Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([NH:11][C@H:12]([C:23]([NH:25][C@H:26]([C:29]([NH:31][C@H:32]([C:41]([NH:43][C@@H:44]([C:46]([NH:48][C@H:49]([C:54]([O:56][CH3:57])=[O:55])[CH2:50][CH:51]([CH3:53])[CH3:52])=[O:47])[CH3:45])=[O:42])[CH2:33][C:34]1[CH:39]=[CH:38][C:37]([OH:40])=[CH:36][CH:35]=1)=[O:30])[CH2:27][OH:28])=[O:24])[CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1)=O)C1C=CC=CC=1.[ClH:58].O.[H][H]>CO.[Pd]>[ClH:58].[NH2:11][C@H:12]([C:23]([NH:25][C@H:26]([C:29]([NH:31][C@H:32]([C:41]([NH:43][C@@H:44]([C:46]([NH:48][C@H:49]([C:54]([O:56][CH3:57])=[O:55])[CH2:50][CH:51]([CH3:53])[CH3:52])=[O:47])[CH3:45])=[O:42])[CH2:33][C:34]1[CH:35]=[CH:36][C:37]([OH:40])=[CH:38][CH:39]=1)=[O:30])[CH2:27][OH:28])=[O:24])[CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1
Reactant: [H][H]
Reactant: COC(=O)[C@H](CC(C)C)NC(=O)[C@@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)OCc1ccccc1
Agent: [Pd]
Agent: Cl
Solvent: O
Solvent: CO
Product: COC(=O)[C@H](CC(C)C)NC(=O)[C@@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1c[nH]c2ccccc12

Procedure:
A solution of 1.58 g. of Nα -benzyloxycarbonyl-L-tryptophyl-L-seryl-L-tyrosyl-D-alanyl-L-leucine, methyl ester in 100 ml. of methanol with 1.6 ml. of 1.3 N hydrogen chloride in methanol is stirred with 150 mg. of palladium on carbon under one inch water pressure of hydrogen for two and a half hours. Thin layer chromatography of samples of the solution shows the disappearance of the starting material in about two hours. The catalyst is removed by filtration and the filtrate evaporated at 40° and reduced pressure. The residue is used without further purification.
Reaction SMILES: F[C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[C:10]3[C:16](I)=[CH:15][N:14]([S:18]([C:21]4[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=4)(=[O:20])=[O:19])[C:11]3=[N:12][CH:13]=2)[CH:5]=[CH:4][C:3]=1[CH:28]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]1.[F:41][C:42]1[CH:43]=[C:44]([CH:61]=[CH:62][CH:63]=1)[CH2:45][N:46]1[CH:50]=[C:49](C2OC(C)(C)C(C)(C)O2)[C:48]([CH3:60])=[N:47]1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:41][C:42]1[CH:43]=[C:44]([CH:61]=[CH:62][CH:63]=1)[CH2:45][N:46]1[CH:50]=[C:49]([C:16]2[C:10]3[C:11](=[N:12][CH:13]=[C:8]([C:6]4[CH:7]=[CH:2][C:3]([CH:28]5[CH2:29][CH2:30][N:31]([C:34]([O:36][C:37]([CH3:39])([CH3:40])[CH3:38])=[O:35])[CH2:32][CH2:33]5)=[CH:4][CH:5]=4)[CH:9]=3)[N:14]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[CH:15]=2)[C:48]([CH3:60])=[N:47]1
Reactant: Cc1nn(Cc2cccc(F)c2)cc1C1OC(C)(C)C(C)(C)O1
Reactant: Cc1ccc(S(=O)(=O)n2cc(I)c3cc(-c4ccc(C5CCN(C(=O)OC(C)(C)C)CC5)c(F)c4)cnc32)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: Cc1ccc(S(=O)(=O)n2cc(-c3cn(Cc4cccc(F)c4)nc3C)c3cc(-c4ccc(C5CCN(C(=O)OC(C)(C)C)CC5)cc4)cnc32)cc1
Yield: 76.3 %

Procedure:
Using similar reaction conditions as described in step-i of example-1, tert-butyl 4-(4-(3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperidine-1-carboxylate (intermediate 67B) (120 mg, 0.182 mmol) was coupled with 1-(3-fluorobenzyl)-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (intermediate 12) (64 mg, 0.200 mmol) using Pd(PPh3)2Cl2 (6 mg, 0.009 mol) and sodium carbonate (58 mg, 0.547 mmol) in acetonitrile/water (3/2 ml) to afford 100 mg (76% yield) of the titled compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.Br.[Br:13][CH2:14][CH2:15][NH2:16].C(N(CC)C(C)C)(C)C>C(Cl)Cl>[Br:13][CH2:14][CH2:15][NH:16][S:8]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)(=[O:10])=[O:9]
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Reactant: NCCBr
Agent: Br
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=S(=O)(NCCBr)c1ccc(Cl)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 98.9 %

Procedure:
To a stirred mixture of 4-chlorobenzenesulfonyl chloride (5.0 g, 23.7 mmol) and 2-bromoethylamine hydrobromide (5.4 g, 26.3 mmol) in anhydrous methylene chloride (50 mL) at 0° C. was slowly added N,N-diisopropylethyl amine (8.6 mL, 52.1 mmol) and the mixture was stirred at 0° C. for 1 hour. The reaction mixture was washed sequentially with water, 2N aqueous hydrochloric acid, saturated aqueous sodium carbonate, and saturated aqueous sodium chloride. The organic layer was dried (anhydrous sodium sulfate), filtered, and concentrated in vacuo to afford a white solid (7 g, 99%). 1H NMR (300 MHz, CDCl3) δ 7.82 (d, 2H, J=8.7 Hz), 7.52 (d, 2H, J=8.7 Hz), 4.96 (s, 1H), 3.50-3.30 (m, 4H).
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]([OH:5])[CH3:4].[CH:6](=O)[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[NH3:1].[CH3:14][O:13][C:10]1[CH:11]=[CH:12][C:7]([CH2:6][NH:1][CH2:2][C@@H:3]([OH:5])[CH3:4])=[CH:8][CH:9]=1
Reactant: COc1ccc(C=O)cc1
Reactant: C[C@H](O)CN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: COc1ccc(CNC[C@H](C)O)cc1
Product: N
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A mixture of (S)-(+)-1-amino-2-propanol (9 g, 0.12 mol), p-anisaldehyde (5.45 g, 0.04 mol), acetic acid (5 ml), and sodium triacetoxyborohydride (9.5 g, 0.045 mol) in methanol (80 ml) was stirred at room temperature for 72 hours. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between dichloromethane (150 ml) and sodium hydroxide solution (100 ml, 0.5N). The layers were separated, and the aqueous phase was extracted with further dichloromethane (4×30 ml). The combined organic solutions were dried (MgSO4) and concentrated under reduced pressure. The residual yellow oil was purified by column chromatography on silica gel using an elution gradient of dichloromethane:methanol:0.88 ammonia (98:2:0.2 to 95:5:0.5) to afford the title compound, 6.2 g. 1H-NMR (CDCl3, 400MHz) δ: 1.10 (d, 3H), 2.24-2.40 (m, 2H), 2.65 (dd, 1H), 3.62-3.80 (m, 6H), 6.82 (d, 2H), 7.19 (d, 2H). LRMS: m/z (ES+) 218 [MNa+]
Reaction SMILES: [Si]([O:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([C:18]2[CH:31]=[CH:30][C:21]3[O:22][C:23]([CH3:29])([CH3:28])[C@@:24]4([CH3:27])[O:26][C@H:25]4[C:20]=3[CH:19]=2)(=[O:17])=[O:16])=[CH:11][CH:10]=1)(C(C)(C)C)(C)C.[OH:32][C:33]1[N:34]=[N:35][C:36]([OH:39])=[CH:37][CH:38]=1.N1C=CC=CC=1>C(O)C>[OH:26][C@:24]1([CH3:27])[C:23]([CH3:28])([CH3:29])[O:22][C:21]2[CH:30]=[CH:31][C:18]([S:15]([C:12]3[CH:11]=[CH:10][C:9]([OH:8])=[CH:14][CH:13]=3)(=[O:17])=[O:16])=[CH:19][C:20]=2[C@H:25]1[O:39][C:36]1[N:35]=[N:34][C:33]([OH:32])=[CH:38][CH:37]=1
Reactant: CC1(C)Oc2ccc(S(=O)(=O)c3ccc(O[Si](C)(C)C(C)(C)C)cc3)cc2[C@@H]2O[C@@]21C
Reactant: Oc1ccc(O)nn1
Solvent: c1ccncc1
Solvent: CCO
Product: CC1(C)Oc2ccc(S(=O)(=O)c3ccc(O)cc3)cc2[C@@H](Oc2ccc(O)nn2)[C@]1(C)O
Yield: 44.5 %

Procedure:
(3S,4S)-6-(4-tert-Butyldimethylsilyloxyphenyl)sulphonyl-3,4-dihydro-3,4-epoxy-2,2,3-trimethyl-2H-benzo[b]pyran (0.35 g) (see Preparation 14) and 3,6-dihydroxypyridazine (0.273 g) were suspended in absolute ethanol (3 ml), dry pyridine (0.065 ml) was added and the mixture was heated under reflux for 4 days. The solvent was then removed under reduced pressure and the residue chromatographed on silica with 1:99 methanol: ethyl acetate as the eluent to yield (3S,4R)-3,4-dihydro-3-hydroxy-6-(4-hydroxyphenyl)sulphonyl-4-(3-hydroxypyridazin-6-yl)oxy-2,2,3-trimethyl-2H-benzo[b]pyran (0.155 g) as a white solid, m.p.>200° C. Found: C,57.54; H,5.35; N,5.57. C22H22N2O7S, 0.20 ethyl acetate requires C,57.50; H,4.99; N,5.88%.
Reaction SMILES: [C:1]1([N:7]2[C:19](=O)[C:18]3[C:17]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[NH:11][CH2:10][C:9]=3[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C)CCN(C)C.C([Li])CCC.I[CH2:35][CH2:36][CH:37]1[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]1.[O:50]1CCCC1>C(#N)C>[O:50]=[C:10]1[C:9]2=[N:8][N:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[C:19]([CH2:35][CH2:36][CH:37]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]3)=[C:18]2[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[NH:11]1
Reactant: C1CCOC1
Reactant: O=c1c2c([nH]n1-c1ccccc1)CNc1ccccc1-2
Reactant: CC(C)(C)OC(=O)N1CCC(CCI)CC1
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: CC#N
Product: CC(C)(C)OC(=O)N1CCC(CCc2c3c(nn2-c2ccccc2)c(=O)[nH]c2ccccc23)CC1
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 75 %

Procedure:
Under a nitrogen atmosphere, a mixture of 2-phenyl-2,5-dihydro-4H-pyrazolo[3,4-c]quinoline-one (1.76 g, 6.76 mmol), N,N,N′,N′-tetramethylethylenediamine (4.5 mL), and tetrahydrofuran (75 mL) was chilled to 0° C. A solution of n-butyllithium in hexanes (8.1 mL of 2.5 M) was added dropwise. After the addition was complete the reaction mixture was stirred for 5 minutes at 0° C. and then cooled to −78° C. To the cooled solution was added tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylate (3.0 g, 8.8 mmol). The reaction mixture was warmed to ambient temperature and stirred for 30 minutes before quenching with saturated aqueous ammonium chloride. The aqueous layer was extracted with chloroform. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford a yellow oil, The yellow oil was stirred in acetonitrile and filtered to provide 1.4 g (75% pure) of tert-butyl 4-[2-(4-oxo-2-phenyl-4,5-dihydro-2H-pyrazolo[3,4-c]quinolin-1-yl)ethyl]piperidine-1-carboxylate as a tan solid.
Reaction SMILES: C1(C)C=CC(S(O[CH2:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=2)(=O)=O)=CC=1.[OH:24][CH2:25][CH2:26][CH2:27][NH2:28].O.C(Cl)(Cl)Cl>O1CCOCC1>[OH:24][CH2:25][CH2:26][CH2:27][NH:28][CH2:11][CH2:12][CH2:13][C:14]1[CH:15]=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=1
Reactant: NCCCO
Reactant: Cc1ccc(S(=O)(=O)OCCCc2ccc([N+](=O)[O-])cc2)cc1
Solvent: C1COCCO1
Solvent: O
Solvent: ClC(Cl)Cl
Product: O=[N+]([O-])c1ccc(CCCNCCCO)cc1
Temperature: 80 °C
Reaction time: 0.5 h

Procedure:
3-(4-nitrophenyl)propyl p-toluenesulfonate (1 g) and 4.1 ml of 3-hydroxypropylamine were dissolved in 10 ml of dioxane and the solution was stirred at 80° C. for 30 minutes. To the solution was added 100 ml of water and 100 ml of chloroform, and the mixture was thoroughly mixed for separation. The chloroform-layer fraction was taken, washed with water and then dried over sodium sulfate anhydrous. The solvent was removed in vacuo and 0.7 g of an oil of N-(3-hydroxypropyl-3-(4-nitrophenyl)propylamine was obtained.
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.[OH:8]N1[C:13](=[O:14])[C:12]2=CC=[CH:17][CH:18]=[C:11]2C1=O.O=O.[C:22]([OH:25])(=O)[CH3:23]>>[OH:8][C:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.[OH:25][C:22]12[CH2:23][CH:11]([CH2:18][CH2:17]1)[CH2:12][CH:13]2[OH:14]
Reactant: C1CC2CCC1C2
Reactant: CC(=O)O
Reactant: O=C1c2ccccc2C(=O)N1O
Agent: O=O
Product: OC12CCC(CC1)C2
Product: OC1CC2CCC1(O)C2
Yield: 44 %
Yield: 55 %

Procedure:
A mixture of 0.96 gram (10 millimoles) of norbornane, 0.13 gram (0.8 millimole) of N-hydroxyphthalimide, 0.015 gram (0.06 millimole) of Co(AA)2 and 10 milliliters of acetic acid was stirred in an oxygen atmosphere at a temperature of 75° C. for 15 hours to give 1-hydroxynorbornane (selectivity for norbornane 44%, yield 44%) and 1,2-dihydroxynorbornane (selectivity for norbornane 55%, yield 55%) with a transformation rate of norbornane of 99% and the selectivity for the alcohols of 99%.
Reaction SMILES: [Cl-].C[Al+]C.[NH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][N:7]=1.C([O:15][C:16]([C:18]1[CH:19]=[C:20]([O:28][C:29]2[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:31][CH:30]=2)[C:21]2[CH:25]=[C:24]([CH3:26])[S:23][C:22]=2[CH:27]=1)=O)C>ClC(Cl)C>[CH3:12][C:9]1[CH:10]=[CH:11][C:6]([NH:5][C:16]([C:18]2[CH:19]=[C:20]([O:28][C:29]3[CH:30]=[CH:31][C:32]([S:35]([CH3:38])(=[O:36])=[O:37])=[CH:33][CH:34]=3)[C:21]3[CH:25]=[C:24]([CH3:26])[S:23][C:22]=3[CH:27]=2)=[O:15])=[N:7][CH:8]=1
Reactant: Cc1ccc(N)nc1
Reactant: CCOC(=O)c1cc(Oc2ccc(S(C)(=O)=O)cc2)c2cc(C)sc2c1
Agent: C[Al+]C
Agent: [Cl-]
Solvent: CC(Cl)Cl
Product: Cc1ccc(NC(=O)c2cc(Oc3ccc(S(C)(=O)=O)cc3)c3cc(C)sc3c2)nc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 53.4 %

Procedure:
Dimethylaluminum chloride (16.1 mmol, 16.1 ml of 1M in hexanes) is added to a solution of 2-amino-5-picoline (1.74g, 16.1 mmol) in dichloroethane (10 ml) at 0 C. The mixture was allowed to warm to room temperature over a period of 1 h, then recooled to 0 C and treated with 4-(4-methanesulfonyl-phenoxy)-2-methyl-benzo[b]thiophene-6-carboxylic acid ethyl ester (0.63 g, crude product from previous step) in dichloroethane (5 ml) at 0 C. The mixture was allowed to warm to room temperature, and held at room temperature for 8 h. The reaction was quenched by the drop wise addition of MeOH (2 ml) at 0 C, followed by 1M aqueous pH6 phosphate buffer (10 ml), then ethyl acetate was added (50 ml). Separation of the organic layer followed by evaporation yields 0.80 g crude product. Purification by silica gel chromatography (0-20% MeOH-CHCl3) yielded 0.39 g (68%) of product 4-(4-methanesulfonyl-phenoxy)-2-methyl-benzo[b]thiophene-6-carboxylic acid(5-methyl-pyridin-2-yl)-amide. LRMS for C23H20N2O4S2 m/z 453 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.80 (s, 1H), 8.56 (s, 1H), 8.22 (d, J=2.3, 1H), 8.08 (d, J=8.3, 1H), 7.93 (d, J=8.8, 2H), 7.74 (d, J=1.2, 2H), 7.67 (dd, J=8.6, 2.0, 1H), 7.22 (d, J=8.8, 2H), 7.09 (s, 1H), 3.21 (s, 3H), 2.59 (d, J=1.0, 3H), 2.28 (s, 3H). Anal. Calcd. for C23H20N2O4S2: C, 61.04; H, 4.45; N, 6.19; Found: C, 61.01; H, 4.47; N, 5.96.
Reaction SMILES: [CH3:1][N:2]([CH2:12][CH2:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][CH:16]=1)[C:3]1[O:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[S:23]1[CH2:27][C:26](=[O:28])[NH:25][C:24]1=[O:29].C([O-])(=O)C.[NH2+]1CCCCC1>C1(C)C=CC=CC=1>[CH3:1][N:2]([CH2:12][CH2:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[C:27]2[S:23][C:24](=[O:29])[NH:25][C:26]2=[O:28])=[CH:17][CH:16]=1)[C:3]1[O:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1
Reactant: CN(CCOc1ccc(C=O)cc1)c1nc2ccccc2o1
Reactant: O=C1CSC(=O)N1
Agent: C1CC[NH2+]CC1
Agent: CC(=O)[O-]
Solvent: Cc1ccccc1
Product: CN(CCOc1ccc(C=C2SC(=O)NC2=O)cc1)c1nc2ccccc2o1

Procedure:
A solution of 4-[2-(N-methyl-N-(2-benzoxazolyl)amino) ethoxy]benzaldehyde (1.6 g) and 2,4-thiazolidinedione (0.63 g) in toluene (100 ml) containing a catalytic quantity of piperidinium acetate was boiled under reflux in a Dean and Stark apparatus for 2 hours. The mixture was cooled and filtered to give the title compound (mp 227°-9° C.).
Reaction SMILES: [OH:1][CH:2]([C:6]1[O:7][CH:8]=[CH:9][CH:10]=1)[CH2:3][CH:4]=[CH2:5].O.CC(C)=[O:14]>>[OH:1][CH:2]([C:6]1[O:7][CH:8]=[CH:9][CH:10]=1)[CH2:3][CH:4]=[CH2:5].[OH:14][CH:6]1[CH:2]([CH2:3][CH:4]=[CH2:5])[C:8](=[O:7])[CH:9]=[CH:10]1
Reactant: CC(C)=O
Agent: C=CCC(O)c1ccco1
Solvent: O
Product: C=CCC1C(=O)C=CC1O
Temperature: 55 °C
Reaction time: 48 h
Yield: 65.5 %

Procedure:
Into 350 ml of a water-acetone (1:6 by volume) mixture, was dissolved 10 g of 2-(1-hydroxy-3-butenyl)-furan. To the solution heated at 55° C. under reflux, was added dropwise 6.6 g of polyphosphoric acid. After having been stirred at 55° C. for 48 hours, the reaction mixture was stripped of the acetone by distillation and the residue was extracted twice with 300 ml of ether. The extract solution was washed with an aqueous sodium hydrogencarbonate solution, then with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and freed from the solvent by distillation to obtain 9.5 g of a concentrate. On distillation of the concentrate, there were obtained 4.2 g of 2-(1-hydroxy-3-butenyl)furan (b.p. 78° C./10 mmHg) and 3.8 g (65.5% yield based on consumed starting material) of the intended 4-hydroxy-5-allyl-2-cyclopentenone (b.p. 97° C./0.7 mmHg).
Reaction SMILES: S(Cl)([Cl:3])=O.[CH3:5][O:6][C:7]1[CH:8]=[C:9]([CH:14]=[CH:15][C:16]=1[N:17]([CH2:21]CO)[CH2:18][CH2:19]O)[C:10]([O:12][CH3:13])=[O:11].[CH2:24]([Cl:26])Cl>>[CH3:5][O:6][C:7]1[CH:8]=[C:9]([CH:14]=[CH:15][C:16]=1[N:17]([CH2:21][CH2:24][Cl:26])[CH2:18][CH2:19][Cl:3])[C:10]([O:12][CH3:13])=[O:11]
Reactant: ClCCl
Reactant: COC(=O)c1ccc(N(CCO)CCO)c(OC)c1
Reactant: O=S(Cl)Cl
Product: COC(=O)c1ccc(N(CCCl)CCCl)c(OC)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 88 %

Procedure:
Thionyl chloride (0.7 ml; 9.6 mmol) was added to a solution of 1.0 g (3.7 mmol) of methyl 3-methoxy-4-[bis(2-hydroxyethyl)amino]benzoate in 20 ml of methylene chloride, followed by stirring at room temperature for 3 hours. After the solvent was distilled out under reduced pressure, methylene chloride was added again in a small amount and was then distilled out under reduced pressure. This procedure was repeated twice. The resultant mixture was evaporated to dryness under reduced pressure, whereby 1.0 g of a brown oil was obtained (yield: 88%).
Reaction SMILES: [CH2:1]([O:4][C:5]1[C:14](C)=[CH:13][C:8]([C:9]([NH:11][OH:12])=[NH:10])=[CH:7][C:6]=1CC)[CH:2]=[CH2:3].O[C:19]1C=CC(C=O)=C(C)C=1>>[CH2:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]([C:9]([NH:11][OH:12])=[NH:10])=[C:13]([CH3:19])[CH:14]=1)[CH:2]=[CH2:3]
Reactant: C=CCOc1c(C)cc(C(=N)NO)cc1CC
Reactant: Cc1cc(O)ccc1C=O
Product: C=CCOc1ccc(C(=N)NO)c(C)c1

Procedure:
The title compound is prepared in analogy to 4-allyloxy-3-ethyl-N-hydroxy-5-methyl-benzamidine starting from commercially available 4-hydroxy-2-methyl-benzaldehyde; LC-MS: tR=0.62 min, [M+1]+=207.10; 13C NMR (CDCl3): δ 20.72, 68.91, 104.72, 112.75, 116.45, 118.32, 118.53, 132.25, 134.19, 144.09, 161.71.
Reaction SMILES: CC1C=C(C)C=C(C)C=1S([O-])(=O)=O.[NH2:14][N+:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[NH2:22].Cl[C:24](=O)[C:25]([O:27][CH2:28][CH3:29])=[O:26]>N1C=CC=CC=1>[Br:21][C:18]1[CH:19]=[CH:20][N:15]2[N:14]=[C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:22]=[C:16]2[CH:17]=1
Reactant: CCOC(=O)C(=O)Cl
Reactant: Nc1cc(Br)cc[n+]1N
Agent: Cc1cc(C)c(S(=O)(=O)[O-])c(C)c1
Solvent: c1ccncc1
Product: CCOC(=O)c1nc2cc(Br)ccn2n1
Yield: 60.3 %

Procedure:
A mixture of 1,2-diamino-4-bromopyridinium 2,4,6-trimethylbenzenesulfonate (4.18 g, 10.8 mmol) and ethyl 2-chloro-2-oxoacetate (2.4 ml, 21.5 mmol) in pyridine (25 ml) is heated for 18 hours to 100° C. The solvent is evaporated and the orange residue triturated with sat. aqueous sodium hydrogencarbonate solution for 2 hours. The solid is collected by filtration, washed several times with water and dried affording ethyl 7-bromo-[1,2,4]triazolo[1,5-a]pyridine-2-carboxylate (1.759 g, 60.5%) as a light pink solid. mp.: 158-160° C. MS: m/z=270.2 (M+H+).
Reaction SMILES: CO[C:3]([C:5]1[C:6]([OH:26])=[C:7]2[C:12](=[C:13]([C:15]#[N:16])[N:14]=1)[N:11]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:10](=[O:24])[C:9]([CH3:25])=[CH:8]2)=[O:4].[NH2:27][CH2:28][C:29]([OH:31])=[O:30].C[O-].[Na+]>>[CH2:17]([N:11]1[C:12]2[C:7](=[C:6]([OH:26])[C:5]([C:3]([NH:27][CH2:28][C:29]([OH:31])=[O:30])=[O:4])=[N:14][C:13]=2[C:15]#[N:16])[CH:8]=[C:9]([CH3:25])[C:10]1=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: NCC(=O)O
Reactant: COC(=O)c1nc(C#N)c2c(cc(C)c(=O)n2Cc2ccccc2)c1O
Agent: C[O-]
Agent: [Na+]
Product: Cc1cc2c(O)c(C(=O)NCC(=O)O)nc(C#N)c2n(Cc2ccccc2)c1=O
Temperature: 25 °C
Yield: 67.7 %

Procedure:
A mixture of 1-benzyl-8-cyano-5-hydroxy-3-methyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (100 mg, 0.29 mmol), glycine (2.86 g, 38 mmol) and NaOMe solution (57 mL, 29 mmol, 0.5M in MeOH) was refluxed for 16 h. After the mixture was cooled to r.t., the solvent was evaporated in vacuo. The residue was dissolved in saturated NaHCO3 and washed with ether. The aqueous layer was acidified to pH 2 with 4M HCl, and the resulting mixture was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated to give 77 mg of the title compound as a white solid. MS: (+) m/z 382.08 (M+1).
Reaction SMILES: [OH-:1].[K+].Cl[C:4](Cl)(Cl)[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:7]=1.S(=O)(=O)(O)O.[CH2:23]([OH:27])[CH2:24][CH2:25][CH3:26]>>[F:13][C:12]([F:15])([F:14])[C:8]1[CH:7]=[C:6]([CH2:5][C:4]([O:27][CH2:23][CH2:24][CH2:25][CH3:26])=[O:1])[CH:11]=[CH:10][CH:9]=1
Reactant: CCCCO
Reactant: FC(F)(F)c1cccc(CC(Cl)(Cl)Cl)c1
Reactant: [OH-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: CCCCOC(=O)Cc1cccc(C(F)(F)F)c1

Procedure:
To 5.6 g. of potassium hydroxide of the grade described above was added 25 ml. of butanol, and the mixture was stirred for 15 minutes. To it was added dropwise 2.8 g. of 1,1,1-trichloro-2-(3-trifluoromethylphenyl)ethane, and the mixture was stirred under reflux for 3.75 hours. It was then cooled to 5°, and to it was added dropwise 6 ml. of concentrated sulfuric acid. The mixture was then stirred under reflux for 30 minutes and cooled overnight. It was then reheated to reflux, and about 22 ml. of butanol and water was distilled away. The mixture was then cooled again, and diluted with about 50 ml. of water. The aqueous layer was separated and extracted with three 25 ml. portions of dichloromethane. The organic layers were combined, washed with 1 N sodium hydroxide, dried over sodium sulfate and evaporated under vacuum to obtain 3.0 g. of impure product. The product was dissolved in 30 ml. of dichloromethane, washed with water, dried over sodium sulfate and concentrated under vacuum again to obtain 2.67 g. of product, found to be 83% pure by vapor phase chromatography.
Reaction SMILES: [Br-].CC1[O:4][C:5](=[CH:12][Br:13])[C:6]([CH3:11])([CH:8]([CH3:10])[CH3:9])[NH+:7]=1>C(O)C>[BrH:13].[Br:13][CH2:12][C:5](=[O:4])[C:6]([CH3:11])([NH2:7])[CH:8]([CH3:10])[CH3:9]
Reactant: CC1=[NH+]C(C)(C(C)C)C(=CBr)O1
Agent: [Br-]
Solvent: CCO
Product: Br
Product: CC(C)C(C)(N)C(=O)CBr

Procedure:
A solution was prepared of 2,4-dimethyl-4-isopropyl-5-(bromomethylene)-2-oxazolinium bromide in ethanol and allowed to stand at room temperature. The solvent gradually evaporated and the solid residue was recrystallized from ethanol to yield 1-bromo-3,4-dimethyl-3-amino-2-pentanone hydrobromide having a melting point of about 158°-160° C. The material was identified by the n.m.r. spectrum.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]([S:14][CH2:15][CH3:16])[N:3]=1.[CH3:17][NH2:18]>CO>[CH2:15]([S:14][C:4]1[N:3]=[C:2]([CH2:17][NH2:18])[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=1)[CH3:16]
Reactant: CCSc1nc(Cl)cc(-c2ccccc2)n1
Reactant: CN
Solvent: CO
Product: CCSc1nc(CN)cc(-c2ccccc2)n1
Temperature: 30 °C

Procedure:
A mixture of compound 4-chloro-2-ethylsulfanyl-6-phenyl-pyrimidine (1 g, 4 mmol) and aqueous methylamine (0.74 g, 24 mmol) in methanol (20 mL) was stirred at refluxing temperature for 16 hours under nitrogen atmosphere. The reaction mixture was then cooled to temperature in the range of 20-40° C. The solid separated was filtered off and dried under reduced pressure. It was finally titrated with petroleum-ether to afford the title compound as an off white solid.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[CH2:10]([OH:12])[CH3:11].[CH2:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][C:14]1=O.[OH-].[Na+]>O>[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[C:11]1[C:17]2[C:16](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:15](=[CH:14][C:13]2[CH:8]=[CH:7][CH:6]=[CH:3][C:2]=2[F:1])[C:10]1=[O:12]
Reactant: O=C1Cc2ccccc2C1
Reactant: CCO
Reactant: O=Cc1ccccc1F
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C1C(=Cc2ccccc2F)c2ccccc2C1=Cc1ccccc1F
Reaction time: 12 h

Procedure:
A solution of 1.88 g (15.13 mmol) of 2-fluorobenzaldehyde in 3.0 mL of abs. ethanol was added over a period of 5 min to a solution containing 1.00 g (7.57 mmol) of 2-indanone and 90 mg (2.27 mmol) of NaOH in 40 mL of a 1:1 mixture of abs.ethanol and water at room temperature. The mixture was allowed to stir for 12 hrs and solids formed were collected by suction filtration and washed with cold ethanol and dried under high vacuum.