis supported full conversion of hydroxyl groups to the octanoic esters.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:21]=[CH:20][C:19]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[C:12]([CH2:26][CH2:27][CH2:28][CH3:29])([CH2:22][CH2:23][CH2:24][CH3:25])[C:11]=3[CH:10]=2)O1.Br[C:32]1[CH:33]=[C:34]([C:39]2[O:40][C:41]([C:44]3[CH:49]=[CH:48][C:47]([O:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])=[CH:46][CH:45]=3)=[N:42][N:43]=2)[CH:35]=[C:36](Br)[CH:37]=1>>[CH2:26]([C:12]1([CH2:22][CH2:23][CH2:24][CH3:25])[C:11]2[CH:10]=[C:9]([C:32]3[CH:33]=[C:34]([C:39]4[O:40][C:41]([C:44]5[CH:49]=[CH:48][C:47]([O:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])=[CH:46][CH:45]=5)=[N:42][N:43]=4)[CH:35]=[C:36]([C:9]4[CH:21]=[CH:20][C:19]5[C:18]6[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=6)[C:12]([CH2:26][CH2:27][CH2:28][CH3:29])([CH2:22][CH2:23][CH2:24][CH3:25])[C:11]=5[CH:10]=4)[CH:37]=3)[CH:21]=[CH:20][C:19]=2[C:18]2[C:13]1=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:27][CH2:28][CH3:29]
Reactant: CCCCC1(CCCC)c2ccccc2-c2ccc(B3OC(C)(C)C(C)(C)O3)cc21
Reactant: CCCCCCCCOc1ccc(-c2nnc(-c3cc(Br)cc(Br)c3)o2)cc1
Product: CCCCCCCCOc1ccc(-c2nnc(-c3cc(-c4ccc5c(c4)C(CCCC)(CCCC)c4ccccc4-5)cc(-c4ccc5c(c4)C(CCCC)(CCCC)c4ccccc4-5)c3)o2)cc1

Procedure:
Using procedures outlined in Part B of Example 12, 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,9-dibutylfluorene (1.88 g, 4.6 mmol) and 2-(3,5-dibromophenyl)-5-[4-(octyloxy)phenyl]-1,3,4-oxadiazole from Example 7 (1.13 g, 2.2 mmole) are reacted to give the corresponding 2-[3,5-Bis-(9,9-dibutyl-9H-fluoren-2-yl)-phenyl]-5-(4-octyloxy-phenyl)-[1,3,4]oxadiazole.
Reaction SMILES: C(O[C:4]([C:6]1[N:7]=[N:8][C:9]([O:12][CH2:13][C:14]2[C:15]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)=[N:16][O:17][CH:18]=2)=[CH:10][CH:11]=1)=[O:5])C.[NH2:26][CH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>>[O:30]1[CH2:31][CH2:32][CH:27]([NH:26][C:4]([C:6]2[N:7]=[N:8][C:9]([O:12][CH2:13][C:14]3[C:15]([C:19]4[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=4)=[N:16][O:17][CH:18]=3)=[CH:10][CH:11]=2)=[O:5])[CH2:28][CH2:29]1
Reactant: NC1CCOCC1
Reactant: CCOC(=O)c1ccc(OCc2conc2-c2ccc(F)cc2)nn1
Product: O=C(NC1CCOCC1)c1ccc(OCc2conc2-c2ccc(F)cc2)nn1
Yield: 82 %

Procedure:
As described for example 121, 6-[3-(4-fluoro-phenyl)-isoxazol-4-ylmethoxy]-pyridazine-3-carboxylic acid ethyl ester (200 mg, 0.58 mmol) was converted, using 4-aminotetrahydropyran instead of isopropylamine, to the title compound (190 mg, 82%) which was obtained as a white solid. MS: m/e=399.1 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:11])[N:6]([CH2:8][CH2:9]O)[CH:7]=1.P(Br)(Br)[Br:13]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:11])[N:6]([CH2:8][CH2:9][Br:13])[CH:7]=1
Reactant: O=c1ccc(Br)cn1CCO
Reactant: BrP(Br)Br
Solvent: ClCCl
Product: O=c1ccc(Br)cn1CCBr
Temperature: 40 °C

Procedure:
To a solution of 5-bromo-1-(2-hydroxyethyl)pyridin-2(1 H)-one (460 mg, 2110 μmol) in CH2Cl2 (5 mL) at 0° C. under nitrogen was added phosphorous tribromide (595 μL, 6329 μmol). A precipitate formed at 0° C. The reaction mixture was heated at 40° C. for 3 days. The mixture was partitioned between CH2Cl2 and 5% NaHCO3 (vigorous gas evolution). The aqueous was extracted with CH2Cl2 (2×10 mL). The combined organics were dried over MgSO4, and concentrated to a white solid. MS (ESI pos. ion) m/z (MH+): 279/281/283. Calc'd exact mass for C7H7Br2NO: 278.
Reaction SMILES: [H-].[K+].O1CCOCC1.[CH:9]([S:12][CH2:13][S:14](=[O:18])[CH:15]([CH3:17])[CH3:16])([CH3:11])[CH3:10].Br[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]Br>C(Cl)Cl>[CH:9]([S:12][C:13]1([S:14](=[O:18])[CH:15]([CH3:17])[CH3:16])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)([CH3:11])[CH3:10]
Reactant: CC(C)SCS(=O)C(C)C
Reactant: BrCCCCCBr
Agent: [H-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: ClCCl
Product: CC(C)SC1(S(=O)C(C)C)CCCCC1
Reaction time: 1 h
Yield: 58.9 %

Procedure:
Potassium hydride (995 mg) was suspended in 15 ml. of dioxane, and with ice cooling, 1.804 g of formaldehyde diisopropyl mercaptal S-oxide was added gradually. The mixture was stirred for 1 hour with ice cooling, and then 2.411 g of 1,5-dibromopentane was added. Then, the mixture was stirred for 18 hours at room temperature. Methylene chloride (100ml) was added, and the isoluble matter was separated by filtration. After the evaporation of the filtrate at reduced pressure, the residue was separated by column chromatography (basic alumina, eluted with benzene, methylene chloride, and ethyl acetate) to afford 1.463 g of cyclohexanone diisopropyl mercaptal S-oxide as a colorless oil. The yield was 59%. The physical properties and the results of elemental analysis were as follows:
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH2:10][C:9]1([CH3:22])[CH3:21])C1C=CC=CC=1>CO.C(OCC)(=O)C.[Pd]>[F:20][C:17]1[CH:16]=[CH:15][C:14]([N:11]2[CH2:12][CH2:13][NH:8][C:9]([CH3:22])([CH3:21])[CH2:10]2)=[CH:19][CH:18]=1
Reactant: CC1(C)CN(c2ccc(F)cc2)CCN1Cc1ccccc1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: CC1(C)CN(c2ccc(F)cc2)CCN1
Temperature: 50 °C
Reaction time: 5 h

Procedure:
To a stirred solution of 1-benzyl-4-(4-fluorophenyl)-2,2-dimethylpiperazine (4.5 g, 15.08 mmol) in methanol and ethyl acetate (5:1, 60 ml) at 25° C. was added 10% palladium on charcoal (1.605 g). The reaction mixture was stirred at 50° C. for 5 h. The progress of reaction was monitored by TLC. The reaction mixture was cooled to room temperature, filtered through a celite bed, washed with ethyl acetate (2×50 ml). The combined filtrate was concentrated under reduced pressure to obtain the title compound which was used in the next step without further purification.
Reaction SMILES: [CH2:1]([CH:5]1[CH2:9][O:8][C:7](=[O:10])[CH2:6]1)[CH:2](C)C.[C:11](OC(=O)CC(CC(C)C)C(O)=O)(C)(C)C.CO>C1COCC1>[CH:1]([CH:5]1[CH2:9][O:8][C:7](=[O:10])[CH2:6]1)([CH3:2])[CH3:11]
Reactant: CC(C)CC(CC(=O)OC(C)(C)C)C(=O)O
Reactant: CC(C)CC1COC(=O)C1
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)C1COC(=O)C1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 89 %

Procedure:
Preparation of 4-Isobutyl-dihydro-furan-2-one (4): A solution of 2-isobutyl-succinic acid-4-t-butyl ester (8.0 g, 34.7 mmol) in 100 mL of THF is cooled to 0° C. under Ar and borane dimethyl sulphide complex (2.6 g, 34.7 mmol) is added. The reaction mixture is stirred at 0° C. for 10 minutes, and at room temperature overnight. The solution is cooled to 0° C. and 100 mL of MeOH is added. The solvents are evaporated, and the remaining oil is dried under hi-vacuum for 2 hrs. The oil remaining is taken up in 100 mL of THF, and a catalytic amount of p-toluene sulfonic acid is added. The solution is warmed to reflux overnight. After being cooled to room temperature, the solvent is evaporated, and the oil is taken up in Et2O (100 mL). The Et2O solution is extracted with 2.0N Na2CO3 (2×50 mL) followed by 100 mL of brine and dried over MgSO4. Evaporation of Et2O followed by medium pressure chromatography (MPLC) of the remaining oil in 20% EtOAc/Hexanes gives 4.4 g (89% yield) of 4-isopropyl-dihydro-furan-2-one as an oil. NMR (H1, 400 MHz, CDCl3) δ0.9 (6H, m); δ1.3 (2H, dd); δ1.5 (1H, m); δ2.1 (1H, m); δ2.6 (2H, m); δ3.6 (1H, m); δ4.4 (1H, m).
Reaction SMILES: Br[CH2:2][C:3]1[O:8][C:7](=[O:9])[CH:6]=[C:5]([OH:10])[CH:4]=1.Cl.[OH-:12].[Na+]>O>[OH:10][C:5]1[CH:4]=[C:3]([CH2:2][OH:12])[O:8][C:7](=[O:9])[CH:6]=1
Reactant: [OH-]
Reactant: O=c1cc(O)cc(CBr)o1
Agent: Cl
Agent: [Na+]
Solvent: O
Product: O=c1cc(O)cc(CO)o1
Temperature: 50 °C
Yield: 69 %

Procedure:
6-Bromomethyl-4-hydroxypyran-2-one (21.1 parts) was dissolved in a solution of sodium hydroxide (4.1 parts) in water (800 parts) at 20°-25° C. This solution was added over about 2 hours to a solution of sodium hydroxide (34.2 parts) in water (3200 parts) at 50° C.±3° C. The mixture was stirred for a further hour at 50° C. before acidifying with 35% hydrochloric acid and distilling off the bulk of the water at 50° C./20 mm. The mixture was cooled to 20° C. and insoluble material was filtered off. The filtrate was saturated with sodium chloride and then extracted with ethyl acetate (15×125 parts). The combined extracts were dried over magnesium sulphate and the solvent removed at 40° C./20 mm to give 4-hydroxy-6-hydroxymethylpyran-2-one (10.2 parts, 69%).
Reaction SMILES: [O:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[NH:5][C:4]([C:13]([O:15]C)=[O:14])=[N:3]1.CO.O>>[O:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[C:4]([C:13]([OH:15])=[O:14])[NH:3]1
Reactant: COC(=O)c1nc(=O)n(-c2ccccc2)[nH]1
Solvent: CO
Solvent: O
Product: O=C(O)c1nn(-c2ccccc2)c(=O)[nH]1
Yield: 64.4 %

Procedure:
Methyl 2,5-dihydro-5-oxo-1-phenyl-1h-1,2,4-triazole-3-carboxylate (300.0 mg, 1.4 mmol) was mixed with MeOH (4.5 mL, 110 mmol) and water (0.5 mL, 30 mmol) at room temperature, then treated with LiOH monohydrate (0.1 g, 2.7 mmol) at room temperature overnight. The mixture was concentrated and the resulting residue was acidified to pH˜1 with 1N aqueous HCl. The resulting solids were filtered and rinsed with water, then dried in vacuo to give the title compound as a yellowish solid (185 mg), which was used without further purification.