Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [BH4-].[Na+].[C:3]([O:11][CH:12]1[CH2:15][CH:14]([CH2:16][OH:17])[C:13]1=[O:18])(=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[BH4-]>C(O)(=O)C>[C:3]([O:11][CH:12]1[CH2:15][CH:14]([CH2:16][OH:17])[CH:13]1[OH:18])(=[O:10])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: O=C(OC1CC(CO)C1=O)c1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Product: O=C(OC1CC(CO)C1O)c1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 101.8 %

Procedure:
Glacial acetic acid (25 mL) in a 250 mL 3-neck flask was cooled in an ice bath under a stream of nitrogen. Sodium borohydride was added cautiously in portions over a 5 minute period. The ice bath removed and the reagent was used after stirring for 15 minutes at ambient temperature. 2-Benzoyloxy-4-hydroxymethylcyclobutanone (1.43 g, 6.5 mmol) from Step H was dissolved in 45 mL of glacial actetic acid and immediately treated with the above borohydride reagent. After stirring the reaction mixture for 35 minutes, the reaction was quenched with ~2 mL of methanol and the reaction mixture was concentrated in vacuo to a syrup. The syrup was dissolved in 250 mL of ethyl acetate and the ethyl acetate solution was washed with water and 5% aqueous sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated to give 1.47 g of the title compound which was taken on to the next step without purification; MS DCI-NH3M/Z: 221 (M+H)+, 238 (M+NH4)+.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13](=[O:14])[C:12]3([CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]([CH2:20][CH2:21][CH2:22][C:23]([O:25]CC)=[O:24])[C:10]2=[O:28])=[CH:5][C:4]=1[C:29]([F:32])([F:31])[F:30])#[N:2].CO.[OH-].[Na+]>O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13](=[O:14])[C:12]3([CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]([CH2:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])[C:10]2=[O:28])=[CH:5][C:4]=1[C:29]([F:30])([F:32])[F:31])#[N:2]
Reactant: CCOC(=O)CCCN1C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=O)C12CCOCC2
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: N#Cc1ccc(N2C(=O)N(CCCC(=O)O)C3(CCOCC3)C2=O)cc1C(F)(F)F
Temperature: 30 °C
Reaction time: 0.5 h
Yield: 70.5 %

Procedure:
522 mg of the product of Example 6 and 20 ml of methanol were mixed together and the solution was heated to 30° C., then returned to ambient temperature 2 ml of 2N sodium hydroxide were added and the reaction medium stood for 4 hours and 30 minutes, then was poured into 30 ml of water and adjusted to pH 2-3. Extraction was carried out 3 times with ethyl acetate and the organic phase was washed with water, then with salt water, dried and purified on silica with methylene chloride-methanol 9-1 as eluant. Then, solidification was carried out by trituration in 0.2 ml of isopropanol and 5 ml of ether to obtain 345 mg of the expected product (white crystals) melting at 151°-152° C.
Reaction SMILES: [N:1]([CH:4]1[CH2:10][C:9]([CH3:12])([CH3:11])[CH2:8][N:7]([S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)(=[O:15])=[O:14])[CH2:6][CH:5]1[OH:22])=[N+]=[N-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1.O>[NH2:1][CH:4]1[CH2:10][C:9]([CH3:12])([CH3:11])[CH2:8][N:7]([S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)(=[O:15])=[O:14])[CH2:6][CH:5]1[OH:22]
Reactant: CC1(C)CC(N=[N+]=[N-])C(O)CN(S(=O)(=O)c2ccccn2)C1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: CC1(C)CC(N)C(O)CN(S(=O)(=O)c2ccccn2)C1
Temperature: 45 °C
Yield: 45 %

Procedure:
4-Azido-6,6-dimethyl-1-(pyridine-2-sulfonyl)-azepan-3-ol from Example 92f (0.4 g, 1.23 mmol) was dissolved in THF (50 ml) and H2O (0.2 ml). PPh3 (0.48 g, 1.85 mmol) was added to this solution. The reaction mixture was stirred at 45° C. over night. TLC showed no starting material left. THF was evaporated, azeotroped with toluene (2×'s). The resulting thick oil was dissolved in MeOH, treated with HCl in ether to adjust pH to acidic. More ether was added and the solution turned cloudy. 0.22 g white precipitate of the title compound was collected. (45% yield); 1H-NMR (400 MHz, CD3OD): •8.68(m, 1H), 8.10-7.93(m, 2H), 7.62(m, 1H), 3.90(m, 1H), 3.68(m, 1H), 3.40-2.90(m, 4H), 1.82(m, 1H), 1.53(d, 1H), 1.05(s, 6H)
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:24])([CH:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1)[CH3:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.ClC1C=C(C=CC=1)C(OO)=[O:30]>ClCCl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:24])([CH:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N+:19]=1[O-:30])[CH3:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(c1ccccn1)C(O)(Cn1cncn1)c1ccc(F)cc1F
Solvent: ClCCl
Product: CC(c1cccc[n+]1[O-])C(O)(Cn1cncn1)c1ccc(F)cc1F
Yield: 54.8 %

Procedure:
A solution of 2-(2,4-difluorophenyl)-3-(pyridin-2-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (diasatereoisomeric pair B from Example 1) (1.60 g) and 85% w/w 3-chloroperoxybenzoic acid (1.60 g) in dichloromethane (10 ml) was stirred at room temperature for 36 hours and then worked up as described in Example 15(i) to give the title compound, (0.92 g), m.p. 159°-160°.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][C:5]=1[C:13]1([C:26]2[NH:27][C:28]3[C:33]([C:34]=2[CH3:35])=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:18][CH2:17][C:16]([N:23]([CH3:25])[CH3:24])([CH2:19][CH2:20][CH2:21][CH3:22])[CH2:15][CH2:14]1.C(N(CC)CC)C.[CH:43]1([S:48](Cl)(=[O:50])=[O:49])[CH2:47][CH2:46][CH2:45][CH2:44]1.[OH-].[Na+]>ClCCl>[CH2:19]([C:16]1([N:23]([CH3:25])[CH3:24])[CH2:17][CH2:18][C:13]([C:5]2[NH:6][C:7]3[C:12]([C:4]=2[CH2:3][CH2:2][NH:1][S:48]([CH:43]2[CH2:47][CH2:46][CH2:45][CH2:44]2)(=[O:50])=[O:49])=[CH:11][CH:10]=[CH:9][CH:8]=3)([C:26]2[NH:27][C:28]3[C:33]([C:34]=2[CH3:35])=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:14][CH2:15]1)[CH2:20][CH2:21][CH3:22]
Reactant: O=S(=O)(Cl)C1CCCC1
Reactant: CCCCC1(N(C)C)CCC(c2[nH]c3ccccc3c2C)(c2[nH]c3ccccc3c2CCN)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCC1(N(C)C)CCC(c2[nH]c3ccccc3c2C)(c2[nH]c3ccccc3c2CCNS(=O)(=O)C2CCCC2)CC1

Procedure:
4-(3-(2-aminoethyl)-1H-indol-2-yl)-1-butyl-N,N-dimethyl-4-(3-methyl-1H-indol-2-yl)cyclohexylamine (120 mg, 0.255 mmol, mixture of the two possible diastereoisomers in a ratio of approx. 30:70) mixed in dichloromethane (5 ml) with triethylamine (0.12 ml, 0.863 mmol) and cyclopentane sulphonyl chloride (65 mg, 0.385 mmol). After a reaction time of 24 h at 25° C. the reaction mixture was mixed with 1N sodium hydroxide solution (10 ml) and extracted with dichloromethane (3×15 ml). The combined organic phases were dried with Na2SO4 and then filtered. The volatile constituents of the filtrate were completely removed in a vacuum. The residue (yellow foam, 173 mg) was purified by column chromatography [silica gel 60 (25 g); ethyl acetate/methanol 4:1 (250 ml), methanol/30% ammonia 9:1 (100 ml)]. The product was obtained as a beige-coloured solid with a yield of 39 mg (25%) (melting point 111-115° C., AS 11227, mixture of the two possible diastereoisomers in a ratio of approx. 30:70).
Reaction SMILES: [K].[C:2]([O:9][CH2:10][CH3:11])(=[O:8])[C:3]([O:5]CC)=O.[CH3:12][O:13][C:14]1[N:19]=[C:18]([CH3:20])[C:17]([N+:21]([O-:23])=[O:22])=[CH:16][CH:15]=1>C(O)C>[CH3:12][O:13][C:14]1[N:19]=[C:18]([CH2:20][C:3](=[O:5])[C:2]([O:9][CH2:10][CH3:11])=[O:8])[C:17]([N+:21]([O-:23])=[O:22])=[CH:16][CH:15]=1
Reactant: CCOC(=O)C(=O)OCC
Reactant: COc1ccc([N+](=O)[O-])c(C)n1
Agent: [K]
Solvent: CCO
Product: CCOC(=O)C(=O)Cc1nc(OC)ccc1[N+](=O)[O-]
Reaction time: 0.08 h

Procedure:
A roundbottom flask was charged with ethanol (540 ml) and (7.2 L). To this was added potassium (81.6 g, 2.09 mol) and mixture was stirred until all the potassium dissolved. Diethyl oxalate (306 g, 2.10 mol) was then added. The mixture was stirred for 5 minutes and then 6-methoxy-2-methyl-3-nitropyridine (320.0 g, 1.87 mol) was added. The resulting solution was stirred at room temperature for 36 hours. The slurry was filtered and the collected solids were washed thoroughly with ether and dried under reduced pressure. The solid was then suspended in 30 ml of water acetic acid was added until the pH=4. The solids that formed were collected by filtration to afford the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]([C:14]([O:16]C)=[O:15])=[C:11]([C:18]3[CH:23]=[CH:22][C:21]([S:24](=[O:27])(=[O:26])[NH2:25])=[CH:20][CH:19]=3)[C:10]=2[CH3:28])=[CH:5][CH:4]=1.[OH-].[Na+].Cl>C(O)C.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[S:13][C:12]([C:14]([OH:16])=[O:15])=[C:11]([C:18]3[CH:23]=[CH:22][C:21]([S:24](=[O:27])(=[O:26])[NH2:25])=[CH:20][CH:19]=3)[C:10]=2[CH3:28])=[CH:7][CH:8]=1
Reactant: COC(=O)c1sc(-c2ccc(OC)cc2)c(C)c1-c1ccc(S(N)(=O)=O)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: COc1ccc(-c2sc(C(=O)O)c(-c3ccc(S(N)(=O)=O)cc3)c2C)cc1
Temperature: 52.5 °C
Reaction time: 2 h
Yield: 96.9 %

Procedure:
Methyl 5-(4-methoxyphenyl)-4-methyl-3-(4-sulfamoylphenyl)thiophene-2-carboxylate (compound 7d, 3.02 g, 7.24 mmol) was suspended in ethanol (50 ml) and NaOH (1.44 g, 36.2 mmol) in water 10 ml was added at 25° C. The reaction mixture was heated at 50-55° C. under stirring for 2 hr. The progress of reaction was monitored by TLC. The reaction mixture was then concentrated under reduced pressure. Water, 50 ml was added to the residue so obtained and the mixture was cooled using icebath. Aqueous hydrochloric acid (10%) was then added to the mixture to bring the pH to between 5 and 6. The mixture was then extracted with ethyl acetate (2×75 ml). The combined organic layer was dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure to obtain a product (2.83 g, 97%).
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[N:6]=[CH:7][C:8]([O:11][C:12]2[CH:29]=[CH:28][C:15]3[CH2:16][CH2:17][N:18]([C:21](OC(C)(C)C)=O)[CH2:19][CH2:20][C:14]=3[CH:13]=2)=[N:9][CH:10]=1)=[O:4].[CH3:30][CH:31]1[CH2:35]C[C:33](=O)[CH2:32]1>>[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[N:9][C:8]([O:11][C:12]2[CH:29]=[CH:28][C:15]3[CH2:16][CH2:17][N:18]([CH:21]4[CH2:33][CH2:32][CH:31]([CH3:35])[CH2:30]4)[CH2:19][CH2:20][C:14]=3[CH:13]=2)=[CH:7][N:6]=1)=[O:4]
Reactant: CNC(=O)c1cnc(Oc2ccc3c(c2)CCN(C(=O)OC(C)(C)C)CC3)cn1
Reactant: CC1CCC(=O)C1
Product: CNC(=O)c1cnc(Oc2ccc3c(c2)CCN(C2CCC(C)C2)CC3)cn1

Procedure:
Example 255 (E255) was prepared from N-methyl-5-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yloxy)-2-pyrazinecarboxamide (D49) and 3-methyl cyclopentanone using the method described for Example 223; MS (ES+) m/e 381 [M+H]+.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].[C:7]([CH2:9][CH2:10][NH:11][N:12]=[CH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)#[N:8].N1C=CC=CC=1>C(OCC)(=O)C>[C:7]([CH2:9][CH2:10][N:11]([C:2]([O:4][CH2:5][CH3:6])=[O:3])[N:12]=[CH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)#[N:8]
Reactant: CCOC(=O)Cl
Reactant: N#CCCNN=Cc1ccccc1
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CCOC(=O)N(CCC#N)N=Cc1ccccc1

Procedure:
1.08 g (10-2 moles) of ethyl chloroformate in solution in 5 ml of anhydrous ethyl acetate are added dropwise to a solution containing 10-2 moles of benzaldehyde (2-cyanoethyl)hydrazone and 0.79 g (10-2 moles) of anhydrous pyridine in 20 ml of anhydrous ethyl acetate, with stirring in the cold. The reaction mixture is slowly heated to reflux temperature and left stirring for 2 hours and then filtered hot.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:23][C:17]3[N:18]=[CH:19][N:20]=[C:21](Cl)[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][N:25]1[C:33]2[C:28](=[CH:29][C:30]([NH2:34])=[CH:31][CH:32]=2)[CH:27]=[N:26]1>CCCCO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:23][C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH:34][C:30]4[CH:29]=[C:28]5[C:33](=[CH:32][CH:31]=4)[N:25]([CH3:24])[N:26]=[CH:27]5)[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CC=C(c2cc3c(Cl)ncnc3[nH]2)CC1
Reactant: Cn1ncc2cc(N)ccc21
Solvent: CCCCO
Product: Cn1ncc2cc(Nc3ncnc4[nH]c(C5=CCN(C(=O)OC(C)(C)C)CC5)cc34)ccc21
Temperature: 120 °C
Reaction time: 15 h

Procedure:
A suspension of 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (638.1 mg, 1.906 mmol, 1 eq) and 1-methyl-1H-indazol-5-ylamine (567.4 mg, 3.855 mmol, 2 eq) in n-BuOH (26 mL) was stirred at 120° C. for 15 h. A white precipitate was filtered off, washed several times with MeOH, and dried under high vacuum, giving the title compound, as a white solid. The filtrate was adsorbed onto Hydromatrix, dry loaded, and purified by chromatography on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with MeOH:DCM 2%→4%→6%]. Fractions containing product were combined and concentrated in vacuo, affording a second batch of the title compound, as a brown solid. 1H NMR (400 MHz, DMSOd6): δ=1.44 (s, 9H), 2.43-2.53 (m, 2H), 3.57 (t, J=5.6 Hz, 2H), 4.03 (s, 5H), 6.38 (s, br, 1H), 6.76 (s, br, 1H), 8.60 (d, J=8.8 Hz, 1H), 7.69 (dd, J=8.8, 2.0 Hz, 1H), 8.01 (d, J=0.8 Hz, 1H), 8.26 (s, 1H), 8.39 (d, J=1.6 Hz, 1H), 9.34 (s, —NH), 11.91 (d, J=2.0 Hz, —NH). MS (ES+): m/z 446.07 (100) [MH+]. HPLC: tR=2.59 min (ZQ2000, polar—5 min).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([N:15]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([N:33]3[CH:37]=[CH:36][N:35]=[CH:34]3)=[CH:29][CH:28]=2)[CH2:16][C:17]([NH:19][O:20]C(OC)(C)C)=[O:18])(=[O:14])=[O:13])=[CH:8][CH:7]=1)[CH2:2][CH:3]=[CH2:4].Cl.C([O-])(O)=O.[Na+]>>[CH2:1]([O:5][C:6]1[CH:7]=[CH:8][C:9]([S:12]([N:15]([CH2:26][C:27]2[CH:28]=[CH:29][C:30]([N:33]3[CH:37]=[CH:36][N:35]=[CH:34]3)=[CH:31][CH:32]=2)[CH2:16][C:17]([NH:19][OH:20])=[O:18])(=[O:13])=[O:14])=[CH:10][CH:11]=1)[CH2:2][CH:3]=[CH2:4]
Reactant: C=CCCOc1ccc(S(=O)(=O)N(CC(=O)NOC(C)(C)OC)Cc2ccc(-n3ccnc3)cc2)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: C=CCCOc1ccc(S(=O)(=O)N(CC(=O)NO)Cc2ccc(-n3ccnc3)cc2)cc1
Reaction time: 0.25 h

Procedure:
To a solution of 0.39 g (0.74 mmol) of 2-[(4-but-3-enyloxy-benzenesulfonyl)-(4-imidazol-1-yl-benzyl)-amino]-N-(1-methoxy-1-methyl-ethoxy)-acetamide (stage 80.4), 2.46 ml of 6 N aqueous hydrochloride is added at r.t. After being stirred for 15 min, the reaction mixture is neutralized with sat. NaHCO3 and extracted with AcOEt. The combined extracts are washed with brine, dried over MgSO4 and concentrated under reduced pressure to give 2-[(4-but-3-enyloxy-benzenesulfonyl)-(4-imidazol-1-yl-benzyl)-amino]-N-hydroxy-acetamide as a colorless powder. To a solution of 0.17 g (0.37 mmol) of the above prepared hydroxy acetamide in 3 ml of dioxane, 0.447 ml of 1 N aqueous hydrochloride is added and stirred for 10 min. The reaction mixture is concentrated under reduced pressure and dried in vacuo to give their title compound. 1H-NMR (400 MHz, DMSO-d6): 2.40-2.50 (m, 2H), 3.61 (s, 2H), 4.07 (t, 2H, J=6.52 Hz), 4.37 (s, 2H), 5.00-5.15 (m, 2H), 5.75-5.90 (m, 1H), 7.04 (d, 2H, J=8.56 Hz), 7.48 (d, 2H, J=8.56 Hz), 7.65-7.75 (m, 5H), 7.81 (s, 1H), 8.19 (s, 1H), 9.57 (s, 1H), 10.54 (brs, 1H).
Reaction SMILES: Cl.[CH3:2][C:3]([NH:15][CH2:16][C:17]([C:19]1[CH:24]=[CH:23][C:22]([O:25]CC2C=CC=CC=2)=[C:21]([O:33]CC2C=CC=CC=2)[C:20]=1[CH3:41])=[O:18])([CH3:14])[CH2:4][C:5]1[C:10]([CH3:11])=[CH:9][CH:8]=[C:7](O)[C:6]=1[CH3:13].C[OH:43]>[Pd]>[CH3:14][C:3]([NH:15][CH2:16][CH:17]([C:19]1[C:20]([CH3:41])=[C:21]([OH:33])[C:22]([OH:25])=[CH:23][CH:24]=1)[OH:18])([CH3:2])[CH2:4][C:5]1[C:10]([CH3:11])=[CH:9][C:8]([OH:43])=[CH:7][C:6]=1[CH3:13]
Reactant: Cc1ccc(O)c(C)c1CC(C)(C)NCC(=O)c1ccc(OCc2ccccc2)c(OCc2ccccc2)c1C
Reactant: CO
Agent: [Pd]
Agent: Cl
Product: Cc1cc(O)cc(C)c1CC(C)(C)NCC(O)c1ccc(O)c(O)c1C

Procedure:
7 g of 2-[1,1-dimethyl-2-(2,6-dimethylhydroxyphenyl)ethylamino]-1-(3,4-dibenzyloxy-2-methylphenyl)ethanone hydrochloride in 125 mL of methanol is hydrogenated using 2 g of palladium on charcoal (5%). After separation of the catalyst, the solvent is distilled off. The solid that crystallizes out is stirred into acetonitrile, suction filtered, and washed. Yield: 3.5 g of hydrochloride; melting point: 182° C.–183° C. (decomposition).
Reaction SMILES: C([O:3][C:4](=[O:36])[CH2:5][O:6][C:7]1[CH:35]=[CH:34][CH:33]=[C:32]2[C:8]=1[CH2:9][CH2:10][C:11]1[S:15][C:14]([S:16]([CH2:18][CH:19]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])=[N:13][C:12]=12)C.[OH-].[Na+]>O1CCCC1.CO>[C:26]1([CH:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:18][S:16]([C:14]2[S:15][C:11]3[CH2:10][CH2:9][C:8]4[C:32](=[CH:33][CH:34]=[CH:35][C:7]=4[O:6][CH2:5][C:4]([OH:36])=[O:3])[C:12]=3[N:13]=2)=[O:17])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: CCOC(=O)COc1cccc2c1CCc1sc(S(=O)CC(c3ccccc3)c3ccccc3)nc1-2
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)COc1cccc2c1CCc1sc(S(=O)CC(c3ccccc3)c3ccccc3)nc1-2
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 76.2 %

Procedure:
To a solution of ethyl[(2-(2,2-diphenylethylsulfinyl)-4,5-dihydronaphtho[1,2-d]thiazol-6-yl)oxy]acetate (0.50 g, 0.965 mmol) in a mixture of tetrahydrofuran (16 mL) and methanol (4 mL) was added 1N-aqueous sodium hydroxide (2 mL) dropwise, and the mixture was stirred at room temperature for 20 minutes. After the solvent was distilled off under reduced pressure, 1N-hydrochloric acid was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride solution, dried over MgSO4, filtered, and concentrated under reduced pressure to provide 0.36 g of the title compound as amorphous solid. Yield 76%.
Reaction SMILES: C([O:4][C@@H:5]1[C@H:12]2[C@H:8]([O:9][CH2:10][CH2:11]2)[O:7][CH2:6]1)(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO.ClCCl>[O:7]1[C@H:8]2[O:9][CH2:10][CH2:11][C@H:12]2[C@@H:5]([OH:4])[CH2:6]1
Reactant: CC(=O)O[C@H]1CO[C@H]2OCC[C@H]21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CO
Product: O[C@H]1CO[C@H]2OCC[C@H]21
Temperature: 30 °C
Reaction time: 7 h
Yield: 99.2 %

Procedure:
(3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl acetate (II, 14.0 g) was dissolved in methanol (42 mL). Potassium carbonate (0.34 g) was added and stirred at 25-35° C. for 6-8 hours. Methanol Was distilled out completely under vacuum, to the distillate methylenedichloride (28 mL) was added, stirred the mass for 30 minutes and again distilled the solvent to get residue. Dissolved the residue in dichloromethane (56 mL), the resultant solution was treated with carbon and the solvent was completely distilled out get title compound I (yield 10.5 g).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([OH:13])=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C([Cl:17])=O>C(Cl)Cl.CN(C=O)C>[N:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([Cl:17])=[O:13])=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)c1ccc2ncccc2c1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)c1ccc2ncccc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.8 %

Procedure:
To a mixture of quinoline-6-carboxylic acid (0-1) (2.0 g, 11.5 mmol) in CH2Cl2 (250 mL) was added 3 drops of DMF at 0° C., followed by oxalyl chloride (7.3 g, 57.5 mmol) dropwise. The resulting reaction was stirred at room temperature overnight, and then concentrated to afford the title compound (2.2 g).
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:20]=[CH:19][C:16]([CH:17]=O)=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[NH2:21][CH:22]1[C:31]2[CH:30]=[C:29]([C:32]([O:34][CH3:35])=[O:33])[CH:28]=[CH:27][C:26]=2[CH2:25][CH2:24][CH2:23]1>>[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:20]=[CH:19][C:16]([CH2:17][NH:21][CH:22]3[C:31]4[CH:30]=[C:29]([C:32]([O:34][CH3:35])=[O:33])[CH:28]=[CH:27][C:26]=4[CH2:25][CH2:24][CH2:23]3)=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ccc(C#Cc2ccc(C=O)cc2)cc1
Reactant: COC(=O)c1ccc2c(c1)C(N)CCC2
Product: CCCCc1ccc(C#Cc2ccc(CNC3CCCc4ccc(C(=O)OC)cc43)cc2)cc1

Procedure:
The titled compound was prepared following the procedure L using 4-[(4-butylphenyl)ethynyl]benzaldehyde and methyl 8-amino-5,6,7,8-tetrahydronaphthalene-2-carboxylate as a yellow oil (95%). 1H NMR (CDCl3, 300 MHz) δ 7.96 (d, J=1.7 Hz, 1H), 7.72 (dd, J=7.9, 1.7 Hz, 1H), 7.29-7.42 (m, 5H), 7.17 (d, J=2.8 Hz, 1H), 7.07 (m, 3H), 3.82 (m, 5H), 3.75 (m, 1H), 2.67-2.82 (m, 2H), 2.50 (m, 2H), 1.92 (m, 1H), 1.82 (m, 2H), 1.62 (m, 1H), 1.51 (m, 2H), 1.28 (m, 2H), 0.83 (m, 3H). M+ (ESI): 452.2. HPLC, Rt: 4.37 min (Purity: 60.1%).
Reaction SMILES: [C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:9]1[O:13][CH:10]1[CH:11]=[CH2:12].Cl>CCOCC.C1COCC1>[C:1]1([CH2:12][CH:11]=[CH:10][CH2:9][OH:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=CC1CO1
Reactant: Br[Mg]c1ccccc1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCOCC
Product: OCC=CCc1ccccc1
Temperature: -10 °C
Reaction time: 16 h
Yield: 30 %

Procedure:
To a -10° C. solution of phenylmagnesium bromide, 3M in ether (68 mL) was added a solution of cupric acetate (5.6 g) and butadiene monoxide (6.43 mL) in THF (200 mL) over 40 min while maintaining the reaction temperature below -5° C. The reaction was stirred at -10° C. for 1 h, room temperature for 16 h, refluxed for 15 min then cooled to room temperature. Aqueous HCl (10%, 100 mL) was added and the mixture extracted with ethyl acetate. The organic solution was washed with aqueous HCl (10%), NaHCO3 (saturated) and brine (saturated), dried (MgSO4) and concentrated to yield a blue liquid. The residue was chromatographed to yield the title compound (6.3 g, 30%).
Reaction SMILES: [Na].[CH2:2]([O:4][C:5]([C:7]1[C:8](=[O:18])[NH:9][C:10]2[C:15]([C:16]=1[NH2:17])=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:6])[CH3:3].CN(C)C=O.[CH2:24](Br)[CH:25]=[CH2:26]>O>[CH2:2]([O:4][C:5]([C:7]1[C:8](=[O:18])[N:9]([CH2:26][CH:25]=[CH2:24])[C:10]2[C:15]([C:16]=1[NH2:17])=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:6])[CH3:3]
Reactant: CCOC(=O)c1c(N)c2ccccc2[nH]c1=O
Reactant: C=CCBr
Agent: [Na]
Solvent: O
Solvent: CN(C)C=O
Product: C=CCn1c(=O)c(C(=O)OCC)c(N)c2ccccc21

Procedure:
To a solution containing 7.6 g. (0.03 mole) of the sodium salt of 4-amino-1,2-dihydro-2-oxo-3-quinolinecarboxylic acid ethyl ester in 50 ml. of dimethylformamide was added 4.8 g. (0.04 mole) of allyl bromide. The reaction mixture was heated on a steam bath for 1/2 hour. The reaction mixture was cooled in ice and poured into 500 ml. of water. The resulting precipitate was collected on a filter and recrystallized from ethyl acetate-petroleum ether giving 4.6 g. of product, m.p. 132°-134° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[CH2:11][CH2:10][C:9]2[C:4](=[C:5]([CH3:14])[C:6]([CH3:13])=[CH:7][C:8]=2[CH3:12])[O:3]1.[Cl:16][S:17](O)(=[O:19])=[O:18]>ClC(Cl)Cl>[S:17]([Cl:16])([C:7]1[C:6]([CH3:13])=[C:5]([CH3:14])[C:4]2[O:3][C:2]([CH3:15])([CH3:1])[CH2:11][CH2:10][C:9]=2[C:8]=1[CH3:12])(=[O:19])=[O:18]
Reactant: O=S(=O)(O)Cl
Reactant: Cc1cc(C)c2c(c1C)OC(C)(C)CC2
Solvent: ClC(Cl)Cl
Product: Cc1c(C)c(S(=O)(=O)Cl)c(C)c2c1OC(C)(C)CC2
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 39.7 %

Procedure:
The starting material for this synthesis was 2,2,5,7,8-pentamethylchroman and 77.55 g, 0.38 mol was dissolved in trichloromethane (1 liter) and cooled to 0° C. Chlorosulphonic acid (176.85 g, 1.52 mol) in a further 800 ml of solvent was added and the mixture stirred for 15 minutes at 0° C. and then for a further hour without cooling. The reaction mixture was poured onto ice and the organic layer separated off. This organic layer was then washed with 5% sodium carbonate solution, with saturated sodium bicarbonate solution and with brine. The aqueous washings were combined and extracted with more solvent. The original organic layer and the organic extract were combined, dried over anhydrous magnesium sulphate, stirred with activated charcoal and filtered through kieselguhr. Most of the trichloromethane was removed in vacuuo and then petroleum ether (40°/60° C.) was added and the remainder of the trichloromethane was removed in vacuuo. This crude product was dissolved in more petroleum ether and the solution cooled to 0° C. and filtered to give 45.96 g of Pmc-Cl (yield 39.7%, melting point 77°-82° C.).