Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4]Br)[CH3:2].[CH:10]1[C:11]([I:19])=[CH:12][C:13]([I:18])=[C:14]([OH:17])[C:15]=1[I:16].C(=O)([O-])[O-].[K+].[K+].IC1C=C(I)C=C(I)C=1OC(CC)C>CN(C=O)C>[CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][O:17][C:14]1[C:15]([I:16])=[CH:10][C:11]([I:19])=[CH:12][C:13]=1[I:18])[CH3:2]
Reactant: CCCCC(CC)CBr
Reactant: Oc1c(I)cc(I)cc1I
Agent: CCC(C)Oc1c(I)cc(I)cc1I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCC(CC)COc1c(I)cc(I)cc1I
Reaction time: 20 h
Yield: 73.7 %

Procedure:
2-Ethyl-bromohexane (10.4 g, 53.0 mmol), triiodophenol (25.5 g, 54.0 mmol) and potassium carbonate (7.5 g, 54.3 mmol) were reacted in dry DMF (110 ml) at 77° C. as for 2-(2,4,6-triiodophenoxy)butane. After stirring for 20 hrs, the reaction was cooled, diluted with DMF, filtered through a pad of celite and evaporated in vacuo. The resulting residue was taken up in EtOAc (500 ml), washed with water (200 ml), 1N aqueous sodium hydroxide (200 ml), water (2×200 ml) and brine (200 ml), dried (Na2SO4), filtered and evaporated. Flash column chromatography (silica, hexanes) provided 2-ethyl-1-(2,4,6-triiodophenoxy)-hexane (22.8 g, 73.7%) as a clear viscous oil. Title Compound: 1H (300 MHz) and 13C (75 MHz) NMR spectra were consistent with the desired structure. Calculated for C14H19I3O: C, 28.79; H, 3.28; I, 65.19. Found: C, 29.13, H, 3.24; I, 65.05.
Reaction SMILES: [CH2:1]([C:25]([OH:27])=[O:26])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]CCC.C(C(O)=O)CCCCCCCCCCCCCCCCCCCCCCCCC.C(C(O)=O)CCCCCCCCCCCCCCCCCCCCCCCCCCC>>[C:25]([OH:27])(=[O:26])[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: CCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: CCCCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)O
Product: CCCCCCCCCCCCCCCCCCCCCC(=O)O

Procedure:
A polymer dispersion of carboxylic acid silver salts - carboxylic acids - silver bromide (Composition H - 5) was produced in the same manner as in Example 1 except that a mixture of 272 g of behenic acid and 82 g of an equimolar mixture of C24H49COOH, C26H53COOH and C28H57COOH was used instead of the mixture of 272 g of behenic acid and 82 g of C26H53COOH.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:40]=[C:41]([F:43])[CH:42]=1)[CH2:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[C:9]2[NH:15][C:16](=[O:39])[C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-])=O)=[CH:19][C:18]=1[N:26]([CH:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1)[C:27](=[O:32])[C:28]([F:31])([F:30])[F:29].C1CCCCC=1>[Pd].O1CCOCC1>[F:43][C:41]1[CH:40]=[C:4]([CH:3]=[C:2]([F:1])[CH:42]=1)[CH2:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[C:9]2[NH:15][C:16](=[O:39])[C:17]1[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][C:18]=1[N:26]([CH:33]1[CH2:34][CH2:35][O:36][CH2:37][CH2:38]1)[C:27](=[O:32])[C:28]([F:31])([F:29])[F:30]
Reactant: O=C(Nc1n[nH]c2ccc(Cc3cc(F)cc(F)c3)cc12)c1ccc([N+](=O)[O-])cc1N(C(=O)C(F)(F)F)C1CCOCC1
Agent: [Pd]
Solvent: C1=CCCCC1
Solvent: C1COCCO1
Product: Nc1ccc(C(=O)Nc2n[nH]c3ccc(Cc4cc(F)cc(F)c4)cc23)c(N(C(=O)C(F)(F)F)C2CCOCC2)c1
Temperature: 100 °C
Reaction time: 4 h
Yield: 74.9 %

Procedure:
A mixture of N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-nitro-2-[tetrahydro-2H-pyran-4-yl(trifluoroacetyl)amino]benzamide (3.86 g, 6.4 mmol), cyclohexene (10 mL), dioxane (70 mL) and 10% Pd/C (0.42 g) was stirred at 100° C. for 4 hours. The reaction mixture was filtered over a celite pad washing thoroughly with THF and MeOH. After evaporation of the organic phase, purification of the crude by chromatography over silica gel (DCM/EtOH 9/1) gave 2.75 g of title compound (82% yield).
Reaction SMILES: [CH2:1]([O:4][CH2:5][C:6]1[C:10]2[N:11]([CH3:27])[CH:12]=[C:13]([C:16]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)=[O:17])[C:14](=[O:15])[C:9]=2[S:8][CH:7]=1)[CH:2]=[CH2:3].[Li+].CC([N-]C(C)C)C.C(NC(C)C)(C)C.Cl.C1C[O:47][CH2:46]C1>C(Cl)Cl.C(Cl)(Cl)Cl.CN(C=O)C>[CH2:1]([O:4][CH2:5][C:6]1[C:10]2[N:11]([CH3:27])[CH:12]=[C:13]([C:16]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)=[O:17])[C:14](=[O:15])[C:9]=2[S:8][C:7]=1[CH:46]=[O:47])[CH:2]=[CH2:3]
Reactant: C=CCOCc1csc2c(=O)c(C(=O)NCc3ccc(Cl)cc3)cn(C)c12
Reactant: C1CCOC1
Agent: CC(C)[N-]C(C)C
Agent: Cl
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: C=CCOCc1c(C=O)sc2c(=O)c(C(=O)NCc3ccc(Cl)cc3)cn(C)c12
Temperature: -78 °C
Reaction time: 0.17 h

Procedure:
To a cold (−78° C.), stirred solution of 922 mg of 3-[(allyloxy)methyl]-N-(4-chlorobenzyl)-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide in 30 mL of dry THF, under argon, is added via cannula a THF solution of LDA, prepared in the usual manner from 1.3 mL of diisopropylamine and 2.7 mL of 2.5 M (hexanes) butyllithium in 20 mL of THF. The solution is stirred at −78° C. for 10 min, then 0.89 mL of dry DMF is added, and the mixture is allowed to warm to 0° C. After 10 min, aqueous workup (CHCl3/dil. HCl) is performed and is followed by flash chromatography on silica using 1.5% MeOH in CH2Cl2 to provide 620 mg of the title compound as a yellow-orange solid. Recrystallization from EtOAc gives yellow crystals.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH:9](OC(=O)C)=[CH2:10].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]=[CH2:10])=[CH:4][CH:3]=1
Reactant: Oc1ccc(Br)cc1
Reactant: C=COC(C)=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: C=COc1ccc(Br)cc1
Temperature: 100 °C
Yield: 73.6 %

Procedure:
To a mixture of 4-bromophenol (75 g, 433.5 mmol), acetic acid ethenyl ester (80.5 mL, 867.0 mmol) and sodium carbonate (27.6 g, 260.10 mmol) in toluene (430 mL) add di-mu-chlorobis((1,2,5,6-eta)-1,5-cyclooctadiene)diiridium (2.9 g, 4.34 mmol) and the heat the mixture at 100° C. for 2.5 hours. Cool the mixture to ambient temperature, dilute with ethyl acetate (EtOAc) (300 mL) and wash once with water (400 mL). Separate the organic portion and wash once with brine (250 mL). Dry the material over sodium sulfate, filter, and concentrate under reduced pressure. Purify the crude mixture by flash chromatography (0% to 5% EtOAc/Hex) to give the title compound (63.5 g, 74%): GCMS: 198.
Reaction SMILES: [C:1]([CH:24]([C:26](=[O:48])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=[CH:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])[OH:25])(=[O:23])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=[CH:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].C(=O)([O-])[O-].[K+].[K+].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.CCOCC>C(Cl)Cl>[C:26]([C:24]([C:1](=[O:23])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=[CH:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[O:25])(=[O:48])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=[CH:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47]
Reactant: CCCCCCCCCC=CC=CC=CC=CC=CC=CC(=O)C(O)C(=O)C=CC=CC=CC=CC=CC=CCCCCCCCCC
Agent: O=[Cr](=O)([O-])Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: ClCCl
Product: CCCCCCCCCC=CC=CC=CC=CC=CC=CC(=O)C(=O)C(=O)C=CC=CC=CC=CC=CC=CCCCCCCCCC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a mixture of didocosahexaenoyl methanol (IV, 1.2 g, 1.9 mmol) and anhydrous potassium carbonate (0.1 g) in 30 mL of CH2Cl2 was added pyridinium chlorochromate (PCC, 1.05 g, 4.8 mmol). The resulting suspension was stirred at room temperature for 2 hours. Ether (120 mL) was then added into the mixture, and the resulting brown suspension was filtered through a pad of silica gel (75 mL). The pad was further washed with ether (3×75 mL). The ether filtrate and washes were combined. Evaporation of the solvent gave 1.3 g of an oily residual as a crude product. The crude product was purified by column chromatography on silica gel (230-400 mesh, 40 mL) eluted with 0-3% ethyl acetate in hexanes. This afforded 0.83 g (69%) of didocosahexaenoyl ketone (V).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.Cl[C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:25][CH3:26])=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][N:14]=1>>[CH3:24][O:23][C:20]1[CH:21]=[C:22]2[C:17](=[CH:18][C:19]=1[O:25][CH3:26])[N:16]=[CH:15][N:14]=[C:13]2[NH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1
Reactant: COc1cc2ncnc(Cl)c2cc1OC
Reactant: Nc1nccc2ccccc12
Product: COc1cc2ncnc(Nc3nccc4ccccc34)c2cc1OC
Yield: 13 %

Procedure:
Using an analogous procedure to that described in Example 9, 1-aminoisoquinoline was reacted with 4-chloro-6,7-dimethoxyquinazoline to give 6,7-dimethoxy-4-(1-isoquinolylamino)quinazoline in 13% yield, m.p. 198°-199° C.;
Reaction SMILES: [NH2:1][C:2]1[C:10]([O:11][C:12]2[CH:17]=[CH:16][C:15]([CH2:18][C:19]([O:21][CH3:22])=[O:20])=[CH:14][C:13]=2[O:23][CH3:24])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30].[Cl:33][C:34]1[CH:39]=[C:38]([Cl:40])[CH:37]=[CH:36][C:35]=1[S:41](Cl)(=[O:43])=[O:42].N1C=CC=CC=1>ClCCl>[Cl:33][C:34]1[CH:39]=[C:38]([Cl:40])[CH:37]=[CH:36][C:35]=1[S:41]([NH:1][C:2]1[C:10]([O:11][C:12]2[CH:17]=[CH:16][C:15]([CH2:18][C:19]([O:21][CH3:22])=[O:20])=[CH:14][C:13]=2[O:23][CH3:24])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])(=[O:43])=[O:42]
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1Cl
Reactant: COC(=O)Cc1ccc(Oc2ccc3c(cnn3COCC[Si](C)(C)C)c2N)c(OC)c1
Solvent: c1ccncc1
Solvent: ClCCl
Product: COC(=O)Cc1ccc(Oc2ccc3c(cnn3COCC[Si](C)(C)C)c2NS(=O)(=O)c2ccc(Cl)cc2Cl)c(OC)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of methyl 2-(4-(4-amino-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yloxy)-3-methoxyphenyl)acetate (42 mg, 0.092 mmol) in dichloromethane (1 mL) was added 2,4-dichlorobenzene sulfonyl chloride (25 mg, 0.1 mmol) and pyridine (10 μl, 0.12 mmol). The resulting mixture was stirred overnight at room temperature. The mixture was then diluted with dichloromethane (20 mL) and washed with dilute aqueous hydrochloric acid (20 mL) and water (20 mL), then dried over magnesium sulfate and concentrated under reduced pressure. The desired sulfonamide was isolated by column chromatography (10% ethyl acetate/hexane). 1H NMR (400 MHz) (CDCl3) δ 8.40 (s, 1H); 7.81 (s, 1H); 7.72 (d, J=8.5 Hz, 1H); 7.32 (d, J=9 Hz, 1H); 7.19 (d, J=1.9 Hz, 1H); 7.15 (dd, J=1.9, 8.5 Hz, 1H); 6.90 (d, J=1.8 Hz, 1H); 6.88 (d, J=9 Hz, 1H); 6.60 (dd, J=1.8, 8.2 Hz, 1H); 6.35 (d, J=8.2 Hz, 1H); 5.68 (s, 2H); 3.84 (s, 3H); 3.75 (s, 3H), 3.62 (s, 2H); 3.57 (t, J=8.2 Hz, 2H); 0.89 (t, J=8.2 Hz, 2H), 0.0 (s, 9H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH:5]=[O:6].[OH:12][CH2:13][C:14]([CH3:18])([CH2:16]O)[CH3:15].O>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]2[O:12][CH2:13][C:14]([CH3:18])([CH3:16])[CH2:15][O:6]2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11]
Reactant: CC(C)(CO)CO
Reactant: COc1ccc(C=O)cc1Br
Solvent: Cc1ccccc1
Solvent: O
Product: COc1ccc(C2OCC(C)(C)CO2)cc1Br

Procedure:
3-Bromo-4-methoxybenzaldehyde (60.0 g, 279 mmol) was dissolved in toluene (600 mL), and after addition of neopentyl glycol (32.0 g, 306 mmol) and Amberlyst-15 (3.6 g) the reaction mixture was heated under reflux for 2 hours on a water separator. After cooling, the reaction mixture was filtered, washed twice with water, and then concentrated under reduced pressure. The oil residue was combined with heptane, and the product which precipitated was filtered off and washed with heptane.
Reaction SMILES: [Na].[NH2:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5](Cl)[C:4]=1[Br:10].Cl.[CH3:12][OH:13]>>[NH2:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([O:13][CH3:12])[C:4]=1[Br:10]
Reactant: CO
Reactant: Nc1ccnc(Cl)c1Br
Agent: Cl
Agent: [Na]
Product: COc1nccc(N)c1Br
Temperature: 0 °C

Procedure:
Methanol (350 mL) was charged in a two-neck round bottom flask equipped with a guard tube and septum and cooled to 0° C. Sodium metal (23 g) was added to it slowly in pieces. After all sodium metal had dissolved, 4-amino-3-bromo-2-chloro pyridine (23 g, 178 mmol) was added and the solution was heated at 180° C. in a pressure vessel for 5-6 h. The reaction mixture was then cooled to 0° C. and adjusted to pH 8 by addition of conc. HCl. Solvent was removed under reduced pressure and the residue was suspended in ethyl acetate. Undissolved impurities were removed by filtration and the filtrate was concentrated under reduced pressure to obtain pure product.
Reaction SMILES: Cl.[NH2:2][C:3]1[N:11]=[CH:10][N:9]=[C:8]2[C:4]=1[N:5]=[CH:6][N:7]2[C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:23]=2)=[O:20])=[CH:14][CH:13]=1.Cl[C:34]([O:36][CH2:37][CH:38]([CH3:40])[CH3:39])=[O:35]>>[CH2:37]([O:36][C:34](=[O:35])[NH:2][C:3]1[N:11]=[CH:10][N:9]=[C:8]2[C:4]=1[N:5]=[CH:6][N:7]2[C:12]1[CH:13]=[CH:14][C:15]([NH:18][C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([C:29]([F:31])([F:32])[F:30])[CH:23]=2)=[O:20])=[CH:16][CH:17]=1)[CH:38]([CH3:40])[CH3:39]
Reactant: CC(C)COC(=O)Cl
Reactant: Nc1ncnc2c1ncn2-c1ccc(NC(=O)Nc2ccc(Cl)c(C(F)(F)F)c2)cc1
Agent: Cl
Product: CC(C)COC(=O)Nc1ncnc2c1ncn2-c1ccc(NC(=O)Nc2ccc(Cl)c(C(F)(F)F)c2)cc1

Procedure:
The title compound can be synthesized from 1-[4-(6-aminopurin-9-yl)phenyl]-3-(4-chloro-3-(trifluoromethyl)phenyl)urea hydrochloride and isobutyl chloroformate by using the same method as in Example 107.
Reaction SMILES: [Si]([O:8][C@@H:9]1[C@@:26]2([CH3:27])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:25]2[CH2:24][CH2:23][C@@:21]2([CH3:22])[C@H:17]3[CH2:18][CH2:19][C@@H:20]2[CH2:28][S:29][CH2:30][CH2:31][C:32]([OH:35])([CH3:34])[CH3:33])[CH2:12][C@@H:11]([O:36][Si](C(C)(C)C)(C)C)[CH2:10]1)(C(C)(C)C)(C)C.O1CCCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[OH:8][C@@H:9]1[C@@:26]2([CH3:27])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:25]2[CH2:24][CH2:23][C@@:21]2([CH3:22])[C@H:17]3[CH2:18][CH2:19][C@@H:20]2[CH2:28][S:29][CH2:30][CH2:31][C:32]([OH:35])([CH3:34])[CH3:33])[CH2:12][C@@H:11]([OH:36])[CH2:10]1
Reactant: CC(C)(O)CCSC[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(O)CCSC[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C
Yield: 83.9 %

Procedure:
To a solution of 1α,3β-bis(tert-butyldimethylsilyloxy)-17β-(3-hydroxy-3-methylbutylthiomethyl)androsta-5,7-diene (130 mg, 0.215 mmol) in tetrahydrofuran (1 ml), was added a 1M tetra-n-butylammonium fluoride tetrahydrofuran solution (2.15 ml, 2.15 mmol), followed by reflux under heating for 5 hours. The reaction mixture was returned to room temperature, diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure to remove the solvent. The thus obtained residue was purified by preparative thin layer chromatography (3 sheets (each 0.5 mm thickness), dichloromethane:ethanol=9:1, developed once) to give the titled compound (75.9 mg, 84%) as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]([C:29]#[N:30])=[C:11]([C:19]2[CH:24]=[CH:23][N:22]=[C:21](S(C)(=O)=O)[N:20]=2)[S:12][C:13]=1[C:14]1[NH:18][CH:17]=[N:16][N:15]=1.O1CCCC1.[CH3:36][NH2:37]>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]([C:29]#[N:30])=[C:11]([C:19]2[CH:24]=[CH:23][N:22]=[C:21]([NH:37][CH3:36])[N:20]=2)[S:12][C:13]=1[C:14]1[NH:18][CH:17]=[N:16][N:15]=1
Reactant: CS(=O)(=O)c1nccc(-c2sc(-c3nnc[nH]3)c(-c3ccc(Cl)cc3Cl)c2C#N)n1
Reactant: CN
Solvent: C1CCOC1
Product: CNc1nccc(-c2sc(-c3nnc[nH]3)c(-c3ccc(Cl)cc3Cl)c2C#N)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 81 %

Procedure:
4-(2,4-dichlorophenyl)-2-[2-(methylsulfonyl)pyrimidin-4-yl]-5-(4H-1,2,4-triazol-3-yl)thiophene-3-carbonitrile (0.047 g, 0.10 mmol) was dissolved in 2.0 M of Methylamine in Tetrahydrofuran (1.74 mL, 0.00349 mol) and the mixture was stirred at room temperature for 1 hour. The solvent was concentrated in vacuo and the residue was purified using ISCO chromatography on silica gel, elution 30% ethyl acetate in hexanes to ethyl acetate to afford the title compound (0.037 g, 81%). LCMS: (FA) ES+, 428, 430. 1H NMR (400 MHz, d4-methanol) δ: 8.07-8.01 (m, 1H), 7.99 (s, 1H), 7.24-7.21 (m, 1H), 7.09-7.02 (m, 2H), 6.97 (d, J=5.04 Hz, 1H), 2.62 (s, 3H).
Reaction SMILES: [CH:1]1([C:7]2[CH:11]=[C:10]([NH2:12])[N:9]([CH3:13])[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:14][O:15][CH2:16][CH2:17][O:18][C:19](=[O:34])[C:20](=[CH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[N+:31]([O-:33])=[O:32])[C:21]([CH3:23])=O>>[CH3:14][O:15][CH2:16][CH2:17][O:18][C:19]([C:20]1[CH:24]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[N+:31]([O-:33])=[O:32])[C:11]2[C:7]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)=[N:8][N:9]([CH3:13])[C:10]=2[NH:12][C:21]=1[CH3:23])=[O:34]
Reactant: Cn1nc(C2CCCCC2)cc1N
Reactant: COCCOC(=O)C(=Cc1ccccc1[N+](=O)[O-])C(C)=O
Product: COCCOC(=O)C1=C(C)Nc2c(c(C3CCCCC3)nn2C)C1c1ccccc1[N+](=O)[O-]

Procedure:
Starting from 3-cyclohexyl-1-methyl-5-pyrazolamine and 2-methoxyethyl-2-(2-nitrobenzyliden)acetoacetate in about equimolar proportions.
Reaction SMILES: C(O[C:4]([C:6]1[C:10]2[CH:11]=[N:12][CH:13]=[CH:14][C:9]=2[NH:8][C:7]=1[NH2:15])=[O:5])C.C([O-])=O.[NH4+].O.[CH:21]([NH2:23])=O>>[N:15]1[C:7]2[NH:8][C:9]3[C:10](=[CH:11][N:12]=[CH:13][CH:14]=3)[C:6]=2[C:4]([OH:5])=[N:23][CH:21]=1
Reactant: NC=O
Reactant: CCOC(=O)c1c(N)[nH]c2ccncc12
Agent: O=C[O-]
Agent: [NH4+]
Solvent: O
Product: Oc1ncnc2[nH]c3ccncc3c12
Temperature: 175 °C

Procedure:
2-Amino-1H-pyrrolo[3,2-c]pyridine-3-carboxylic acid ethyl ester (600 mg, 3 mmol) and ammonium formate (185 mg, 3 mmol) were suspended in 10 mL formamide and heated at 175° C. for 5 hours. Water was added to the cooled reaction mixture and the resulting precipitate collected and dried in vacuo. Unprecipitated product was recovered from the filtrate by using a MP-TsOH SPE cartridge and eluting with 7 N ammonia to give a combined mass of 330 mg of the title compound. LCMS (1): Rt 0.67 min; m/z 188 [M+H]+.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH:2]=[CH2:3].C([O:12][CH2:13][CH2:14][CH2:15][CH3:16])=C>>[CH2:13]([O:12]/[CH:3]=[CH:2]\[CH2:1][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH2:14][CH2:15][CH3:16]
Reactant: C=COCCCC
Reactant: C=CCc1ccccc1
Product: CCCCO/C=C\Cc1ccccc1
Reaction time: 2 h
Yield: 76.1 %

Procedure:
Following the general procedure for enol ether cross metathesis, allyl benzene (50.0 mg, 0.423 mmol, 7) was treated with butyl vinyl ether (424 mg, 4.23 mmol), 2.5 mol % of in situ-generated complex 1a (106 μL, 0.10 M, 10.6 μmol; final substrate concentration=4.0 M), and allowed to stir for 2 h. The unpurified product is 98% Z (as determined by 400 MHz 1H NMR analysis). The resulting brown oil was purified by neutral alumina chromatography (100% hexanes) to afford 8a (61.3 mg, 0.322 mmol, 76.0% yield, >98% Z isomer) as a colorless oil. The physical and spectral data were identical to those previously reported for compound 8a.9 IR (neat): 3028 (w), 2959 (m), 2933 (m), 2872 (m), 1663 (s), 1495 (m), 1453 (m), 1373 (m), 1253 (m), 1108 (s); 1H NMR (400 MHz, CDCl3): δ 7.32-7.16 (5H, m), [diagnostic E isomer signal: 6.37 (1H, dt, J=16.0, 1.2 Hz)], 6.08 (1H, dt, J=6.0, 1.6 Hz), 4.57 (1H, td, J=7.6, 6.2 Hz), 3.79 (2H, t, J=6.4 Hz), 3.45 (2H, d, J=7.6 Hz), 1.69-1.61 (2H, m), 1.49-1.39 (2H, m), 0.97 (3H, t, J=7.6 Hz); 13C NMR (100 MHz, CDCl3): δ 145.7, 142.1, 128.4, 128.4, 125.8, 105.4, 72.2, 32.0, 30.4, 19.2, 14.0; HRMS (ESI+) [M+H]+ calcd for C13H19O: 191.1436, found: 191.1432.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]([N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[CH2:20][NH2:21])=[CH:15][CH:14]=1>>[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]([N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[CH2:20][NH:21][C:4](=[O:6])[C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=2[CH3:1])=[CH:15][CH:14]=1
Reactant: Cc1ccccc1C(=O)O
Reactant: COc1ccc(C(CN)N2CCCCC2)cc1
Product: COc1ccc(C(CNC(=O)c2ccccc2C)N2CCCCC2)cc1

Procedure:
From 2-methylbenzoic acid and 2-(4-methoxy-phenyl)-2-piperidin-1-yl-ethylamine.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[O:20][CH2:19][CH:18]([NH:24][C:25](=O)[CH2:26][CH3:27])[CH2:17]3)(=[O:12])=[O:11])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[O:20][CH2:19][CH:18]([NH:24][CH2:25][CH2:26][CH3:27])[CH2:17]3)(=[O:11])=[O:12])=[CH:8][CH:9]=1)([CH3:3])[CH3:2]
Reactant: CCC(=O)NC1COc2ccc(NS(=O)(=O)c3ccc(C(C)C)cc3)cc2C1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CCCNC1COc2ccc(NS(=O)(=O)c3ccc(C(C)C)cc3)cc2C1
Temperature: 25 °C
Reaction time: 18 h
Yield: 2.1 %

Procedure:
N-[6-(4-Isopropyl-benzenesulfonylamino)-chroman-3-yl]-propionamide (0.48 g, 1.20 mmol) was dissolved in THF (5 mL) and added dropwise to a stirred suspension of LiAlH4 (0.43 g, 11.3 mmol) in THF (5 mL) at 0° C. The resulting mixture was stirred at room temperature for 18 h. The solution was heated to reflux for 3 h, cooled and quenched by addition of water and 2 N HCl. The mixture was extracted with ethyl acetate and the organic phase dried over MgSO4, filtered, and the filtrate was evaporated in vacuo to give the product which was further purified by preparative HPLC (20-90% MeOH) to give a white solid (10 mg, 6%).
Reaction SMILES: [F:1][C:2]1[C:7]([CH:8]=[O:9])=[C:6]([O:10]C)[C:5]([O:12]C)=[CH:4][CH:3]=1.B(Br)(Br)Br.Cl>ClCCl>[F:1][C:2]1[C:7]([CH:8]=[O:9])=[C:6]([OH:10])[C:5]([OH:12])=[CH:4][CH:3]=1
Reactant: COc1ccc(F)c(C=O)c1OC
Agent: BrB(Br)Br
Agent: Cl
Solvent: ClCCl
Product: O=Cc1c(F)ccc(O)c1O
Temperature: 25 °C
Reaction time: 4 h
Yield: 63.4 %

Procedure:
To a cold (−78° C.) solution of 6-fluoro-2,3-dimethoxy-benzaldehyde (4.50 g, 24.43 mmol) in anhydrous dichloromethane (30 mL) was added BBr3 (1M in DCM, 48.8 mL, 48.87 mmol) dropwise (duration 30 min). The reaction was warmed to room temperature and stirred for 4 h. Again cooled it to −78° C. and added 2N HCl (60 mL) to it dropwise. The reaction was stirred for overnight at room temperature and extracted with DCM. Combined organic layers were washed with water, sat. NaHCO3 solution, brine and dried over MgSO4. Filtration and removal of solvent provided 2.42 g (15.50 mmol, 64%) of the title compound as a yellow solid. This was used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.22 (s, 1H), 7.04 (dd, J=8.6, 5.5 Hz, 1H), 6.61 (dd, J=10.4, 8.8 Hz, 1H); 19F NMR (376 MHz, DMSO-d6) δ ppm −131.69-−131.65 (m, 1F).
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3](=O)[CH3:4].[NH2:8][C:9]([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)=[C:10](Br)[C:11]#[N:12]>C(O)(=O)C.O>[Cl:20][C:17]1[CH:16]=[CH:15][C:14]([C:9]2[NH:8][C:3]([C:2]([F:7])([F:6])[F:1])=[CH:4][C:10]=2[C:11]#[N:12])=[CH:19][CH:18]=1
Reactant: CC(=O)C(F)(F)F
Reactant: N#CC(Br)=C(N)c1ccc(Cl)cc1
Solvent: O
Solvent: CC(=O)O
Product: N#Cc1cc(C(F)(F)F)[nH]c1-c1ccc(Cl)cc1
Temperature: 100 °C

Procedure:
A solution of trifluoroacetone (3.36 g, 2.7 mL,0.03 mol) in acetic acid is added dropwise at 100° C. to a solution of β-amino-α-bromo-p-chlorocinnamonitrile, (E)- or (Z)- (5.15 g, 0.02 mol) in acetic acid over 41/2 hours. The reaction mixture is heated at 100° C. overnight, diluted with water and extracted with ethyl acetate. The combined organic extracts are washed with water, dried over anhydrous Na2SO4 and concentrated in vacuo to obtain a gum. The gum is flash chromatographed using silica gel and a 15% ethyl acetate in heptane solution to give the title product as a yellow solid (1.8 g, mp 129°-131° C.) which is identified by 1H and 19FNMR spectral analyses.