Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.C([Si](C)(C)[O:24][C:25]1[C:26]([CH3:44])=[C:27]([NH:31][C:32](=[O:43])[CH2:33][NH:34][C:35]2[CH:40]=[CH:39][C:38]([F:41])=[C:37]([F:42])[CH:36]=2)[CH:28]=[CH:29][CH:30]=1)(C)(C)C>C1COCC1>[F:42][C:37]1[CH:36]=[C:35]([NH:34][CH2:33][C:32]([NH:31][C:27]2[CH:28]=[CH:29][CH:30]=[C:25]([OH:24])[C:26]=2[CH3:44])=[O:43])[CH:40]=[CH:39][C:38]=1[F:41]
Reactant: Cc1c(NC(=O)CNc2ccc(F)c(F)c2)cccc1O[Si](C)(C)C(C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Cc1c(O)cccc1NC(=O)CNc1ccc(F)c(F)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of tetrabutylammonium fluoride in THF (1M, 4.6 ml) was added to a solution of the product from step (c) (1.71 g) in THF (20 ml). The mixture was stirred at room temperature for 1 hour and evaporated to dryness. The residue was purified by flash chromatography eluting with 3% ethanol (EtOH) in dichloromethane (CH2Cl2) to give the product as a white solid. Yield 0.82 g.
Reaction SMILES: [CH3:1][C:2](OCC)([CH3:12])[CH2:3][C:4]([O:9]CC)(OCC)[CH3:5].[CH3:16][C:17]([CH3:21])=[CH:18][CH2:19]O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[O-]CC.[Na+]>C(O)C>[CH3:12][C:2]([CH2:1][CH2:19][CH:18]=[C:17]([CH3:21])[CH3:16])=[CH:3][C:4](=[O:9])[CH3:5]
Reactant: CC(C)=CCO
Reactant: CCOC(C)(C)CC(C)(OCC)OCC
Agent: CC[O-]
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na+]
Solvent: CCO
Product: CC(=O)C=C(C)CCC=C(C)C
Temperature: 140 °C
Yield: 86 %

Procedure:
A mixture of 100 parts of 4-methyl-2,2,4-triethoxypentane, 40 parts of prenol and 0.08 part of p-toluenesulfonic acid is heated for 6 hours at 140°C, the ethyl alcohol formed being distilled off continuously. On completion of the reaction, the reaction mixture is neutralized with sodium ethoxide and the reaction product is fractionally distilled. There are obtained 45.2 parts of 4,8-dimethyl-3,7-nonadien-2-one, equivalent to a yield of 86% and a conversion of 68% based on prenol.
Reaction SMILES: [CH2:1]([O:8][CH:9]([C:14]1[CH:15]=[C:16]([CH:36]=[CH:37][CH:38]=1)[CH2:17][C:18]1[N:19]=[C:20](O)[C:21]2[C:29]3[C:24](=[CH:25][C:26]([C:30]([O:32][CH3:33])=[O:31])=[CH:27][CH:28]=3)[NH:23][C:22]=2[N:34]=1)[C:10]([F:13])([F:12])[F:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:41])=O>C([O-])(O)=O.[Na+]>[CH2:1]([O:8][CH:9]([C:14]1[CH:15]=[C:16]([CH:36]=[CH:37][CH:38]=1)[CH2:17][C:18]1[N:19]=[C:20]([Cl:41])[C:21]2[C:29]3[C:24](=[CH:25][C:26]([C:30]([O:32][CH3:33])=[O:31])=[CH:27][CH:28]=3)[NH:23][C:22]=2[N:34]=1)[C:10]([F:13])([F:12])[F:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COC(=O)c1ccc2c(c1)[nH]c1nc(Cc3cccc(C(OCc4ccccc4)C(F)(F)F)c3)nc(O)c12
Agent: O=C([O-])O
Agent: [Na+]
Product: COC(=O)c1ccc2c(c1)[nH]c1nc(Cc3cccc(C(OCc4ccccc4)C(F)(F)F)c3)nc(Cl)c12
Temperature: 90 °C
Reaction time: 1 h
Yield: 91.7 %

Procedure:
A mixture of methyl 2-(3-(1-(benzyloxy)-2,2,2-trifluoroethyl)benzyl)-4-hydroxy-9H-pyrimido[4,5-b]indole-7-carboxylate (0.395 g, 0.757 mmol) in phosphorus oxychloride (6 mL, 64.4 mmol) was heated to 90° C. for 2 hours then after cooling, it was concentrated to dryness to give 650 mg as a brown foam which was suspended in sat. NaHCO3 (15 mL) and stirred for 1 hour. The solid was filtered, washed with water (3×2 mL) and dried at 40° C. under high vacuum until constant weight to afford methyl 2-(3-(1-(benzyloxy)-2,2,2-trifluoroethyl)benzyl)-4-chloro-9H-pyrimido[4,5-b]indole-7-carboxylate (375 mg, 92% yield) as a tan solid and used as such in the next step: MS m/z 540.2 (M+H)+; HPLC 92%, RT 2.51 minutes.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:15]=[CH:14][CH:13]=[C:12]3[C:8]=2[CH2:9][C:10](=[O:16])[NH:11]3)[CH2:3][CH2:2]1.[CH3:17][C:18]1[C:22]([C:23]([N:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[O:24])=[CH:21][NH:20][C:19]=1[CH:31]=O>C(O)C>[CH3:17][C:18]1[C:22]([C:23]([N:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[O:24])=[CH:21][NH:20][C:19]=1[CH:31]=[C:9]1[C:8]2[C:12](=[CH:13][CH:14]=[CH:15][C:7]=2[CH:4]2[CH2:3][CH2:2][NH:1][CH2:6][CH2:5]2)[NH:11][C:10]1=[O:16]
Reactant: Cc1c(C(=O)N2CCCCC2)c[nH]c1C=O
Reactant: O=C1Cc2c(cccc2C2CCNCC2)N1
Solvent: CCO
Product: Cc1c(C(=O)N2CCCCC2)c[nH]c1C=C1C(=O)Nc2cccc(C3CCNCC3)c21
Temperature: 25 °C
Reaction time: 96 h
Yield: 31.1 %

Procedure:
A mixture of 4-piperidin-4-yl-1,3-dihydroindol-2-one (86.5 mg, 0.4 mmol) and 3-methyl-4-(piperidine-1-carbonyl)-1H-pyrrole-2-carbaldehyde (88.1 mg, 0.4 mmol) in ethanol (2 mL) was stirred at room temperature for 4 days. The reaction was concentrated and the residue was column chromatographed to give 52 mg (31%) of the title compound as a yellow solid.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][NH2:10])=[C:4]([O:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])[CH:3]=1.[CH2:17]([N:24]1[CH:28]=[C:27]([C:29](O)=[O:30])[CH:26]=[N:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][NH:10][C:29]([C:27]2[CH:26]=[N:25][N:24]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:28]=2)=[O:30])=[C:4]([O:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])[CH:3]=1
Reactant: O=C(O)c1cnn(Cc2ccccc2)c1
Reactant: COC(=O)COc1cc(N)nc(C)c1CN
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COC(=O)COc1cc(N)nc(C)c1CNC(=O)c1cnn(Cc2ccccc2)c1
Temperature: 25 °C

Procedure:
Methyl 2-(6-amino-3-(aminomethyl)-2-methylpyridin-4-yloxy)acetate (271 mg, 0.909 mmol), 1-benzyl-1H-pyrazole-4-carboxylic acid (synthesis description below) (184 mg, 0.909 mmol) and DIPEA (0.794 ml, 4.54 mmol) were dissolved in DMF (2 ml), then HATU (518 mg, 1.363 mmol) was added and the reaction mixture was stirred over night at rt. Purification by prep HPLC (Sun-Fire C18, 100×30mm 5 to 100% ACN and 0.1% TFA, flow 40 mml/min.) offered the titled compound after lyophilisation. HPLC (Method C) Rtc=2.789 min, MS (Method D): [M+H]+=410.0.
Reaction SMILES: [C:1]1(=[O:5])[CH2:4][CH2:3][CH2:2]1.[CH2:6]([Mg]Cl)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.O1CCC[CH2:16]1>>[CH2:6]([C:1]1([OH:5])[CH2:4][CH2:3][CH2:2][CH2:16]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: O=C1CCC1
Reactant: C1CCOC1
Reactant: Cl[Mg]Cc1ccccc1
Product: OC1(Cc2ccccc2)CCCC1
Temperature: 25 °C
Reaction time: 17 h
Yield: 53 %

Procedure:
To 2.85 g (33.88 mmol) of cyclobutanone in 170 mL of tetrahydrofuran at 0° C. was added 25.41 mL (50.82 mmol) of a 2 M solution of benzyl magnesium chloride in tetrahydrofuran and the mixture was allowed to warm to RT and stirred for 17 h. The reaction was quenched with ice, then acidified with 1 N hydrochloric acid. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride. The organic layer was dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography eluting with an ethyl acetate:hexanes solution (1:6) to give 3.14 g (53%) of 1-benzylcyclopentanol. 1H NMR (300 MHz, DMSO-d6) δ 7.27-7.19 (m, 5H), 4.19 (s, 1H), 2.78 (s, 2H), 1.69 (br m, 2H), 1.51 (br m, 6H); ES-LCMS m/z 176 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=[C:5]([CH3:13])[C:4]=1[CH:14]([C:16]1[C:17]([Cl:30])=[N:18][C:19]([Cl:29])=[C:20]([CH:26]([OH:28])[CH3:27])[C:21]=1[C:22]([F:25])([F:24])[F:23])[OH:15]>[O-2].[O-2].[Mn+4].C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=[C:5]([CH3:13])[C:4]=1[C:14]([C:16]1[C:21]([C:22]([F:25])([F:24])[F:23])=[C:20]([C:26](=[O:28])[CH3:27])[C:19]([Cl:29])=[N:18][C:17]=1[Cl:30])=[O:15]
Reactant: COc1cc(C)c(C(O)c2c(Cl)nc(Cl)c(C(C)O)c2C(F)(F)F)c(OC)c1OC
Agent: [Mn+4]
Agent: [O-2]
Solvent: Cc1ccccc1
Product: COc1cc(C)c(C(=O)c2c(Cl)nc(Cl)c(C(C)=O)c2C(F)(F)F)c(OC)c1OC
Temperature: 25 °C
Yield: 64.3 %

Procedure:
10 g of manganese dioxide was added to a toluene (80 ml) solution of 2.3 g (5 mmol) of (2,3,4-trimethoxy-6-methylphenyl)(2,6-dichloro-5-(1-hydroxyethyl)-4-trifluoromethyl-3-pyridyl)methanol obtained in step (a), followed by stirring under reflux by heating for 1 hour. The reaction solution was cooled to room temperature and then subjected to filtration, and toluene was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 1.5 g (yield 66%) of 5-(2,3,4-trimethoxy-6-methylbenzoyl)-3-acetyl-2,6-dichloro-4-trifluoromethylpyridine (compound No. 62; m.p. 109-112° C.).
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.Cl.[NH2:28][C:29]1[S:30][C:31]([Cl:34])=[CH:32][N:33]=1.C(N(CC)CC)C>CN(C)C=O.C(Cl)Cl>[Cl:34][C:31]1[S:30][C:29]([NH:28][C:8](=[O:10])[CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[N:33][CH:32]=1
Reactant: Nc1ncc(Cl)s1
Reactant: CS(=O)(=O)c1ccc(C(CC2CCCC2)C(=O)O)cc1
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)c1ccc(C(CC2CCCC2)C(=O)Nc2ncc(Cl)s2)cc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 25.4 %

Procedure:
A solution of 3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-propionic acid (300 mg, 1.01 mmol) and dry N,N-dimethylformamide (2 drops) in methylene chloride (3 mL) was cooled to 0° C. and then treated dropwise with oxalyl chloride (115 μL, 1.32 mmol). The reaction mixture was stirred at 0° C. for 10 min and then stirred at 25° C. for 1 h. The reaction mixture was concentrated in vacuo. The resulting yellow oil was dissolved in a small amount of methylene chloride and then slowly added to a solution of 2-amino-5-chlorothiazole hydrochloride (259 mg, 1.52 mmol) and triethylamine (424 μL, 3.04 mmol) in N,N-dimethylformamide (3 mL). The resulting reaction mixture was then stirred at 25° C. for 15 h. The reaction mixture was then partitioned between water (50 mL) and ethyl acetate (50 mL), and the layers were separated. The aqueous layer was back-extracted with ethyl acetate (50 mL). The combined organic layers were then dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1/1 hexanes/ethyl acetate) afforded the N-(5-chloro-thiazol-2-yl)-3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-propionamide (106 mg, 25%) as a tan foam: mp 76–79° C. (foam to gel); EI-HRMS m/e calcd for C18H21ClN2O3S2 (M+) 412.0682, found 412.0683.
Reaction SMILES: [CH:1]1[C:6]([Cl:7])=[CH:5][C:4]2[NH:8][CH:9]=[C:10]([CH2:11][CH:12]([NH2:16])[C:13]([OH:15])=[O:14])[C:3]=2[CH:2]=1.[CH:17](OC(=O)C)=[O:18]>>[CH:17]([NH:16][C@H:12]([C:13]([OH:15])=[O:14])[CH2:11][C:10]1[C:3]2[C:4](=[CH:5][C:6]([Cl:7])=[CH:1][CH:2]=2)[NH:8][CH:9]=1)=[O:18]
Reactant: NC(Cc1c[nH]c2cc(Cl)ccc12)C(=O)O
Reactant: CC(=O)OC=O
Product: O=CN[C@@H](Cc1c[nH]c2cc(Cl)ccc12)C(=O)O

Procedure:
15 g(628 mM) of dl-6-chlorotryptophan was treated with 15 ml of acetic-formic anhydride. An exothermic reaction ensued, accompanied by solidification of the reaction slurry. Excess solvents were distilled off under vacuum and the resultant solids, after first leaching with dilute acid, were recrystallized from ethyl acetate to yield 12.45 g, 74%, of product, m.p. 181°-3° dec.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]#[C:9][CH:10]=[C:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[N:3]=1.[CH:17](=O)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)Cl>O>[CH2:17]([N:14]1[CH2:13][CH2:12][C:11](=[CH:10][C:9]#[C:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[N:3]=2)[CH2:16][CH2:15]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=Cc1ccccc1
Reactant: Cc1cccc(C#CC=C2CCNCC2)n1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: Cc1cccc(C#CC=C2CCN(Cc3ccccc3)CC2)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of the compound of Example 3 (0.22 g, 1.04 mmol), benzaldehyde (0.13 mL, 1.25 mmol), sodium triacetoxyborohydride (0.33 g, 1.56 mmol) and 15 mL of CH2Cl2 was stirred overnight at r.t. Afterwards, it was diluted with water, the organic layer was separated, washed with brine (2×15 mL), dried (Na2SO4) and evaporated to dryness in vacuo the give a crude, which was purified by automated flash liquid chromatography (Horizon™-Biotage) eluting with a gradient Petroleum Ether-EtOAc from 85:15 to 0:100 affording the title compound, which was further purified by preparative RP LC-MS chromatography, using MS-C18 XTerra column 30×50 mm eluting with ammonium bicarbonate 20 mM pH 8 buffer-acetonitrile gradient (0.12 g).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C@H:11]2[CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:9])=[CH:4][CH:3]=1.Br.Br[CH2:23][C:24]1[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=1>>[N:26]1[CH:27]=[CH:28][CH:29]=[C:24]([CH2:23][O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]([N:10]3[CH2:14][CH2:13][CH2:12][C@H:11]3[CH2:15][N:16]3[CH2:17][CH2:18][CH2:19][CH2:20]3)=[O:9])=[CH:4][CH:3]=2)[CH:25]=1
Reactant: BrCc1cccnc1
Reactant: O=C(c1ccc(O)cc1)N1CCC[C@H]1CN1CCCC1
Agent: Br
Product: O=C(c1ccc(OCc2cccnc2)cc1)N1CCC[C@H]1CN1CCCC1

Procedure:
The title compound is prepared in a manner substantially analogous to Procedure B using (4-Hydroxy-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone and 3-(bromomethyl)pyridine hydrobromide. MS (ES+) 366.2
Reaction SMILES: [C:1]1([CH2:7][CH2:8][C:9]([OH:11])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:12]([C:15]1[C:21]([OH:22])=[CH:20][CH:19]=[CH:18][C:16]=1[OH:17])[CH2:13][CH3:14]>OS(C(F)(F)F)(=O)=O>[OH:17][C:16]1[CH:18]=[CH:19][C:20]([C:9](=[O:11])[CH2:8][CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[C:21]([OH:22])[C:15]=1[CH2:12][CH2:13][CH3:14]
Reactant: O=C(O)CCc1ccccc1
Reactant: CCCc1c(O)cccc1O
Agent: O=S(=O)(O)C(F)(F)F
Product: CCCc1c(O)ccc(C(=O)CCc2ccccc2)c1O

Procedure:
Using the procedure in Example 51, step 1, 3-phenylpropionic acid and 2-(n-propyl)resorcinol were condensed in triflic acid to form 1,3-dihydroxy-4-(3-phenylpropionyl)-2-(n-propyl)benzene.
Reaction SMILES: [CH2:1]1[CH2:14][O:13][C:8]23[O:9][CH2:10][CH2:11][O:12][C:3]2([C@:4]2([CH2:27][CH2:26][C@H:25]4[C@@H:15]([C:16](=[O:28])[CH:17]=[C:18]5[C@:23]4([CH3:24])[CH2:22][CH2:21][CH2:20][CH2:19]5)[C@@H:6]2[CH2:7]3)[CH3:5])[O:2]1.C(O[C@H]1CC[C@@]2(C)C(CC(=O)[C@@H]3[C@@H]2CC[C@@]2(C)[C@H]3CCC2=O)C1)(=O)C>CCOC(C)=O>[CH2:11]1[CH2:10][O:9][C:8]23[O:13][CH2:14][CH2:1][O:2][C:3]2([C@:4]2([CH2:27][CH2:26][C@H:25]4[C@@H:15]([C:16](=[O:28])[CH2:17][CH:18]5[C@:23]4([CH3:24])[CH2:22][CH2:21][CH2:20][CH2:19]5)[C@@H:6]2[CH2:7]3)[CH3:5])[O:12]1
Reactant: C[C@]12CCCCC1=CC(=O)[C@@H]1[C@@H]2CC[C@@]2(C)[C@H]1CC13OCCOC12OCCO3
Agent: CC(=O)O[C@H]1CC[C@@]2(C)C(CC(=O)[C@@H]3[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]32)C1
Solvent: CCOC(C)=O
Product: C[C@]12CCCCC1CC(=O)[C@@H]1[C@@H]2CC[C@@]2(C)[C@H]1CC13OCCOC12OCCO3
Yield: 82 %

Procedure:
17,17-Bis(ethylendioxy)androstane-7-one was prepared in 82% yield from 3,3:17,17-bis(ethylendioxy)-5-androsten-7-one by the procedure described above for the preparation of 3β-acetoxyandrostane-7,17-dione (Prepn. 41) using EtOAc instead of EtOH. The crude product was purified by flash chromatography (SiO2, n-hexane/EtOAc 6/4). 1H-NMR (300 MHz, acetone-d6, ppm from TMS: δ 3.96-3.75 (m, 8H), 2.54-1.10 (m, 20H), 1.13 (s, 3H), 0.83 (s, 3H).
Reaction SMILES: [CH2:1]([OH:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[C:20](O)(=[O:23])[CH:21]=[CH2:22].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C=CC(O)=CC=1)O>O.C1(C)C(C)=CC=CC=1>[C:20]([O:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])(=[O:23])[CH:21]=[CH2:22]
Reactant: CCCCCCCC/C=C\CCCCCCCCO
Reactant: C=CC(=O)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Oc1ccc(O)cc1
Solvent: Cc1ccccc1C
Solvent: O
Product: C=CC(=O)OCCCCCCCC/C=C\CCCCCCCC
Yield: 80 %

Procedure:
To a 500 ml round bottom flask equipped with a stirrer, condenser, water trap and thermometer, was added oleyl alcohol (100 g, 0.373 moles), acrylic acid (27 g, 0.373) moles), p-toluenesulfonic acid monohydrate (1g, 1 wt%, hydroquinone (0.2 g, 0.2 wt%) and xylene (I00 ml). The reaction mixture was heated to reflux and maintained until no more water was collected (~4 hrs). The xylene solution was then concentrated to about half of its original volume. The crude product was then washed successively with water, saturated sodium bicarbonate solution, and then again with water. The organic solution was dried over sodium sulfate, filtered and the solvent evaporated under reduced pressure. The product was stabilized by 0.01 wt% of MEHQ. The yield was 80%.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[Cl:5][CH2:6][C:7](Cl)=[O:8].[C:10]1([CH:17]=[CH:16][CH:15]=[C:13]([OH:14])[CH:12]=1)[OH:11].Cl>[N+](C1C=CC=CC=1)([O-])=O.O.C(Cl)(Cl)Cl>[Cl:5][CH2:6][C:7]([C:15]1[CH:16]=[CH:17][C:10]([OH:11])=[CH:12][C:13]=1[OH:14])=[O:8]
Reactant: Oc1cccc(O)c1
Reactant: O=C(Cl)CCl
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: O=[N+]([O-])c1ccccc1
Solvent: ClC(Cl)Cl
Product: O=C(CCl)c1ccc(O)cc1O
Temperature: 0 °C
Reaction time: 16 h
Yield: 64 %

Procedure:
A mixture of 4.91 g (51.84 mmol) of chloroacetic acid, 4 mL (54.84 mmol) of thionyl chloride and one drop of DMF was stirred at 90° C. for 3 hours. The resulting solution was cooled and evaporated to remove excess thionyl chloride, hydrogen chloride and sulfur dioxide to yield crude chloroacetyl chloride as a colorless oil, pure enough to use in the next step without further purification. To a stirred suspension of 8.01 g (60.07 mmol) of anhydrous aluminum chloride in 10 mL of nitrobenzene were added 2 mL of chloroacetyl chloride and 2.37 g (21.52 mmol) of resorcinol at 0° C. The mixture was stirred at 0° C. for 10 minutes and at room temperature for 16 hours, poured into ice (ca. 20 mL), hydrolyzed by conc. HCl (10 mL), diluted with water (20 mL) and chloroform (50 mL) and separated. The organic layer was dried over MgSO4, evaporated and purified by column chromatography (75 g of SiO2, 20% ethyl acetate-hexane) to yield 2.57 g (13.77 mmol, 64.0% yield) of 4-(2-chloroacetyl)resorcinol. A mixture of 167.2 mg (0.896 mmol) of 4-(2-chloroacetyl)resorcinol and 109.0 mg (0.990 mmol) of resorcinol in methanesulfonic acid (0.5 mL) was stirred at 85° C. for 1 hour. To the resulting deep red solution, ice (ca. 10 mL) was added to precipitate a product as a black gummy material which eventually became reddish brown fine powder after scratching with a spatula. The precipitate was collected by filtration, washed with water and dried over P2O5 under vacuum to yield 196.6 mg (0.754 mmol, 84% yield) of 9-chloromethylxanthene as a reddish brown solid. 1H NMR (D2O+K2CO3) δ 7.66 (1H, d, J=9 Hz). 6.60 (1H, dd, J=9 & 2 Hz), 6.30 (1H, d, J=2 Hz), 4.82 (2H, s); MS (ES, positive) 261.4, 263.4; UV (KMOPS, pH 7.2) λmax (ε) 515 nm (41,200 M−1cm−1).
Reaction SMILES: C(C1C=C(NC(=O)CCCC2C=CC([B:25]([OH:27])[OH:26])=CC=2)C=CC=1S(CC)(=O)=O)#N.[C:29]([C:31]1[CH:32]=[C:33]([NH:42][C:43](=[O:54])[O:44][CH2:45][CH2:46][C:47]2[CH:52]=[CH:51][C:50](Br)=[CH:49][CH:48]=2)[CH:34]=[CH:35][C:36]=1[S:37]([CH2:40][CH3:41])(=[O:39])=[O:38])#[N:30]>>[C:29]([C:31]1[CH:32]=[C:33]([NH:42][C:43]([O:44][CH2:45][CH2:46][C:47]2[CH:52]=[CH:51][C:50]([B:25]([OH:27])[OH:26])=[CH:49][CH:48]=2)=[O:54])[CH:34]=[CH:35][C:36]=1[S:37]([CH2:40][CH3:41])(=[O:39])=[O:38])#[N:30]
Reactant: CCS(=O)(=O)c1ccc(NC(=O)CCCc2ccc(B(O)O)cc2)cc1C#N
Reactant: CCS(=O)(=O)c1ccc(NC(=O)OCCc2ccc(Br)cc2)cc1C#N
Product: CCS(=O)(=O)c1ccc(NC(=O)OCCc2ccc(B(O)O)cc2)cc1C#N
Yield: 82 %

Procedure:
Using a procedure analogous to that used to prepare 6D, 26A (600 mg, 2.54 mmol) was reacted with 5,5′,5′-tetramethyl-[2,2′]bi[[1,3,2]dioxaborinanyl] to give 26B (455 mg, 82%) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm 1.24 (t, J=7.47 Hz, 3 H) 3.01 (t, J=6.81 Hz, 2 H) 3.35 (q, J=7.32 Hz, 2 H) 4.42 (t, J=6.59 Hz, 2 H) 7.29 (d, J=7.91 Hz, 2 H) 7.56 (d, J=7.91 Hz, 2 H) 7.86 (dd, J=9.01, 1.98 Hz, 1 H) 7.99 (d, J=8.79 Hz, 1 H) 8.11 (d, J=2.20 Hz, 1 H) 10.12 (s, 1 H).
Reaction SMILES: [CH:1]([NH2:3])=[O:2].Br[CH:5]([C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=1)[C:6](=O)[CH3:7].C(=O)(O)[O-].[Na+]>ClCCl>[C:13]([C:12]1[CH:15]=[CH:16][C:9]([C:5]2[O:2][CH:1]=[N:3][C:6]=2[CH3:7])=[CH:10][CH:11]=1)#[N:14]
Reactant: CC(=O)C(Br)c1ccc(C#N)cc1
Reactant: NC=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: Cc1ncoc1-c1ccc(C#N)cc1
Yield: 63.9 %

Procedure:
A stirred, two-phase mixture of formamide (0.6 ml, 15 mmol) and 4-(1-bromo-2-oxopropyl)benzonitrile (0.8 g, 3.4 mmol) was heated to 120° for 2 hours. After cooling, dichloromethane (15 ml) and saturated aqueous sodium bicarbonate (10 ml) were added, the organic phase was separated, dried (magnesium sulphate) and the solvent removed under reduced pressure to yield 0.4 g of an amorphous yellow solid. The product was purified by silica gel chromatography, eluting with dichloromethane to yield the title compound (0.29 g, 47%) as a pale yellow solid, m.p. 120°-121° C.
Reaction SMILES: [F:1][C:2]([F:15])([O:6][C:7]1[CH:8]=[C:9]([CH:12]=[CH:13][CH:14]=1)[CH:10]=[O:11])[CH:3]([F:5])[F:4].[C-:16]#[N:17].[K+].OS([O-])=O.[Na+]>C(OCC)(=O)C.O>[OH:11][CH:10]([C:9]1[CH:12]=[CH:13][CH:14]=[C:7]([O:6][C:2]([F:15])([F:1])[CH:3]([F:4])[F:5])[CH:8]=1)[C:16]#[N:17]
Reactant: [C-]#N
Reactant: O=Cc1cccc(OC(F)(F)C(F)F)c1
Agent: O=S([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: N#CC(O)c1cccc(OC(F)(F)C(F)F)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 3-(1,1,2,2-tetrafluoroethoxy)benzaldehyde (222 mg, 1.0 mmol) in ethyl acetate (5 mL) was added a solution of KCN (195 mg, 3.0 mmol) and NaHSO3 (312 mg, 3.0 mmol) dissolved in H2O (10 mL). The reaction was stirred at rt for 8 h. Another portion of KCN (195 mg, 3.0 mmol) and NaHSO3 (312 mg, 3.0 mmol) dissolved in H2O (10 mL) was added. It was left stirring overnight before it was extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried and concentrated to give 130A as an oil. It was used for next step without purification. 1H NMR (400 MHz, CDCl3) δ ppm 5.57 (s, 1H) 5.78-6.04 (m, 1H) 7.28 (d, J=6.15 Hz, 1H) 7.39 (s, 1H) 7.43-7.52 (m, 2H). 19F NMR (376 MHz, CDCl3) δ ppm −136.72, −88.04.
Reaction SMILES: O.[C@@H]1([N:11]2[C:21]3[N:20]=[C:18]([NH2:19])[NH:17][C:15](=[O:16])[C:14]=3[N:13]=[CH:12]2)O[C@H](CO)[C@@H](O)[C@H]1O.[C:22]([C:24]1[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=1[CH2:26]Br)#[N:23].Cl>CS(C)=O>[NH2:19][C:18]1[NH:17][C:15](=[O:16])[C:14]2[N:13]([CH2:26][C:25]3[CH:28]=[CH:29][CH:30]=[CH:31][C:24]=3[C:22]#[N:23])[CH:12]=[N:11][C:21]=2[N:20]=1
Reactant: N#Cc1ccccc1CBr
Reactant: Nc1nc2c(ncn2[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)[nH]1
Agent: Cl
Solvent: O
Solvent: CS(C)=O
Product: N#Cc1ccccc1Cn1cnc2nc(N)[nH]c(=O)c21

Procedure:
Prepared by reacting 20.00 g of guanosine-hydrate with 22.54 g of 2-cyano-benzylbromide in dimethylsulphoxide at 60° C. and subsequent treatment with 57 ml of conc. hydrochloric acid.