Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1(S([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[C:11]2[C:19]([C:26]2[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([CH3:33])[CH:27]=2)=[CH:20][CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)(=O)=O)C=CC=CC=1.[OH-].[Na+]>C(O)C.O1CCCC1.C(OCC)(=O)C>[CH:21]1([CH:20]=[C:19]([C:11]2[NH:10][C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=2)[C:26]2[CH:27]=[C:28]([CH3:33])[CH:29]=[C:30]([CH3:32])[CH:31]=2)[CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: Cc1cc(C)cc(C(=CC2CCCC2)c2cc3cccnc3n2S(=O)(=O)c2ccccc2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: C1CCOC1
Product: Cc1cc(C)cc(C(=CC2CCCC2)c2cc3cccnc3[nH]2)c1
Yield: 101.6 %

Procedure:
A mixture of 1-benzenesulfonyl-2-[2-cyclopentyl-1-(3,5-dimethyl-phenyl)-vinyl]-1H-pyrrolo[2,3-b]pyridine (130 mg, 0.28 mmol) in ethanol (3 mL), tetrahydrofuran (3 mL), and aqueous sodium hydroxide solution (10%, 1 mL) was heated at reflux for 24 h. The mixture was diluted with ethyl acetate (100 mL), washed with water, dried over anhydrous sodium sulfate and then concentrated in vacuo to afford 2-[2-cyclopentyl-1-(3,5-dimethyl-phenyl)-vinyl]-1H-pyrrolo[2,3-b]pyridine (90 mg, 99%) as a white solid: LC/MS m/e calcd for C22H24N2 [M+H]+ 317.45, observed 317.2.
Reaction SMILES: [CH3:1][C:2]1[CH:9]=[C:8]([C:10]2[CH:14]=[CH:13][NH:12][N:11]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Br[CH2:16][C@H:17]([N:19]1[C:27](=[O:28])[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]1=[O:29])[CH3:18]>>[O:29]=[C:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:27](=[O:28])[N:19]1[C@H:17]([CH3:18])[CH2:16][N:12]1[CH:13]=[CH:14][C:10]([C:8]2[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([CH3:1])[CH:9]=2)=[N:11]1
Reactant: C[C@H](CBr)N1C(=O)c2ccccc2C1=O
Reactant: Cc1cc(-c2cc[nH]n2)ccc1C#N
Product: Cc1cc(-c2ccn(C[C@@H](C)N3C(=O)c4ccccc4C3=O)n2)ccc1C#N
Yield: 16.7 %

Procedure:
2-Methyl-4-(1H-pyrazol-3-yl)benzonitrile (2.23 g, 12.2 mmol) was reacted with (R)-2-(1-bromopropan-2-yl)isoindoline-1,3-dione (3.92 g, 14.6 mmol) using the method of Example 27(a). Crude product was purified by chromatography (CombiFlash, silica column, eluent: 0-100% EtOAc/heptane) to yield 0.753 g (17%) of the title compound. Product was used in the next step without analysis.
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([O:13][CH3:14])[CH:6]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH:22]([CH3:27])[CH2:23][CH2:24][C:25]#[N:26].O>CN(C)C=O>[CH3:1][N:2]([CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([O:13][CH3:14])[CH:6]=1)[CH2:27][CH2:22][CH2:23][CH2:24][CH2:25][NH2:26]
Reactant: CC(Br)CCC#N
Reactant: CNCCc1ccc(OC)c(OC)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc(CCN(C)CCCCCN)cc1OC
Yield: 55 %

Procedure:
2.5 g of N-methyl-(2-(3,4-dimethoxyphenyl)ethyl)amine was dissolved in 25 ml of N,N-dimethylformamide, followed by the addition of 1.95 g of anhydrous potassium carbonate and 1.65 ml of 4-bromovaleronitrile. The obtained mixture was reacted at a room temperature for 16 hours, followed by the addition of water. The obtained mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and a saturated aqueous solution of common salt, dried over anhydrous potassium carbonate and distilled to remove the solvent. 40 ml of ethanol, 3.2 ml of concentrated hydrochloric acid and 0.3 g of platinum oxide were added to the obtained residue to carry out hydrogenation at a room temperature under 3 kg/cm2 for 6 hours. The catalyst was filtered out and the filtrate was concentrated under a reduced pressure, followed by the addition of concentrated aqueous ammonia. The obtained mixture was extracted with chloroform. The chloroform phase was dried over anhydrous potassium carbonate and distilled to remove the solvent. The residue was purified by silica gel column chromatography [solvent: dichloromethane/methanol/concentrated aqueous ammonia (100:10:1)] to obtain 1.95 g of the title compound as a yellow oil (yield: 55%).
Reaction SMILES: [CH2:1]([NH:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:36](Cl)(=[O:39])[CH:37]=[CH2:38]>CN(C=O)C>[CH2:1]([NH:8][C:9]([N:11]1[CH2:12][CH2:13][N:14]([S:17]([C:20]2[CH:21]=[CH:22][C:23]([NH:26][C:36](=[O:39])[CH:37]=[CH2:38])=[CH:24][CH:25]=2)(=[O:19])=[O:18])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C=CC(=O)Cl
Reactant: Nc1ccc(S(=O)(=O)N2CCN(C(=O)NCc3ccccc3)CC2)cc1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: C=CC(=O)Nc1ccc(S(=O)(=O)N2CCN(C(=O)NCc3ccccc3)CC2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 10.1 %

Procedure:
4-(4-Amino-benzenesulfonyl)-piperazine-1-carboxylic acid benzylamide (0.47 g, 1.25 mmol) was dissolved in DMF (10 ml). To this was added diisopropylethylamine (0.33 ml, 1.9 mmol) in one portion followed by the drop wise addition of acryloyl chloride (0.12 ml, 1.5 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The THF was removed under vacuum and the resulting crude material was purified by column chromatography (elution: 50% heptane, 50% ethyl acetate to 100% ethyl acetate) to give the title compound (54 mg, 10% yield) as a white solid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([OH:14])[CH:9]=2)=[C:4]([CH3:15])[CH:3]=1.Br[CH2:17][C:18]1[CH:19]=[C:20]([C:28]([O:30]C)=O)[C:21](=[CH:26][CH:27]=1)[C:22]([O:24]C)=O.[C:32](=[O:35])([O-])[O-].[K+].[K+]>>[OH:30][CH2:28][C:20]1[CH:19]=[C:18]([CH:27]=[CH:26][C:21]=1[CH2:22][OH:24])[CH2:17][O:14][C:10]1[CH:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([CH:32]([OH:35])[C:4]([CH3:15])([CH3:5])[CH3:3])=[CH:3][C:4]=2[CH3:15])[CH:13]=[CH:12][CH:11]=1
Reactant: Cc1cc(Br)ccc1-c1cccc(O)c1
Reactant: O=C([O-])[O-]
Reactant: COC(=O)c1ccc(CBr)cc1C(=O)OC
Agent: [K+]
Product: Cc1cc(C(O)C(C)(C)C)ccc1-c1cccc(OCc2ccc(CO)c(CO)c2)c1

Procedure:
In a manner similar to that of Example 1(i), by reaction of 11.8 g (44.8 mmol) of 4′-bromo-2′-methylbiphenyl-3-ol with 14.2 g (49 mmol) of dimethyl 4-bromomethylphthalate and 6.5 g (47 mmol) of potassium carbonate, the desired product is obtained in the form of a yellow oil (m=16.4 g; Y=78%).
Reaction SMILES: [CH2:1]([Si:3]([CH2:17][CH3:18])([CH2:15][CH3:16])[O:4][C@@H:5]1[C@H:8]([C:9]2[O:10][CH:11]=[CH:12][CH:13]=2)[NH:7][C:6]1=[O:14])[CH3:2].C(N(C(C)C)CC)(C)C.[CH:28]([O:31][C:32](Cl)=[O:33])([CH3:30])[CH3:29]>ClCCl.CN(C1C=CN=CC=1)C>[CH2:17]([Si:3]([CH2:15][CH3:16])([CH2:1][CH3:2])[O:4][C@@H:5]1[C@H:8]([C:9]2[O:10][CH:11]=[CH:12][CH:13]=2)[N:7]([C:32]([O:31][CH:28]([CH3:30])[CH3:29])=[O:33])[C:6]1=[O:14])[CH3:18]
Reactant: CC[Si](CC)(CC)O[C@H]1C(=O)N[C@H]1c1ccco1
Reactant: CC(C)OC(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC[Si](CC)(CC)O[C@H]1C(=O)N(C(=O)OC(C)C)[C@H]1c1ccco1
Reaction time: 1 h
Yield: 96.1 %

Procedure:
(3R, 4R)-3-Triethylsilyloxy-4-(2-furyl)azetidin-2-one (0.51 g, 1.91 mmol) in 25 mL of dichloromethane was stirred with diisopropylethyl amine (0.78 mL, 4.4 mmol) and i-propylchloroformate (4.0 mL, 1.0M in toluene, 4.0 mmol) in addition to a catalytic amount of DMAP. The solution was stirred for 1 h and diluted with dichloromethane and washed with brine, dried over MgSO4 and concentrated. The residue was chromatographed over silica gel (eluted with 5:1 hexane/ethyl acetate) to give 649 mg of the title product (Y: 96%); IR(KBr) 1822, 1812, 1716, 1374, 1314, 1186, 1018, 1004, 746 cm−1 ; 1H-NMR (CDCl3, 300 MHz) δ 7.39 (m, 1H), 6.35 (m, 2H), 5.08 (ABq, J=15.6, 5.6 Hz, 2H), 4.96 (d, J=10.0 Hz, 1H), 1.25 (d, J=6.3 Hz, 3H), 1.17 (d, J=6.3 Hz, 3H)), 0.83 (t, J=7.8, 9H), 0.50 (m, 6H); 13C-NMR (CDCl3, 75.5 Hz) δ 165.5, 148.6, 147.8, 142.9, 110.5, 109.9, 77.6, 71.1, 55.9, 21.7, 21.6, 6.3, 4.4; DCIMS M+H calcd for C17H28NO5Si: 354, Found: 354.
Reaction SMILES: [Cl:1][C:2]1[C:10]([OH:11])=[CH:9][C:8]([C:12]2[N:13]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([CH2:21][N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:16][CH:15]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:35].C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[N:43]1[CH:48]=[CH:47][CH:46]=[C:45]([CH2:49]Cl)[CH:44]=1.O>C(#N)C>[Cl:1][C:2]1[C:10]([O:11][CH2:49][C:45]2[CH:44]=[N:43][CH:48]=[CH:47][CH:46]=2)=[CH:9][C:8]([C:12]2[N:13]([C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([CH2:21][N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:16][CH:15]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:35]
Reactant: ClCc1cccnc1
Reactant: CC(C)(C)OC(=O)n1c(-c2cc(O)c(Cl)c3c2C(=O)NC3)cc2cc(CN3CCCCC3)ccc21
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CC#N
Product: CC(C)(C)OC(=O)n1c(-c2cc(OCc3cccnc3)c(Cl)c3c2C(=O)NC3)cc2cc(CN3CCCCC3)ccc21
Temperature: 50 °C
Reaction time: 12 h
Yield: 60 %

Procedure:
4-Chloro-5-hydroxy-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone (70.0 mg, 0.141 mmol) was suspended in acetonitrile (3.5 mL), and the suspension was added with cesium carbonate (91.9 mg, 0.282 mmol) and 3-pyridylmethyl chloride hydrochloride (23.1 mg, 0.141 mmol), followed by stirring at 50° C. for 12 hours under nitrogen atmosphere. The reaction mixture was added with water. The obtained solid was collected by filtration and washed with water, followed by drying under reduced pressure to obtain 4-chloro-5-(3-pyridylmethoxy)-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone (49.7 mg, yield 60%).
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6]2.[Na].C(C1C=CC(S)=C(C)C=1)(C)(C)C.O.Cl>CCOC(C)=O>[OH:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6]2
Reactant: COc1ccc2c(c1)CCC2=O
Agent: Cc1cc(C(C)(C)C)ccc1S
Agent: Cl
Agent: [Na]
Solvent: O
Solvent: CCOC(C)=O
Product: O=C1CCc2cc(O)ccc21
Temperature: 25 °C
Yield: 45.8 %

Procedure:
5-Methoxy-indan-1-one (8 g, 49.3 mmol), and 4-tert-butyl-2-methyl-benzenethiol sodium salt (11.92 g, 59.2 mmol) were heated at 142° C. for 1 hr under argon. After cooling to RT, water (80 ml) was added followed by 1N HCl (80 ml) and EtOAc (120 ml). The mixture was shaken and the aqueous phase extracted with EtOAc (100 ml), the combined organic extracts were washed with satd.NaCl solution (100 ml) and dried with Na2SO4, filtered and evaporated. The residue was chomatographed over SiO2 (Merck 230-400 mesh) eluting with EtOAc-nHexane (2:3), producing 5-hydroxy-indan-1-one (3.55g, 22.6 mmol, 45.9 %) as orange crystals Mp. 185-187° C., MS m/e=148.2 (M+).
Reaction SMILES: Br[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[N:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[Cl:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[N:20][CH:21]=1>>[Cl:15][C:16]1[CH:17]=[C:18]([C:2]2[N:7]=[N:6][C:5]([NH2:8])=[N:4][C:3]=2[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:19]=[N:20][CH:21]=1
Reactant: Nc1nnc(Br)c(-c2ccccc2)n1
Reactant: OB(O)c1cncc(Cl)c1
Product: Nc1nnc(-c2cncc(Cl)c2)c(-c2ccccc2)n1
Yield: 10.4 %

Procedure:
6-(5-Chloropyridin-3-yl)-5-phenyl-1,2,4-triazin-3-amine (35 mg, 10%) was prepared from 6-bromo-5-phenyl-1,2,4-triazin-3-amine (0.30 g, 1.19 mmol) and 5-chloropyridine-3-ylboronic acid (0.20 g, 1.30 mmol) according to the general procedure of Example 1.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:10])[C:7]=1[CH2:8]O.ClC1C=C(OC)C=C(F)C=1C[N:15]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[S:18](=[O:26])(=[O:25])[N:17]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[C:29]([O:35][CH3:36])[CH:28]=2)[C:16]1=[O:37]>>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:10])[C:7]=1[CH2:8][N:15]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[S:18](=[O:26])(=[O:25])[N:17]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[C:29]([O:35][CH3:36])[CH:28]=2)[C:16]1=[O:37]
Reactant: COc1cc(F)c(CN2C(=O)N(c3ccc(OC)c(OC)c3)S(=O)(=O)c3ccccc32)c(Cl)c1
Reactant: OCc1c(Cl)cncc1Cl
Product: COc1ccc(N2C(=O)N(Cc3c(Cl)cncc3Cl)c3ccccc3S2(=O)=O)cc1OC

Procedure:
The title compound (217 mg, 0.44 mmol) was prepared from (IntA1) (167 mg, 0.50 mmol), and 3,5-dichloro-4-hydroxymethylpyridine (133 mg, 0.75 mmol) using the methods of (113).
Reaction SMILES: C(N)(=O)CC.[CH2:6]1[O:14][C:13]2[CH:12]=[CH:11][C:10]([NH:15][C:16](=O)[CH:17]([N:19]3[CH2:24][CH2:23][N:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=4)[CH2:21][CH2:20]3)[CH3:18])=[CH:9][C:8]=2[O:7]1>C1COCC1>[N:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[N:22]1[CH2:23][CH2:24][N:19]([CH:17]([CH3:18])[CH2:16][NH:15][C:10]2[CH:11]=[CH:12][C:13]3[O:14][CH2:6][O:7][C:8]=3[CH:9]=2)[CH2:20][CH2:21]1
Reactant: CC(C(=O)Nc1ccc2c(c1)OCO2)N1CCN(c2ccccn2)CC1
Agent: CCC(N)=O
Solvent: C1CCOC1
Product: CC(CNc1ccc2c(c1)OCO2)N1CCN(c2ccccn2)CC1

Procedure:
The propionamide prepared according to part (b) is finally reduced with AlLiH4 in THF by the conventional method. The crude reaction product in the form of a dense oil is purified by column chromatography, (petroleum ether-ethyl acetate-triethylamine, 80:10:10), thus obtaining the desired product (22). The melting point is 91°-92° C.; Rf 0.19 (petroleum ether-ethyl acetate Et3N 8:1:1), IR (nujol) νmax: 3340, 3310, 1595, 1500, 1480, 1440, 1315, 1250, 1235, 1210, 1170, 1050, 930, 780 cm-1. 1H-NMR (CDCl3): 1.03 (d, J=5 Hz; 3H); 2.20-3.13 (m; 7H); 3.30-3.63 (m; 4H); 4.13 (s broadened; 1H); 5.77 (s, 2H); 5.97 (doublet d, J1 =8 Hz, J2 =2 Hz; 1H); 6.20 (d, J=2 Hz; 1H); 6.33-6.70 (m; 3H); 7.13-7.55 (m; 1H); 8.00-8.20 (m; 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]([Br:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:12][NH:13][C:14]([CH:16]1[CH2:20][CH2:19][O:18][CH2:17]1)=O.O=S(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1>[Br:11][C:9]1[CH:10]=[C:2]2[C:3]([C:4](=[O:6])[N:13]([CH3:12])[C:14]([CH:16]3[CH2:20][CH2:19][O:18][CH2:17]3)=[N:1]2)=[CH:7][CH:8]=1
Reactant: Nc1cc(Br)ccc1C(=O)O
Reactant: CNC(=O)C1CCOC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O=S(Cl)Cl
Product: Cn1c(C2CCOC2)nc2cc(Br)ccc2c1=O
Temperature: 80 °C
Reaction time: 5 h

Procedure:
The mixture of 2-amino-4-bromobenzoic acid (349 mg, 1.62 mmol), N-methyltetrahydrofuran-3-carboxamide (190 mg, 1.47 mmol), SOCl2 (0.13 mL, 1.76 mmol) and toluene (10 mL) was stirred at 80° C. for 5 h, and Na2CO3 aqueous solution was added after the mixture was cooled to room temperature. The water layer was extracted with ethyl acetate (3×10 mL) and the combined organic layers were dried over Na2SO4, filtered, and evaporated to give the desired product, which was directly used for the next step. MS (ESI): 309, 311 (MH+).
Reaction SMILES: [OH:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[C:7]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([N:24]5[CH2:32][C:31]6[C:26](=[CH:27][C:28]([CH3:33])=[CH:29][CH:30]=6)[C:25]5=[O:34])[C:19]=4[CH3:35])=[CH:8][CH:9]=[C:10]([C:15]([NH2:17])=[O:16])[C:11]=3[NH:12]2)=[CH:4][CH:3]=1.[C:36](=O)([O-])[O-].[K+].[K+].CC1C=CC(S(O[CH2:53][CH:54]2[O:58][C:57]([CH3:60])(C)[CH2:56][O:55]2)(=O)=O)=CC=1>CN(C=O)C.O>[CH3:36][C:54]1([CH3:53])[O:58][CH:57]([CH2:60][O:1][C:2]2[CH:14]=[C:13]3[C:5]([C:6]4[C:7]([C:18]5[CH:23]=[CH:22][CH:21]=[C:20]([N:24]6[CH2:32][C:31]7[C:26](=[CH:27][C:28]([CH3:33])=[CH:29][CH:30]=7)[C:25]6=[O:34])[C:19]=5[CH3:35])=[CH:8][CH:9]=[C:10]([C:15]([NH2:17])=[O:16])[C:11]=4[NH:12]3)=[CH:4][CH:3]=2)[CH2:56][O:55]1
Reactant: O=C([O-])[O-]
Reactant: Cc1ccc(S(=O)(=O)OCC2OCC(C)(C)O2)cc1
Reactant: Cc1ccc2c(c1)C(=O)N(c1cccc(-c3ccc(C(N)=O)c4[nH]c5cc(O)ccc5c34)c1C)C2
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc2c(c1)C(=O)N(c1cccc(-c3ccc(C(N)=O)c4[nH]c5cc(OCC6COC(C)(C)O6)ccc5c34)c1C)C2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 48.3 %

Procedure:
A mixture of 7-hydroxy-4-(2-methyl-3-(6-methyl-1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 40-2, 50 mg, 0.108 mmol) and potassium carbonate (30 mg, 0.217 mmol) in DMF (1.7 mL) was stirred at rt for 30 min, then was treated with racemic (4,4-dimethyl-1,3-dioxolan-2-yl)methyl 4-methylbenzenesulfonate (46.5 mg, 0.163 mmol). The resulting mixture was heated at 80° C. overnight. The mixture was cooled to rt, diluted with water and extracted with EtOAc. The organic phase was washed with brine, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 50:50 to 80:20 EtOAc-hexane) to provide racemic 7-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-4-(2-methyl-3-(6-methyl-1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide as a light yellow solid (30 mg, 48%). Mass spectrum m/z 576.1 (M+H)+.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH:13]1([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:17][CH2:16][CH2:15][CH2:14]1.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1COCC1>[CH2:21]([O:20][C:18]([C:13]1([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:19])[CH3:22]
Reactant: CCOC(=O)C1CCCC1
Reactant: BrCc1ccccc1
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CCOC(=O)C1(Cc2ccccc2)CCCC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 49.2 %

Procedure:
A solution of diisopropylamine (1.0 mL, 7.7 mmol) in 20 mL of dry THF was cooled to −78° C. in a dry ice-acetone bath under argon. n-Butyl lithium in hexanes (2.5 M, 3.6 mL, 7.7 mmol) was added all at once and the mixture was stirred for 0.5 hour and transferred to a precooled (−30° C.) solution of 1.0 g (7.0 mmol) of ethyl cyclopentane carboxylate in 10 mL of THF. After a further 45 min, benzyl bromide (0.92 mL, 7.7 mmol) was added and the mixture was allowed to warm to room temperature over night. The resulting mixture was concentrated, and the residue was taken up in 70 mL of ether, washed with water, 1 N HCl, water, saturated brine and was dried (MgSO4). The residue obtained after filtration and evaporation was purified by flash chromatography over 100 g of silica gel, eluting with 3% ethyl acetate-hexane to give 1-benzylcyclopentane carboxylic acid ethyl ester (0.80 g, 45%) as a colorless oil.
Reaction SMILES: [CH2:1](O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[H-].[Na+].C1(C)C(C)=CC=CC=1.Cl[C:27]1[S:31][C:30]([C:32]([OH:34])=[O:33])=[CH:29][CH:28]=1.C(O)(=[O:37])C>>[CH3:1][CH2:2][CH2:3][CH2:4][CH:5]([O:37][C:30]1([C:32]([OH:34])=[O:33])[CH2:29][CH:28]=[CH:27][S:31]1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: O=C(O)c1ccc(Cl)s1
Reactant: CC(=O)O
Reactant: CCCCCCCCCCCCCCO
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1C
Product: CCCCCCCCCC(CCCC)OC1(C(=O)O)CC=CS1
Reaction time: 2 h

Procedure:
A mixture of 214 g (1.0 mole) of 1-tetradecanol, 59 g (1.46 mole) of sodium hydride (59.5% in oil) and 3 l. of dried xylene is heated to reflux with stirring for two hours, then allowed to cool after which 75 g (0.46 mole) of 5-chloro-2-thiophene carboxylic acid is added. The mixture is refluxed for 64 hours after which it is cooled and poured into a waterice mixture, acidified with acetic acid and extracted with the addition of ether. The ether is evaporated, and the xylene layer extracted five times with water:strong ammonia solution (1:1). The combined aqueous extract is acidified with acetic acid. The solid obtained is crystallized twice from hexane to give 2-(5-tetradecyloxy)thiophene carboxylic acid, M.P. 95°-96° C.
Reaction SMILES: [CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([CH2:31][CH:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[C:14](=O)[CH2:15][CH2:16][C:17]([C:19]3[CH:24]=[CH:23][C:22]([CH:25]4[O:29]CCO4)=[CH:21][N:20]=3)=O)=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.C([O-])(=O)C.[NH4+:42]>C(O)(=O)C.C(OCC)(=O)C>[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([C:14]3[NH:42][C:17]([C:19]4[N:20]=[CH:21][C:22]([CH:25]=[O:29])=[CH:23][CH:24]=4)=[CH:16][CH:15]=3)[CH2:31][CH:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:2][CH2:3]1
Reactant: O=C(CCC(=O)C(CC1CCOCC1)c1ccc(S(=O)(=O)C2CC2)cc1)c1ccc(C2OCCO2)cn1
Reactant: [NH4+]
Agent: CC(=O)[O-]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: O=Cc1ccc(-c2ccc(C(CC3CCOCC3)c3ccc(S(=O)(=O)C4CC4)cc3)[nH]2)nc1
Temperature: 110 °C
Reaction time: 0.75 h
Yield: 83.1 %

Procedure:
To a solution of 5-[4-(cyclopropylsulfonyl)phenyl]-1-[5-(1,3-dioxolan-2-yl)pyridin-2-yl]-6-(tetrahydro-2H-pyran-4-yl)hexane-1,4-dione (4.40 g) in acetic acid (35 mL) was added ammonium acetate (10.3 g), and the mixture was stirred at 110° C. for 45 min. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and washed with water. The ethyl acetate layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (3.22 g, yield 83%) was obtained as a yellow amorphous solid from a fraction eluted with ethyl acetate-hexane (2:1, volume ratio). MS: 465 (MH+).
Reaction SMILES: [C:1](O)(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/C=C\CCCCCC.[C:19]([OH:38])(=O)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]/[CH:27]=[CH:28]\[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]C.C=C>>[CH2:23]1[CH2:22][CH2:21][CH2:20][C:19](=[O:38])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH:28]=[CH:27][CH2:26][CH2:25][CH2:24]1.[CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCC/C=C\CCCCCCCC(=O)O
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: C=C
Agent: O=C1CCCCCCC/C=C\CCCCCCC1
Product: C=CCCCCCC
Product: O=C1CCCCCCCC=CCCCCCCC1

Procedure:
In another embodiment, fatty acid esters of palmitoleic acid and oleic acid are reacted with ethene to produce a reaction mixture; and subsequently reacting at least a portion of this reaction mixture (or a derivative thereof) in a condensation reaction; and then conducting a second metathesis reaction, followed by hydrolysis and decarboxylation to produce civetone and 1-Octene (C8H16).
Reaction SMILES: [C:1]([CH2:4][C:5]1[CH:6]=[C:7]([CH3:19])[C:8]([C:11]2[CH:16]=[CH:15][N+:14]([O-:17])=[C:13]([CH3:18])[CH:12]=2)=[N:9][CH:10]=1)([OH:3])=O.[N:20]1[CH:25]=[CH:24][N:23]=[CH:22][C:21]=1[C:26]1[CH:27]=[CH:28][C:29]([NH2:32])=[N:30][CH:31]=1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.CN(C=O)C>[CH3:18][C:13]1[CH:12]=[C:11]([C:8]2[C:7]([CH3:19])=[CH:6][C:5]([CH2:4][C:1](=[O:3])[NH:32][C:29]3[CH:28]=[CH:27][C:26]([C:21]4[CH:22]=[N:23][CH:24]=[CH:25][N:20]=4)=[CH:31][N:30]=3)=[CH:10][N:9]=2)[CH:16]=[CH:15][N+:14]=1[O-:17]
Reactant: Nc1ccc(-c2cnccn2)cn1
Reactant: Cc1cc(CC(=O)O)cnc1-c1cc[n+]([O-])c(C)c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: CN(C)C=O
Product: Cc1cc(CC(=O)Nc2ccc(-c3cnccn3)cn2)cnc1-c1cc[n+]([O-])c(C)c1
Temperature: 25 °C
Reaction time: 10 h

Procedure:
A mixture of 4-(5-(carboxymethyl)-3-methylpyridin-2-yl)-2-methylpyridine 1-oxide 156-6 from Step 4 (0.41 mmol), 5-(pyrazin-2-yl)pyridin-2-amine 86-3 (141 mg, 0.82 mmol), 1,3-dicyclohexylcarbodiimide (188 mg, 0.90 mmol) and 4-(dimethylamino)pyridine (16 mg, 0.16 mmol) in DMF (2 mL) was stirred at room temperature for 10 hours. The crude product was filtered to remove the insoluble and the filtrate was purified by reverse phase HPLC to give 2-methyl-4-(3-methyl-5-(2-oxo-2-(5-(pyrazin-2-yl)pyridin-2-ylamino)ethyl)pyridin-2-yl)pyridine 1-oxide 156 as white solid. MS m/z 413.2 (M+1); 1H NMR 400 MHz (DMSO-d6) δ 11.12 (s, 1H), 9.31 (d, 1H), 9.11 (d, 1H), 8.72 (m, 1H), 8.62 (d, 1H), 8.52 (dd, 1H), 8.48 (d, 1H), 8.31 (d, 1H), 8.21 (d, 1H), 7.73 (m, 2H), 7.52 (dd, 1H), 3.86 (s, 2H), 2.41 (s, 3H), 2.40 (s, 3H).