Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:4][C:5]1[CH:32]=[CH:31][C:8]([C:9]([C:11]2[CH:30]=[CH:29][C:14]([CH2:15][S:16][C:17]3[N:18]([CH3:28])[C:19](=[O:27])[C:20]4[C:25]([CH3:26])=[CH:24][S:23][C:21]=4[N:22]=3)=[CH:13][CH:12]=2)=[O:10])=[CH:7][CH:6]=1)(=O)C.[OH-].[Na+].O>O1CCCC1>[CH3:28][N:18]1[C:19](=[O:27])[C:20]2[C:25]([CH3:26])=[CH:24][S:23][C:21]=2[N:22]=[C:17]1[S:16][CH2:15][C:14]1[CH:13]=[CH:12][C:11]([C:9](=[O:10])[C:8]2[CH:7]=[CH:6][C:5]([OH:4])=[CH:32][CH:31]=2)=[CH:30][CH:29]=1
Reactant: CC(=O)Oc1ccc(C(=O)c2ccc(CSc3nc4scc(C)c4c(=O)n3C)cc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: Cc1csc2nc(SCc3ccc(C(=O)c4ccc(O)cc4)cc3)n(C)c(=O)c12
Yield: 60.9 %

Procedure:
A solution of 2-[4-(4-acetoxybenzoyl)benzylthio]-3,5-dimethylthieno [2,3-d]pyrimidin-4(3H)-one (1.40 g) and 1N-sodium hydroxide/water (6.7 ml) in tetrahydrofuran (20 ml) was stirred at room temperature for 10 minutes. This reaction mixture was concentrated and the residue was dissolved in water and acidified with 1N-HCl. The resulting precipitate was extracted with ethyl acetate, washed with water, dried, and concentrated. The residue was recrystallized from methanol-ethyl acetate to provide the title compound as colorless solid (775 mg).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([CH2:8][F:9])[CH:5]=[C:4]([F:10])[CH:3]=1.C([Li])CCC.CN([CH:19]=[O:20])C>C1COCC1>[F:10][C:4]1[CH:3]=[C:2]([CH:7]=[C:6]([CH2:8][F:9])[CH:5]=1)[CH:19]=[O:20]
Reactant: CN(C)C=O
Reactant: FCc1cc(F)cc(Br)c1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: O=Cc1cc(F)cc(CF)c1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
1-bromo-3-fluoro-5-(fluoromethyl)benzene (1.30 g, 6.28 mmol) was dissolved in THF (31.4 mL), then cooling down to −78° C., butyllithium (2.5M in Hexanes) (2.76 mL, 6.91 mmol) was added at −78° C., the reaction mixture was then stirred at −78° C. for 30 min. DMF (0.972 mL, 12.56 mmol) was added, after stirred at −78° C. for 1h, The reaction mixture was quenched by HCl and the reaction mixture was then extracted by EtOAc, the organic was dried and concentrated to yield the crude product. The crude material was used in next step reaction without purification. LCMS (m/z): no mass (MH+), 0.60 min. 1H NMR (400 MHz, CDCl3) δ ppm 10.08-9.93 (m, 1H), 7.68 (s, 1H), 7.56 (d, J=8.2 Hz, 1H), 7.37 (d, J=7.8 Hz, 1H), 5.53 (s, 1H), 5.42 (s, 1H)
Reaction SMILES: N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[Cl:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:29][CH3:30])=[C:25]([OH:28])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[N:31]1([CH2:37][CH2:38]O)[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Cl:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:29][CH3:30])=[C:25]([O:28][CH2:38][CH2:37][N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:26]=2)[N:21]=[CH:20][N:19]=1
Reactant: OCCN1CCOCC1
Reactant: COc1cc2ncnc(Cl)c2cc1O
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COc1cc2ncnc(Cl)c2cc1OCCN1CCOCC1
Reaction time: 2 h
Yield: 75.9 %

Procedure:
Di-tert-butyl azodicarboxylate (1.44 g, 6.26 mmol) was added portionwise at room temperature to a stirred suspension of 4-chloro-7-methoxyquinazolin-6-ol (1.20 g, 5.70 mmol), 2-morpholin-4-ylethanol (0.82 g, 6.26 mmol) and triphenylphosphine (1.8 g, 6.87 mmol) in dichloromethane (25 ml). The reaction mixture was stirred for 2 hour and then the resulting orange solution was purified directly by silica gel chromatography eluting with a mixture of 3% methanol in dichloromethane and then purified further by chromatography on neutral alumina eluting with a 3% mixture of methanol in dichloromethane to give 4-chloro-7-methoxy-6-(2-morpholin-4-ylethoxy)quinazoline (1.40 g, 76% yield) as a pale yellow solid:
Reaction SMILES: [NH2:1][C@@H:2]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:21][CH:20]=1)[C:3]([NH:5][C:6]1[C:11]([CH:12]([CH3:14])[CH3:13])=[CH:10][CH:9]=[CH:8][C:7]=1[CH:15]([CH3:17])[CH3:16])=[O:4].C(N(CC)CC)C.[CH3:40][O:41][C:42](Cl)=[O:43]>C1COCC1>[CH3:17][CH:15]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([CH:12]([CH3:14])[CH3:13])[C:6]=1[NH:5][C:3](=[O:4])[C@@H:2]([NH:1][C:42](=[O:43])[O:41][CH3:40])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[CH:21][CH:20]=1)[CH3:16]
Reactant: COC(=O)Cl
Reactant: CC(C)c1cccc(C(C)C)c1NC(=O)[C@@H](N)Cc1ccc(OCc2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC(=O)N[C@@H](Cc1ccc(OCc2ccccc2)cc1)C(=O)Nc1c(C(C)C)cccc1C(C)C
Temperature: 0 °C
Reaction time: 1 h
Yield: 58.5 %

Procedure:
To a coded (0° C.) solution of (S)-α-amino-N-[2,6-bis(1-Methylethyl)phenyl]-4-(phenylmethoxy)benzenepropanamide (4.50 g, 10.5 mmol) and triethylamine (1.75 mL, 12.5 mmol) in THF (125 mL) was added methylchloroformate (0.97 mL, 12.5 mmol). The resulting slurry was stirred (1 hr, 0° C.) then filtered, and the filtrate was concentrated. The residue was taken up in ethyl acetate (300 mL), washed with water (1×mL), washed with saturated sodium bicarbonate (1×100 mL), washed with brine (1×100 mL), then dried (MgSO4) and concentrated in vacuo. The resulting solid was recrystallized from ethyl acetate to yield 3.0 g (59%) of the title compound, mp 179°-182° C.
Reaction SMILES: [CH:1]([NH2:14])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]([NH:22][C@:23]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:28](O)=[O:29])[CH2:24][C:25]([OH:27])=[O:26])([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].C1CCC(N=C=NC2CCCCC2)CC1.N[C@H](C(O)=O)CC(O)=O>C(Cl)Cl.CCN(CC)CC>[C:15]([NH:22][C@:23]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:28]([NH:14][CH:1]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:29])[CH2:24][C:25](=[O:26])[OH:27])([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16]
Reactant: CC(C)(C)OC(=O)N[C@](CC(=O)O)(Cc1ccccc1)C(=O)O
Reactant: NC(c1ccccc1)c1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: N[C@@H](CC(=O)O)C(=O)O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N[C@](CC(=O)O)(Cc1ccccc1)C(=O)NC(c1ccccc1)c1ccccc1
Reaction time: 0.25 h

Procedure:
Benzhydrylamine resin (10 g., 0.4 mmol/g.) was stirred with 250 ml. of 25% Et3N in CH2Cl2 for 10 minutes and then washed a few times with fresh CH2Cl2. It was then suspended in 240 ml. of CH2Cl2 and stirred with Boc-α-benzyl-L-aspartic acid (3.24 g., 10 mmol) and DCC (2.06 g., 10 mmol) for 17 hours. The amino acylated resin was collected, washed thoroughly with CH2Cl2, DMF and MeOH. It was dried and benzoylated with 1.5 ml. of pyridine and 1.65 ml. of benzoyl chloride in 110 ml. of CH2Cl2 for 15 minutes at 0° C. The resin was washed with CH2Cl2, MeOH to give 10.7 g. of desired material. Amino acid analysis indicated that there was 0.40 mmol/g. of aspartic acid.
Reaction SMILES: [Cl-].[CH3:2][Ga+:3][CH3:4].[CH3:5][N:6]([CH2:8][CH2:9][CH2:10][Li])[CH3:7]>CCCCC>[CH3:5][N:6]([CH2:8][CH2:9][CH2:10][Ga:3]([CH3:4])[CH3:2])[CH3:7]
Reactant: [Li]CCCN(C)C
Reactant: C[Ga+]C
Agent: [Cl-]
Solvent: CCCCC
Product: CN(C)CCC[Ga](C)C
Reaction time: 24 h

Procedure:
12 g (89 mmol) of dimethylgallium chloride are made ready for use in 300 ml of pentane and cooled to -78°. 8.3 g (89 mmol) of dimethylaminopropyllithium are added thereto as a solid. The solution is allowed to come to room temperature and is stirred for a further 24 hours. The lithium chloride precipitated is separated off, the solvent is removed and the residue is distilled in vacuo. Dimethylaminopropyl(dimethyl)gallium is obtained as a white solid with a B.p. of 65°/10 mbar.
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11](O)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:22][CH2:23][CH2:24]Cl>CCC(C)=O.CO>[O:1]([C:8]1[CH:13]=[CH:12][C:11]([CH2:22][CH2:23][CH3:24])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: ClCCCCl
Reactant: Oc1ccc(Oc2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Solvent: CO
Product: CCCc1ccc(Oc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 88.6 %

Procedure:
The compound of 4-phenoxyphenol (81.03 g, 435.5 mmol) was dissolved in 810 ml MEK at ambient temperature under Nitrogen. Powdered potassium carbonate (577.16 g, 4,176.27 mmol) was added followed by 1,3-dichloropropane (300.00 g, 2,655.1 mmol), and the resulting solution was heated to reflux for 15.5 hours. The solution was cooled to room temperature, filtered and washed with 750 ml MEK. The filtrate was concentrated under vacuum to give a crude orange liquid. The crude liquid was dissolved in 260 ml absolute MeOH at ambient temperature and stirred 5 minutes, which was then cooled in an ice/acetone/water bath for 1.5 hours. White precipitate was filtered off and washed with 480 ml cold absolute MeOH. The white solid was collected and dried under vacuum at 30° C. for 16 hours to afford about 81.87 g of compound (a).
Reaction SMILES: [C:1](Cl)(Cl)=[O:2].[NH2:5][C:6]1[S:7][C:8]2[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=2[N:10]=1>C(OCC)(=O)C>[S:7]1[C:8]2[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=2[N:10]=[C:6]1[N:5]=[C:1]=[O:2]
Reactant: Nc1nc2ccccc2s1
Reactant: O=C(Cl)Cl
Solvent: CCOC(C)=O
Product: O=C=Nc1nc2ccccc2s1

Procedure:
A saturated solution of phosgene in ethyl acetate (1200 ml) is charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. 2-Aminobenzothiazole (100.0 grams; 0.67 mole) is then added with stirring. After the addition is completed, the reaction mixture is heated at reflux for a period of about one hour. After this time the reaction mixture is evaporated to dryness to yield the desired product benzothiazol-2-yl isocyanate dimer as a yellow solid having a melting point of 250° to 252° C.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.C(O)(=O)C.[CH3:15][C@@:16]12[C:24](=O)[CH2:23][CH2:22][C@H:21]1[C@@H:20]1[CH2:26][CH2:27][C:28]3[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:29]=3[C@H:19]1[CH2:18][CH2:17]2.O1CCCC1>C(OCC)(=O)C.CO>[OH:10][C:7]1[CH:8]=[CH:9][C:4]([CH2:3][CH2:2][NH:1][C@H:24]2[CH2:23][CH2:22][C@H:21]3[C@H:20]4[C@H:19]([CH2:18][CH2:17][C@:16]23[CH3:15])[C:29]2[CH:30]=[CH:31][C:32]([O:34][CH3:35])=[CH:33][C:28]=2[CH2:27][CH2:26]4)=[CH:5][CH:6]=1
Reactant: COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Reactant: NCCc1ccc(O)cc1
Solvent: CO
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](NCCc3ccc(O)cc3)CC[C@@H]12
Temperature: 25 °C
Reaction time: 21 h

Procedure:
Tyramine (5.27 g), glacial acetic acid (5.27 g), estrone methyl ether (4.92 g) sodium cyanoborohydride (1.09 g), tetrahydrofuran (43 ml) were added to methanol (58 ml). The reacting mixture was allowed to stir for 21 hours at room temperature. TLC (ethyl acetate) revealed the formation of a more polar product (Rf 0.25). After 19 hours TLC revealed that the starting material still remained in the reaction solution. The system was warmed at 40° C in an oil bath. The solution remained as a white undissolved solid. After 29 hours the system was allowed to reach room temperature. Excess solvent was removed under reduced pressure. Water was added and made basic (pH 9) with aqueous 50% NaOH. The whim solid did not dissolve in ether and was slightly soluble in ethyl acetate. The solid was filtered and mixed with 34 g of flash silica gel and ethyl acetate. The solvent was removed under reduced pressure. The silica gel was poured on top of the chromatographic column. The compound was eluted with ethyl acetate. Solid was obtained and was recrystallized from ethyl acetate, mp 184°-185 ° C. (diabetes)
Reaction SMILES: [CH2:1]([CH:19]1[C:27]2[C:22](=[CH:23][CH:24]=[C:25]([C:28]([O:30]C)=[O:29])[CH:26]=2)[NH:21][CH2:20]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][CH3:18].[OH-].[K+].C>C(O)C.O>[CH2:1]([CH:19]1[C:27]2[C:22](=[CH:23][CH:24]=[C:25]([C:28]([OH:30])=[O:29])[CH:26]=2)[NH:21][CH2:20]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][CH3:18]
Reactant: CCCCCCCCCCCCCCCCCCC1CNc2ccc(C(=O)OC)cc21
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCCCCCCCCCCCCCCCCCC1CNc2ccc(C(=O)O)cc21
Reaction time: 24 h
Yield: 69.2 %

Procedure:
(RS)-Methyl 3-(n-octadecyl)indoline-5-carboxylate (13.6 g) in ethanol (380 ml), containing potassium hydroxide (2.7 g) and water (50 ml), was refluxed with stirring for 24 hours. The solvent was removed in vacuo to give an off-white solid. The solid was dissolved in water, and the solution treated with charcoal and filtered through diatomaceous earth. Glacial acetic acid (50 ml) was slowly added to the stirred solution and an off-white solid was collected, which was recrystallised from ethyl acetate to give (RS)-3-(n-octadecyl)indoline-5-carboxylic acid (9.1 g), in the form of a white solid, m.p. 84°-87° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([OH:16])=O)=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18].[CH3:21][S:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1>>[Cl:20][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Cl:1])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([NH:27][C:26]2[CH:28]=[CH:29][C:23]([S:22][CH3:21])=[CH:24][CH:25]=2)=[O:16])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18]
Reactant: O=C(O)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1
Reactant: CSc1ccc(N)cc1
Product: CSc1ccc(NC(=O)c2cc([N+](=O)[O-])c(Sc3c(Cl)cncc3Cl)s2)cc1

Procedure:
Prepared according to the procedure described for example 70 from 5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-thiophene-2-carboxylic acid (150 mg, 0.43 mmol) and 4-(methylthio)aniline (72.0 mg, 0.51 mmol). The title compound was obtained as a solid (28.0 mg, 15% yield). 1H NMR (400 MHz, d6-DMSO) δ: 10.53 br), 9.00 (2H, s), 8.74 (1H, m), 7.62 (2H, m), 7.28 (2H, m). MS m/z: 470.13, 472.11 [M+H]+.
Reaction SMILES: [C:1]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[O:8][C:9]([CH3:25])=[C:10]([CH2:12][CH2:13][O:14]S(C3C=CC(C)=CC=3)(=O)=O)[N:11]=2)[CH:2]=1.[CH2:32]([O:34][C:35](=[O:47])[C:36]([O:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42](O)[CH:41]=1)([CH3:38])[CH3:37])[CH3:33]>CN(C=O)C>[CH2:32]([O:34][C:35](=[O:47])[C:36]([O:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([O:14][CH2:13][CH2:12][C:10]2[N:11]=[C:7]([C:3]3[CH:2]=[C:1]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:6]=[CH:5][CH:4]=3)[O:8][C:9]=2[CH3:25])[CH:41]=1)([CH3:38])[CH3:37])[CH3:33]
Reactant: CCOC(=O)C(C)(C)Oc1cccc(O)c1
Reactant: Cc1ccc(S(=O)(=O)OCCc2nc(-c3cccc(-c4ccccc4)c3)oc2C)cc1
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)(C)Oc1cccc(OCCc2nc(-c3cccc(-c4ccccc4)c3)oc2C)c1

Procedure:
A mixture of the toluene-4-sulfonic acid 2-(2-biphenyl-3-yl-5-methyloxazol-4-yl)ethyl ester (66.9 mmol) and 2-(3-hydroxyphenoxy)-2-methylpropanoic acid ethyl ester (Columbia University WO 9731530) (12.5 g, 55.71 mmol) and CS2CO3 (22.7 g, 69.6 mmol) was heated at 55° C. in DMF (45 mL) for 18 h. The reaction was partitioned between ethyl acetate (160 mL) and H2O (180 mL), and the aqueous phase extracted with ethyl acetate (150 mL). The combined organic phases were dried (MgSO4) and concentrated under reduced pressure to an oil which was purified by column chromatography (1500 mL SiO2, 10% ethyl acetate/hexanes to 20% ethyl acetate/hexanes) to provide 2-{3-[2-(2-biphenyl-3-yl-5-methyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid ethyl ester. Rf=0.50 in 20% ethyl acetate/hexanes; 1H NMR (400 MHz, CDCl3) δ8.18 (s, 1H), 7.95 (d, 1H), 7.65-7.59 (m, 3H), 7.44-7.39 (m, 3H), 7.36 (t, 1H), 7.08 (t, 1H), 6.55 (d, 1H), 6.41 (s, 1H), 6.37 (d, 1H), 4.20-4.14 (m, 4H), 2.97 (t, 2H), 2.38 (s, 3H), 1.57 (s, 6H), 1.20 (t, 3H); MS (EI) 508.2 (M+Na)+, 486.2 (M+H)+.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH:11]=[CH:12][C:13]([O:15]C(C)(C)C)=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH:11]=[CH:12][C:13]([OH:15])=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)(C)OC(=O)C=CCCCCc1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(O)C=CCCCCc1ccccc1
Yield: 48.6 %

Procedure:
t-butyl 7-phenylhept-2-enoate (19 g; 70 mmol) is dissolved in dry CH2Cl2 (120 mL) and trifluoroacetic acid (25 mL) is added slowly. After 5 hours the reaction is concentrated in vacuo and purified by column chromatography using CH2Cl2 to obtain 7-phenylhept-2-enoic acid (7 g; 34 mmol). 1H NMR (300 MHz, CDCl3) δ 12-10 (br, 1H), 7.30-7.24 (m, 2H), 7.20-7.12 (m, 3H), 7.06 (dd, J=15.7, 7 Hz, 1H), 5.80 (d, J=15.7 Hz, 1H), 2.62 (t, J=7.5 HZ, 2H), 2.25 (q, J=7 HZ, 2H), 1.70-1.61 (m, 2H), 1.56-1.46 (m, 2H).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[CH:10][C:5]=1[CH2:6][CH2:7][CH:8]=O)([O-])=O.CCCN1[C@@H]2CCC3C=CC(O)=CC=3[C@H]2[O:20]CC1.C(OCC)C>CS(C)=O.N1CCC[C@H]1C(O)=O.CO.[Pd]>[NH:1]1[C:4]2[C:5](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:6][C@@H:7]([OH:20])[CH2:8]1
Reactant: CCCN1CCO[C@@H]2c3cc(O)ccc3CC[C@H]21
Reactant: O=CCCc1ccccc1[N+](=O)[O-]
Agent: [Pd]
Agent: O=C(O)[C@@H]1CCCN1
Solvent: CCOCC
Solvent: CO
Solvent: CS(C)=O
Product: O[C@H]1CNc2ccccc2C1
Reaction time: 0.33 h

Procedure:
To a stirred solution of o-nitrohydrocinnamaldehyde 4a-e (6 mmol) and PhNO (6 mmol) in DMSO (20 mL), L-proline (20 mol %) was added at 25° C. and allowed to stir for 20 min. After completion of reaction, as indicated by the change in color from green to yellow, large excess (100 mL) of diethyl ether was poured into the reaction mixture and stirred for additional 10 min. The combined organic mixture was washed with H2O (5×20 mL). The organic layer was separated and aqueous layer was extracted with diethyl ether (2×50 mL). Combined organic layers were washed with brine (5×50 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the crude product. The crude α-aminooxylated aldehyde was dissolved in MeOH (20 mL) and to this mixture 10% Pd/C (5 wt %) was added. The reaction mixture was then stirred at 25° C. for additional 6 h. After the completion of reaction (monitored by TLC), it was filtered through celite and the solvent evaporated under reduced pressure. Chromatographic purification of the crude product [flash silica gel (230-400 mesh) and pet. ether:EtOAc:Et3N (60:38:2)] gave the pure (R)-tetrahydroquinolin-3-ol derivatives 5a-e.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[CH2:19]([O:23][C:24]1[N:29]=[CH:28][CH:27]=[CH:26][N:25]=1)[CH2:20][C:21]#[CH:22].Cl[Si:31]([CH3:34])([CH3:33])[CH3:32]>O1CCCC1.O>[CH3:32][Si:31]([CH3:34])([CH3:33])[C:22]#[C:21][CH2:20][CH2:19][O:23][C:24]1[N:25]=[CH:26][CH:27]=[CH:28][N:29]=1
Reactant: C[Si](C)(C)Cl
Reactant: C#CCCOc1ncccn1
Agent: [Li]CCCC
Solvent: O
Solvent: CC(C)NC(C)C
Solvent: CCCCCC
Product: C[Si](C)(C)C#CCCOc1ncccn1
Reaction time: 2 h
Yield: 96.1 %

Procedure:
To a solution of diisopropylamine (1.37 g, 13.5 mmol) in tetrahydrofuran (20 mL) was added 1.6M butyllithium/hexane solution (8.44 mL, 13.5 mmol) at −78° C., and the mixture was stirred for 2 hr. A solution of 2-(but-3-yn-1-yloxy)pyrimidine (1.00 g, 6.75 mmol) in tetrahydrofuran (2.5 mL) was added thereto, and the mixture was stirred for 1 hr. Chlorotrimethylsilane (1.80 mL, 14.2 mmol) was added, the reaction solution was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→40/60) to give the title compound (1.43 g, yield 91%).
Reaction SMILES: [C:1](Cl)(Cl)=[O:2].[CH3:5][O:6][C:7]1[S:11][C:10]([NH2:12])=[N:9][N:8]=1>C(OCC)(=O)C>[CH3:5][O:6][C:7]1[S:11][C:10]([N:12]=[C:1]=[O:2])=[N:9][N:8]=1
Reactant: COc1nnc(N)s1
Reactant: O=C(Cl)Cl
Solvent: CCOC(C)=O
Product: COc1nnc(N=C=O)s1
Reaction time: 16 h

Procedure:
A saturated solution of phosgene in ethyl acetate (100 ml) is charged into a glass reaction vessel equipped with a mechanical stirrer. A slurry of 5-methoxy-2-amino-1,3,4-thiadiazole (40 grams) in ethyl acetate (300 ml) is added to the reaction vessel and the resulting mixture is stirred for a period of about 16 hours, resulting in the formation of a precipitate. The reaction mixture is then purged with nitrogen gas to remove unreacted phosgene. The purged mixture is then filtered to recover the precipitate. The precipitate is then recrystallized to yield the desired product 5-methoxy-1,3,4-thiadiazol-2-yl isocyanate dimer.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([OH:12])=O.Cl.[C:14]1([C:20]2([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C@H:28]3[C@H:24]([CH2:25][NH:26][CH2:27]3)[C:23](=[O:29])[CH2:22][CH2:21]2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C>ClCCl>[C:30]1([C:20]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C@H:28]3[C@H:24]([CH2:25][N:26]([C:10](=[O:12])[CH2:9][C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])[CH2:27]3)[C:23](=[O:29])[CH2:22][CH2:21]2)[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: COc1ccccc1CC(=O)O
Reactant: O=C1CCC(c2ccccc2)(c2ccccc2)[C@@H]2CNC[C@H]12
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccccc1CC(=O)N1C[C@@H]2C(=O)CCC(c3ccccc3)(c3ccccc3)[C@@H]2C1
Reaction time: 0.67 h
Yield: 64.3 %

Procedure:
N,N'-Carbonyldiimidazole (1 g) is added to a solution, cooled to +5° C., of 2-methoxyphenylacetic acid (1 g) in dry dichloromethane (30 cc). The mixture is stirred for 40 minutes at +5° C. and a solution of (3aR,7aR)-7,7-diphenylperhydro-4-isoindolone hydrochloride (2 g) and triethylamine (1.7 cc) in dichloromethane (40 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with water (2×50 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (0.2-0.063 mm, diameter 1.8 cm, height 13 cm), eluting with ethyl acetate and collecting 25-cc fractions. Fractions 3 to 5 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized in a mixture of acetonitrile (5 cc) and isopropyl ether (10 cc). The crystals are drained, washed with isopropyl ether (25 cc) and dried. (3aR,7aR)-(-)-7,7-Diphenyl-2-[(2-methoxyphenyl)acetyl]perhydro-4-isoindolone (1.7 g) is obtained in the form of white crystals, m.p. 200° C.; [α]D20 =-274° (c=0.49, acetic acid).
Reaction SMILES: [NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[C:11](NC(C)CCl)(=[O:13])[CH3:12]>>[OH:13][CH2:11][CH2:12][N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: c1ccc2c(c1)CCCN2
Reactant: CC(=O)NC(C)CCl
Product: OCCN1CCCc2ccccc21

Procedure:
N-(2-Acetamidopropyl)-1,2,3,4-tetrahydroquinoline was obtained in an analogous way by reacting 1,2,3,4-tetrahydroquinoline with 2-acetamidopropyl chloride.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[C:5]([C:7]1[C:12]([C:13](OC)=[O:14])=[CH:11][CH:10]=[CH:9][N:8]=1)=O.O.[NH2:21][NH2:22]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[C:7]3[N:8]=[CH:9][CH:10]=[CH:11][C:12]=3[C:13](=[O:14])[NH:22][N:21]=2)[CH:17]=[CH:18][CH:19]=1
Reactant: NN
Reactant: COC(=O)c1cccnc1C(=O)c1cccc(Cl)c1
Solvent: CCO
Solvent: O
Product: O=c1[nH]nc(-c2cccc(Cl)c2)c2ncccc12
Yield: 50.5 %

Procedure:
A solution of 2-(3-chlorobenzoyl)-3-methoxycarbonylpyridine (0.55 g, 2.0 mmoles), hydrazine hydrate (0.15 ml, 3.0 mmoles) in ethanol (50 ml) was stirred at 100° C. for 18 hours under an inert atmosphere. The solution was cooled and solid in the solution was collected, washed with ethyl ether and dried to give 0.26 g of 8-(3-chlorophenyl)pyrido-[2,3-d]pyridazin-5-one (50.5%), mp 268°-269° C.