Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[CH:3]([CH2:8][N:9]1[CH2:14][CH2:13][CH2:12][CH:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[CH2:10]1)[CH2:4][C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:52][CH2:53][C:54]([C:56]1[CH:61]=[CH:60][C:59]([Cl:62])=[CH:58][CH:57]=1)=[O:55].CCN(C(C)C)C(C)C>C(OCC)(=O)C.CN(C=O)C>[Cl:62][C:59]1[CH:58]=[CH:57][C:56]([C:54](=[O:55])[CH2:53][NH:52][C:5](=[O:7])[CH2:4][CH:3]([CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][CH:11]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=3)[CH2:10]2)[C:2]([F:25])([F:26])[F:1])=[CH:61][CH:60]=1
Reactant: O=C(O)CC(CN1CCCC(c2cccc(C(F)(F)F)c2)C1)C(F)(F)F
Reactant: NCC(=O)c1ccc(Cl)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(CC(CN1CCCC(c2cccc(C(F)(F)F)c2)C1)C(F)(F)F)NCC(=O)c1ccc(Cl)cc1
Reaction time: 0.08 h
Yield: 64.7 %

Procedure:
In a 10 mL pear-shaped flask, 4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanoic acid (40 mg, 104 μmol) and HATU (39.7 mg, 104 μmol) were combined with DMF (1 ml) to give a colorless solution. After 5 min of stirring, 2-amino-1-(4-chlorophenyl)ethanone HCl (21.5 mg, 104 μmol) was added followed by drop-wise addition of DIEA (47.2 mg, 63.8 μl, 365 μmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (30 ml), washed with brine and H2O, dried over MgSO4, filtered and concentrated in vacuo to give an oil. The crude material was purified by flash chromatography (silica gel, 12 g, 0% to 50% ethyl acetate in CH2Cl2) to afford 36 mg (65%) of N-(2-(4-chlorophenyl)-2-oxoethyl)-4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanamide as an oil. MH+=535.
Reaction SMILES: [CH3:1][C:2]([CH3:4])=[O:3].[Br:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[CH:8][CH:7]=1>N1CCC[C@H]1C(O)=O.CN(C=O)C>[OH:11][CH:10]([C:9]1[CH:12]=[CH:13][C:6]([Br:5])=[CH:7][CH:8]=1)[CH2:1][C:2](=[O:3])[CH3:4]
Reactant: CC(C)=O
Reactant: O=Cc1ccc(Br)cc1
Agent: O=C(O)[C@@H]1CCCN1
Solvent: CN(C)C=O
Product: CC(=O)CC(O)c1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 68 h

Procedure:
A stirred solution of catalyst 35 (0.01 g, 0.011 mmol) in dry DMF (0.785 mL) and acetone (0.392 mL, 2.72 mmol) was treated with 4-bromobenzaldehyde (0.0072 g, 0.04 mmol), stirred at room temperature for 68 h and Resin 35 was filtered off. The mixture was treated with Et2O and washed twice with water Et2O phase was dried and concentrated The product was analyzed by the 1H NMR spectroscopy of the crude 1H NMR spectroscopy of the crude showed a 70% conversion by measuring the CHOH peak of the aldol product at 5.12 ppm vs the CHO peak of the p-bromobenzaldehyde at 9.90 ppm 1H NMR (CDCl3, 400 MHz): δ=2.20 (s, 3H), 2.82 (m, 2H), 5.12 (m, 1H), 3.58-3.69 (m, 1H), 4.11-4.17 (m, 1H), 4.29-4.35 (m, 2H), 7.24-47 (m, 4H). Moreover, examination of the aldol product by chiral HPLC using a Chiralpak AS Daicel (i-PrOH/hexane 15/85), UV 280 nm, flow rate 1.0 mL/min, tRminor 8.950 min and tRmajor 10.143 min showed the presence of one single peak at 8.950 min retention time.
Reaction SMILES: O[C:2]1([C:12]2[C:21]([OH:22])=[CH:20][C:15]3[N:16]=[C:17]([CH3:19])[S:18][C:14]=3[CH:13]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][C:3]1=[O:11].I>O.C(OCC)(=O)C>[OH:22][C:21]1[C:12]([CH:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[NH:4][C:3]2=[O:11])=[CH:13][C:14]2[S:18][C:17]([CH3:19])=[N:16][C:15]=2[CH:20]=1
Reactant: Cc1nc2cc(O)c(C3(O)C(=O)Nc4ccccc43)cc2s1
Agent: I
Solvent: O
Solvent: CCOC(C)=O
Product: Cc1nc2cc(O)c(C3C(=O)Nc4ccccc43)cc2s1
Temperature: 25 °C
Yield: 99 %

Procedure:
A mixture of 3-hydroxy-3-(5-hydroxy-2-methyl-1,3-benzothiazol-6-yl)-1,3-dihydro-2H-indol-2-one (4.81 g, 15.4 mmol) and 48% aqueous hydroiodic acid (25 mL) was heated at reflux for 1 h. The reaction mixture was allowed to cool to ambient temperature and was diluted with water (50 mL) and ethyl acetate (50 mL). The mixture was briefly sonicated, causing a precipitate to be deposited. The solid was collected by filtration, washed with water (20 mL) and dried in vacuo to afford 3-(5-hydroxy-2-methyl-1,3-benzothiazol-6-yl)-1,3-dihydro-2H-indol-2-one (4.52 g, 99%) as a pale yellow solid: MS (ES+) m/z 297.2 (M+1).
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[CH2:3][NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[OH-].[Na+].[Cl:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]([C:22](Cl)=[O:23])[CH:17]=1.C(=O)([O-])O.[Na+]>ClCCl.C(O)C>[Cl:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]([C:22]([N:4]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH2:3][C:2]([F:11])([F:12])[F:1])=[O:23])[CH:17]=1
Reactant: FC(F)(F)CNc1ccccc1
Reactant: O=C(Cl)c1cc(Cl)ncn1
Agent: O=C([O-])O
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CCO
Product: O=C(c1cc(Cl)ncn1)N(CC(F)(F)F)c1ccccc1
Reaction time: 2 h

Procedure:
200 mg (1.14 mmol) N-(2,2,2-trifluoroethyl)aniline and 1.14 mL (1.14 mmol) of a 1M sodium hydroxide solution were added dropwise to 212 mg (1.2 mmol) 6-chloropyrimidine-4-carboxylic acid chloride in 20 mL dichloromethane while cooling with a bath of ice and ethanol. The mixture was first stirred for 2 h with cooling and then stirred for 1 h at RT. 50 mL of a saturated sodium hydrogen carbonate solution were added and the mixture was stirred for 10 min. The organic phase was separated off, washed with water and 1M hydrochloric acid, dried on sodium sulphate, filtered and concentrated by rotary evaporation i.vac.
Reaction SMILES: [C:1]([CH2:3][C:4](O)=O)#[N:2].[C:7]([CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)([O:9][CH2:10][CH3:11])=[O:8].C=O.[C:20](=O)=O>O.O1CCOCC1>[C:7]([CH:12]1[CH2:13][CH2:14][N:15]([CH2:20][C:3](=[CH2:4])[C:1]#[N:2])[CH2:16][CH2:17]1)([O:9][CH2:10][CH3:11])=[O:8]
Reactant: O=C=O
Reactant: CCOC(=O)C1CCNCC1
Reactant: N#CCC(=O)O
Agent: C=O
Solvent: O
Solvent: C1COCCO1
Product: C=C(C#N)CN1CCC(C(=O)OCC)CC1
Reaction time: 12 h

Procedure:
Cyanoacetic acid (8.6 g., 0.1 mole) was dissolved in 35 ml. of dioxane. 4-Carboethoxypiperidine (15.7 g., 0.1 mole) was added--a precipitate rapidly formed. When one-half was added 10 ml. of water was then admixed and the temperature controlled below 24° C. until complete addition. With ice bath cooling, 37% aqueous formaldehyde (18 g., 0.2 mole) was dripped in over an 8-minute period and the temperature allowed to rise to 29° C. accompanied by vigorous carbon dioxide evolution. Two phases separated and stirring was continued for an additional 12 hours. After concentration in a bath at 45° C. and under reduced pressure, 22.4 g. of an oil resulted. The product was distilled, b.p., 130°-132° C./0.6 mm., yield, 16.3 g.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])[CH2:12][N:13]1[C:21]2[N:20]=[C:19]([CH:22]([CH3:24])[CH3:23])[NH:18][C:17]=2[C:16](=O)[N:15]=[CH:14]1)C1C=CC=CC=1.P(Cl)(Cl)([Cl:33])=O>>[ClH:33].[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])[CH2:12][N:13]1[C:21]2[C:17]([N:18]=[C:19]([CH:22]([CH3:23])[CH3:24])[N:20]=2)=[C:16]([NH:13][CH2:21][CH3:17])[N:15]=[CH:14]1)[C:9]1[CH:10]=[CH:11][CH:26]=[CH:27][CH:28]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COc1ccc(Cn2cnc(=O)c3[nH]c(C(C)C)nc32)cc1OCc1ccccc1
Product: CCNc1ncn(Cc2ccc(OC)c(OCc3ccccc3)c2)c2nc(C(C)C)nc1-2
Product: Cl

Procedure:
3-(3-Benzyloxy-4-methoxy-benzyl)-8-isopropyl-hypoxanthine (2.02 g, 5 mmole) and phosphorus oxychloride (20 ml) were heated to 70° C. for 35 min. The solution was evaporated to dryness and evaporation repeated twice after the addition of toluene (50 ml). The crude chloropurine residue was dissolved in THF (20 ml) and added at 0-5° C. to 70% aqueous ethylamine (20 ml). After 1 hour at room temperature the solvents were removed in vacuo, the residue was dissolved in dichloromethane (70 ml) and washed with 1M NaOH. The organic phase was filtered through 9 g of silicagel in a column and evaporated to dryness in vacuo. The residue was dissolved in methanol (20 ml), treated with 1M methanolic HCl (4.8 ml) and evaporated to dryness in vacuo to give 3-(3-benzyloxy-4-methoxy-benzyl)-6-ethylamino-8-isopropyl-3H-purine hydrochloride (2.20 g, 94.0%), mp 79-83° C. (after crystallization from water-saturated ether).
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([S:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][NH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[NH:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:32][O:33][C:34]1[CH:39]=[C:38]([O:40][CH3:41])[CH:37]=[CH:36][C:35]=1[N:42]=[C:43]=[O:44]>CCCCCC>[CH3:32][O:33][C:34]1[CH:39]=[C:38]([O:40][CH3:41])[CH:37]=[CH:36][C:35]=1[NH:42][C:43](=[O:44])[N:24]([CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][S:18][C:9]1[NH:8][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[C:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:10]=1)[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]
Reactant: COc1ccc(N=C=O)c(OC)c1
Reactant: CCCCCCCNCCCCCSc1nc(-c2ccccc2)c(-c2ccccc2)[nH]1
Solvent: CCCCCC
Product: CCCCCCCN(CCCCCSc1nc(-c2ccccc2)c(-c2ccccc2)[nH]1)C(=O)Nc1ccc(OC)cc1OC
Yield: 82.4 %

Procedure:
To a solution of N-[5-(4,5-diphenyl-1H-imidazol-2-ylthio)pentyl]-1-heptanamine (0.75 g, 0.0017 mol), prepared according to the procedure of Example 1, Part D, in hexane (40 mL) was added, dropwise, a solution of 2,4-dimethoxyphenylisocyanate (0.358 g, 0.002 mol) in hexane (20 mL) and the reaction mixture was stirred at ambient temperature for 4.5 hours. The reaction mixture was concentrated under vacuum and the residue was chromatographed with 7:3 hexane-ethyl acetate. The resulting solid was triturated with hexane to give the title compound (0.83 g, 0.0014 mol) as a glassy solid. 1H NMR (CDCl3) δ7.7-7.1(m,10H), 6.8-6.1(m,3H), 3.8(s,3H), 3.7(s,3H), 3.45(s,1H), 3.4-3.3(m,2H), 3.2(t,2H,J=7Hz), 3.0(t,2H,J=7Hz), 1.8-1.1(m,16H), 0.9(t,3H,J=8Hz).
Reaction SMILES: O=C1C2C(=CC=CC=2)C(=O)[N:3]1[O:12][CH2:13][C:14]1[N:15]=[CH:16][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH:18]=1.C(Cl)Cl.O.NN>C(O)C>[NH2:3][O:12][CH2:13][C:14]1[N:15]=[CH:16][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH:18]=1
Reactant: CC(C)(C)OC(=O)n1cnc(CON2C(=O)c3ccccc3C2=O)c1
Agent: NN
Solvent: ClCCl
Solvent: O
Solvent: CCO
Product: CC(C)(C)OC(=O)n1cnc(CON)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 50.6 %

Procedure:
To a mixture of tert-butyl 4-{[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)oxy]methyl}-1H-imidazole-1-carboxylate 121 (1.72 g, 5.00 mmol) in a solution of DCM (20 mL) and ethanol (4 mL) was added hydrazine hydrate (0.287 mL, 5.00 mmol) at room temperature. The mixture was stirred at room temperature overnight, filtered and concentrated to provide a residue which was washed with ether and methanol to give 122 (0.54 g, 51%) as a white solid.
Reaction SMILES: [CH:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[C:19]([C:22]([OH:24])=O)[N:20]=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:25]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].CN(C)C=O.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.[C:64]([N:68]1[CH2:73][CH2:72][NH:71][CH2:70][CH2:69]1)([CH3:67])([CH3:66])[CH3:65]>>[C:64]([N:68]1[CH2:73][CH2:72][N:71]([C:22]([C:19]2[N:20]=[CH:21][C:16]3[O:15][CH2:14][CH2:13][N:12]4[CH:25]=[C:9]([C:8]5[N:4]([CH:1]([CH3:3])[CH3:2])[N:5]=[CH:6][N:7]=5)[N:10]=[C:11]4[C:17]=3[CH:18]=2)=[O:24])[CH2:70][CH2:69]1)([CH3:67])([CH3:66])[CH3:65]
Reactant: CC(C)(C)N1CCNCC1
Reactant: CC(C)n1ncnc1-c1cn2c(n1)-c1cc(C(=O)O)ncc1OCC2
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)n1ncnc1-c1cn2c(n1)-c1cc(C(=O)N3CCN(C(C)(C)C)CC3)ncc1OCC2
Reaction time: 0.17 h

Procedure:
[2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepine-10-carboxylic acid (0.140 g, 0.411 mmol) was dissolved in N,N-Dimethylformamide (3.18 mL, 0.0411 mol) at room temperature. N,N-Diisopropylethylamine (0.287 mL, 0.00164 mol) was added followed by N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium Hexafluorophosphate (0.172 g, 0.452 mmol). The suspension was stirred for 10 minutes. 1-tert-butylpiperazine (0.0878 g, 0.617 mmol) was added and the reaction mixture was stirred for 1 hour. LCMS shows complete conversion to product. The reaction mixture was concentrated to dryness and was purified by reversed phase HPLC to give 203. 1H NMR (400 MHz, DMSO) δ 8.42 (s, 1H), 8.39 (s, 1H), 8.14 (s, 1H), 8.09 (s, 1H), 7.94 (s, 1H), 7.94 (s, 1H), 5.76 (dt, J=13.2, 6.6 Hz, 1H), 4.64 (s, 4H), 3.56 (br d, J=48.6 Hz, 8H), 1.49 (d, J=6.6 Hz, 6H), 1.02 (s, 9H). LCMS 465.3.
Reaction SMILES: [OH-].[Li+].C([O:5][C:6]([C:8]1[C:12]([CH2:13][CH2:14][CH2:15][S:16]([CH3:19])(=[O:18])=[O:17])=[C:11]([CH:20]=[O:21])[NH:10][C:9]=1[CH3:22])=[O:7])C.Cl>CO.O>[CH:20]([C:11]1[NH:10][C:9]([CH3:22])=[C:8]([C:6]([OH:7])=[O:5])[C:12]=1[CH2:13][CH2:14][CH2:15][S:16]([CH3:19])(=[O:17])=[O:18])=[O:21]
Reactant: CCOC(=O)c1c(C)[nH]c(C=O)c1CCCS(C)(=O)=O
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: Cc1[nH]c(C=O)c(CCCS(C)(=O)=O)c1C(=O)O
Temperature: 65 °C
Yield: 86.8 %

Procedure:
Lithium hydroxide (179.6 mg, 7.5 mmol) was added to a suspension of 5-formyl 4-(3-methanesulfonyl-propyl)2-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (450 mg, 1.5 mmol) in methanol (6 mL) and water (6 mL). The mixture was heated under nitrogen in a 65° C. oil bath for 20 hours. The cooled reaction was adjusted to pH 2 using 1N HCl, the resulted precipitate was collected by vacuum filtration, washed with water and dried to give 356 mg (87%) of 5-formyl-4-(3-methanesulfonyl-propyl)-2-methyl-1H-pyrrole-3-carboxylic acid.
Reaction SMILES: [CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH:21]=[CH:20][CH:19]=[C:18]3[C:22]#[N:23])=[CH:13][CH:12]=2)[C:8]2[C:24]([C:28]([O:30][CH3:31])=[O:29])=[CH:25][CH:26]=[CH:27][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4].C[Sn]([N:36]=[N+:37]=[N-:38])(C)C>C1(C)C=CC=CC=1>[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([N:17]3[CH:21]=[CH:20][CH:19]=[C:18]3[C:22]3[NH:38][N:37]=[N:36][N:23]=3)=[CH:15][CH:16]=2)[C:8]2[C:24]([C:28]([O:30][CH3:31])=[O:29])=[CH:25][CH:26]=[CH:27][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc2cccc(C(=O)OC)c2n1Cc1ccc(-n2cccc2C#N)cc1
Reactant: C[Sn](C)(C)N=[N+]=[N-]
Solvent: Cc1ccccc1
Product: CCCCc1nc2cccc(C(=O)OC)c2n1Cc1ccc(-n2cccc2-c2nnn[nH]2)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 74.1 %

Procedure:
A solution of methyl 2-butyl-1-[[4-(2-cyano-1-pyrrolyl)phenyl]methyl]benzimidazole-7-carboxylate (2.2 g) and trimethyltin azide (3.3 g) in toluene (35 ml) was heated under reflux for 3 days. After concentration, the residue was dissolved in methanol (40 ml) and 1N hydrochloric acid (20 ml) and the mixture was stirred at room temperature for 15 minutes. The reaction mixture was concentrated to dryness and the residue was extracted with ethyl acetate. The extract was washed with water, dried and evaporated. The residue was purified by column chromatography on silica gel to give crystals which were recrystallized from ethyl acetate to afford colorless crystals (1.8 g, 75%), m.p. 186°-187° C.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][OH:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=[CH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(O)C1C=CC=CC=1>[Co]>[C:1]1([CH2:7][CH2:8][OH:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:12]1([CH3:11])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: C=Cc1ccccc1
Agent: [Co]
Solvent: OCCc1ccccc1
Solvent: OCc1ccccc1
Product: Cc1ccccc1
Yield: 50 %

Procedure:
It has long been desirable to prepare 2-phenylethyl alcohol in a low cost process. This material is a valuable intermediate in the preparation of fragrances and of styrene, a commercial chemical with widely varying uses. In the past, it has been proposed that 2-phenylethyl alcohol be prepared from benzyl alcohol. For example, the reaction has been described by Wender, I. et al., J. Amer. Chem. Soc., 71 (1949), pages 4160-4161 wherein the use of a cobalt catalyst was described. This early work is summarized by Orchin in Advances in Catalysis, Vol. V (1953), pages 393-414. This auther reports that, at 183° C., a 50-60 percent yield of toluene and a 23-35 percent yield of 2-phenylethyl alcohol is obtained. Other workers have experimented with this reaction, particularly Y. B. Kryukov et al., Neftekhimiya, 1970, 10 (1), at page 83. Here, a vapor phase reaction is described over an iron, alumina, vanadium and potassium catalyst at 430° C. and 50 atmospheres pressure. Unfortunately, in this latter reaction extremely low selectivities to the 2-phenylethyl alcohol were obtained.
Reaction SMILES: C1(C([NH:15][S:16]([C:19]2[CH:24]=[CH:23][C:22](CBr)=[CH:21][CH:20]=2)(=[O:18])=[O:17])CC2C=CC=CC=2)C=CC=CC=1>C1COCC1.CN(C=O)C>[C:19]1([S:16]([NH2:15])(=[O:18])=[O:17])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=S(=O)(NC(Cc1ccccc1)c1ccccc1)c1ccc(CBr)cc1
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: NS(=O)(=O)c1ccccc1
Yield: 1 %

Procedure:
N-Ethyl-N-(S)-1-isobutyl-2-ethoxyethyl 3-chloro-4-(3H-2-methylimidazo [4,5-c]pyridylmethyl)benzenesulphonamide and (B) N-ethyl-N-(S)-1-isobutyl-2-ethoxyethyl 3-chloro-4-(1 H-2-methylimidazo [4,5-c]pyridylmethyl)benzenesulphonamide were prepared by the method of Example 17 utilizing N-Ethyl-N-(S)-1-isobutyl-2-ethoxyethyl 3-chloro-4-bromo-methylbenzenesulphonamide in lieu of N-1,2-diphenylethyl 4-bromomethylbenzenesulphonamide and 3:1 THF/DMF as solvent.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10])#[CH:2].[CH2:11]([O:13][C:14](=[O:18])/[CH:15]=[CH:16]\I)[CH3:12]>>[CH2:11]([O:13][C:14](=[O:18])[CH:15]=[CH:16][C:2]#[C:1][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10])[CH3:12]
Reactant: CCOC(=O)/C=C\I
Reactant: C#Cc1ccccc1OC
Product: CCOC(=O)C=CC#Cc1ccccc1OC

Procedure:
The general procedure was used to convert 1-Ethynyl-2-methoxy-benzene and (Z)-ethyl-3-iodoacrylate to the title product. Purification by flash chromatography (20% ethyl acetate in hexane as the eluent) gave the analytically pure product as a light yellow oil (480 mg, 98% yield). 1H NMR (400 MHz, CDCl3) δ 7.52-7.50 (dd, J=7.5, 1.7, 1H), 7.33-7.29 (m, 1H), 6.93-6.89 (dt, J=7.6, 0.9, 1H), 6.88-6.86 (d, J=8.3, 1H), 6.42-6.39 (d, J=11.4, 1H), 6.11-6.08 (d, J=11.4, 1H), 4.28-4.22 (q, J=7.1, 2H), 3.88 (s, 3H), 1.33-1.29 (t, J=7.1, 3H). 13C NMR (100 MHz, CDCl3) δ 164.86, 160.32, 134.25, 130.84, 127.67, 123.10, 120.54, 111.96, 110.73, 97.93, 90.45, 60.32, 55.81, 14.28. Anal. Calcd. for C14H14O3: C, 73.03; H, 6.13; Found C, 73.08; H, 6.19.
Reaction SMILES: [CH2:1]([NH:4][CH2:5][C:6]([O:8]CC)=O)[C:2]#[CH:3].[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]=[C:19]=[S:20])=[C:14]([CH3:21])[CH:13]=1.C(N(CC)CC)C>C(Cl)Cl>[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[C:6](=[O:8])[CH2:5][N:4]([CH2:1][C:2]#[CH:3])[C:19]2=[S:20])=[C:14]([CH3:21])[CH:13]=1
Reactant: Cc1cc(Cl)ccc1N=C=S
Reactant: C#CCNCC(=O)OCC
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C#CCN1CC(=O)N(c2ccc(Cl)cc2C)C1=S
Temperature: 25 °C
Yield: 26.6 %

Procedure:
A mixture of ethyl N-propargylaminoacetate (10.0 g), 4-chloro-2-methylphenylisothiocyanate (12.9 g), triethylamine (7.1 g), and methylene chloride (150 mL) was heated at reflux for 3 hours. The reaction mixture was cooled to ambient temperature, washed with 1 N HCl (100 mL), then with water. The organic layer was dried over anhydrous magnesium sulfate, then evaporated to dryness. The residual oil was triturated with hexane. The solid was collected by filtration. Recrystallization from Hexane-EtOAc afford the title compound (5.2 g) as yellow solid, m.p. 99°-102° C. Anal. Calcd. for. C13H11N2O Cl S: C, 56.01; H, 3.98; N, 10.05. Found: C, 55.61; H, 3.83; N, 10.0. Mass spectrum (EI, M.+) m/z 278.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:18])[CH:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:10][CH3:11])=[CH:4][CH:3]=1.[O:19]1[CH:24]=[CH:23][CH2:22][CH2:21][CH2:20]1.[Cl-].[Cl-].[Ca+2]>ClCCCl>[C:12]1([CH:9]([CH2:10][CH3:11])[C:8]([C:5]2[CH:4]=[CH:3][C:2]([O:1][CH:20]3[CH2:21][CH2:22][CH2:23][CH2:24][O:19]3)=[CH:7][CH:6]=2)=[O:18])[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CCC(C(=O)c1ccc(O)cc1)c1ccccc1
Reactant: C1=COCCC1
Agent: [Ca+2]
Agent: [Cl-]
Solvent: ClCCCl
Product: CCC(C(=O)c1ccc(OC2CCCCO2)cc1)c1ccccc1
Temperature: 30 °C
Reaction time: 1 h
Yield: 92.5 %

Procedure:
A mixture of compound 8 (908 g, 3.78 mol) in 1,2-dichloroethane (6.36 L) stirred at 30° C. was treated with dihydropyran (1590 g, 18.9 mol) in a single portion. The resulting solution was treated with CaCl2 (83.8 g, 0.76 mmol) in a single portion and the reaction warmed at 70° C. for 16 h. The reaction was filtered through celite and the solid washed with 1,2-dichloroethane (2×900 mL). The filtrate was concentrated by distillation to approximately 5 L and heptane added (9 L). The reaction solution was again concentrated by distillation to approximately 7 L and then cooled slowly and held at 5° C. for 1 h. The solids were filtered, washed with heptane (2×1.8 L) and dried in vacuo at 40° C. to afford 1134 g (93%) of 9 as a solid. 1HNMR (400 MHz, DMSO-d6): δ 0.79 (t, J=7.3 Hz, 3H), 1.49-1.83 (m, 8H), 2.03 (h, J=7.0 Hz, 1H), 3.49-3.66 (m, 2H), 4.65 (t, J=7.2 Hz, 1H), 7.02 (d, J=8.4 Hz, 2H), 7.13-7.30 (m, 5H), 7.97 (d, J=8.4 Hz, 2H).
Reaction SMILES: O=[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:13]([NH2:15])=[O:14])[C:5]2[CH:16]=[CH:17][CH:18]=[CH:19][C:4]=2[CH2:3]1.Cl.[CH3:21][O:22][C:23](=[O:28])[CH2:24][CH2:25][CH2:26][NH2:27].B(F)(F)F.CCOCC>C1(C)C(C)=CC=CC=1>[CH3:21][O:22][C:23]([CH2:24][CH2:25][CH2:26][N:27]=[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:13]([NH2:15])=[O:14])[C:5]2[CH:16]=[CH:17][CH:18]=[CH:19][C:4]=2[CH2:3]1)=[O:28]
Reactant: COC(=O)CCCN
Reactant: NC(=O)N1c2ccccc2CC(=O)c2ccccc21
Agent: Cl
Agent: FB(F)F
Solvent: CCOCC
Solvent: Cc1ccccc1C
Product: COC(=O)CCCN=C1Cc2ccccc2N(C(N)=O)c2ccccc21
Temperature: 135 °C

Procedure:
To a suspension of 0.2 g (0.79 mmol) of 10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide and 0.1 g (0.67 mmol) of methyl-4-aminobutyrate hydrochloride in 5 mL of xylene was added 0.07 g (0.49 mmol) of boron trifluoride diethyl etherate. The resulting mixture was heated at 135° C. for seven hours and then allowed to cool to room temperature. The mixture was then filtered and the residue was extracted with toluene. The combined extracts were evaporated under reduced pressure and the residue chromatographed on silica gel using a 4:1 mixture of petroleum ether-ethyl acetate. Chromatographically homogenous fractions were pooled and the solvents were removed under reduced pressure to give the desired product as a yellow oil which crystallised on standing to give yellow crystals which decomposed on heating without melting.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[N:10]=[C:11]([O:19][CH3:20])[C:12]2[CH2:18][NH:17][CH2:16][CH2:15][C:13]=2[N:14]=1.[CH3:21][CH:22]([CH3:30])[C:23](=[O:29])[CH2:24][C:25](OC)=[O:26]>CN(C1C=CN=CC=1)C.C1(C)C=CC=CC=1>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[C:9]1[N:10]=[C:11]([O:19][CH3:20])[C:12]2[CH2:18][N:17]([C:25](=[O:26])[CH2:24][C:23](=[O:29])[CH:22]([CH3:30])[CH3:21])[CH2:16][CH2:15][C:13]=2[N:14]=1
Reactant: COc1nc(-c2c(C)cccc2C)nc2c1CNCC2
Reactant: COC(=O)CC(=O)C(C)C
Agent: CN(C)c1ccncc1
Solvent: Cc1ccccc1
Product: COc1nc(-c2c(C)cccc2C)nc2c1CN(C(=O)CC(=O)C(C)C)CC2
Temperature: 150 °C

Procedure:
A mixture of 2-(2,6-dimethylphenyl)-4-methoxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (4.8 g, 17.82 mmol), methyl 4-methyl-3-oxopentanoate (5.14 g, 35.6 mmol), and DMAP (0.327 g, 2.67 mmol) was dissolved in toluene (70 mL). The mixture was evenly divided into four 20 mL microwave vials. Each vial was heated to 150° C. for 30 min via microwave irradiation. The reaction mixtures were combine and directly concentrated. The resulting residue was purified via silica gel FCC (0-80% EtOAc/heptane) to give 1-(2-(2,6-dimethylphenyl)-4-methoxy-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpentane-1,3-dione. MS (ESI+) m/z 382.3 (M+H)+.