Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH3:29])[C:3]([N:5]1[CH2:10][CH:9]=[C:8]([C:11]2[NH:28][C:14]3[N:15]=[CH:16][N:17]=[C:18]([C:19]4[CH:24]=[C:23](F)[CH:22]=[C:21]([NH2:26])[C:20]=4C)[C:13]=3[CH:12]=2)[CH2:7][CH2:6]1)=[O:4].[F:30]C1C=C(B2OC(C)(C)C(C)(C)O2)C(C)=C(C=1)N>>[CH3:29][N:2]([CH3:1])[C:3]([N:5]1[CH2:10][CH:9]=[C:8]([C:11]2[NH:28][C:14]3[N:15]=[CH:16][N:17]=[C:18]([C:19]4[CH:24]=[CH:23][C:22]([F:30])=[C:21]([NH2:26])[CH:20]=4)[C:13]=3[CH:12]=2)[CH2:7][CH2:6]1)=[O:4]
Reactant: Cc1c(N)cc(F)cc1-c1ncnc2[nH]c(C3=CCN(C(=O)N(C)C)CC3)cc12
Reactant: Cc1c(N)cc(F)cc1B1OC(C)(C)C(C)(C)O1
Product: CN(C)C(=O)N1CC=C(c2cc3c(-c4ccc(F)c(N)c4)ncnc3[nH]2)CC1

Procedure:
Intermediate 10 was prepared analogue to Intermediate 6 by replacing Intermediate 5 with 5-fluoro-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline.
Reaction SMILES: [OH-].[K+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1.[CH:12]1[C:20]2[N:15]([CH:16]=[CH:17][C:18](=O)[CH:19]=2)[CH2:14][CH:13]=1>O>[CH2:12]1[CH:20]2[N:15]([CH2:16][CH:17]=[C:18]([C:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[NH:3][CH:4]=3)[CH2:19]2)[CH2:14][CH2:13]1
Reactant: c1ccc2[nH]ccc2c1
Reactant: O=c1ccn2c(c1)C=CC2
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: C1=C(c2c[nH]c3ccccc23)CC2CCCN2C1
Temperature: 25 °C
Yield: 83.5 %

Procedure:
Potassium hydroxide (10% in methanol, 15 ml, 26.8 mmol), 1H-indole (1.5 g, 13 mmol), and 7-indolizinone (1.39 g, 10 mmol) were combined and heated to reflux for 15 hours. The mixture was diluted with water and the precipitate was filtered. The brown filter cake was triturated with hot methanol, cooled to room temperature, and the solid collected to give 1.99 g of desired product. (84%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[C:12]([C:32]#[N:33])=[C:13]([C:21]3[CH:26]=[CH:25][N+:24]([O-])=[C:23]([NH:28][C:29](=[O:31])[CH3:30])[CH:22]=3)[S:14][C:15]=2[C:16]2[NH:20][CH:19]=[N:18][N:17]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[H][H]>CO.[Pd]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[C:12]([C:32]#[N:33])=[C:13]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:28][C:29](=[O:31])[CH3:30])[CH:22]=3)[S:14][C:15]=2[C:16]2[NH:20][CH:19]=[N:18][N:17]=2)(=[O:9])=[O:10])=[CH:4][CH:3]=1
Reactant: [H][H]
Reactant: CC(=O)Nc1cc(-c2sc(-c3nnc[nH]3)c(S(=O)(=O)c3ccc(Cl)cc3)c2C#N)cc[n+]1[O-]
Agent: [Pd]
Solvent: CO
Product: CC(=O)Nc1cc(-c2sc(-c3nnc[nH]3)c(S(=O)(=O)c3ccc(Cl)cc3)c2C#N)ccn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 64.1 %

Procedure:
N-{4-[4-[(4-chlorophenyl)sulfonyl]-3-cyano-5-(4H-1,2,4-triazol-3-yl)-2-thienyl]-1-oxidopyridin-2-yl}acetamide (0.0229 g, 0.0457 mmol) was dissolved in methanol (3.00 mL), followed by the addition of 10% Pd—C (5 mg). The flask was filled with hydrogen at 40 psi, and the suspension was stirred at room temperature for overnight. The solid was filtered off, and the residue was concentrated followed by purification by column chromatography. The eluent was 0-8% methanol in ethyl acetate to yield a solid product (0.0142 g, yield 64.0%). LCMS: (AA) ES+ 485, 487. 1H NMR (300 MHz, MeOD) δ: 8.60 (s, 1H), 8.53 (s, 1H), 8.45 (d, 1H), 8.35 (d, 2H), 7.66 (d, 2H), 7.48 (d, 1H), 2.20 (s, 3H).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH3:12])[C:6]([C:9]([OH:11])=[O:10])=[N:7][CH:8]=1)#[N:2].S(Cl)(Cl)=O.[C:17]1(C)C=CC=CC=1>CO>[CH3:17][O:10][C:9]([C:6]1[C:5]([CH3:12])=[CH:4][C:3]([C:1]#[N:2])=[CH:8][N:7]=1)=[O:11]
Reactant: Cc1cc(C#N)cnc1C(=O)O
Reactant: Cc1ccccc1
Solvent: O=S(Cl)Cl
Solvent: CO
Product: COC(=O)c1ncc(C#N)cc1C
Reaction time: 1 h

Procedure:
To a solution of 5-cyano-3-methylpyridine-2-carboxylic acid (2 g, 12.4 mmol) in methanol (20 mL) was added thionyl chloride dropwise under reflux. The mixture was then heated at reflux with stirring. After 60 min, HPLC analysis revealed completion of reaction. To the reaction mixture was added toluene and the mixture was concentrated in vacuo to give the title compound as a pale yellow solid: ESIMS: 177; [(M+H)+]; 1H NMR (400 MHz, DMSO-d6): δ 8.92 (s, 1H), 8.39 (s, 1H), 3.90 (s, 3H), 2.46 (s, 3H).
Reaction SMILES: CN(C)[C:3]1[CH:4]=[CH:5][C:6]2[C:15]3(C4C(=CC=CC=4)C(=O)O3)[C:14]3[CH:13]=[CH:12][C:11](N(C)C)(N(C)C)[CH2:10][C:9]=3[C:7]=2[CH:8]=1.C(N(CC)C1C=CC2C3(C4C(=CC(N(CC)CC)=CC=4)C(=O)O3)C3C(=CC(N(CC)CC)=CC=3)C=2C=1)C>>[CH:5]1[C:6]2[CH2:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:7]=2[CH:8]=[CH:3][CH:4]=1
Reactant: CN(C)c1ccc2c(c1)C1=C(C=CC(N(C)C)(N(C)C)C1)C21OC(=O)c2ccccc21
Agent: CCN(CC)c1ccc2c(c1)C(=O)OC21c2ccc(N(CC)CC)cc2-c2cc(N(CC)CC)ccc21
Product: c1ccc2c(c1)Cc1ccccc1-2

Procedure:
3,6,6-Tris(dimethylamino)spiro[fluorene-9,3′-phthalide] and 3,6,6′-tris(diethylamino)spiro[fluorene-9,3′-phthalide].
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)[CH3:8].[CH2:15]([O:22][C:23]1[CH:50]=[CH:49][C:48]([O:51][CH2:52][CH2:53]Br)=[CH:47][C:24]=1[C:25]([NH:27][C:28]1[CH:40]=[C:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH:38]=[CH:37][C:29]=1[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:26])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CC(C)=O>[CH2:15]([O:22][C:23]1[CH:50]=[CH:49][C:48]([O:51][CH2:52][CH2:53][N:12]2[CH2:13][CH2:14][N:9]([CH2:7][CH3:8])[CH2:10][CH2:11]2)=[CH:47][C:24]=1[C:25]([NH:27][C:28]1[CH:40]=[C:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH:38]=[CH:37][C:29]=1[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:26])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CCN1CCNCC1
Reactant: CC(C)(C)OC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(OCCBr)ccc1OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCN1CCN(CCOc2ccc(OCc3ccccc3)c(C(=O)Nc3cc(-c4ccccc4)ccc3C(=O)OC(C)(C)C)c2)CC1
Temperature: 25 °C

Procedure:
Potassium carbonate (1.5 g) and 1-ethylpiperazine (1.0 mL) were added to an acetone (8.0 mL) solution of tert-butyl 2-(2-(benzyloxy)-5-(2-bromoethoxy)benzamido)-4-phenylbenzoate (1.6 g), followed by heating to reflux for 5 hours. After cooling the reaction mixture to room temperature, the insoluble substance was removed by filtration, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 100-90% chloroform/methanol] to obtain tert-butyl 2-(2-(benzyloxy)-5-(2-(4-ethylpiperazin-1-yl)ethoxy)benzamido)-4-phenylbenzoate as a yellow oily substance.
Reaction SMILES: C([O:3][C:4](=O)[C:5]([C:11]#[N:12])([CH3:10])[CH2:6][CH2:7][CH2:8][CH3:9])C.[Cl-].[Li+].[BH4-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.C(O)C>[C:11]([C:5]([CH3:10])([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][OH:3])#[N:12]
Reactant: CCCCC(C)(C#N)C(=O)OCC
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [BH4-]
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: CCO
Product: CCCCC(C)(C#N)CO
Temperature: 25 °C
Yield: 63.8 %

Procedure:
A solution of 915 mg (5 mM) of (+)-2-cyano-2methylhexanoic acid-ethyl-ester ([α]D +2.2 degrees (c 2.782, methanol)) in 8 ml of dry tetrahydrofuran was added dropwise to a mixture of 423 mg (10 mM) of anhydrous lithium chloride and 379 mg (10 mM) of sodium borohydride under stirring at room temperature. Then, 17 ml of dry ethanol was added thereto, followed by reaction for 18 hours at room temperature. After the reaction, the reaction mixture was cooled on an ice bath and acidified to pH 4 by adding 10% citric acid. A precipitate formed at that time was removed by filtration, and the solvent in the filtrate was removed by reduced pressure distillation. Then, 5 ml of distilled water was added to the remaining product, and the mixture was subjected to extraction with dichlocomethane. The organic layer was dried on sodium sulfate, and the solvent was distilled off under reduced pressure, followed further by distillation to obtain (-)-2-cyano-2-methylhexanol. Yield:63.8%, [α]D -1.2 degree (c 2.393, methylene chloride).
Reaction SMILES: [Br:1][C:2]1[O:6][C:5]([C:7]([N:9]2[CH2:15][CH2:14][CH2:13][CH2:12]C[C:10]2=[O:16])=[O:8])=[CH:4][CH:3]=1.C1(=O)NCCCC1>>[Br:1][C:2]1[O:6][C:5]([C:7]([N:9]2[CH2:15][CH2:14][CH2:13][CH2:12][C:10]2=[O:16])=[O:8])=[CH:4][CH:3]=1
Reactant: O=C1CCCCCN1C(=O)c1ccc(Br)o1
Agent: O=C1CCCCN1
Product: O=C1CCCCN1C(=O)c1ccc(Br)o1

Procedure:
Synthesized as for N-(5-bromo-2-furoyl)caprolactam (Example XV) using valerolactam (Aldrich) in place of caprolactam.
Reaction SMILES: [CH3:1][O:2][C:3]1[NH:4][C:5](=[O:27])[C:6]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=3)=[CH:15][CH:14]=2)=[C:7]([CH2:9][CH2:10][CH3:11])[N:8]=1.[CH:28]([O:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)([CH3:30])[CH3:29].C(N(CC)CC)C.N1C=CC=CC=1>ClCCl.C(OCC)(=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH:28]([O:31][C:32]1[CH:37]=[CH:36][C:35]([N:4]2[C:5](=[O:27])[C:6]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]4[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=4)=[CH:15][CH:14]=3)=[C:7]([CH2:9][CH2:10][CH3:11])[N:8]=[C:3]2[O:2][CH3:1])=[CH:34][CH:33]=1)([CH3:30])[CH3:29]
Reactant: CC(C)Oc1ccc(B(O)O)cc1
Reactant: CCCc1nc(OC)[nH]c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCCc1nc(OC)n(-c2ccc(OC(C)C)cc2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Reaction time: 48 h
Yield: 81.6 %

Procedure:
To a suspension of 4′-[(2-methoxy-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (0.5 g), 4-isopropoxyphenylboronic acid (0.56 g), triethylamine (0.97 mL), pyridine (0.57 mL) and molecular sieves 4 A (1 g) in dichloromethane (10 mL) was added copper(II) acetate (0.51 g), and the mixture was stirred for 2 days. The reaction mixture was diluted with ethyl acetate, the insoluble material was filtered off through celite, and the filtrate was concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow solid (0.56 g, 82%).
Reaction SMILES: C([NH:9][C:10]([NH:12][CH:13]1[C:22]2[N:21]=[CH:20][C:19]([CH3:23])=[CH:18][C:17]=2[CH2:16][CH2:15][CH2:14]1)=[S:11])(=O)C1C=CC=CC=1.[OH-].[Na+]>>[C:10]([NH:12][CH:13]1[C:22]2[N:21]=[CH:20][C:19]([CH3:23])=[CH:18][C:17]=2[CH2:16][CH2:15][CH2:14]1)(=[S:11])[NH2:9]
Reactant: Cc1cnc2c(c1)CCCC2NC(=S)NC(=O)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Product: Cc1cnc2c(c1)CCCC2NC(N)=S
Yield: 98 %

Procedure:
8-Benzoylthiocarbamoylamino-3-methyl-5,6,7,8-tetrahydroquinoline (6 g.) was treated with a 10% sodium hydroxide solution (24 ml.) and the mixture heated on a steam bath for 15 minutes. The cooled reaction mixture was adjusted to pH 1.0 with conc. HC1, filtered to remove benzoic acid and the filtrate adjusted to pH 10.0 with aqueous ammonia. The resultant solid was recrystallised from ethanol to give the hydrate of the title compound as colourless needles (4 g.). m.p. 114° C. (Found C, 55.3; H, 7.3; N, 17.2. C11H15N3S.H2O requires: C,55.1; H, 7.3; N, 17.4%). The product displayed anti-ulcer activity.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[N:8]=[C:9]3[NH:16][CH2:15][CH2:14][N:10]3[C:11](=[O:13])[CH:12]=2)=[CH:3][CH:2]=1.[H-].[Na+].[C:19]1([CH2:25][CH2:26][C:27](Cl)=[O:28])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C)C=O>[C:19]1([CH2:25][CH2:26][C:27]([N:16]2[C:9]3=[N:8][C:7]([C:4]4[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=4)=[CH:12][C:11](=[O:13])[N:10]3[CH2:14][CH2:15]2)=[O:28])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=C(Cl)CCc1ccccc1
Reactant: O=c1cc(-c2ccncc2)nc2n1CCN2
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(CCc1ccccc1)N1CCn2c1nc(-c1ccncc1)cc2=O
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A suspension of 0.2 g (0.93 mmol) of 7-pyridin-4-yl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one in 5 ml of N,N-dimethylformamide was treated with 48 mg (1.20 mmol) of sodium hydride (60% suspension in mineral oil) and the resulting mixture was stirred at room temperature for 15 min and then cooled to 0° C. 0.251 g (1.49 mmol) of 3-phenylpropionyl chloride was added and the reaction mixture was stirred at room temperature during 18 h.
Reaction SMILES: C(OC(N[C@H](C(O)=O)CCCCN)=O)(C)(C)C.C[Si](C=[N+]=[N-])(C)C.C(=O)C1C=CC=CC=1.[BH4-].[Na+].C=O.[Na].[NH2:38][C@H:39]([C:45]([O:47][CH3:48])=[O:46])[CH2:40][CH2:41][CH2:42][CH2:43][NH2:44].C[Si]([Cl:53])(C)C>C(O)C.CO>[ClH:53].[ClH:53].[NH2:38][C@H:39]([C:45]([O:47][CH3:48])=[O:46])[CH2:40][CH2:41][CH2:42][CH2:43][NH2:44]
Reactant: C[Si](C)(C)Cl
Agent: C=O
Agent: CC(C)(C)OC(=O)N[C@@H](CCCCN)C(=O)O
Agent: COC(=O)[C@@H](N)CCCCN
Solvent: O=Cc1ccccc1
Solvent: CCO
Solvent: CO
Product: Cl

Procedure:
Nα-tert-Butyloxycarbonyl-lysine was reacted with trimethylsilyldiazomethan in ethanol. The resulting methyl ester amine was transformed to the Nε-methyl derivative via benzaldehyde and sodium borohydride, formaldehyde and sodium boronhydride and hydrogenolysis (Andruszkiewicz, J. Pol. Chem. 1988, 62, 257) followed by N-alkylation with 2-(pinacolborono)benzyl bromide. The resulting Nα-tert-butyloxycarbonyl, Nε-methyl, Nε-(2-pinacolboronobenzyl) methyl lysinate was treated with methanol and trimethylsilyl chloride, 10:1, to give Nε-methyl, Nε-(2-boronobenzyl), methyl lysinate, dihydrochloride:
Reaction SMILES: S1CC(=O)NC1=O.OCCOC1C=CC(C=O)=CC=1.N1CCCCC1.[OH:26][CH2:27][CH2:28][O:29][C:30]1[CH:43]=[CH:42][C:33]([CH:34]=[C:35]2[S:39][C:38](=[O:40])[NH:37][C:36]2=[O:41])=[CH:32][CH:31]=1.[Mg]>C1(C)C=CC=CC=1.O.C(O)(=O)C>[OH:26][CH2:27][CH2:28][O:29][C:30]1[CH:43]=[CH:42][C:33]([CH2:34][CH:35]2[S:39][C:38](=[O:40])[NH:37][C:36]2=[O:41])=[CH:32][CH:31]=1
Reactant: O=C1NC(=O)C(=Cc2ccc(OCCO)cc2)S1
Agent: O=C1CSC(=O)N1
Agent: O=Cc1ccc(OCCO)cc1
Agent: [Mg]
Solvent: C1CCNCC1
Solvent: O
Solvent: CC(=O)O
Product: O=C1NC(=O)C(Cc2ccc(OCCO)cc2)S1

Procedure:
2,4-Thiazolidinedione (46g) and 4-(2-hydroxyethoxy)-benzaldehyde (65g) were mixed in toluene (400ml) containing acetic acid (1.0 ml) and piperidine (1.0 ml) in an apparatus incorporating a water-trap. The mixture was boiled under reflux with vigorous stirring for 30 minutes, during which time the theoretical quantity of water was obtained and 5-[4-(2-hydroxyethoxy)benzylidene]-2,4-thiazolidinedione started to crystallise. The solution was cooled and the benzylidene compound (mp 194° C.-196° C.) collected by filtration. This product was suspended in methanol (2 l.) and treated portionwise with magnesium turnings (2 g). When the vigorous reaction started a cooling bath was applied and the rest of the magnesium (78 g) was added portionwise with stirring. The mixture was stirred overnight at ambient temperature and the solvent was then evaporated. 5% Hydrochloric acid solution (1000 ml), water (500 ml) and methanol (500 ml) were added. When gas evolution ceased the mixture was extracted with dichloromethane, the organic phase dried (MgSO4), filtered and evaporated under reduced pressure. The title compound was obtained pure by crystallisation from aqueous methanol (m.p. 137°-9° C.).
Reaction SMILES: [C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8](Cl)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[C:12]([O:15][C:16]1[CH:17]=[C:18]([CH:21]=[C:22]([O:24][C:25](=[O:27])[CH3:26])[CH:23]=1)[CH:19]=[CH2:20])(=[O:14])[CH3:13].[O-]P(OP(OP([O-])([O-])=O)([O-])=O)(=O)[O-].[K+].[K+].[K+].[K+].[K+].C12(P(C34CC5CC(CC(C5)C3)C4)CCCC)CC3CC(CC(C3)C1)C2>>[C:12]([O:15][C:16]1[CH:17]=[C:18](/[CH:19]=[CH:20]/[C:8]2[CH:9]=[CH:10][C:5]([O:4][C:1](=[O:3])[CH3:2])=[CH:6][CH:7]=2)[CH:21]=[C:22]([O:24][C:25](=[O:27])[CH3:26])[CH:23]=1)(=[O:14])[CH3:13]
Reactant: CC(=O)Oc1ccc(Cl)cc1
Reactant: C=Cc1cc(OC(C)=O)cc(OC(C)=O)c1
Agent: CCCCP(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2
Agent: O=P([O-])([O-])OP(=O)([O-])OP(=O)([O-])[O-]
Agent: [K+]
Product: CC(=O)Oc1ccc(/C=C/c2cc(OC(C)=O)cc(OC(C)=O)c2)cc1
Temperature: 120 °C
Reaction time: 15.5 h

Procedure:
A 10 ml Schlenk tube equipped with magnetic stirrer was charged with 119 mg (0.7 mmol) of 4-acetoxychlorobenzene, 200 mg (0.84 mmol, 1.2 eq) of 3,5-diacetoxystyrene, 177 mg (0.84 mmol, 1.2 eq) of potassium triphosphate, 5 mg of diadamantyl-n-butylphosphine (0.014 mmol, 2 mol %) and 3.7 mg (0.003 mmol, 0.5 mol %) of tris(dibenzylideneacetone)-dipalladium chloroform complex. The tube was evacuated and flushed with argon three times, and 2 ml of de-aerated DMAc was added under inert conditions. The reaction was carried out under stirring for 15.5 hours at 120° C. Work-up of the reaction mixture following the procedure of Example 5 gave (E)-3,4′,5-triacetoxystilbene.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:10]=[C:9]([Br:11])[C:8](=[O:12])[N:7]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:6]=1[CH2:20][N:21]([CH2:32][C:33]([O:35][CH3:36])=[O:34])S(C1C=CC(C)=CC=1)(=O)=O)=O.C[O-].[Na+].[NH4+].[Cl-].Cl>CO>[CH3:36][O:35][C:33]([C:32]1[C:3]([OH:2])=[C:5]2[C:6](=[CH:20][N:21]=1)[N:7]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8](=[O:12])[C:9]([Br:11])=[CH:10]2)=[O:34]
Reactant: COC(=O)CN(Cc1c(C(=O)OC)cc(Br)c(=O)n1Cc1ccccc1)S(=O)(=O)c1ccc(C)cc1
Agent: C[O-]
Agent: Cl
Agent: [Cl-]
Solvent: CO
Product: COC(=O)c1ncc2c(cc(Br)c(=O)n2Cc2ccccc2)c1O
Reaction time: 5 h
Yield: 44.3 %

Procedure:
1-Benzyl-5-bromo-2-{[methoxycarbonylmethyl-(toluene-4-sulfonyl)-amino]-methyl}-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid methyl ester (169 mg, 0.29 mmol) was dissolved in 2 mL of MeOH. NaOMe solution (0.2 mL, 0.88 mmol, 25 wt % in MeOH) was added and the mixture was stirred for 5 h. Saturated NH4Cl (10 mL) was added, followed by addition of 1M HCl until pH about 2. The resulting mixture was extracted several times with EtOAc. The organic layers were combined, dried over MgSO4, and concentrated in vacuo. The crude product was purified by silica gel chromatography (0-60% EtOAc/hexanes+2% AcOH) to give 50 mg of the title compound as a yellow solid. MS: (+) m/z 388.95, 390.92 (M+1, 79/81Br).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]([NH:13][C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[C:24]([O:30][CH3:31])[CH:23]=3)[CH2:18][CH2:17]2)=[O:15])=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.[H-].[Na+].[CH2:34](Br)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>CN(C)C=O>[CH2:34]([N:13]([C:12]1[C:3]([O:2][CH3:1])=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[C:24]([O:30][CH3:31])[CH:23]=2)[CH2:18][CH2:17]1)=[O:15])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: COc1cc(OC)cc(N2CCN(C(=O)Nc3cc4ccccc4nc3OC)CC2)c1
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cc(OC)cc(N2CCN(C(=O)N(Cc3ccccc3)c3cc4ccccc4nc3OC)CC2)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 90 %

Procedure:
1-[(2-Methoxyquinolin-3-yl)aminocarbonyl]-4-(3,5-dimethoxyphenyl)piperazine(114 mg, 0.27 mmol) was dissolved in dimethylformamide(15 ml) and sodium hydride(6.6 mg, 0.27 mmol) was added and the solution was stirred at room temperature for 15 min. Benzylbromide(46 mg, 0.27 mmol) was added to the above solution. The mixture was stirred at room temperature for 16 hours and concentrated under the reduced pressure to remove dimethylformamide. The concentrate was purified by column chromatography(ethylacetate:hexane=1:2) to obtain the titled compound.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[CH2:5]([C:12]1([CH:19]=[O:20])[CH2:17][CH:16]2[CH2:18][CH:13]1[CH:14]=[CH:15]2)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].S(=O)(=O)(O)O>C(Cl)Cl>[CH2:5]([CH:12]1[CH2:17][CH:16]2[CH2:15][CH:14]([CH:13]=[CH:18]2)[C:19]1=[O:20])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: CCCCCCCC1(C=O)CC2C=CC1C2
Agent: O=S(=O)(O)O
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CCCCCCCC1CC2C=CC(C2)C1=O
Temperature: 0 °C
Reaction time: 2 h
Yield: 28.8 %

Procedure:
Aluminum chloride (279 g, 2 mol) was dissolved in one liter of methylene chloride in a three liter flask and cooled to 0° C. Structure III (909 g, 4.1 mol) was loaded into an addition funnel and fed into the reaction flask while maintaining this temperature. After two hours the reaction was complete as shown by GC measurements. The reaction mixture was then poured onto ice and 10% sulfuric acid, and the organic layers were separated and washed once with 10% sodium hydroxide solution. The methylene chloride solvent was then removed under reduced pressure, and the resulting oil was purified by simple distillation to yield 260 g (28% yield) of IV. Structure IV, 3-heptylbicyclo[3.2.1]oct-6-en-2-one, possesses weak, methyl salicylate like and slightly fruity fragrance notes.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:33]=[C:32]5[C:27]([CH2:28][CH2:29][N:30]([CH3:34])[CH2:31]5)=[CH:26][CH:25]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[F:35][C:36]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:37]=1[C:38](Cl)=[O:39]>C(Cl)Cl>[F:35][C:36]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:37]=1[C:38]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:33]=[C:32]5[C:27]([CH2:28][CH2:29][N:30]([CH3:34])[CH2:31]5)=[CH:26][CH:25]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:3]=1)=[O:39]
Reactant: CN1CCc2ccc(Nc3nccc(-c4c(-c5cccc(N)c5)nn5ccccc45)n3)cc2C1
Reactant: O=C(Cl)c1cc(F)ccc1F
Solvent: ClCCl
Product: CN1CCc2ccc(Nc3nccc(-c4c(-c5cccc(NC(=O)c6cc(F)ccc6F)c5)nn5ccccc45)n3)cc2C1
Reaction time: 16 h
Yield: 51 %

Procedure:
To a solution of N-{4-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-2-methyl-1,2,3,4-tetrahydro-7-isoquinolinamine (96 mg, 0.21 mmol) and TEA (45 μL, 0.32 mmol) in DCM (2 mL) was added 2,5-difluorobenzoyl chloride (28 μL, 0.23 mmol). After 16 h at rt, the reaction mixture was adsorbed onto silica and purified by column chromatography to generate the title compound in 51% yield (63 mg, 0.11 mmol). 1H NMR (400 MHz, d6-DMSO) δ 10.65 (s, 1H), 9.44 (s, 1H), 8.87 (d, J=6.9 Hz, 1H), 8.47 (d, J=9.3 Hz, 1H), 8.26 (d, J=5.7 Hz, 1H), 8.05 (s, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.34-7.55 (m, 8H), 7.13 (t, J=6.9 Hz, 1H), 6.99 (d, J=8.4 Hz, 1H), 6.51 (d, J=5.3 Hz, 1H), 3.41 (s, 2H), 2.76 (t, J=5.7 Hz, 2H), 2.58-2.60 (m, 2H), 2.33 (s, 3H). HRMS=588.23178 (calculated for C34H27F2N7O=587.6313).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([S:18]([N:21]([CH2:23][C:24]([O:26]C(C)(C)C)=[O:25])[CH3:22])(=[O:20])=[O:19])=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.[Li+].[OH-]>CO.C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([S:18]([N:21]([CH2:23][C:24]([OH:26])=[O:25])[CH3:22])(=[O:20])=[O:19])=[CH:14][CH:13]=2)=[CH:4][CH:3]=1
Reactant: CN(CC(=O)OC(C)(C)C)S(=O)(=O)c1ccc(OCC#Cc2ccc(Cl)cc2)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: CN(CC(=O)O)S(=O)(=O)c1ccc(OCC#Cc2ccc(Cl)cc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 89 %

Procedure:
To a solution of tert-butyl [[(4-{[3-(4-chlorophenyl)-2-propynyl]oxy}phenyl)-sulfonyl](methyl)amino]acetate (0.331 g, 0.736 mmol in methanol/THF was added 1.23 mL (3.5 eq) of a 1.0N solution of LiOH and the reaction was stirred at room temp overnight. The solvent was removed in vacuo and the residue was suspended in water, adjusted to pH to 3 with 2N HCl. The resulting solid was rinsed with ether and dried in vacuo to afford 0.27 g (89%) of [[(4-{[3-(4-chlorophenyl)-2-propynyl]oxy}phenyl)sulfonyl](methyl)amino]acetic acid. Electrospray Mass Spec 392.1 (M+H)+