Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[C:9]1[N:14]2[C:15](I)=[CH:16][N:17]=[C:13]2[CH:12]=[C:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:10]=1)C1C=CC=CC=1.C(N(CC)CC)C.[C:32]([C:34]1[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=1)#[CH:33].CN([CH:43]=[O:44])C>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.[Cu]I>[CH3:43][O:44][C:16]1[N:17]=[C:13]2[CH:12]=[C:11]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:10]=[CH:9][N:14]2[C:15]=1[C:33]#[C:32][C:34]1[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=1
Reactant: C#Cc1cccnc1
Reactant: Ic1cnc2cc(-c3ccccc3)cc(OCc3ccccc3)n12
Reactant: CN(C)C=O
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: COc1nc2cc(-c3ccccc3)ccn2c1C#Cc1cccnc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
5-(benzyloxy)-3-iodo-7-phenylimidazo[1,2-a]pyridine (32.0 mg, 0.091 mmol), tetrakis(triphenylphosphine)palladium(0) (10.6 mg, 9.14 μmol) and copper(I)iodide (10.44 mg, 0.055 mmol) were suspended in DMF (1 mL). Triethylamine (0.025 mL, 0.183 mmol) and 3-ethynylpyridine (28.3 mg, 0.274 mmol) were added, and the mixture was sparged with argon for 5 minutes. The reaction was stirred at room temperature for 1 hour, diluted with acetonitrile, DMSO and water. The solution was directly purified by preparative HPLC Reverse phase (C-18), eluting with acetonitrile/water+0.05% TFA. The fractions containing product were combined and diluted in ethyl acetate, then washed with aqueous sodium bicarbonate and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure to afford impure material, which was additionally purified by column chromatography on silica gel (methanol/dichloromethane gradient) to afford -methoxy-7-phenyl-3-(pyridin-3-ylethynyl)imidazo[1,2-a]pyridine. 1H NMR (500 MHz, CDCl3) δ 8.75 (d, 1H), 8.53 (dd, 1H), 7.89 (s, 1H), 7.75-7.79 (m, 1H), 7.62-7.67 (m, 2H), 7.53 (s, 1H), 7.45-7.50 (m, 2H), 7.39-7.43 (m, 1H), 7.27-7.31 (m, 1H), 6.37 (s, 1H), 4.16 (s, 3H). LRMS (ESI) calculated for C21H16N3O [M+H]+, 326.1; found 326.0.
Reaction SMILES: [CH3:1][CH:2]1[CH2:8][CH2:7][N:6]2[C:9](=[O:20])[C:10]3[C:15]4[CH2:16][CH2:17][CH2:18][CH2:19][C:14]=4[S:13][C:11]=3[N:12]=[C:5]2[CH2:4][CH2:3]1.[O-:21]S(OOS([O-])(=O)=O)(=O)=O.[K+].[K+]>O>[CH3:1][CH:2]1[CH2:8][CH2:7][N:6]2[C:9](=[O:20])[C:10]3[C:15]4[CH2:16][CH2:17][CH2:18][C:19](=[O:21])[C:14]=4[S:13][C:11]=3[N:12]=[C:5]2[CH2:4][CH2:3]1
Reactant: O=S(=O)([O-])OOS(=O)(=O)[O-]
Reactant: CC1CCc2nc3sc4c(c3c(=O)n2CC1)CCCC4
Agent: [K+]
Solvent: O
Product: CC1CCc2nc3sc4c(c3c(=O)n2CC1)CCCC4=O

Procedure:
To compound 14 (4.0 g, 13.9 mmol), potassium peroxodisulfate (11.3 g, 41.6 mmol) and CuSO4.5H2O, 250 ml of acetinitrile/water 1:1 were added. The reaction mixture was heated to reflux for 30 minutes. The reaction was quenched with water and extracted with CH2Cl2. The organic layer was washed with 10% sodium thiosulfate and brine, and dried over Na2SO4. After filtration the solvent w as evaporated and the product purified by flash chromatography using CH2Cl2/EtOAc 9:1 as an eluent.
Reaction SMILES: [I:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][C:8]([OH:10])=O)=[CH:4][CH:3]=1.[NH2:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17]([NH2:19])=[O:18].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[I:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][C:8]([NH:13][C:14]2[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=2)[C:17]([NH2:19])=[O:18])=[O:10])=[CH:11][CH:12]=1
Reactant: O=C(O)COc1ccc(I)cc1
Reactant: NC(=O)c1cccc(N)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: NC(=O)c1cccc(NC(=O)COc2ccc(I)cc2)c1
Reaction time: 8 h
Yield: 88.4 %

Procedure:
To (4-iodo-phenoxy)acetic acid (83.5 mg, 0.3 mmol), 3-amino-benzamide (61.3 mg, 0.45 mmol), N-(3-dimethylaminopropyl)-N′-ethyl carbodiimide HCl (EDC) (86.3 mg, 0.45 mmol) and 1-hydroxybenzotriazole (HOBt) (61.3 mg, 0.45 mmol) in DMF (3 ml) was added N,N-diisopropylethylamine, redistilled (DIPEA) (0.08 ml, 0.45 mmol). The mire was stirred overnight, and then partitioned between ethyl acetate and water. The organic phase was washed with brine, dried (MgSO4 anh), and concentrated. The residue was purified by silica gel flash column chromatography (CH2CH2:MeOH=6:1) to give 3-[2-(4-iodo-phenoxy)acetyl-amino]-benzamide as a white solid (105.1 mg, 88.4% yield).
Reaction SMILES: [Cl:1][C:2]1[N:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:6]([C:12]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=1)=[N:7]2.[CH3:26][Mg]Br.C(OCC)(=O)C>C(Cl)Cl>[Cl:1][C:2]1[N:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:6]([C:12]1[CH:19]=[CH:18][C:15]([CH:16]([OH:17])[CH3:26])=[CH:14][CH:13]=1)=[N:7]2
Reactant: C[Mg]Br
Reactant: O=Cc1ccc(-c2nc3ccnc(Cl)c3cc2-c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(O)c1ccc(-c2nc3ccnc(Cl)c3cc2-c2ccccc2)cc1
Reaction time: 0.25 h

Procedure:
To a solution of 4-(5-chloro-3-phenyl-1,6-naphthyridin-2-yl)benzaldehyde (9-1, 0.500 g, 1.450 mmol) in anhydrous methylene chloride (10 mL) was added methymagnesium bromide (2.072 mL, 2.9 mmol, 1.4M in toluene/tetrahydrofuran (75:25)) at 0° C. After 15 minutes, the reaction mixture was poured into ethyl acetate, and the organic layer was washed with a saturated solution of sodium bicarbonate, water, then brine, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure gave the title compound. MS (M+H+): calculated=361.85, observed=361.1.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([CH3:19])[CH:15]=[C:14]2[CH2:20][OH:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].CI.[C:26](=O)(O)[O-].[Na+]>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([CH3:19])[CH:15]=[C:14]2[CH2:20][O:21][CH3:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C([O-])O
Reactant: Cc1cc(CO)c2cccc(OCc3ccccc3)c2n1
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: CI
Product: COCc1cc(C)nc2c(OCc3ccccc3)cccc12
Reaction time: 0.25 h

Procedure:
To a solution of 8-benzyloxy-4-hydroxymethyl-2-methylquinoline (148 mg) in N,N-dimethylformamide (1.5 ml) was added sodium hydroxide (60% in oil, 23.3 mg) under ice-cooling, and the mixture was stirred for 15 minutes at the same temperature. To the mixture was added methyl iodide (82.7 mg) under ice-cooling, and the mixture was stirred for 15 minutes at the same temperature and then overnight at ambient temperature. To the mixture was added saturated sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water twice, dired over magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (Ethyl acetate:n-hexane=1:3, V/V) to give 8-benzyloxy-4-methoxymethyl-2-methylquinoline (123 mg) as pale yellow solid.
Reaction SMILES: [N+:1]([C:4]1[C:9]([CH3:10])=[C:8]([CH3:11])[C:7]([CH3:12])=[C:6]([CH3:13])[C:5]=1[CH3:14])([O-])=O.CO.[Cl-].[NH4+]>[Zn].O>[CH3:10][C:9]1[C:4]([NH2:1])=[C:5]([CH3:14])[C:6]([CH3:13])=[C:7]([CH3:12])[C:8]=1[CH3:11]
Reactant: Cc1c(C)c(C)c([N+](=O)[O-])c(C)c1C
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CO
Solvent: O
Product: Cc1c(C)c(C)c(N)c(C)c1C
Reaction time: 20 h

Procedure:
A one neck 2000 ml round bottom flask was charged with 50 grams of 1-nitro-2,3,4,5,6-pentamethylbenzene and 1000 ml methanol. A solution of 50 g of ammonium chloride and 200 ml of water was then added. Zinc dust (50 g) was then added in portions. The mixture was allowed to stir for 20 hours. The solids were filtered and the solvent was removed from the mother liquor. The product was purified by silica gel column with dichlormethane as the eluent. The good fractions are combined to yield pentamethylaniline as a white solid.
Reaction SMILES: [CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:18]([C:23]([O:25]C(C)(C)C)=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:13][CH:12]=2)[C:8]2[CH:30]=[C:31]([N:34]([CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH:47]=C=O)NC3CCCCC3)[CH:32]=[CH:33][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4].FC(F)(F)[C:52]([OH:54])=O>>[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[C:18]([C:23]([OH:25])=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:15][CH:16]=2)[C:8]2[CH:30]=[C:31]([N:34]([CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])[C:52]([NH:6][CH:7]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:8]3)=[O:54])[CH:32]=[CH:33][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc2ccc(N(CCCCCC=C=O)NC3CCCCC3)cc2n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Reactant: O=C(O)C(F)(F)F
Product: CCCCCCN(C(=O)NC1CCCCC1)c1ccc2nc(CCCC)n(Cc3ccc(-c4ccccc4C(=O)O)cc3)c2c1

Procedure:
Prepared in analogous manner to Example 9 from tert.butyl 4'-[(2-n-butyl-6-(N-cyclohexylamino-carbonyl-n-hexylamino)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylate and trifluoroacetic acid.
Reaction SMILES: [OH:1][C@:2]1([C@:23]2([CH3:24])[C@H:9]([C@H:10]3[C:20](=[CH:21][CH2:22]2)[C@:18]2([CH3:19])[C:13](=[CH:14][C:15](=[O:25])[CH2:16][CH2:17]2)[CH2:12][CH2:11]3)[CH2:8][CH2:7]1)[C:3](=[O:6])[CH2:4][OH:5].F[C:27](F)(F)[C:28]([OH:30])=O.O1CCO[CH2:35][CH2:34]1>C([O-])([O-])(OCC)CCC>[C:28]([O:1][C@:2]1([C@:23]2([CH3:24])[C@H:9]([C@H:10]3[C:20](=[CH:21][CH2:22]2)[C@:18]2([CH3:19])[C:13](=[CH:14][C:15](=[O:25])[CH2:16][CH2:17]2)[CH2:12][CH2:11]3)[CH2:8][CH2:7]1)[C:3](=[O:6])[CH2:4][OH:5])(=[O:30])[CH2:27][CH2:34][CH3:35]
Reactant: C1COCCO1
Reactant: C[C@]12CCC(=O)C=C1CC[C@@H]1C2=CC[C@@]2(C)[C@H]1CC[C@]2(O)C(=O)CO
Reactant: O=C(O)C(F)(F)F
Agent: CCCC([O-])([O-])OCC
Product: CCCC(=O)O[C@]1(C(=O)CO)CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)C3=CC[C@@]21C
Temperature: 45 °C

Procedure:
4 g (11.6 mM) of 17a,21-dihydroxy-pregna-4,9(11)-diene-3,20-dione were reacted with 20 mg of trifluoroacetic acid in 20 ml of dioxane and 10 ml of ethyl orthobutyrate for 5 hours at 100° C., and the low boiling head fraction was distilled off. The solution was cooled, then treated with 5 ml of a tartaric acid molar solution and heated to 40-50° C. for about 5 minutes to obtain 17α-butanoyloxy-21-hydroxy-pregna-4,9(11)-diene-3,20-dione. The solvent was evaporated off under vacuum and the residue was repeatedly taken up with dioxane. The resulting residue was dissolved in 200 ml of acetone and then 12 g trifluoroethyl octadecanoate (prepared from octadecanoyl chloride and trifluoroethanol), 20 g of Candida cylindracea lipase were added and the resulting suspension was stirred for 8-10 hours at 50° C., adding 2 g of C. cylindracea at regular time intervals. The lipase was filtered off, the filtrate was concentrated under vacuum and the residue was chromatographed on a silica gel column with a dichloromethane/methanol 98.5:1.5 mixture. The neat fraction was evaporated to obtain 4.9 g (7.17 mM) of 17α-butanoyloxy-21-octadecanoyloxy-pregna-4,9(11)-diene-3,20-dione.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5](CO)=[CH:4][CH:3]=1.N1C=CN=C1.[Si:15](Cl)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16].CN([CH:26]=[O:27])C>O>[Br:1][C:2]1[CH:9]=[CH:8][CH:5]=[C:4]([CH2:26][O:27][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH:3]=1
Reactant: CN(C)C=O
Reactant: OCc1ccc(Br)cc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCc1cccc(Br)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 62 %

Procedure:
To a 1-L round-bottomed flask were added 4-bromobenzyl alcohol (100.0 g, 0.53 mol), imidazole (91.0 g, 1.34 mol), t-butyldimethylsilyl chloride (TBDMS-Cl) (96.5 g, 0.64 mol), and DMF 100 mL. The reaction mixture was stirred at room temperature under nitrogen overnight. The reaction was poured into water and extracted with ether three times and the combined organic phase was washed with water three times and dried over MgSO4. After solvent was removed, the product was obtained as light yellow liquid 154 g (62% yield). 1H NMR (CDCl3) δ (Ppm): 0.07 (s, 9H), 0.91 (s, 6H), 4.65 (s, 2H), 7.17 (d, J=8.2 Hz, 2H), 7.42 (s, J=8.3 Hz, 2H); 13C NMR (CDCl3): −1.71, 21.93, 29.48, 67.89, 124.13, 131.27, 134.82, 144.02; FD-MS: m/z 301 (M+).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[N:9]=[C:10]=[S:11].[OH:12][CH2:13][CH2:14][CH2:15][NH2:16]>C1C=CC=CC=1>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([NH:16][CH2:15][CH2:14][CH2:13][OH:12])=[S:11]
Reactant: Cc1ccc(N=C=S)c(C)c1
Reactant: NCCCO
Solvent: c1ccccc1
Product: Cc1ccc(NC(=S)NCCCO)c(C)c1
Reaction time: 16 h

Procedure:
A solution of 2,4-dimethylphenylisothiocyanate in about 70 ml. of benzene was added dropwise to an agitated solution of 3-hydroxypropylamine (3.8 grams) in about 80 ml. of benzene. The resulting reaction mixture was maintained, with stirring, at ambient temperatures for about 16 hours. Following such period, the benzene in the reaction mixture was removed in vacuo and the residual oil triturated with ethyl ether and the desired product crystallized therefrom and washed again with ethyl ether. As a result of such operations, the desired N-(2,4-dimethylphenyl)-N'-(3-hydroxypropyl)-thiourea product was obtained as a white solid having a melting point of 90° - 93°C.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH3:12])[CH:3]=1.[CH2:13]([N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)[CH3:14].C(N(C(C)C)CC)(C)C>C(#N)C>[CH2:13]([N:15]1[CH2:20][CH2:19][N:18]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH3:12])[CH:3]=2)[CH2:17][CH2:16]1)[CH3:14]
Reactant: CCN1CCNCC1
Reactant: COc1cc(F)ccc1[N+](=O)[O-]
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CCN1CCN(c2ccc([N+](=O)[O-])c(OC)c2)CC1
Temperature: 85 °C
Reaction time: 1 h
Yield: 77.3 %

Procedure:
A mixture of 3.42 g (20 mmol) of 4-fluoro-2-methoxy-1-nitrobenzene, 2.67 mL (21 mmol) of 1-ethylpiperazine and 5.14 mL (30 mmol) of diisopropylethylamine in 25 mL of acetonitrile is heated for 2.5 hours at 85°C. and then for 1 hour at 95°C., and is then stirred overnight while allowing to return to room temperature. The acetonitrile is evaporated off and the residue is then taken up in 50 mL of ether and 25 mL of water. The aqueous phase is extracted with ether. The organic phases are combined, dried over Na2SO4, filtered and concentrated under vacuum. The oil obtained is triturated in an ether/cyclohexane mixture (1/1) and the precipitate is isolated by filtration, rinsed with pentane and dried in an oven. 4.1 g of the expected product are finally obtained. Yield=77%.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Br[CH2:10][CH2:11][N:12]1[C:16](=[O:17])[C:15]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:14]2[C:13]1=[O:22].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:10][CH2:11][N:12]2[C:13](=[O:22])[C:14]3[C:15](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]2=[O:17])=[CH:4][CH:3]=1
Reactant: Oc1ccc(Br)cc1
Reactant: O=C1c2ccccc2C(=O)N1CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCOc1ccc(Br)cc1
Temperature: 50 °C

Procedure:
4-Bromophenol, N-(2-bromoethyl)phthalimide and potassium carbonate were suspended in dimethylformamide and heated to 50° C. overnight under nitrogen. The dimethylformamide was removed under reduced pressure. The resulting residue was partitioned between ethyl acetate and water. The aqueous phase was extracted twice with ethyl acetate. The organics were combined, washed several times with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. Yield: 2 g, 98%; LCMS: RT method: 2, RT: 5.33 min, MI: 382-384 [M+1].
Reaction SMILES: Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][CH2:13][NH:14][C:15](=[O:16])[C:8]3=[CH:7][C:6]=2[CH:5]=[C:4]([F:17])[CH:3]=1.[F:18][C:19]([F:30])([F:29])[C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1>>[F:17][C:4]1[CH:3]=[C:2]([C:23]2[CH:24]=[CH:25][C:20]([C:19]([F:30])([F:29])[F:18])=[CH:21][CH:22]=2)[C:10]2[N:9]3[CH2:11][CH2:12][CH2:13][NH:14][C:15](=[O:16])[C:8]3=[CH:7][C:6]=2[CH:5]=1
Reactant: O=C1NCCCn2c1cc1cc(F)cc(Br)c12
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Product: O=C1NCCCn2c1cc1cc(F)cc(-c3ccc(C(F)(F)F)cc3)c12

Procedure:
The title compound, grey solid (88 mg, 97%), MS (ISP) m/z=363.2 [(M+H)+], mp 257° C., was prepared in accordance with the general method of example 1 from 7-bromo-9-fluoro-2,3,4,5-tetrahydro-[1,4]diazepino[1,2-a]indol-1-one (intermediate 2) (74.3 mg, 0.25 mmol) and commercially available 4-trifluoromethyl-phenylboronic acid (61.7 mg, 0.325 mmol).
Reaction SMILES: [C:1]([CH2:4][CH2:5][CH2:6][C:7]([C:10]1[CH:16]=[C:15]([OH:17])[C:14]([C:18]([CH3:26])([CH2:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])[CH3:19])=[CH:13][C:11]=1[OH:12])([CH3:9])[CH3:8])([OH:3])=[O:2].[CH2:27](O)[CH3:28].S(=O)(=O)(O)O.[CH3:35][CH2:36]OCC>>[CH2:35]([O:2][C:1]([CH2:4][CH2:5][CH2:6][C:7]([C:10]1[CH:16]=[C:15]([OH:17])[C:14]([C:18]([CH3:26])([CH2:20][CH2:21][CH2:22][C:23]([O:25][CH2:27][CH3:28])=[O:24])[CH3:19])=[CH:13][C:11]=1[OH:12])([CH3:9])[CH3:8])=[O:3])[CH3:36]
Reactant: CC(C)(CCCC(=O)O)c1cc(O)c(C(C)(C)CCCC(=O)O)cc1O
Reactant: CCO
Reactant: CCOCC
Agent: O=S(=O)(O)O
Product: CCOC(=O)CCCC(C)(C)c1cc(O)c(C(C)(C)CCCC(=O)OCC)cc1O

Procedure:
5.0 Parts of 2,5-bis-(5-carboxy-2-methylpent-2-yl)-hydroquinone, 100 parts of absolute ethanol, and 1.0 parts of 98% sulphuric acid are refluxed for 16 hours. The solution is then stripped down under reduced pressure, the residue taken up in ether, and washed with sodium bicarbonate solution. The ethereal solution after being concentrated and diluted with 40°-60° petroleum ether yields 2,5-bis-(5-ethoxycarbonyl-2-methylpent-2-yl)-hydroquinone, [formula (103)] m.p. 146°-149° C. with the following percentage composition by weight:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[S:11][C:10]([CH:12]=O)=[CH:9][CH:8]=1.N1(C2C=C[C:22]([CH:23]=[O:24])=CC=2)C=CC=N1>>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[S:11][C:10]([CH:12]=[CH:22][CH:23]=[O:24])=[CH:9][CH:8]=1
Reactant: O=Cc1ccc(-n2cccn2)cc1
Reactant: O=Cc1ccc(-c2ccccn2)s1
Product: O=CC=Cc1ccc(-c2ccccn2)s1

Procedure:
The title compound was prepared by a procedure analogous to Reference Example 30 by substituting 5-(2-pyridinyl)-2-thiophenecarboxaldehyde (prepared as described in J. Chem Soc., Perkin Trans. 2 1998, 437) for the 4-(1H-pyrazol-1-yl)-benzaldehyde of Reference Example 30. MS 216 (M+H)+.
Reaction SMILES: [O:1]=[S:2]1(=[O:28])[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]([C:11]([C:13]2[CH:14]=[C:15]([C:24]([F:27])([F:26])[F:25])[C:16]([O:22][CH3:23])=[C:17]([CH:21]=2)[C:18](O)=[O:19])=[O:12])[CH2:3]1.[S:29]1[CH2:33][CH2:32][NH:31][CH2:30]1.Cl.C(N=C=NCCCN(C)C)C>ClCCl>[CH3:23][O:22][C:16]1[C:15]([C:24]([F:27])([F:26])[F:25])=[CH:14][C:13]([C:11]([N:4]2[C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[S:2](=[O:28])(=[O:1])[CH2:3]2)=[O:12])=[CH:21][C:17]=1[C:18]([N:31]1[CH2:32][CH2:33][S:29][CH2:30]1)=[O:19]
Reactant: COc1c(C(=O)O)cc(C(=O)N2CS(=O)(=O)c3ccccc32)cc1C(F)(F)F
Reactant: C1CSCN1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: COc1c(C(=O)N2CCSC2)cc(C(=O)N2CS(=O)(=O)c3ccccc32)cc1C(F)(F)F
Temperature: 25 °C
Reaction time: 19 h

Procedure:
5-(1,1-dioxo-2,3-dihydro-1,3-benzothiazole-3-carbonyl)-2-methoxy-3-trifluoromethylbenzoic acid (277 mg) was dissolved in dichloromethane (3 mL), thiazolidine (0.10 mL) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (238 mg) were added to the solution, and then the mixture was stirred at room temperature for 19 hours. The solvent was distilled off under reduced pressure and 1N hydrochloric acid was added and then the mixture was extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid, 1N sodium hydroxide and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1) to obtain the title compound (138 mg) as a colorless oily substance.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][C:15]1[N:19]=[C:18]([CH2:20][O:21][C:22]2[CH:23]=[C:24]([CH2:28][C:29]([O:31]C)=[O:30])[CH:25]=[CH:26][CH:27]=2)[O:17][N:16]=1.O1CCCC1.[OH-].[Na+].Cl>O.CO>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][C:15]1[N:19]=[C:18]([CH2:20][O:21][C:22]2[CH:23]=[C:24]([CH2:28][C:29]([OH:31])=[O:30])[CH:25]=[CH:26][CH:27]=2)[O:17][N:16]=1
Reactant: COC(=O)Cc1cccc(OCc2nc(CCc3nc(-c4ccccc4)oc3C)no2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: Cc1oc(-c2ccccc2)nc1CCc1noc(COc2cccc(CC(=O)O)c2)n1
Temperature: 50 °C
Reaction time: 1 h
Yield: 96.5 %

Procedure:
To a mixture of methyl 2-[3-[[3-[2-(5-methyl-2-phenyl-4-oxazolyl)ethyl]-1,2,4-oxadiazol-5-yl]methoxy]phenyl]acetate (0.30 g), tetrahydrofuran (3 mL) and methanol (3 mL) was added a 1N aqueous sodium hydroxide solution (3 mL) and the mixture was stirred at 50° C. for 1 hr. 1N Hydrochloric acid (3 mL) and water were added to the reaction mixture, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give crystals (0.28 g, 97%) of 2-[3-[[3-[2-(5-methyl-2-phenyl-4-oxazolyl)ethyl]-1,2,4-oxadiazol-5-yl]methoxy]phenyl]acetic acid. Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 93-94° C.
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]1[C@H:7]([OH:8])[CH2:6][N:5]([CH2:9][CH2:10][N:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:23])[CH2:4]1.[Cl:24][C:25]1[C:34]([CH:35]=O)=[N:33][C:32]2[NH:31][C:30](=[O:37])[CH2:29][O:28][C:27]=2[CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CO>[ClH:24].[ClH:24].[Cl:24][C:25]1[C:34]([CH2:35][NH:1][CH2:2][C@@H:3]2[C@H:7]([OH:8])[CH2:6][N:5]([CH2:9][CH2:10][N:11]3[C:20]4[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=4)[CH:14]=[CH:13][C:12]3=[O:23])[CH2:4]2)=[N:33][C:32]2[NH:31][C:30](=[O:37])[CH2:29][O:28][C:27]=2[CH:26]=1
Reactant: O=Cc1nc2c(cc1Cl)OCC(=O)N2
Reactant: COc1ccc2ccc(=O)n(CCN3C[C@H](CN)[C@H](O)C3)c2c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: COc1ccc2ccc(=O)n(CCN3C[C@H](CNCc4nc5c(cc4Cl)OCC(=O)N5)[C@H](O)C3)c2c1
Product: Cl
Reaction time: 18 h
Yield: 87 %

Procedure:
1-{2-[(3S,4S)-3-(Aminomethyl)-4-hydroxy-1-pyrrolidinyl]ethyl}-7-(methyloxy)-2(1H)-quinolinone (68 mg, 0.214 mmol) and 7-chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxaldehyde (for a synthesis see WO2003064421, Example 15(c)) (50 mg, 0.236 mmol) were combined in anhydrous DCM (5 mL) and anhydrous MeOH (1 ml) with a spatula of solid sodium carbonate. The reaction mixture was stirred under nitrogen for 18 h then sodium triacetoxyborohydride (143 mg, 0.643 mmol) was added and stirred for 1 h. The reaction mixture was concentrated and purified to obtain the free base of the title compound as a pale oil (96 mg; 87%) after column chromatography (90:10:1:DCM:MeOH:NH4OH).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][CH2:8][C:9]2=[O:12])=[CH:5][CH:4]=1.[CH:13](=O)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[OH-].[K+].Cl>C(O)C.O>[CH:13](=[C:8]1[CH2:7][C:6]2[C:10](=[CH:11][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C:9]1=[O:12])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: COc1ccc2c(c1)C(=O)CC2
Reactant: O=Cc1ccccc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: COc1ccc2c(c1)C(=O)C(=Cc1ccccc1)C2
Reaction time: 1 h
Yield: 72.4 %

Procedure:
To a 0° C. mixture of 9.66 g (59.6 mmol) of 6-methoxy-1-indanone and 6.32 g (59.6 mmol) of benzaldehyde in 10 ml ethanol was added 9.66 ml of a 4% KOH in ethanol solution. The reaction was stirred 1 hour and then added to 300 ml water and the pH of the quench adjusted to 2 with 1N hydrochloric acid. The resultant mixture was extracted with 3×300 ml ether, and the extracts combined, dried over MgSO4, evaporated and the residue triturated with ether to yield 10.8 g (72%) of present title compound as a solid. 1 -NMR(CDCl3, 300 MHz)delta(ppm): 3.80 (s, OCH3), 3.92 (s, CH2), 7.13 (dd, J=8, 2 Hz, ArH), 7.35 (m, 4ArH and vinyl H) and 7.6 (m, 3ArH).